詳細

松本　久子 （マツモト　ヒサコ）

  • 医学科　教授/主任
Last Updated :2024/04/25

コミュニケーション情報 byコメンテータガイド

  • コメント

    気管支喘息、慢性咳嗽を中心に臨床研究を行っていました。

研究者情報

学位

  • 医学博士号（京都大学）

ホームページURL

J-Global ID

研究キーワード

  • 呼吸器疾患   喘息・慢性咳嗽   気管支拡張症   COPD   

現在の研究分野（キーワード）

    気管支喘息、慢性咳嗽を中心に臨床研究を行っていました。

研究分野

  • ライフサイエンス / 呼吸器内科学

経歴

  • 2021年04月 - 現在  近畿大学内科学教室 呼吸器・アレルギー内科主任教授
  • 2018年06月 - 2021年03月  京都大学大学院医学研究科呼吸器内科学准教授
  • 2017年05月 - 2018年05月  京都大学大学院医学研究科呼吸器内科学講師
  • 2012年05月 - 2017年04月  京都大学医学部附属病院呼吸器内科院内講師
  • 2002年06月 - 2012年04月  京都大学医学部附属病院呼吸器内科助手（現称助教）
  • 2005年05月 - 2006年08月  University of SydneyDepartment of PharmacologyVisiting Academics

学歴

  • 1995年04月 - 1999年03月   京都大学大学院   医学研究科
  • 1984年04月 - 1990年03月   京都大学   医学部

所属学協会

  • 日本呼吸器内視鏡   日本感染症   日本アレルギー   日本呼吸器   日本内科   日本咳嗽学会   American Thoracic Society   日本喘息学会   

研究活動情報

論文

  • Yusuke Hayashi; Naoya Tanabe; Hisako Matsumoto; Kaoruko Shimizu; Ryo Sakamoto; Tsuyoshi Oguma; Hironobu Sunadome; Atsuyasu Sato; Susumu Sato; Toyohiro Hirai
    Allergology international : official journal of the Japanese Society of Allergology 2024年02月 
    BACKGROUND: Associations of fractional exhaled nitric oxide (FeNO) with airway wall remodeling and mucus plugs remain to be explored in smokers and nonsmokers with asthma. Ultra-high-resolution computed tomography (U-HRCT), which allows accurate structural quantification of airways >1 mm in diameter, was used in this study to examine whether higher FeNO was associated with thicker walls of the 3rd to 6th generation airways and mucus plugging in patients with asthma. METHODS: The retrospective analyses included consecutive former smokers and nonsmokers with asthma who underwent U-HRCT in a hospital. The ratio of wall area to summed lumen and wall area was calculated as the wall area percent (WA%). Mucus plugging was visually scored. RESULTS: Ninety-seven patients with asthma (including 59 former smokers) were classified into low (<20 ppb), middle (20-35 ppb), and high (>35 ppb) FeNO groups (n = 24, 26, and 47). In analysis including all patients and subanalysis including nonsmokers or former smokers, WA% in the 6th generation airways was consistently higher in the high FeNO group than in the low FeNO group, whereas WA% in the 3rd to 5th generation airways was not. In multivariable models, WA% in the 6th generation airways and the rate of mucus plugging were higher in the high FeNO group than in the low FeNO group after adjusting for age, sex, body mass index, smoking status, lung volume, and allergic rhinitis presence. CONCLUSIONS: Higher FeNO may reflect the inflammation and remodeling of relatively peripheral airways in asthma in both former smokers and nonsmokers.
  • Chie Morimoto; Hisako Matsumoto; Natsuko Nomura; Hironobu Sunadome; Tadao Nagasaki; Susumu Sato; Atsuyasu Sato; Tsuyoshi Oguma; Isao Ito; Mariko Kogo; Keisuke Tomii; Tomoko Tajiri; Kai Ohashi; Takamitsu Tsukahara; Toyohiro Hirai
    The journal of allergy and clinical immunology. Global 3 1 100194 - 100194 2024年02月 
    BACKGROUND: Airway microbiota in asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) remains unknown. OBJECTIVE: This study with ACO-enriched population aimed to clarify airway microbiota in ACO and in mixed granulocytic inflammation, often detected in ACO and chronic airway diseases. METHODS: This is an observational cross-sectional study. Patients with asthma with airflow limitation, ACO, and COPD were enrolled. Blood tests, pulmonary function, exhaled nitric oxide, and sputum tests were conducted. Sputum microbiota was evaluated using the 16S rRNA gene sequencing technique. RESULTS: A total of 112 patients (13 asthma, 67 ACO, and 32 COPD) were examined. There were no significant differences in α-diversity among the 3 diseases. The relative abundances of phylum Bacteroidetes, class Bacteroidia, and genus Porphyromonas were associated with decreased eosinophilic inflammation, and were significantly lower in ACO than in COPD. In a comparison of sputum inflammatory subtypes, the proportion of Haemophilus was numerically highest in the mixed granulocytic subtype, followed by the neutrophilic subtype. Likewise, the proportion of Haemophilus was the highest in the intermediate-high (2%-8%) sputum eosinophil group and lowest in the severe (≥8%) eosinophil group. Clinically, Haemophilus proportion was associated with sputum symptoms. Finally, the proportion of Streptococcus was associated with higher blood eosinophil counts and most severe airflow limitation. CONCLUSIONS: Bacteroidia and Porphyromonas abundances in sputum are associated with the eosinophil-low phenotype, and ACO may be characterized by a decrease in these taxa. A mild elevation in sputum eosinophil does not preclude the presence of Haemophilus, which should be noted in the management of obstructive airway diseases.
  • Kenta Nishi; Tadao Nagasaki; Hisako Matsumoto; Tsuyoshi Oguma; Satoru Terada; Natsuko Nomura; Mariko Kogo; Noriyuki Tashima; Hironobu Sunadome; Kimihiko Murase; Takeshi Matsumoto; Takahisa Kawaguchi; Yasuharu Tabara; Fumihiko Matsuda; Susumu Sato; Kazuo Chin; Toyohiro Hirai
    Allergology international : official journal of the Japanese Society of Allergology 2023年11月 
    BACKGROUND: Asthma in the elderly needs more attention in an aging society. However, it is likely to remain underdiagnosed and undertreated. This study aimed to clarify clinical characteristics of new-onset asthma in the elderly, describing the prevalence, predictive factors, and comorbidities after asthma diagnosis of new-onset asthma in the elderly in the general population. METHODS: This community-based prospective cohort study enrolled 9804 generally healthy participants (30-74 years old) in Nagahama City, and conducted a follow-up assessment after 5 years. Elderly participants were those aged ≥65 years at baseline. Patients with new-onset asthma were defined as participants without asthma at baseline assessment and with asthma at the follow-up assessment. RESULTS: Among the 7948 participants analyzed in this study, 28 (1.4%) elderly and 130 (2.2%) non-elderly had new-onset asthma. Multiple logistic regression analysis revealed low forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and high blood eosinophil counts at baseline as predicting factors for new-onset asthma in the elderly. Additionally, subsequent incidence of new-onset asthma was higher in elderly participants with both predictors (high blood eosinophil counts and low FEV1/FVC at baseline) than those with none or one of the predictors before asthma diagnosis. Lastly, elderly patients with new-onset asthma had more frequent comorbidity of moderate to sleep disordered breathing than those non-elderly. CONCLUSIONS: Eosinophilic inflammation and airflow obstruction may predict subsequent new-onset asthma after the age of 65 years. Revealing the characteristics of new-onset asthma in the elderly can aid in the prevention of underdiagnosed asthma.
  • Akiko Sano; Takenori Kozuka; Nanase Watatani; Yuuki Kunita; Yoshiyuki Kawabata; Kyuya Gose; Ken Shirahase; Kazuya Yoshikawa; Ryo Yamazaki; Yusaku Nishikawa; Takashi Omori; Osamu Nishiyama; Takashi Iwanaga; Hiroyuki Sano; Ryuta Haraguchi; Yuji Tohda; Hisako Matsumoto
    Allergology international : official journal of the Japanese Society of Allergology 2023年11月 
    BACKGROUND: Obstructive sleep apnea (OSA) is one of the major co-morbidities and aggravating factors of asthma. In OSA-complicated asthma, obesity, visceral fat, and systemic inflammation are associated with its severity, but the role of bronchial hyperresponsiveness (BHR) is unclear. We investigated the involvement of BHR and mediastinal fat width, as a measure of visceral fat, with OSA severity in patients with OSA and asthma-like symptoms. METHODS: Patients with OSA who underwent BHR test and chest computed tomography scan for asthma-like symptoms were retrospectively enrolled. We evaluated the relationship between apnea-hypopnea index (AHI) and PC20 or anterior mediastinal fat width, stratified by the presence or absence of BHR. RESULTS: OSA patients with BHR (n = 29) showed more obstructive airways and frequent low arousal threshold and lower mediastinal fat width, and tended to show fewer AHI than those without BHR (n = 25). In the overall analysis, mediastinal fat width was significantly positively correlated with AHI, which was significant even after adjustment with age and gender. This was especially significant in patients without BHR, while in OSA patients with BHR, there were significant negative associations between apnea index and airflow limitation, and hypopnea index and PC20. CONCLUSIONS: Risk factors for greater AHI differed depending on the presence or absence of BHR in OSA patients with asthma-like symptoms. In the presence of BHR, severity of asthma may determine the severity of concomitant OSA.
  • Tomoki Maetani; Naoya Tanabe; Atsuyasu Sato; Yusuke Shiraishi; Ryo Sakamoto; Emiko Ogawa; Hiroaki Sakai; Hisako Matsumoto; Susumu Sato; Hiroshi Date; Toyohiro Hirai; Shigeo Muro
    ERJ open research 9 5 2023年09月 
    INTRODUCTION: Airway eosinophilic inflammation is a pathological feature in a subgroup of patients with COPD and in some smokers with a high COPD risk. Although blood eosinophil count is used to define eosinophilic COPD, the association between blood eosinophil count and airway eosinophilic inflammation remains controversial. This cross-sectional study tested this association in smokers with and without COPD while considering potential confounders, such as smoking status and comorbidities. METHODS: Lung specimens were obtained from smokers with and without COPD and non-COPD never-smokers undergoing lung lobectomy. Those with any asthma history were excluded. The infiltration of eosinophils into the small airway wall was quantified on histological sections stained with major basic protein (MBP). RESULTS: The number of airway MBP-positive cells was greater in smokers (n=60) than in never-smokers (n=14). Smokers with and without COPD (n=30 each) exhibited significant associations between blood eosinophil count and airway MBP-positive cells (ρ=0.45 and 0.71). When smokers were divided into the high and low airway MBP groups based on their median value, blood eosinophil count was higher in the high-MBP group, with no difference in age, smoking status, comorbidities, emphysema or coronary artery calcification on computed tomography, and inhaled corticosteroid (ICS) use. The association between greater blood eosinophil count and the high-MBP group was confirmed in multivariable models adjusted for smoking status, airflow limitation and ICS use. CONCLUSION: The blood eosinophil count may reflect eosinophilic inflammation in the small airways in smokers with and without COPD.
  • Satoru Terada; Hisako Matsumoto; Kenta Nishi; Mariko Kogo; Natsuko Nomura; Noriyuki Tashima; Chie Morimoto; Hironobu Sunadome; Tadao Nagasaki; Tsuyoshi Oguma; Yoshinari Nakatsuka; Kimihiko Murase; Takahisa Kawaguchi; Yasuharu Tabara; Kazuhiro Sonomura; Fumihiko Matsuda; Kazuo Chin; Toyohiro Hirai
    Scientific reports 13 1 13921 - 13921 2023年08月 
    Little is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as "new-onset prolonged cough". Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.
  • Mariko Kogo; Susumu Sato; Shigeo Muro; Hisako Matsumoto; Natsuko Nomura; Tsuyoshi Oguma; Hironobu Sunadome; Tadao Nagasaki; Kimihiko Murase; Takahisa Kawaguchi; Yasuharu Tabara; Fumihiko Matsuda; Kazuo Chin; Toyohiro Hirai
    Annals of the American Thoracic Society 20 11 1578 - 1586 2023年08月 
    Rationale Subjects with preserved ratio impaired spirometry (PRISm) experience increased respiratory symptoms, although they present heterogeneous characteristics. However, the longitudinal changes in these symptoms and respiratory function are not well known. Objective To investigate PRISm from the viewpoint of respiratory symptoms in a longitudinal large-scale general population study. Methods The Nagahama study included 9,789 inhabitants, and a follow-up evaluation was conducted after 5 years. Spirometry and self-administered questionnaires regarding respiratory symptoms, including prolonged cough, sputum and dyspnea, and comorbidities were conducted. Results In total, 9,760 subjects were analyzed, and 438 subjects had PRISm. Among the subjects with PRISm, 53% presented with respiratory symptoms; dyspnea was independently associated with PRISm. Follow-up assessment revealed that 73% of the subjects with PRISm with respiratory symptoms were consistently symptomatic, whereas 39% of the asymptomatic subjects with PRISm developed respiratory symptoms within 5 years. Additionally, among subjects with respiratory symptoms without airflow limitation at baseline, PRISm was a risk factor for the development of airflow limitation independent of smoking history and comorbidities. Conclusions This study demonstrated that 53% of the subjects with PRISm had respiratory symptoms; dyspnea was a distinct characteristic of PRISm. Approximately three-fourths of the symptomatic subjects with PRISm consistently complained of respiratory symptoms within five years. Together with our result that PRISm itself is an independent risk factor for the development of COPD among subjects with respiratory symptoms, the clinical course of subjects with PRISm with symptoms requires careful monitoring.
  • Noriyuki Tashima; Hisako Matsumoto; Kenta Nishi; Satoru Terada; Mariko Kogo; Natsuko Nomura; Chie Morimoto; Hironobu Sunadome; Tadao Nagasaki; Tsuyoshi Oguma; Yoshinari Nakatsuka; Kimihiko Murase; Takahisa Kawaguchi; Yasuharu Tabara; Kazuo Chin; Kazuhiro Sonomura; Fumihiko Matsuda; Toyohiro Hirai
    Allergology international : official journal of the Japanese Society of Allergology 2023年05月 
    BACKGROUND: Obesity and increased body mass index (BMI) are the known risk factors for adult-onset asthma. Serum free fatty acid (FFA) and other blood lipid levels are generally elevated in patients with obesity and may be involved in the onset of asthma. However, it remains largely unknown. This study aimed to elucidate the relationship between plasma fatty acids and new-onset asthma. METHODS: This community-based Nagahama Study in Japan enrolled 9804 residents. We conducted self-reporting questionnaires, lung function tests, and blood tests at baseline and 5 years later as follow-up. At the follow-up, plasma fatty acids were measured using gas chromatography-mass spectrometry. Body composition analysis was also measured at the follow-up. The associations between fatty acids and new-onset asthma were evaluated using a multifaceted approach, including targeted partial least squares discriminant analysis (PLS-DA). RESULTS: In PLS-DA for new-onset asthma, palmitoleic acid was identified as the fatty acid most associated with asthma onset. In the multivariable analysis, higher levels of FFA, palmitoleic acid, or oleic acid were significantly associated with new-onset asthma, independent of other confounding factors. The high body fat percentage itself was not the relevant factor, but showed a positive interaction with plasma palmitoleic acid for new-onset asthma. When stratified by gender, the impacts of higher levels of FFA or palmitoleic acid on new-onset asthma remained significant in females, but not in males. CONCLUSIONS: Elevated levels of plasma fatty acids, particularly palmitoleic acid, may be a relevant factor for new-onset asthma.
  • Natsuko Nomura; Hisako Matsumoto; Hironobu Sunadome; Tsuyoshi Oguma; Toyohiro Hirai
    The Journal of allergy and clinical immunology 151 5 1410 - 1411 2023年05月
  • Ryo Yamazaki; Osamu Nishiyama; Kazuya Yoshikawa; Yuji Tohda; Hisako Matsumoto
    Respiratory investigation 61 3 339 - 346 2023年03月 
    BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have a slowly progressive clinical course, although some develop acute exacerbations (AEs). An easily obtained composite score is desirable for predicting the survival rate in patients with AE of IPF (AE-IPF). We investigated the quick sequential organ failure assessment (qSOFA), originally developed to identify sepsis, as a predictor of mortality in patients with AE-IPF and compared it to other composite assessments. METHODS: Consecutive patients with IPF admitted for their first AE between 2008 and 2019 were recruited retrospectively. The association between the qSOFA score obtained at admission and mortality was investigated. RESULTS: During the study period, 97 patients with AE-IPF were hospitalized. The hospital mortality was 30.9%. Multivariate logistic regression analysis revealed that both the qSOFA and the Japanese Association for Acute Medicine (JAAM)-disseminated intravascular coagulation (DIC) scores were significant predictors of hospital mortality (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.43-10.3; p = 0.007 and OR 2.71, 95% CI 1.56-4.67; p = 0.0004; respectively). Kaplan-Meier survival curves showed that both scores were consistently associated with survival. Furthermore, the sum of the two scores was a more effective predictor than the individual scores. CONCLUSIONS: The qSOFA score of patients admitted with AE-IPF was associated with both in-hospital and long-term mortality, which was also true for the JAAM-DIC score. The qSOFA score plus the JAAM-DIC score should be determined during the diagnostic evaluation of a patient with AE-IPF. Both scores combined may be more effective at predicting outcomes than individual scores.
  • Kenta Nishi; Chie Yoshimura; Kyohei Morita; Ryoichi Ishikawa; Erika Toyokura; Tadao Nagasaki; Hisako Matsumoto; Yasuo Nishizaka
    The World Allergy Organization journal 16 3 100756 - 100756 2023年03月 
    Bronchial thermoplasty (BT) is effective in some severe asthma patients; however, the specific asthma phenotypes that produce a good response to BT are not fully understood. Clinical data were retrospectively reviewed in severe asthma patients who underwent BT at a single institution in Japan. At the follow-up assessment, the Asthma Quality of Life Questionnaire (AQLQ) scores (P = 0.003), maintenance oral corticosteroid doses (P = 0.027), and exacerbation frequency (P = 0.017) were significantly improved, while prebronchodilator-forced expiratory volume in 1 second (% predicted) did not significantly change (P = 0.19). When we grouped the patients into 2 groups according to their body mass index levels, the AQLQ scores were more improved in patients with overweight/obesity than those with normal weight (P = 0.01). This study showed that patients with non-controlled severe asthma exhibiting overweight/obesity and low quality of life had potential benefits from BT.
  • Soichiro Hanada; Masato Muraki; Yoshiyuki Kawabata; Kazuya Yoshikawa; Toshiyuki Yamagata; Tadao Nagasaki; Yushiro Ohara; Naoki Oiso; Hisako Matsumoto; Yuji Tohda
    Patient preference and adherence 17 2847 - 2853 2023年 
    PATIENTS AND METHODS: A questionnaire survey was administered to 18, 14, and 3 patients introduced to home self-injection of dupilumab or mepolizumab using a pen-type device for atopic dermatitis, asthma alone, and asthma plus chronic rhinosinusitis with nasal polyps, respectively. RESULTS: All but one participant wished to continue self-injection. Most participants affirmed the reduction in copayment (88.6%) and saving time and labor for hospital visits (88.6%). Six patients who received dupilumab complained of side effects, but all, except for one, continued the treatment. Of the 13 patients who had previously used a syringe-type device, 10 preferred the pen type because of its ease of use, while 3 (23%) preferred the syringe type because of the self-adjustable injection speed for pain control. CONCLUSION: Administration of biologics using pen-type devices is easier, and the introduction of home self-injection leads to a reduction in outpatient visits and copayment.
  • Chie Morimoto; Hisako Matsumoto; Isao Ito; Tadao Nagaski; Tsuyoshi Oguma; Toyohiro Hirai
    Respiratory investigation 61 1 23 - 26 2023年01月 
    Staphylococcus aureus (S. aureus) is an inducer of mucosal type 2 immune response. To test the hypothesis that airway colonization with S. aureus may reflect allergic predisposition with staphylococcal enterotoxin (SE) sensitization in bronchiectasis, we retrospectively examined the association between SE sensitization and S. aureus and Pseudomonas aeruginosa (P. aeruginosa) in sputum of patients with bronchiectasis (n = 35). Overall, 14 (40%) patients with bronchiectasis were sensitized to either staphylococcal enterotoxin A (SEA) or staphylococcal enterotoxin B (SEB). SEA sensitization was more frequently observed in patients with sputum S. aureus than those without it. Patients with sputum S. aureus but without P. aeruginosa exhibited the highest SEA sensitization frequency and serum total IgE levels. Patients with both S. aureus and P. aeruginosa exhibited the highest blood eosinophils. In conclusion, S. aureus in the lower airway may indicate an allergic predisposition with SE sensitization and blood eosinophilia in bronchiectasis.
  • Natsuko Nomura; Hisako Matsumoto; Akihito Yokoyama; Yoshihiro Nishimura; Koichiro Asano; Akio Niimi; Yuji Tohda; Norihiro Harada; Hiroyuki Nagase; Makoto Nagata; Hiromasa Inoue; Mitsuko Kondo; Takahiko Horiguchi; Nobuaki Miyahara; Nobuyuki Hizawa; Masayuki Hojo; Noboru Hattori; Naozumi Hashimoto; Akira Yamasaki; Toru Kadowaki; Tomoki Kimura; Mari Miki; Hirokazu Taniguchi; Mikio Toyoshima; Tetsuji Kawamura; Osamu Matsuno; Yoko Sato; Hironobu Sunadome; Tadao Nagasaki; Tsuyoshi Oguma; Toyohiro Hirai
    Respiratory research 23 1 365 - 365 2022年12月 
    RATIONALE: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control. OBJECTIVE: We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them. METHODS: We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed. RESULTS: In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO. CONCLUSIONS: Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.
  • Mariko Kogo; Susumu Sato; Shigeo Muro; Hisako Matsumoto; Natsuko Nomura; Noriyuki Tashima; Tsuyoshi Oguma; Hironobu Sunadome; Tadao Nagasaki; Kimihiko Murase; Takahisa Kawaguchi; Yasuharu Tabara; Fumihiko Matsuda; Kazuo Chin; Toyohiro Hirai
    Scientific reports 12 1 20060 - 20060 2022年11月 
    Subjects with subclinical respiratory dysfunction who do not meet the chronic obstructive pulmonary disease (COPD) criteria have attracted attention with regard to early COPD intervention. Our aim was to longitudinally investigate the risks for the development of airflow limitation (AFL) and dyspnoea, the main characteristics of COPD, in a large-scale community-based general population study. The Nagahama study included 9789 inhabitants, and a follow-up evaluation was conducted after 5 years. AFL was diagnosed using a fixed ratio (forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) < 0.7). We enrolled normal subjects aged 40-75 years with no AFL, dyspnoea or prior diagnosis of asthma or COPD at baseline. In total, 5865 subjects were analysed, 310 subjects had subclinical respiratory dysfunction (FEV1/FVC < the lower limit of normal; n = 57, and FEV1 < 80% of the predicted value (preserved ratio impaired spirometry); n = 256). A total of 5086 subjects attended the follow-up assessment, and 449 and 1021 subjects developed AFL and dyspnoea, respectively. Of these, 100 subjects developed AFL with dyspnoea. Baseline subclinical respiratory dysfunction was independently and significantly associated with AFL with dyspnoea development within 5 years. Subjects with subclinical respiratory dysfunction are at risk of developing COPD-like features and require careful monitoring.
  • Issei Oi; Isao Ito; Naoya Tanabe; Satoshi Konishi; Nobuyoshi Hamao; Masahiro Shirata; Seiichiro Imai; Yoshiro Yasutomo; Seizo Kadowaki; Hisako Matsumoto; Yu Hidaka; Satoshi Morita; Toyohiro Hirai
    PLOS ONE 17 10 e0274685 - e0274685 2022年10月 
    Introduction Despite the poor prognosis for nursing home acquired pneumonia (NHAP), a useful prognostic factor is lacking. We evaluated protein C (PC) activity as a predictor of in-hospital death in patients with NHAP and community-acquired pneumonia (CAP). Methods This prospective, observational study included all patients hospitalized with pneumonia between July 2007 and December 2012 in a single hospital. We measured PC activity at admission and investigated whether it was different between survivors and non-survivors. We also examined whether PC activity < 55% was a predictor for in-hospital death of pneumonia by logistic regression analysis with CURB-65 items (confusion, blood urea >20 mg/dL, respiratory rate >30/min, and blood pressure <90/60 mmHg, age >65). When it was a useful prognostic factor for pneumonia, we combined PC activity with the existing prognostic scores, the pneumonia severity index (PSI) and CURB-65, and analyzed its additional effect by comparing the areas under the receiver operating characteristic curves (AUCs) of the modified and original scores. Results Participants comprised 75 NHAP and 315 CAP patients. PC activity was lower among non-survivors than among survivors in NHAP and all-pneumonia (CAP+NHAP). PC activity <55% was a useful prognostic predictor for NHAP (Odds ratio 7.39 (95% CI; 1.59–34.38), and when PSI or CURB-65 was combined with PC activity, the AUC improved (from 0.712 to 0.820 for PSI, and 0.657 to 0.734 for CURB-65). Conclusions PC activity was useful for predicting in-hospital death of pneumonia, especially in NHAP, and became more useful when combined with the PSI or CURB-65.
  • Kae Okoshi; Koya Hida; Koichi Kinoshita; Toshitaka Morishima; Yoshie Nagai; Yasuko Tomizawa; Kyoko Yorozuya; Takehiro Nishida; Hisako Matsumoto; Hiroshi Yamato
    Surgery today 52 9 1348 - 1349 2022年09月
  • Ryo Yamazaki; Osamu Nishiyama; Kazuya Yoshikawa; Yuji Tohda; Hisako Matsumoto
    Respiratory medicine 201 106933 - 106933 2022年09月 
    BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is diagnosed incidentally in some patients with minimal or no respiratory symptoms. The clinical features of such patients are unknown. Herein we aimed to clarify the prevalence, clinical course, and prognostic factors of patients who were incidentally diagnosed with IPF. METHODS: The files of consecutive patients with newly diagnosed IPF were retrospectively reviewed to determine the methods involved in their diagnosis, and their outcomes. RESULTS: Among a total of 107 patients with newly diagnosed IPF, 35 (32.7%) were diagnosed incidentally, including 18 undergoing annual health check-ups and 17 undergoing assessment for other medical problems. The median survival from the time of diagnosis was 4.9 years for the 35 patients diagnosed incidentally, which was comparable to the median survival of 3.9 years for the 72 who were not diagnosed incidentally. The body mass index (BMI) was the sole independent predictor of survival (hazard ratio 0.78, 95% confidence interval 0.65-0.93, p = 0.006) in patients diagnosed incidentally. CONCLUSIONS: Nearly one third of patients with IPF were diagnosed incidentally, and their survival was still poor. Identifying patients during the earliest stage of IPF, particularly those with a low BMI, is warranted.
  • Kae Okoshi; Koya Hida; Koichi Kinoshita; Toshitaka Morishima; Yoshie Nagai; Yasuko Tomizawa; Kyoko Yorozuya; Takehiro Nishida; Hisako Matsumoto; Hiroshi Yamato
    Surgery Today 52 9 1341 - 1347 2022年09月 [査読有り]
     
    PURPOSE: Surgical smoke is generated during the cauterization, coagulation, and incision of biological tissues by electrocautery, ultrasonic coagulation, incising devices, and lasers. Surgical smoke comprises water, water vapor, steam, and some particulate matter, including bacteria, viruses, cell fragments, and volatile organic compounds, which can pose health risks to the operating room personnel. In this study, we measured the concentration of particulate matter 2.5 (particles with a diameter of ≤ 2.5 μm) in surgical smoke. METHODS: We used digital dust counters for real-time monitoring of particulate matter 2.5 generated intraoperatively in breast and gastrointestinal surgeries performed at our hospitals between 2019 and 2020. RESULTS: Concentrations of particulate matter 2.5 were measured in surgical smoke generated when performing 14 different surgeries. Immediately after electrocautery, the concentration of particulate matter 2.5 increased to 2258 μg/m3 and then, when we stopped using the devices, it decreased rapidly to the initial levels. Interestingly, the concentrations increased after each intermittent electrocautery procedure. Higher concentrations of particulate matter 2.5 were observed during breast surgeries than during laparoscopic procedures. CONCLUSION: Surgical smoke poses potential health risks to operating room personnel by contaminating their breathing zone with high concentrations of particulate matter 2.5. A local exhaust ventilation system is needed to reduce exposure.
  • 西 健太; 長崎 忠雄; 松本 久子; 小熊 毅; 寺田 悟; 野村 奈都子; 古郷 摩利子; 砂留 広伸; 村瀬 公彦; 川口 喬久; 田原 康玄; 松田 文彦; 佐藤 晋; 陳 和夫; 平井 豊博
    アレルギー 71 6-7 822 - 822 (一社)日本アレルギー学会 2022年08月
  • Hisako Matsumoto
    Respiratory investigation 60 2 187 - 196 2022年03月 
    Asthma and bronchiectasis are different diseases; however, differentiating them can be difficult because they share several symptomatic and physiological similarities. Approximately 20% of patients with bronchiectasis have eosinophilic inflammation, 34% show wheezing, and 7-46% have comorbid asthma, although comorbidity with severe asthma may be limited as shown in 3.3% of cases of bronchiectasis. Meanwhile, 25-68% of patients with severe asthma have comorbid bronchiectasis, and at least two phenotypes are present in the accompanying bronchiectasis: eosinophilic bronchiectasis and chronic infectious bronchiolitis/bronchiectasis. Recent studies show that type-2-targeted biologics are effective for eosinophilic bronchiectasis and theoretically effective for some of the remaining cases when used before oral corticosteroids. Further studies are needed to identify treatment strategies for severe asthma with comorbid bronchiectasis and vice versa.
  • Tadao Nagasaki; Hisako Matsumoto
    Arerugi = [Allergy] 71 1 17 - 21 2022年
  • Hisako Matsumoto
    Arerugi = [Allergy] 71 9 1065 - 1071 2022年
  • Masahiro Shirata; Isao Ito; Tadashi Ishida; Hiromasa Tachibana; Naoya Tanabe; Satoshi Konishi; Issei Oi; Nobuyoshi Hamao; Kensuke Nishioka; Hisako Matsumoto; Yoshiro Yasutomo; Seizo Kadowaki; Hisashi Ohnishi; Hiromi Tomioka; Takashi Nishimura; Yoshinori Hasegawa; Atsushi Nakagawa; Toyohiro Hirai
    Scientific reports 11 1 23878 - 23878 2021年12月 
    The discriminative power of CURB-65 for mortality in community-acquired pneumonia (CAP) is suspected to decrease with age. However, a useful prognostic prediction model for older patients with CAP has not been established. This study aimed to develop and validate a new scoring system for predicting mortality in older patients with CAP. We recruited two prospective cohorts including patients aged ≥ 65 years and hospitalized with CAP. In the derivation (n = 872) and validation cohorts (n = 1,158), the average age was 82.0 and 80.6 years and the 30-day mortality rate was 7.6% (n = 66) and 7.4% (n = 86), respectively. A new scoring system was developed based on factors associated with 30-day mortality, identified by multivariate analysis in the derivation cohort. This scoring system named CHUBA comprised five variables: confusion, hypoxemia (SpO2 ≤ 90% or PaO2 ≤ 60 mmHg), blood urea nitrogen ≥ 30 mg/dL, bedridden state, and serum albumin level ≤ 3.0 g/dL. With regard to 30-day mortality, the area under the receiver operating characteristic curve for CURB-65 and CHUBA was 0.672 (95% confidence interval, 0.607-0.732) and 0.809 (95% confidence interval, 0.751-0.856; P < 0.001), respectively. The effectiveness of CHUBA was statistically confirmed in the external validation cohort. In conclusion, a simpler novel scoring system, CHUBA, was established for predicting mortality in older patients with CAP.
  • Yuji Tohda; Hisako Matsumoto; Masanori Miyata; Yurie Taguchi; Maki Ueyama; Florence Joulain; Ichiro Arakawa
    The Journal of asthma : official journal of the Association for the Care of Asthma 59 11 1 - 12 2021年12月 
    BACKGROUND: Asthma is a common, chronic inflammatory airway disorder, with up to 1,177,000 people receiving asthma treatment in Japan. Dupilumab is a first-in-class, monoclonal antibody for the treatment of atopic diseases, including persistent asthma. The objective of this study was to assess the cost-effectiveness of dupilumab, compared with other biologics, as add-on treatment to background therapy in patients aged ≥12 years with uncontrolled, persistent asthma in Japan. METHODS: A life-time Markov cohort model was used to conduct cost-effectiveness analysis from the Japanese healthcare payer perspective with an annual discount rate of 2%. Dupilumab was compared with benralizumab and mepolizumab, and against omalizumab (as a hypothetical scenario). Inputs were informed by dupilumab clinical trials (VENTURE [NCT02528214] and QUEST [NCT02414854] trials), the literature, official Japanese sources and expert opinions. RESULTS: The base case results suggest that treatment with dupilumab leads to fewer severe exacerbations and increased life-years (LYs) and quality-adjusted LYs (QALYs) than benralizumab and mepolizumab. At a willingness-to-pay (WTP) threshold of \5,000,000 per QALY gained, dupilumab was the dominant strategy (lower cost, increased QALYs) versus benralizumab, and cost-effective versus mepolizumab with an incremental cost-effectiveness ratio (ICER) of \1,010,921 (US$9,190, US$1 = \110). Versus omalizumab, dupilumab was not cost-effective (ICER of \10,802,368 [US$98,203]). CONCLUSIONS: In Japan, dupilumab, as an add-on to background therapy, is economically dominant compared with benralizumab, and cost-effective versus mepolizumab.
  • Ryuhei Sato; Tomohiro Handa; Hisako Matsumoto; Kota Hirai; Noriyuki Ohkura; Takeshi Kubo; Toyohiro Hirai
    Internal Medicine 60 23 3701 - 3707 2021年12月 
    Objective Evidence supporting the efficiency of clinically administered therapies against interstitial lung disease (ILD)-related cough is limited. Thus, we conducted a study to evaluate the efficacy of short-term use of chest bands on cough in patients with ILD. Methods This pre-post intervention study was performed at two university hospitals between April 2017 and August 2020. Scores of the visual analog scale (VAS) for cough severity (in terms of frequency and intensity), Leicester Cough Questionnaire (LCQ)-acute, and frequency scale for symptoms of gastroesophageal reflux disease (FSSG) were assessed before and after the use of the chest band (24/48 hours). Patients The study included patients with idiopathic interstitial pneumonias (IIPs) or connective tissue disease-associated interstitial lung disease (CTD-ILD). Results Four patients with IIPs and seven with CTD-ILD were included in the analysis. The cough intensity and LCQ-acute total score improved significantly after the use of the chest band (p=0.007 and p=0.005, respectively), although the cough frequency showed no significant reduction (p=0.074). Furthermore, the FSSG total and acid-reflux symptom scores improved (p=0.018 and p=0.027, respectively), and a negative correlation between the change in LCQ-acute total score and that in FSSG score for acid-reflux symptoms was observed (Spearman rho =-0.841, p=0.001). Conclusion The results of the current study suggest that chest bands might be useful for treating chronic refractory cough in patients with ILD and gastroesophageal reflux disease. However, these results should be interpreted with caution due to methodological limitations associated with this study.
  • Protein C活性は介護施設関連肺炎に特有の予後予測マーカーとなりうるか
    大井 一成; 伊藤 功朗; 濱尾 信叔; 白田 全弘; 西岡 憲亮; 林 康之; 今井 誠一郎; 安友 佳朗; 松本 久子; 平井 豊博; 田辺 直也; 小西 聡史; 門脇 誠三
    日本感染症学会西日本地方会学術集会・日本感染症学会中日本地方会学術集会・日本化学療法学会西日本支部総会プログラム・抄録集 91回・64回・69回 200 - 200 日本感染症学会西日本地方会・日本感染症学会中日本地方会・日本化学療法学会西日本支部 2021年10月
  • 間質性肺疾患患者に対する胸部固定帯の鎮咳効果を評価した前後比較試験 胃食道逆流との関連
    佐藤 隆平; 半田 知宏; 松本 久子; 大倉 徳幸; 平井 豊博
    日本呼吸ケア・リハビリテーション学会誌 31 Suppl. 194s - 194s (一社)日本呼吸ケア・リハビリテーション学会 2021年10月
  • Tomoko Tajiri; Hisako Matsumoto; Makiko Jinnai; Yoshihiro Kanemitsu; Tadao Nagasaki; Toshiyuki Iwata; Hideki Inoue; Hitoshi Nakaji; Tsuyoshi Oguma; Isao Ito; Akio Niimi
    Allergology International 71 2 193 - 199 2021年10月 
    BACKGROUND: Airway mucus hypersecretion is an important pathophysiological feature of asthma. MUC5AC and MUC5B are the major secreted polymeric mucins in airways, and their compositions affect mucus properties. Despite the increasing appreciation of MUC5AC and MUC5B compositions in asthmatic airways, their pathophysiological relevance remains to be fully understood in humans. METHODS: In this cross-sectional study, we prospectively enrolled newly referred steroid-untreated patients with mild asthma and healthy controls. We compared induced sputum MUC5AC and MUC5B levels between patients and controls. Subsequently, we assessed the correlation between MUC5AC and MUC5B levels and clinical indices in patients. Sputum MUC5AC and MUC5B levels were measured using enzyme-linked immunosorbent assays. RESULTS: Sputum MUC5AC and MUC5B levels were significantly higher in patients (n = 87) than in controls (n = 22) (p = 0.0002 and p = 0.006, respectively). The ratio of sputum MUC5AC to MUC5B tended to be higher in patients than in controls (p = 0.07). Sputum MUC5AC levels significantly and positively correlated with fractional exhaled nitric oxide at expiratory flow of 50 mL/s (Spearman's rho = 0.29, p = 0.006), sputum eosinophil proportion (rho = 0.34, p = 0.0013), and airway sensitivity (rho = 0.39, p = 0.0005). By contrast, sputum MUC5B levels significantly and positively correlated with airway sensitivity (rho = 0.35, p = 0.002) and negatively correlated with airway reactivity (rho = -0.33, p = 0.004). CONCLUSIONS: Sputum MUC5AC is increased by protein levels and involved in airway type 2/eosinophilic inflammation and airway hyperresponsiveness in steroid-untreated patients with mild asthma.
  • Mariko Kogo; Hisako Matsumoto; Naoya Tanabe; Toyofumi F Chen-Yoshikawa; Naoki Nakajima; Akihiko Yoshizawa; Tsuyoshi Oguma; Susumu Sato; Natsuko Nomura; Chie Morimoto; Hironobu Sunadome; Shimpei Gotoh; Akihiro Ohsumi; Hiroshi Date; Toyohiro Hirai
    ERJ open research 7 4 2021年10月 
    Background: Bronchiolitis obliterans (BO) is a clinical syndrome characterised by progressive small airway obstruction, causing significant morbidity and mortality. Central airway dilatation is one of its radiological characteristics, but little is known about the clinical and pathological associations between airway dilatation and BO. Methods: This retrospective study consecutively included patients who underwent lung transplantation due to BO at Kyoto University Hospital from 2009 to 2019. Demographic and histopathological findings of the resected lungs were compared between patients with and without airway dilatation measured by chest computed tomography (CT) at registration for lung transplantation. Results: Of a total of 38 included patients (median age, 30 years), 34 (89%) had a history of hematopoietic stem-cell transplantation, and 22 (58%) had airway dilatation based on CT. Patients with airway dilatation had a higher frequency of Pseudomonas aeruginosa isolation with greater residual volume than those without airway dilatation. Quantitative CT analysis revealed an increase in lung volume to predictive total lung capacity and a percentage of low attenuation volume <-950 HU at inspiration in association with the extent of airway dilatation. Airway dilatation on CT was associated with an increased number of bronchioles with concentric narrowing of the lumen and thickening of the subepithelium of the walls on histology. Conclusions: In patients with BO, airway dilatation may reflect increased residual volume or air trapping and pathological extent of obstructive bronchioles, accompanied by a risk of Pseudomonas aeruginosa isolation. More attention should be paid to the development of airway dilatation in the management of BO.
  • 睡眠時呼吸障害のバイオマーカーとしての血清尿酸値の有用性の検討 ながはまスタディ
    砂留 広伸; 村瀬 公彦; 田原 康玄; 高橋 順美; 松本 健; 濱田 哲; 長崎 忠雄; 谷澤 公伸; 半田 知宏; 松本 久子; 若村 智子; 森田 智視; 平井 豊博; 松田 文彦; 陳 和夫
    日本睡眠学会定期学術集会プログラム・抄録集 46回 214 - 214 (一社)日本睡眠学会 2021年09月
  • Haruna Kitazawa; Nobuyuki Hizawa; Yoshihiro Nishimura; Takao Fujisawa; Takashi Iwanaga; Akiko Sano; Hiroyuki Nagase; Hisako Matsumoto; Takahiko Horiguchi; Satoshi Konno; Koichiro Asano
    Respiratory investigation 59 5 670 - 674 2021年09月 
    The coronavirus disease 2019 (COVID-19) pandemic has had a great influence on medical practice in Japan. In this study, an online questionnaire-based survey was conducted among doctors routinely involved in the treatment of asthma. The questions included in the survey pertained to their thoughts on asthma treatment amidst COVID-19, changes in their clinical approach toward patients with asthma, and the behavioral changes in patients in the pandemic era. The results revealed a significant impact of the pandemic on asthma treatment. Regardless of whether or not they were directly involved in the treatment of patients with COVID-19, the doctors had avoided using nebulizers in outpatient wards/clinics and routine pulmonary function testing. An increase in canceled appointments and inappropriate/non-adherence to treatment among their patients were noticeable. Furthermore, the survey revealed an extensive impact of the pandemic on the doctors engaged in asthma treatment irrespective of the differences in their medical backgrounds.
  • Hiroyuki Nagase; Yoshihiro Nishimura; Hisako Matsumoto; Naoya Sugimoto; Takashi Iwanaga; Akiko Sano; Satoshi Konno; Nobuyuki Hizawa; Koichiro Asano; Takahiko Horiguchi; Akihito Yokoyama
    Respiratory investigation 59 5 679 - 682 2021年09月 
    There is a concern that persons with underlying respiratory disease may have increased susceptibility to COVID-19 and/or increased severity/mortality if infected. However, information regarding such patients during the first wave of the epidemic is lacking in Japan. We surveyed chest physicians nationwide, and collected anonymous data concerning 1444 patients. Among COVID-19 patients, the prevalence of asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung diseases (ILD) was 3.4%, 4.8%, and 1.5%, respectively. Among COVID-19 patients with these 3 comorbidities, exacerbation of the comorbidity occurred in 12.2%, 18.8%, and 36.4%, respectively, and mortality (6.2% overall) was 4.1%, 13.0%, and 31.8%, respectively. The prevalence of asthma among COVID-19 patients was not higher than that for the general population, and mortality in COVID-19 patients with asthma was not higher than mortality in COVID-19 patients without underlying respiratory disease. COVID-19 patients having COPD or ILD had relatively high mortality, especially for ILD.
  • Satoshi Ikeo; Yuki Yamamoto; Kazuhiro Ikeda; Naoyuki Sone; Yohei Korogi; Lucia Tomiyama; Hisako Matsumoto; Toyohiro Hirai; Masatoshi Hagiwara; Shimpei Gotoh
    Biomaterials 276 121031 - 121031 2021年09月 
    Lung transplantation is the only treatment available for end-stage lung diseases; however, donor shortage is a global issue. The use of human pluripotent stem cells (hPSCs) for organ regeneration is a promising approach. Nevertheless, methods for the expansion of isolated hPSC-derived lung progenitors (hLPs) for transplantation purposes have not yet been reported. Herein, we established an expansion system of hLPs based on their three-dimensional culture in core-shell hydrogel microfibers, that ensures the maintenance of their bipotency for differentiation into alveolar and airway epithelial cells including alveolar type II (AT2) cells. Further, we developed an efficient in vivo transplantation method using an endoscope-assisted transtracheal administration system; the successful engraftment and in vivo differentiation of hLPs into alveolar epithelial cells (incorporated into the alveoli) was observed. Importantly, expanded hLPs in the context of microfibers were successfully transplanted into the murine lungs, opening avenues for cell-based therapies of lung diseases. Therefore, our novel method has potential regenerative medicine applications; additionally, the high-quality hLPs and AT2 cells generated via the microfiber-based technology are valuable for drug discovery purposes.
  • 砂留 広伸; 松本 久子; 村瀬 公彦; 田原 康玄; 西 健太; 寺田 悟; 野村 奈都子; 古郷 摩利子; 田嶋 範之; 森本 千絵; 高橋 順美; 松本 健; 濱田 哲; 長崎 忠雄; 小熊 毅; 谷澤 公伸; 半田 知宏; 佐藤 晋; 森田 智視; 平井 豊博; 松田 文彦; 陳 和夫
    アレルギー 70 6-7 804 - 804 (一社)日本アレルギー学会 2021年08月
  • 古郷 摩利子; 佐藤 晋; 室 繁郎; 松本 久子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 長崎 忠雄; 村瀬 公彦; 川口 喬久; 田原 康玄; 松田 文彦; 陳 和夫; 平井 豊博
    アレルギー 70 6-7 790 - 790 (一社)日本アレルギー学会 2021年08月
  • 森本 千絵; 松本 久子; 小熊 毅; 佐藤 晋; 田辺 直也; 佐藤 篤靖; 古郷 摩利子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 富井 啓介; 田尻 智子; 西村 尚志; 北 英夫; 月野 光博; 上田 哲也; 塚原 隆充; 平井 豊博
    アレルギー 70 6-7 813 - 813 (一社)日本アレルギー学会 2021年08月
  • 検査法 ながはまコホート研究における気流閉塞,呼吸困難の発症リスク因子
    古郷 摩利子; 佐藤 晋; 室 繁郎; 松本 久子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 長崎 忠雄; 村瀬 公彦; 川口 喬久; 田原 康玄; 松田 文彦; 陳 和夫; 平井 豊博
    アレルギー 70 6-7 790 - 790 (一社)日本アレルギー学会 2021年08月
  • 気管支喘息(成人) 管理:合併症,COVID-19 中高年発症喘息と睡眠呼吸障害の関係 ながはまスタディ
    砂留 広伸; 松本 久子; 村瀬 公彦; 田原 康玄; 西 健太; 寺田 悟; 野村 奈都子; 古郷 摩利子; 田嶋 範之; 森本 千絵; 高橋 順美; 松本 健; 濱田 哲; 長崎 忠雄; 小熊 毅; 谷澤 公伸; 半田 知宏; 佐藤 晋; 森田 智視; 平井 豊博; 松田 文彦; 陳 和夫
    アレルギー 70 6-7 804 - 804 (一社)日本アレルギー学会 2021年08月
  • 喘息関連疾患・病態 閉塞性気道疾患における黄色ブドウ球菌エンテロトキシン(SE)感作と喀痰細菌叢の検討
    森本 千絵; 松本 久子; 小熊 毅; 佐藤 晋; 田辺 直也; 佐藤 篤靖; 古郷 摩利子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 富井 啓介; 田尻 智子; 西村 尚志; 北 英夫; 月野 光博; 上田 哲也; 塚原 隆充; 平井 豊博
    アレルギー 70 6-7 813 - 813 (一社)日本アレルギー学会 2021年08月
  • Kenta Nishi; Hisako Matsumoto; Noriyuki Tashima; Satoru Terada; Natsuko Nomura; Mariko Kogo; Chie Morimoto; Hironobu Sunadome; Tadao Nagasaki; Tsuyoshi Oguma; Yoshinari Nakatsuka; Kimihiko Murase; Takahisa Kawaguchi; Yasuharu Tabara; Kazuhiro Sonomura; Fumihiko Matsuda; Kazuo Chin; Toyohiro Hirai
    Scientific reports 11 1 15373 - 15373 2021年07月 
    Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30-74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of MDC1, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of MDC1 rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers.
  • Issei Oi; Isao Ito; Masataka Hirabayashi; Kazuo Endo; Masahito Emura; Toru Kojima; Hitokazu Tsukao; Keisuke Tomii; Atsushi Nakagawa; Kojiro Otsuka; Masaya Akai; Masahiro Oi; Takakazu Sugita; Motonari Fukui; Daiki Inoue; Yoshinori Hasegawa; Kenichi Takahashi; Hiroaki Yasui; Kohei Fujita; Tadashi Ishida; Akihiro Ito; Hideo Kita; Yusuke Kaji; Michiko Tsuchiya; Hiromi Tomioka; Takashi Yamada; Satoru Terada; Hitoshi Nakaji; Nobuyoshi Hamao; Masahiro Shirata; Kensuke Nishioka; Masatoshi Yamazoe; Yusuke Shiraishi; Tatsuya Ogimoto; Kazutaka Hosoya; Hitomi Ajimizu; Hiroshi Shima; Hisako Matsumoto; Naoya Tanabe; Toyohiro Hirai
    Open forum infectious diseases 8 7 ofab282  2021年07月 
    Background: Detailed differences in clinical information between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia (CP), which is the main phenotype of SARS-CoV-2 disease, and influenza pneumonia (IP) are still unclear. Methods: A prospective, multicenter cohort study was conducted by including patients with CP who were hospitalized between January and June 2020 and a retrospective cohort of patients with IP hospitalized from 2009 to 2020. We compared the clinical presentations and studied the prognostic factors of CP and IP. Results: Compared with the IP group (n = 66), in the multivariate analysis, the CP group (n = 362) had a lower percentage of patients with underlying asthma or chronic obstructive pulmonary disease (P < .01), lower neutrophil-to-lymphocyte ratio (P < .01), lower systolic blood pressure (P < .01), higher diastolic blood pressure (P < .01), lower aspartate aminotransferase level (P < .05), higher serum sodium level (P < .05), and more frequent multilobar infiltrates (P < .05). The diagnostic scoring system based on these findings showed excellent differentiation between CP and IP (area under the receiver operating characteristic curve, 0.889). Moreover, the prognostic predictors were different between CP and IP. Conclusions: Comprehensive differences between CP and IP were revealed, highlighting the need for early differentiation between these 2 pneumonias in clinical settings.
  • Naoya Tanabe; Susumu Sato; Tsuyoshi Oguma; Hiroshi Shima; Takeshi Kubo; Satoshi Kozawa; Koji Koizumi; Atsuyasu Sato; Kaori Togashi; Hisako Matsumoto; Toyohiro Hirai
    Journal of thoracic imaging 36 4 224 - 230 2021年07月 
    PURPOSE: Asthma onset before the age of 40 years is associated with distinct clinical manifestations in chronic obstructive pulmonary disease (COPD) patients, but its morphologic features remain unestablished. This study aimed to explore airway morphology in COPD patients with asthma onset before 40 years of age using ultra-high-resolution computed tomography (U-HRCT), which allows a more accurate quantitation of the lumen and the wall in smaller airways than using conventional CT. MATERIALS AND METHODS: Clinical data of 500 consecutive patients undergoing full inspiratory U-HRCT (1024×1024 matrix and 0.25 mm slice thickness) were retrospectively analyzed. COPD patients without asthma, COPD patients with asthma onset at age below or 40 years and above, and non-COPD smoker controls (N=137, 29, 34, and 22, respectively) were enrolled. The length, lumen area (LA), wall thickness and area (WA), and wall area percent (WA%) of the segmental (third-generation) to sub-subsegmental (fifth-generation) bronchus and the low attenuation volume percent (LAV%) were measured. RESULTS: LA and WA were smaller in the fourth and fifth generation in COPD patients than in non-COPD controls, regardless of the age of asthma onset. LA was smaller and WA% was larger in the fourth-generation and fifth-generation airways in COPD with asthma onset before 40 years than COPD without asthma, whereas WA did not differ between them. In multivariate analyses, asthma onset before 40 years was associated with smaller LA in COPD patients independent of demographics, use of inhaled corticosteroids and long-acting bronchodilators, airflow limitation, and LAV%. CONCLUSIONS: Asthma onset before 40 years of age could be associated with greater lumen narrowing of the airways in COPD.
  • Masahiro Shirata; Isao Ito; Naoya Tanabe; Satoshi Konishi; Issei Oi; Nobuyoshi Hamao; Hisako Matsumoto; Yoshiro Yasutomo; Seizo Kadowaki; Toyohiro Hirai
    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 9 1323 - 1328 2021年05月 
    INTRODUCTION: Risk factors associated with the new detection of methicillin-resistant Staphylococcus aureus (MRSA) during hospitalization remain unclear. This study aimed to identify risk factors associated with MRSA isolation from the sputum of patients admitted with pneumonia, during their hospitalization. METHODS: Patients were prospectively enrolled from 2003 to 2012. Sputum samples were collected for bacterial cultures on days 1, 4, 7, 11, and 14 of hospitalization and thereafter. Cases of MRSA first isolated from sputum obtained before day 4 were defined as "carriage on admission." Cases of MRSA first isolated on day 4 and thereafter, were defined as "new detection after admission." Statistical analysis was used to investigate the risk factors associated with MRSA isolation. RESULTS: MRSA was isolated from 167 of 1,008 patients (carriage: 47; new detection: 120). Multivariate analysis revealed that the risk factors for MRSA carriage were activities of daily living (ADL) disability prior to admission (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.37-6.22) and hospitalization within the previous 90 days (OR, 3.75; 95% CI, 1.90-7.41). ADL disability prior to admission (risk ratio [RR], 1.82; 95% CI, 1.17-2.84) and a high pneumonia severity index score upon admission (RR, 2.20; 95% CI, 1.37-3.65) were risk factors for new detection of MRSA. CONCLUSIONS: Several risk factors were found to be associated with MRSA carriage and/or its new detection, based on the sputum samples from patients admitted with pneumonia. These factors may be indicators for selective surveillance and the early implementation of infection control measures.
  • 砂留 広伸; 村瀬 公彦; 田原 康玄; 南 卓馬; 武山 博文; 高橋 順美; 松本 健; 濱田 哲; 長崎 忠雄; 谷澤 公伸; 半田 知宏; 松本 久子; 若村 智子; 森田 智視; 平井 豊博; 松田 文彦; 陳 和夫
    日本呼吸器学会誌 10 増刊 206 - 206 (一社)日本呼吸器学会 2021年04月
  • 砂留 広伸; 村瀬 公彦; 田原 康玄; 南 卓馬; 武山 博文; 高橋 順美; 松本 健; 濱田 哲; 長崎 忠雄; 谷澤 公伸; 半田 知宏; 松本 久子; 若村 智子; 森田 智視; 平井 豊博; 松田 文彦; 陳 和夫
    日本呼吸器学会誌 10 増刊 206 - 206 (一社)日本呼吸器学会 2021年04月
  • 森本 千絵; 松本 久子; 小熊 毅; 佐藤 晋; 田辺 直也; 佐藤 篤靖; 古郷 摩利子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 平井 豊博; 富井 啓介; 田尻 智子; 西村 尚志; 北 英夫; 月野 光博; 上田 哲也
    日本呼吸器学会誌 10 増刊 211 - 211 (一社)日本呼吸器学会 2021年04月
  • 進藤 允; 田辺 直也; 佐藤 篤靖; 小川 惠美子; 室 繁郎; 伊達 洋至; 佐藤 晋; 松本 久子; 平井 豊博
    日本呼吸器学会誌 10 増刊 149 - 149 (一社)日本呼吸器学会 2021年04月
  • 古郷 摩利子; 佐藤 晋; 松本 久子; 室 繁郎
    呼吸器内科 39 4 360 - 366 (有)科学評論社 2021年04月
  • 進藤 允; 田辺 直也; 佐藤 篤靖; 小川 惠美子; 室 繁郎; 伊達 洋至; 佐藤 晋; 松本 久子; 平井 豊博
    日本呼吸器学会誌 10 増刊 149 - 149 (一社)日本呼吸器学会 2021年04月
  • 古郷 摩利子; 松本 久子; 田辺 直也; 芳川 豊史; 中島 直樹; 吉澤 明彦; 小熊 毅; 佐藤 晋; 野村 奈都子; 森本 千絵; 砂留 広伸; 後藤 慎平; 大角 明宏; 伊達 洋至; 平井 豊博
    日本呼吸器学会誌 10 増刊 195 - 195 (一社)日本呼吸器学会 2021年04月
  • 森本 千絵; 松本 久子; 小熊 毅; 佐藤 晋; 田辺 直也; 佐藤 篤靖; 古郷 摩利子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 平井 豊博; 富井 啓介; 田尻 智子; 西村 尚志; 北 英夫; 月野 光博; 上田 哲也
    日本呼吸器学会誌 10 増刊 211 - 211 (一社)日本呼吸器学会 2021年04月
  • 長瀬 洋之; 西村 善博; 松本 久子; 岩永 賢司; 佐野 安希子; 今野 哲; 浅野 浩一郎; 檜澤 伸之; 堀口 高彦; 横山 彰仁
    日本呼吸器学会誌 10 増刊 186 - 186 (一社)日本呼吸器学会 2021年04月
  • 寺田 悟; 松本 久子; 田嶋 範之; 西 健太; 野村 奈都子; 古郷 摩利子; 森本 千絵; 砂留 広伸; 長崎 忠雄; 小熊 毅; 中塚 賀也; 村瀬 公彦; 川口 喬久; 田原 康玄; 園村 和弘; 松田 文彦; 陳 和夫; 平井 豊博
    日本呼吸器学会誌 10 増刊 175 - 175 (一社)日本呼吸器学会 2021年04月
  • 西 健太; 松本 久子; 田嶋 範之; 寺田 悟; 野村 奈都子; 古郷 摩利子; 森本 千絵; 砂留 広伸; 長崎 忠雄; 小熊 毅; 中塚 賀也; 村瀬 公彦; 川口 喬久; 田原 康玄; 園村 和弘; 松田 文彦; 陳 和夫; 平井 豊博
    日本呼吸器学会誌 10 増刊 203 - 203 (一社)日本呼吸器学会 2021年04月
  • 田嶋 範之; 松本 久子; 寺田 悟; 西 健太; 古郷 摩利子; 野村 奈都子; 森本 千絵; 砂留 広伸; 長崎 忠雄; 小熊 毅; 中塚 賀也; 村瀬 公彦; 川口 喬久; 田原 康玄; 陳 和夫; 園村 和弘; 松田 文彦; 平井 豊博
    日本呼吸器学会誌 10 増刊 235 - 235 (一社)日本呼吸器学会 2021年04月
  • 日本発のCOPDコホート研究 ながはまコホート研究
    古郷 摩利子; 佐藤 晋; 松本 久子; 室 繁郎
    呼吸器内科 39 4 360 - 366 (有)科学評論社 2021年04月
  • Hironobu Sunadome; Hisako Matsumoto; Yuji Tohda; Takahiko Horiguchi; Hideo Kita; Kazunobu Kuwabara; Keisuke Tomii; Kojiro Otsuka; Masaki Fujimura; Noriyuki Ohkura; Takashi Iwanaga; Soichiro Hozawa; Akio Niimi; Yoshihiro Kanemitsu; Tadao Nagasaki; Noriyuki Tashima; Yumi Ishiyama; Chie Morimoto; Tsuyoshi Oguma; Tomoko Tajiri; Isao Ito; Junya Ono; Shoichiro Ohta; Kenji Izuhara; Toyohiro Hirai
    Allergology international : official journal of the Japanese Society of Allergology 70 2 252 - 254 2021年04月
  • Chie Morimoto; Hisako Matsumoto; Tadao Nagasaki; Yoshihiro Kanemitsu; Yumi Ishiyama; Hironobu Sunadome; Tsuyoshi Oguma; Isao Ito; Kimihiko Murase; Takahisa Kawaguchi; Yasuharu Tabara; Akio Niimi; Shigeo Muro; Fumihiko Matsuda; Kazuo Chin; Toyohiro Hirai
    Respiratory research 22 1 6 - 6 2021年01月 
    BACKGROUND: Chronic sputum production in the general population is historically associated with clinical indices including male sex and smoking history. However, its relationship with gastroesophageal reflux disease (GERD), which may prove an underlying factor in sputum production, is unclear. We aimed to clarify factors associated with sputum production in the general population in cross-sectional and longitudinal manners. METHODS: In the Nagahama study, a community-based cohort study, 9804 subjects were recruited between 2008 and 2010 (baseline assessment), 8293 of whom were followed from 2013 to 2015 (follow-up assessment). This study contained a self-completed questionnaire which included medical history, assessment of sputum production, and a frequency scale for symptoms of GERD. A Frequency Scale for Symptoms of Gastroesophageal Reflux Disease score of ≥ 8 was defined as GERD. In addition to the frequency of sputum production at each assessment, frequency of persistent sputum production defined as sputum production at both assessments was examined. RESULTS: Frequency of sputum production was 32.0% at baseline and 34.5% at follow-up. Multivariable analysis demonstrated that sputum production at baseline was significantly associated with GERD [odds ratio (OR), 1.92; 95% confidence interval (CI) 1.73-2.13] and post-nasal drip (PND) (OR, 2.40; 95% CI 2.15-2.68), independent of other known factors such as older age, male sex and smoking history. These associations between sputum production and GERD or PND were also observed at follow-up. In longitudinal analysis, 19.4% had persistent sputum production and 12.3% had transient sputum production, i.e., at baseline only. Multivariable analysis for risk of persistence of sputum production revealed that persistent sputum production was associated with GERD and PND, in addition to the known risk factors listed above. The proportion of subjects with GERD at both assessments was highest among subjects with persistent sputum production. CONCLUSIONS: Cross-sectional and longitudinal analysis demonstrated an association in the general population between sputum production and GERD, as well as PND, independent of known risk factors. The presence of GERD should be assessed in patients complaining of sputum production.
  • Tadao Nagasaki; Hisako Matsumoto
    Arerugi = [Allergy] 70 5 349 - 358 2021年
  • Hironobu Sunadome; Susumu Sato; Hisako Matsumoto; Kimihiko Murase; Takahisa Kawaguchi; Yasuharu Tabara; Kazuo Chin; Fumihiko Matsuda; Toyohiro Hirai
    The European respiratory journal 57 1 2021年01月
  • Kazuto Matsunaga; Ichiro Kuwahira; Masayuki Hanaoka; Junpei Saito; Takahiro Tsuburai; Koichi Fukunaga; Hisako Matsumoto; Hisatoshi Sugiura; Masakazu Ichinose
    Respiratory investigation 59 1 34 - 52 2021年01月 
    Nitric oxide (NO) is produced in the body and has been shown to have diverse actions in the abundance of research that has been performed on it since the 1970s, leading to Furchgott, Murad, and Ignarro receiving the Nobel Prize in Physiology or Medicine in 1998. NO is produced by nitric oxide synthase (NOS). NOS is broadly distributed, being found in the nerves, blood vessels, airway epithelium, and inflammatory cells. In asthma, inflammatory cytokines induce NOS activity in the airway epithelium and inflammatory cells, producing large amounts of NO. Measurement of fractional exhaled nitric oxide (FeNO) is a simple, safe, and quantitative method of assessing airway inflammation. The FeNO measurement method has been standardized and, in recent years, this noninvasive test has been broadly used to support the diagnosis of asthma, monitor airway inflammation, and detect asthma overlap in chronic obstructive pulmonary disease (COPD) patients. Since the normal upper limit of FeNO for healthy Japanese adults is 37 ppb, values of 35 ppb or more are likely to be interpreted as a signature of inflammatory condition presenting features with asthma, and this value is used in clinical practice. Research is also underway for clinical application of these measurements in other respiratory diseases such as COPD and interstitial lung disease. Currently, there remains some confusion regarding the significance of these measurements and the interpretation of the results. This statement is designed to provide a simple explanation including the principles of FeNO measurements, the measurement methods, and the interpretation of the measurement results.
  • サージカルスモークに含まれる微小粒子状物質の測定
    大越 香江; 木下 浩一; 西田 雄大; 冨澤 康子; 松本 久子; 武藤 容典; 永井 美江; 森島 敏隆; 萬谷 京子; 大和 浩
    日本消化器外科学会総会 75回 P334 - 5 (一社)日本消化器外科学会 2020年12月
  • 西 健太; 松本 久子; 寺田 悟; 小熊 毅; 岸本 曜; 平井 豊博
    日本呼吸器学会誌 9 6 463 - 467 (一社)日本呼吸器学会 2020年11月 
    24歳、女性。約3年前より咳嗽時の喘鳴、約6ヵ月前より労作時呼吸困難を自覚していた。呼吸困難悪化のため受診した。病歴やアトピー素因は気管支喘息を疑わせたが、スパイロメトリーとモストグラフから中枢気道閉塞が疑われた。頸部CTと喉頭ファイバーでは声門下に狭窄を認めた。精査の結果、特発性声門下狭窄と診断し、待機的にレーザー治療を行い改善した。特発性声門下狭窄は稀な疾患であるが、気管支喘息として治療されていることも多く、治療の遅れにつながりやすい。呼吸器科医にとって念頭に置くべき疾患の一つである。(著者抄録)
  • Naoya Tanabe; Hisako Matsumoto; Satoshi Hamada; Isao Ito; Toyohiro Hirai
    Allergology International 70 2 274 - 276 2020年11月
  • Koichiro Asano; Kazuya Sumi; Hajime Yoshisue; Noriko Nakamura; Makoto Nagasaki; Takayoshi Sasajima; Hisako Matsumoto
    Pulmonary pharmacology & therapeutics 64 101950 - 101950 2020年10月 
    BACKGROUND: Omalizumab is an anti-immunoglobulin E monoclonal antibody approved for patients with severe allergic asthma in Japan. With regard to omalizumab dosage in Japanese adults with severe allergic asthma in clinical practice settings, this post-marketing surveillance evaluated safety and efficacy of the dosing table revision (DTR) based on a dosing regimen of omalizumab administration every 4 weeks dosing regimen and dosing table expansion (DTE) for patients with baseline IgE levels >700 IU/mL. METHODS: This 52-week, multicenter study, conducted from September 2013 to November 2018, evaluated omalizumab safety outcomes including adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), efficacy outcomes including Global Evaluation of Treatment Effectiveness (GETE), change in oral corticosteroid dose, and asthma exacerbation-related events such as hospitalization, emergency room visits, and worsening of symptoms. RESULTS: Of the 405 patients registered in the study, safety was evaluated in 392 and efficacy in 390. The mean age of patients was 58.5 years and 58.7% were women. In total, 41.3% of the patients were subjected to DTE and 58.7% to DTR. In the safety dataset, 6.6% experienced an ADR, 32.9% experienced an AE, and 16.1% experienced an SAE. In the efficacy dataset, 63.3% of patients at Week 16 and 63.5% at Week 52 had an 'effective' or 'good' GETE score. Omalizumab was associated with a reduction in worsening of asthma symptoms requiring systemic corticosteroids and frequency of hospitalization. All outcomes were comparable among the DTE and DTR subgroups. CONCLUSION: The findings from this study support the safety and efficacy of omalizumab administered based on the revised and expanded dosing table in Japanese patients with severe allergic asthma.
  • 重症喘息患者におけるデュピルマブ併用療法の費用効果分析
    荒川 一郎; 松本 久子; 宮田 将徳; 田口 有里恵; 上山 真紀; ジュラン・フローレンス; 東田 有智
    アレルギー 69 臨時増刊号 308 - 308 (一社)日本アレルギー学会 2020年10月
  • 今泉 和良; 山谷 睦雄; 須田 隆文; 礒部 威; 大平 徹郎; 長内 忍; 川山 智隆; 國近 尚美; 佐野 博幸; 柴田 陽光; 新海 正晴; 多賀谷 悦子; 千葉 弘文; 松本 久子; 金子 猛; 日本呼吸器学会将来計画委員会
    日本呼吸器学会誌 9 5 311 - 318 (一社)日本呼吸器学会 2020年09月 
    呼吸器病理診断の現状と問題点を明らかにする目的で日本呼吸器学会認定施設にアンケートを送付し、呼吸器病理に関心の深い病理医94人(10.5%)から回答を得た。86%が呼吸器病理における人材不足を感じ、71%が呼吸器病理医を目指す若い医師は"増えていないまたは減っている"と回答した。人材が増えない理由として病理医全体数の不足、呼吸器病理の難解さ、指導医不足が挙げられた。65%は他施設の呼吸器病理診断に疑義を感じた経験があった。呼吸器病理診断は憂慮すべき人材不足にあり、日本呼吸器学会は日本病理学会と協力して教育・人材育成にあたる必要がある。(著者抄録)
  • サージカルスモークの健康リスク 外科医への課題
    大越 香江; 木下 浩一; 松本 久子; 森島 敏隆; 冨澤 康子; 萬谷 京子; 永井 美江; 石川 明子; 増田 純一
    日本外科学会定期学術集会抄録集 120回 DP - 4 (一社)日本外科学会 2020年08月
  • 鋒山 香苗; 杉本 充弘; 米澤 淳; 寺尾 真琴; 山本 浩貴; 吉田 優子; 朝倉 佳代子; 深津 祥央; 谷村 和哉; 佐藤 晋; 松本 久子; 中川 俊作; 北田 徳昭; 平井 豊博; 松原 和夫
    医療薬学 46 8 405 - 413 (一社)日本医療薬学会 2020年08月 
    喘息や慢性閉塞性肺疾患(COPD)患者に対し吸入指導外来の支援体制開始によってもたらされる治療アウトカムについて、観察研究により評価を行った。2013年7月〜2019年7月末に呼吸器内科医師・病院薬剤師・保険薬局薬剤師との合同講習会を11回実施し、吸入デバイス、スペーサー、補助具の理解度が上昇したことがアンケート調査から分かった。当院では2013年12月に吸入指導外来を開設してから2018年12月まで、延べ3120回の吸入指導(月平均約50名)を行った。吸入薬説明手順、評価項目表の評価の内訳は、特に問題なしが88.9%(1642件)となっていたが、吸入方法不備・吸入意義の理解不足の報告も3.5%(65件)と一定数あった。吸入指導外来開設前後の緊急入院患者数、同時期の喘息またはCOPD外来受診患者数は、有意差はなかったものの開設前と比較して緊急入院患者数は減少傾向を示した。開設4年後、COPD(喘息合併を含む)の症例では、緊急入院患者数/外来受診患者数は、開設前と比較し、緊急入院患者数は有意に減少していた。また、緊急入院となったCOPD患者の重症度別では、Stage IV以外の比較的軽症のCOPD症例で緊急入院患者数が減少していた。一方、喘息のみの診断歴の患者では、緊急入院患者数の顕著な減少は認められなかった。医師を対象としたアンケート調査では、呼吸器内科担当の外来看護師中87%が吸入指導を業務負担と感じていた。吸入指導外来開設後は、全ての看護師が業務負担の軽減を実感していた。
  • 田嶋 範之; 松本 久子; 田尻 智子; 森本 千絵; 古郷 摩利子; 野村 奈都子; 砂留 広伸; 小熊 毅; 太田 昭一郎; 小野 純也; 小賀 徹; 新実 彰男; 出原 賢治; 平井 豊博
    日本呼吸器学会誌 9 増刊 226 - 226 (一社)日本呼吸器学会 2020年08月
  • 喘息既往で層別化した超高精細CTによるCOPDの気道形態解析
    田辺 直也; 小熊 毅; 佐藤 晋; 島 寛; 久保 武; 小澤 聡; 佐藤 篤靖; 松本 久子; 富樫 かおり; 平井 豊博
    日本呼吸器学会誌 9 増刊 233 - 233 (一社)日本呼吸器学会 2020年08月
  • 森本 千絵; 松本 久子; 小熊 毅; 伊藤 功朗; 佐藤 晋; 佐藤 篤靖; 古郷 摩利子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 平井 豊博
    日本呼吸器学会誌 9 増刊 282 - 282 (一社)日本呼吸器学会 2020年08月
  • 鋒山 香苗; 杉本 充弘; 米澤 淳; 寺尾 真琴; 山本 浩貴; 吉田 優子; 朝倉 佳代子; 深津 祥央; 谷村 和哉; 佐藤 晋; 松本 久子; 中川 俊作; 北田 徳昭; 平井 豊博; 松原 和夫
    医療薬学 46 8 405 - 413 (一社)日本医療薬学会 2020年08月 
    喘息や慢性閉塞性肺疾患(COPD)患者に対し吸入指導外来の支援体制開始によってもたらされる治療アウトカムについて、観察研究により評価を行った。2013年7月〜2019年7月末に呼吸器内科医師・病院薬剤師・保険薬局薬剤師との合同講習会を11回実施し、吸入デバイス、スペーサー、補助具の理解度が上昇したことがアンケート調査から分かった。当院では2013年12月に吸入指導外来を開設してから2018年12月まで、延べ3120回の吸入指導(月平均約50名)を行った。吸入薬説明手順、評価項目表の評価の内訳は、特に問題なしが88.9%(1642件)となっていたが、吸入方法不備・吸入意義の理解不足の報告も3.5%(65件)と一定数あった。吸入指導外来開設前後の緊急入院患者数、同時期の喘息またはCOPD外来受診患者数は、有意差はなかったものの開設前と比較して緊急入院患者数は減少傾向を示した。開設4年後、COPD(喘息合併を含む)の症例では、緊急入院患者数/外来受診患者数は、開設前と比較し、緊急入院患者数は有意に減少していた。また、緊急入院となったCOPD患者の重症度別では、Stage IV以外の比較的軽症のCOPD症例で緊急入院患者数が減少していた。一方、喘息のみの診断歴の患者では、緊急入院患者数の顕著な減少は認められなかった。医師を対象としたアンケート調査では、呼吸器内科担当の外来看護師中87%が吸入指導を業務負担と感じていた。吸入指導外来開設後は、全ての看護師が業務負担の軽減を実感していた。
  • 喘息既往で層別化した超高精細CTによるCOPDの気道形態解析
    田辺 直也; 小熊 毅; 佐藤 晋; 島 寛; 久保 武; 小澤 聡; 佐藤 篤靖; 松本 久子; 富樫 かおり; 平井 豊博
    日本呼吸器学会誌 9 増刊 233 - 233 (一社)日本呼吸器学会 2020年08月
  • 森本 千絵; 松本 久子; 小熊 毅; 伊藤 功朗; 佐藤 晋; 佐藤 篤靖; 古郷 摩利子; 野村 奈都子; 田嶋 範之; 砂留 広伸; 平井 豊博
    日本呼吸器学会誌 9 増刊 282 - 282 (一社)日本呼吸器学会 2020年08月
  • Noriyuki Tashima; Hisako Matsumoto; Natsuko Nomura; Akihiko Yoshizawa; Akihiko Kitoh; Kenji Kabashima; Toyohiro Hirai
    Allergology international : official journal of the Japanese Society of Allergology 70 1 131 - 133 2020年07月 [査読有り]
  • Hironobu Sunadome; Hisako Matsumoto; Ryo Tachikawa; Takeshi Matsumoto; Kiminobu Tanizawa; Toru Oga; Junya Ono; Shoichiro Ohta; Kenji Izuhara; Toyohiro Hirai; Kazuo Chin
    Respiratory research 21 1 143 - 143 2020年06月 [査読有り]
     
    BACKGROUND: Periostin is a matricellular protein and is a useful marker in respiratory diseases. However, the roles of periostin in patients with obstructive sleep apnea (OSA) remain unclear. Several in vitro studies have suggested that mechanical stress, hypoxia, impaired metabolism, and kidney injury, which often accompany OSA, may upregulate the expression of periostin. Meanwhile, serum periostin level has been negatively associated with body mass index (BMI) in the general population. In this study, we hypothesized that a high level of serum periostin despite being overweight/obese may discriminate severe OSA or OSA with comorbidities from mild OSA with obesity alone. We aimed to clarify the roles of periostin in patients with OSA to assist in elucidating the heterogeneity of OSA with comorbidities. METHODS: Among patients diagnosed as OSA, we examined the associations between serum periostin levels and clinical indices, including the severity of OSA, BMI, and comorbidities, using a multifaceted approach. The serum periostin levels and clinical indices were assessed after 3 months of continuous positive airway pressure (CPAP) treatment. RESULTS: In 96 patients with OSA, serum periostin level was negatively correlated with BMI, albeit marginally, and tended to be higher in severe OSA than in others when adjusted for BMI. Cluster analysis identified four clusters, including two severe OSA clusters, one of which was characterized by high serum periostin levels and the presence of comorbidities, including albuminuria. In a comparative analysis of severe OSA cases (n = 53), the level of serum-free fatty acids and the frequency of albuminuria were higher in patients with high serum periostin level of ≥87 ng/mL, which was the highest quintile among all participants, than in those with low serum periostin levels (< 87 ng/mL, n = 41). In patients with severe OSA and high serum periostin levels, the levels of serum periostin and urinary albumin significantly decreased after 3 months of CPAP treatment. CONCLUSIONS: Elevated serum periostin in patients with OSA despite being overweight/obese may be an indicator of severe OSA with comorbidities, particularly albuminuria.
  • Nobuyoshi Hamao; Isao Ito; Satoshi Konishi; Naoya Tanabe; Masahiro Shirata; Issei Oi; Mitsuhiro Tsukino; Hisako Matsumoto; Yoshiro Yasutomo; Seizo Kadowaki; Toyohiro Hirai
    BMC pulmonary medicine 20 1 160 - 160 2020年06月 [査読有り]
     
    BACKGROUND: Ceftriaxone (CTRX) and ampicillin/sulbactam (ABPC/SBT) are recommended by various guidelines as the first-line antibiotics for community-acquired pneumonia (CAP). However, which of these antibiotics is more effective for treating non-aspiration CAP remains unclear. METHODS: This study was a prospective, single-center, open-label, quasi-randomized controlled trial. Patients with adult CAP without risk for aspiration were allocated to either a CTRX or ABPC/SBT group based on the date of hospital admission. Macrolide was added to patients in each group. The primary outcome was the clinical response in the validated per-protocol (VPP) population at end of treatment (EOT). The secondary outcomes were clinical response during treatment and at end of study (EOS) in the VPP population, and mortality rate at day 30 in the modified intention-to-treat (MITT) population. RESULTS: Of 696 screened patients, 433 patients were excluded and 263 patients were allocated to receive either of the treatments. Males comprised 54% of patients and mean age and PSI were 62.1 ± 19.8 years and 69.3 ± 30.0, respectively, with 124 patients allocated to the CTRX group and 138 patients allocated to the ABPC/SBT group. The clinical effectiveness rate for the VPP population at EOT was 90% in the CTRX and 96% in the ABPC/SBT group (p = 0.072, 95% confidence interval [CI] of risk difference [RD]: - 12.6-0.8%). No significant difference in effectiveness at day 4 was observed between the CTRX and ABPC/SBT groups (p = 0.079, 95%CI of RD: - 12.1-0.4%), but at day 7, ABPC/SBT was significantly more effective than CTRX in the VPP population (p = 0.047, 95%CI of RD: - 13.3--0.4%). No significant difference in late response at EOS was seen between CTRX and ABPC/SBT groups: cure (89 [86%] and 102 [94%]), relapse (5 [5%] and 1 [1%]) and failure (10 [10%] and 5 [5%]; p = 0.053). Deaths within 30 days in MITT population was higher in CTRX group (4 [3%]) than in ABPC/SBT group (0 [0%]) (p = 0.048, 95%CI of RD: 0.1-6.3%). CONCLUSION: No significant difference in effectiveness was found between ABPC/SBT and CTRX at EOT. However, ABPC/SBT might be more effective in the early phase of treatment. TRIAL REGISTRATION: UMIN-CTR, UMIN000037464. Registered 25 July 2019 - Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042262.
  • Ryobu Mori; Hisako Matsumoto; Shigeo Muro; Hiroko Morisaki; Ryozo Otsuki
    The journal of allergy and clinical immunology. In practice 8 6 2058 - 2059 2020年06月 [査読有り]
  • Chie Morimoto; Hisako Matsumoto; Tomoko Tajiri; Yasuhiro Gon; Reiko Ito; Shu Hashimoto; Maho Suzukawa; Ken Ohta; Kenji Izuhara; Junya Ono; Shoichiro Ohta; Isao Ito; Tsuyoshi Oguma; Yoshihiro Kanemitsu; Tadao Nagasaki; Yumi Izuhara; Akio Niimi; Toyohiro Hirai
    The Journal of asthma : official journal of the Association for the Care of Asthma 58 9 1 - 10 2020年05月 [査読有り]
     
    Objective: Omalizumab is more effective in severe allergic patients with eosinophilic asthma than those with non-eosinophilic asthma. IL-18, a unique cytokine involved in allergic but non-eosinophilic inflammation, might be associated with the latter condition. We aimed to clarify the roles of IL-18 related pathways in insufficient response to omalizumab treatment.Methods: Patients with severe allergic asthma who completed 2-year omalizumab treatments at Kyoto University Hospital were included in this study (UMIN000002389). Associations between pretreatment levels of serum free IL-18 in addition to other mediators and asthma phenotypes including responses to omalizumab treatment were analyzed. Changes in serum free IL-18, periostin and total IgE levels during the treatment were also examined.Results: Twenty-seven patients (19 females, average age of 55.7 years) were examined. Fifteen incomplete responders who experienced exacerbations in the second year, were significantly and more frequently obese and showed significantly earlier asthma onset, lower blood eosinophils and more exacerbations before omalizumab treatment than complete responders. Significantly more patients showed high baseline serum free IL-18 levels (≥141 pg/mL, a threshold for the highest tertile) among the incomplete responders than complete responders. Patients with high serum free IL-18 levels shared similar characteristics with incomplete responders, showing significant reductions in serum total IgE levels during omalizumab treatment. Finally, serum free IL-18 levels negatively correlated with serum periostin levels at baseline and in change ratios.Conclusions: High baseline serum free IL-18 levels may predict reduced omalizumab efficacy in severe allergic patients with type-2 low asthma, regarding reduction of exacerbations.
  • Hisako Matsumoto
    Respiratory investigation 58 3 129 - 130 2020年05月 [査読有り]
  • Hisako Matsumoto
    Respiratory investigation 58 3 144 - 154 2020年05月 [査読有り]
     
    Type-2 airway inflammation is a major characteristic of asthma. Assessing its degree of severity is, therefore, essential in asthma management. Periostin, a matricellular protein belonging to the fasciclin family, is a key molecule linking type-2 airway inflammation and airway remodeling. Fortunately, periostin can be detected in the blood and used to provide sustaining airway information on type-2 inflammation and remodeling. Serum periostin is elevated in the eosinophilic/type 2 subtype of severe asthma, and its levels remain relatively stable and reflect genetic backgrounds. This suggests that serum periostin may serve as a marker of geno-endophenotype with type-2 airway inflammation and thus could be a predictive marker of the long-term prognosis of asthma under treatment. As expected, serum periostin is particularly elevated in comorbidities associated with the eosinophilic/type 2 subtype of severe asthma, including eosinophilic chronic rhinosinusitis, aspirin-exacerbated respiratory diseases, allergic bronchopulmonary aspergillosis, and eosinophilic granulomatosis with polyangiitis. Conversely, serum periostin levels are relatively lower in the overweight/obese. Serum periostin measurements may help to significantly improve the management of patients with severe asthma.
  • Yoshimichi Okayama; Hisako Matsumoto; Hiroshi Odajima; Shunsuke Takahagi; Michihiro Hide; Kimihiro Okubo
    Allergology international : official journal of the Japanese Society of Allergology 69 2 167 - 177 2020年04月 [査読有り]
     
    IgE and mast cells play a pivotal role in various allergic diseases, including asthma, allergic rhinitis, and urticaria. Treatment with omalizumab, a monoclonal anti-IgE antibody, has significantly improved control of these allergic diseases and introduced a new era for the management of severe allergic conditions. About 10 years of experience with omalizumab treatment for severe allergic asthma confirmed its effectiveness and safety, reducing symptoms, frequency of reliever use, and severe exacerbations in patients with intractable conditions. Omalizumab is particularly useful in childhood asthma, where atopic conditions often determine clinical courses of asthma. Recently, omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) with the fixed dose of 300 mg. Although the mechanisms underlying the actions of omalizumab in CSU are not fully clarified, nearly 90% of patients with CSU showed a complete or a partial response to omalizumab treatment. Furthermore, omalizumab is just approved for the treatment of severe Japanese cedar pollinosis (JC) based on the successful results of an add-on study of omalizumab for inadequately controlled severe pollinosis despite antihistamines and nasal corticosteroids. For proper use of omalizumab to treat severe JC, co-administration of antihistamines is necessary, while patients should meet the criteria including strong sensitization to Japanese cedar pollen (≥class 3) and poor control under standard treatment. In the management of severe allergic diseases using omalizumab, issues including cost and concerns about relapse after its discontinuation should be overcome. At the same time, possibilities for application to other intractable allergic diseases should be considered.
  • Takafumi Niwamoto; Tomohiro Handa; Shoko Matsui; Hiroshi Yamamoto; Hajime Yoshifuji; Hiroyasu Abe; Hisako Matsumoto; Yuzo Kodama; Tsutomu Chiba; Hiroshi Seno; Tsuneyo Mimori; Toyohiro Hirai
    Modern rheumatology 31 1 1 - 6 2020年01月 [査読有り]
     
    Objectives: Immunoglobulin G4-related disease (IgG4-RD) is a systemic, multiorgan disease of unknown etiology. We aimed to classify IgG4-RD by a combination pattern of affected organs and identify the clinical features, including the comorbidities of each subgroup.Methods: Patients diagnosed with IgG4-RD between April 1996 and June 2018 were enrolled from three institutes. Hierarchical cluster analysis was performed using six frequently affected organs (lacrimal gland and/or orbit, salivary gland, lung, pancreas, kidney, and retroperitone and/or aorta). Clinical features, such as comorbidities and outcomes, were compared between clusters.Results: In total, 108 patients enrolled in this cohort could be stratified into five distinct subgroups: group 1, lung dominant group; group 2, retroperitoneal fibrosis and/or aortitis dominant group; group 3, salivary glands limited group; group 4, Mikulicz's disease dominant group; and group 5, autoimmune pancreatitis with systemic involvement group. There were significant between-group differences in sex (male dominant in group 1, 2, and 5), history of asthma and allergies on the respiratory tract (most frequent in group 5), and malignancy (most frequent in group 5).Conclusion: IgG4-RD can be classified into subgroups according to the pattern of affected organs. Group 5 may have frequent complications with allergies and malignancies.
  • Hisako Matsumoto
    Arerugi = [Allergy] 69 9 893 - 896 2020年
  • Hironobu Sunadome; Hisako Matsumoto; Yumi Izuhara; Tadao Nagasaki; Yoshihiro Kanemitsu; Yumi Ishiyama; Chie Morimoto; Tsuyoshi Oguma; Isao Ito; Kimihiko Murase; Shigeo Muro; Takahisa Kawaguchi; Yasuharu Tabara; Kazuo Chin; Fumihiko Matsuda; Toyohiro Hirai
    Allergology international : official journal of the Japanese Society of Allergology 69 1 46 - 52 2020年01月 [査読有り]
     
    BACKGROUND: Obesity affects the pathogenesis of various chronic diseases, including asthma. Research on correlations between obesity/BMI and eosinophilic inflammation in asthma has yielded contradictory results, which could be partly ascribed to the absence of epidemiological data on the correlations. We aimed to elucidate the correlations between blood eosinophil count, its genetic backgrounds, and BMI in the general population. METHODS: This community-based Nagahama study in Japan enrolled 9789 inhabitants. We conducted self-reporting questionnaires, lung function tests, and blood tests in the baseline and 5-year follow-up studies. A genome-wide association study (GWAS) was performed in 4650 subjects at the baseline and in 4206 of these at the follow-up to determine single-nucleotide polymorphisms for elevated blood eosinophil counts. We assessed the correlations between BMI and eosinophil counts using a multifaceted approach, including the cluster analysis. RESULTS: Eosinophil counts positively correlated with BMI, observed upon the interchange of an explanatory variable, except for subjects with the highest quartile of eosinophils (≥200/μL), in whom BMI negatively correlated with eosinophil counts. GWAS and human leukocyte antigen (HLA) imputation identified rs4713354 variant (MDC1 on chromosome 6p21) for elevated eosinophil counts, independent of BMI and IgE. Rs4713354 was accumulated in a cluster characterized by elevated eosinophil counts (mean, 498 ± 178/μL) but normal BMI. CONCLUSIONS: Epidemiologically, there may be a positive association between blood eosinophil counts and BMI in general, but there was a negative correlation in the population with high eosinophil counts. Factors other than BMI, particularly genetic backgrounds, may contribute to elevated eosinophil counts in such populations.
  • Ryuhei Sato; Tomohiro Handa; Hisako Matsumoto; Takeshi Kubo; Toyohiro Hirai
    BMC pulmonary medicine 19 1 247 - 247 2019年12月 [査読有り]
     
    BACKGROUND: The intensity and frequency of cough remain unclear in interstitial lung disease (ILD). The aim of this study was to evaluate the intensity and frequency of cough in idiopathic interstitial pneumonias (IIPs), connective tissue disease-associated interstitial lung disease (CTD-ILD), and chronic hypersensitivity pneumonia (CHP), and examine their associations with clinical indices. METHODS: In this cross-sectional study, the intensity and frequency of cough were evaluated using a 100-mm visual analogue scale. Scores on the Leicester Cough Questionnaire, chronic dyspnoea scale, and a frequency scale for symptoms of gastro-oesophageal reflux disease (FSSG) were collected. The correlations of cough intensity and frequency with potential predictor variables were tested using bivariate and multiple logistic regression analysis. RESULTS: The study included 70 patients with IIPs, 49 with CTD-ILD, and 10 with CHP. Patients with IIPs had the most severe cough intensity among the three patient groups. In patients with IIPs, both the intensity and frequency of cough were negatively associated with the diffusing capacity of the lung for carbon monoxide and positively with the Composite Physiologic Index (CPI). In CTD-ILD, both the intensity and frequency of cough were correlated with a higher FSSG score. In multivariate analysis of patients with ILD, IIPs and the FSSG score were independently associated with both components of cough, and CPI tended to be independently associated with cough frequency. Finally, we examined the features of the differences between cough intensity and frequency in all patients with ILD. Patients in whom cough frequency was predominant had a greater impairment of health status relative to other patients. CONCLUSIONS: Cough intensity was greater in IIPs than in other ILDs. Different clinical indices were associated with patient-reported cough intensity and frequency according to the subtype of ILD. Cough frequency was more strongly associated with health status than was cough intensity. These findings suggest that medical staff could manage patients with ILD by considering cough-related factors when assessing the intensity and frequency of cough.
  • Tadao Nagasaki; Keiko Sato; Naoto Kume; Tsuyoshi Oguma; Hironobu Sunadome; Isao Ito; Yumi Izuhara; Kazuya Okamoto; Shinji Kobayashi; Tomoya Ohno; Akiko Mizukami; Akihiro Kobayashi; Toshihiko Kaise; Tomohiro Kuroda; Michiaki Mishima; Hisako Matsumoto
    The Journal of asthma : official journal of the Association for the Care of Asthma 56 11 1147 - 1158 2019年11月 [査読有り]
     
    Background: There are limited data on the prevalence and burden of severe eosinophilic asthma (SEA) both in Japan and globally. This study aimed to assess the prevalence and burden of SEA in Japan. Methods: This study was a retrospective, observational cohort analysis using health records or health insurance claims from patients with severe asthma treated at Kyoto University Hospital. The primary outcome was the prevalence of SEA, defined as a baseline blood eosinophil count ≥300 cells/μL. Secondary outcomes included frequency and risk factors of asthma exacerbations, and asthma-related healthcare resource utilization and costs. Results: Overall, 217 patients with severe asthma were included; 160 (74%) had eosinophil assessments. Of these, 97cases (61%), 54cases (34%), and 33cases (21%) had a blood eosinophil count ≥150, ≥300, and ≥500 cells/μL, respectively. Proportion of SEA was 34%. Blood eosinophil count was not associated with a significantly increased frequency of exacerbations. In the eosinophilic group, lower % forced expiratory volume in 1 second and higher fractional exhaled nitric oxide were predictive risk factors, while the existence of exacerbation history was a predictive risk factor for asthma exacerbations in the non-eosinophilic group. Severe asthma management cost was estimated as \357,958/patient-year, and asthma exacerbations as \26,124/patient-year. Conclusions: Approximately, one-third of patients with severe asthma in Japan have SEA. While risk factors for exacerbations differed between SEA and severe non-eosinophilic asthma, both subgroups were associated with substantial disease and economic burden. From subgroup analysis, blood eosinophil counts could be an important consideration in severe asthma management.
  • Satoshi Konishi; Tomoki Yano; Hiroo Tanaka; Tomoaki Mizuno; Hatsuho Kanoh; Kazuto Tsukita; Toshinori Namba; Atsushi Tamura; Shigenobu Yonemura; Shimpei Gotoh; Hisako Matsumoto; Toyohiro Hirai; Sachiko Tsukita
    Life science alliance 2 4 2019年08月 [査読有り]
     
    The paracellular barrier function of tight junctions (TJs) in epithelial cell sheets is robustly maintained against mechanical fluctuations, by molecular mechanisms that are poorly understood. Vinculin is an adaptor of a mechanosensory complex at the adherens junction. Here, we generated vinculin KO Eph4 epithelial cells and analyzed their confluent cell-sheet properties. We found that vinculin is dispensable for the basic TJ structural integrity and the paracellular barrier function for larger solutes. However, vinculin is indispensable for the paracellular barrier function for ions. In addition, TJs stochastically showed dynamically distorted patterns in vinculin KO cell sheets. These KO phenotypes were rescued by transfecting full-length vinculin and by relaxing the actomyosin tension with blebbistatin, a myosin II ATPase activity inhibitor. Our findings indicate that vinculin resists mechanical fluctuations to maintain the TJ paracellular barrier function for ions in epithelial cell sheets.
  • Korogi Y; Gotoh S; Ikeo S; Yamamoto Y; Sone N; Tamai K; Konishi S; Nagasaki T; Matsumoto H; Ito I; Chen-Yoshikawa TF; Date H; Hagiwara M; Asaka I; Hotta A; Mishima M; Hirai T
    Stem cell reports 13 1 235 - 235 2019年07月 [査読有り]
  • Hisako Matsumoto
    Respiratory investigation 57 4 293 - 294 2019年07月 [査読有り]
  • ヒトiPS細胞由来肺胞オルガノドを用いたHermansky-Pudlak症候群2型の疾患モデリング
    興梠 陽平; 後藤 慎平; 池尾 聡; 山本 佑樹; 曽根 尚之; 玉井 浩二; 小西 聡史; 長崎 忠雄; 松本 久子; 伊藤 功朗; 陳 豊史; 伊達 洋至; 萩原 正敏; 浅香 勲; 堀田 秋津; 三嶋 理晃; 平井 豊博
    組織培養研究 38 2 68 - 68 日本組織培養学会 2019年06月 [査読有り]
  • 森本 千絵; 松本 久子; 小熊 毅; 佐藤 晋; 佐藤 篤靖; 田嶋 範之; 石山 裕美; 砂留 広伸; 長崎 忠雄; 田辺 直也; 伊藤 功朗; 室 繁郎; 平井 豊博
    アレルギー 68 4-5 498 - 498 (一社)日本アレルギー学会 2019年05月
  • 砂留 広伸; 松本 久子; 東田 有智; 堀口 高彦; 北 英夫; 富井 啓介; 藤村 政樹; 岩永 賢司; 保澤 総一郎; 新実 彰男; 金光 禎寛; 長崎 忠雄; 森本 千絵; 小熊 毅; 田尻 智子; 伊藤 功朗; 小野 純也; 太田 昭一郎; 出原 賢治; 平井 豊博; 近畿北陸気道疾患研究会(KiHAC)
    アレルギー 68 4-5 491 - 491 (一社)日本アレルギー学会 2019年05月 [査読有り]
  • Shilei Cui; Isao Ito; Hitoshi Nakaji; Toshiyuki Iwata; Hisako Matsumoto; Tsuyoshi Oguma; Tomoko Tajiri; Tadao Nagasaki; Yoshihiro Kanemitsu; Hiromi Izuhara; Michiaki Mishima; Akio Niimi
    Respiratory physiology & neurobiology 263 1 - 8 2019年05月 [査読有り]
     
    BACKGROUND: A previous study involving guinea pigs showed that repeated cough could increase peripheral airway smooth muscle area, which can also aggravate cough. The airway pathologic changes produced by prolonged cough are still unknown. OBJECTIVE: To study the airway pathologic changes in prolonged cough models of guinea pigs. METHODS: Guinea pigs were assigned to three treatment groups: citric acid inhalation (CA) alone, citric acid inhalation with codeine pretreatment (COD), or saline solution inhalation (SA). Animals were challenged with citric acid or saline solution three times weekly. The intervention period was 22 or 43 days. Animals were challenged with citric acid on the first and last days of exposure. Lung specimens were obtained for pathologic analysis 72 h after the last exposure. RESULTS: Compared with the other two groups, the CA group had increased frequency of cough on both 22 and 43 days of exposure. Tracheal basement membrane (BM) thickness was increased after 43 days of exposure, correlating with the frequency of cough. The area of airway smooth muscles (ASM index) in small airways increased in the CA group after both 22 and 43 days of exposure, compared with the SA group. Compared with the COD group, the ASM index in small airways increased in the CA group after 22 days of exposure instead of 43 days of exposure. CONCLUSIONS: An increase in peripheral smooth muscle area by repeated cough was confirmed. Moreover, this is the first study to show that tracheal BM thickness increased after prolonged exposure (43 days). Repeated cough may lead to airway remodeling, which was also associated with an increased frequency of cough.
  • Korogi Y; Gotoh S; Ikeo S; Yamamoto Y; Sone N; Tamai K; Konishi S; Nagasaki T; Matsumoto H; Ito I; Chen-Yoshikawa TF; Date H; Hagiwara M; Asaka I; Hotta A; Mishima M; Hirai T
    Stem cell reports 12 3 431 - 440 2019年03月 [査読有り]
     
    It has been challenging to generate in vitro models of alveolar lung diseases, as the stable culture of alveolar type 2 (AT2) cells has been difficult. Methods of generating and expanding AT2 cells derived from induced pluripotent stem cells (iPSCs) have been established and are expected to be applicable to disease modeling. Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by dysfunction of lysosome-related organelles, such as lamellar bodies (LBs), in AT2 cells. From an HPS type 2 (HPS2) patient, we established disease-specific iPSCs (HPS2-iPSCs) and their gene-corrected counterparts. By live cell imaging, the LB dynamics were visualized and altered distribution, enlargement, and impaired secretion of LBs were demonstrated in HPS2-iPSC-derived AT2 cells. These findings provide insight into the AT2 dysfunction in HPS patients and support the potential use of human iPSC-derived AT2 cells for future research on alveolar lung diseases.
  • 森本 千絵; 松本 久子; 小熊 毅; 佐藤 晋; 佐藤 篤靖; 田嶋 範之; 石山 祐美; 砂留 広伸; 長崎 忠雄; 伊藤 功朗; 室 繁郎; 平井 豊博
    日本呼吸器学会誌 8 増刊 191 - 191 (一社)日本呼吸器学会 2019年03月
  • Independent factors contributing to the daytime and nighttime asthmatic cough refractory to inhaled corticosteroids.
    Kanemitsu Y; Matsumoto H; Oguma T; Nagasaki T; Ito I; Izuhara Y; Tajiri T; Iwata T; Mishima M; Niimi A
    J Investig Allergol Clin Immunol 29 2019年 [査読有り]
  • Hisako Matsumoto
    Advances in experimental medicine and biology 1132 145 - 159 2019年 [査読有り]
     
    Periostin is a matricellular protein that is deeply involved in type-2/eosinophilic airway inflammation and remodeling in asthma. While its expression in airway epithelial cells is correlated with the thickness of airway basement membrane, more importantly, periostin can be detected stably in blood with little variability, reflecting airway type-2 inflammation and remodeling. As for a result, serum periostin can serve as a valuable marker to identify patients with type-2 severe asthma who are insensitive to inhaled corticosteroids, and consequently have the excess decline of pulmonary function with asthma exacerbations. Serum periostin may significantly help to improve management of patients with severe asthma.
  • 森本 千絵; 松本 久子; 田尻 智子; 鈴川 真穂; 出原 裕美; 権 寧博; 伊藤 玲子; 橋本 修; 出原 賢治; 太田 昭一郎; 小野 純也; 大田 健; 金光 禎寛; 長崎 忠雄; 小熊 毅; 伊藤 功朗; 新実 彰男; 平井 豊博
    アレルギー 67 4-5 574 - 574 (一社)日本アレルギー学会 2018年05月
  • 森本 千絵; 小熊 毅; 石山 裕美; 砂留 広伸; 長崎 忠雄; 伊藤 功朗; 松本 久子; 平井 豊博
    アレルギー 67 4-5 596 - 596 (一社)日本アレルギー学会 2018年05月
  • 一般人口における喫煙とIgEが好酸球数に及ぼす影響 ながはま疫学研究
    砂留 広伸; 松本 久子; 出原 裕美; 長崎 忠雄; 金光 禎寛; 石山 祐美; 森本 千絵; 小熊 毅; 伊藤 功朗; 室 繁郎; 陳 和夫; 平井 豊博
    アレルギー 67 4-5 685 - 685 (一社)日本アレルギー学会 2018年05月
  • 森本 千絵; 小熊 毅; 石山 祐美; 砂留 広伸; 長崎 忠雄; 松本 久子; 平井 豊博
    日本呼吸器学会誌 7 増刊 215 - 215 (一社)日本呼吸器学会 2018年03月
  • Yamamoto Yuki; Gotoh Shimpei; Korogi Yohei; Seki Masahide; Konishi Satoshi; Ikeo Satoshi; Sone Naoyuki; Nagasaki Tadao; Matsumoto Hisako; Muro Shigeo; Ito Isao; Hirai Toyohiro; Kohno Takashi; Suzuki Yutaka; Mishima Michiaki
    日本呼吸器学会誌 7 増刊 348 - 348 2018年03月
  • 砂留 広伸; 松本 久子; 出原 裕美; 長崎 忠雄; 金光 禎寛; 石山 祐美; 森本 千絵; 小熊 毅; 伊藤 功朗; 田原 康玄; 室 繁郎; 陳 和夫; 平井 豊博
    日本呼吸器学会誌 7 増刊 179 - 179 (一社)日本呼吸器学会 2018年03月
  • Kei Shikuma; Toyofumi F Chen-Yoshikawa; Tsuyoshi Oguma; Takeshi Kubo; Keiji Ohata; Masatsugu Hamaji; Atsushi Kawaguchi; Hideki Motoyama; Kyoko Hijiya; Akihiro Aoyama; Hisako Matsumoto; Shigeo Muro; Hiroshi Date
    The Annals of thoracic surgery 105 3 909 - 914 2018年03月 [査読有り]
     
    BACKGROUND: Whether compensatory lung growth occurs in adult humans is controversial. The aim of this study was to confirm compensatory lung growth by analyzing ipsilateral residual lung after lower lobectomy in living lung transplant donors with quantitative and qualitative computed tomography assessments. METHODS: Chest computed tomography and pulmonary function tests were performed in 31 eligible donors before and 1 year after donor lobectomy. Ipsilateral residual lung volume was measured with three-dimensional computed tomography volumetry. The computed tomography-estimated volumes of low, middle, and high attenuations in the lung were calculated. Assessment of the D value, a coefficient of the cumulative size distribution of low-density area clusters, was performed to evaluate the structural quality of the residual lung. RESULTS: Postoperative pulmonary function test values were significantly larger than preoperative estimated values. Although postoperative total volume, low attenuation volume, middle attenuation volume, and high attenuation volume of the ipsilateral residual lung were significantly larger than the preoperative volumes, with 50.2%, 50.0%, 41.5%, and 43.1% increase in the median values, respectively (all p < 0.0001), the differences in D values before and after donor lobectomy were not significant (p = 0.848). The total volume of ipsilateral residual lung was increased by more than 600 mL (50%). CONCLUSIONS: The volume of ipsilateral residual lung increased, but its structural quality did not change before and after donor lobectomy. The existence of compensatory lung growth in adult humans was suggested by quantitative and qualitative computed tomography assessments.
  • Maho Suzukawa; Hisako Matsumoto; Nobuharu Ohshima; Hiroyuki Tashimo; Isao Asari; Tomoko Tajiri; Akio Niimi; Hiroyuki Nagase; Hirotoshi Matsui; Nobuyuki Kobayashi; Shunsuke Shoji; Ken Ohta
    Respiratory medicine 134 95 - 102 2018年01月 [査読有り]
     
    BACKGROUND: Omalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients. OBJECTIVES: This study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab. METHODS: Thirty-one patients with severe, persistent asthma were enrolled in this study and administered omalizumab for at least 1 year. Response to omalizumab was assessed based on the physician's global evaluation of treatment effectiveness (GETE) at 48 weeks of treatment. Blood samples were collected at baseline and 16 and 32 weeks after starting omalizumab and measured for 30 cytokines by Luminex 200 and ELISA. Exhaled nitric oxide (FeNO) levels, peripheral blood eosinophil counts, pre-bronchodilator pulmonary functions and Asthma Quality of Life Questionnaire scores were determined at baseline and 16, 32 and 48 weeks after starting omalizumab. The numbers of clinically significant asthma exacerbations in the previous year and during 48 weeks of treatment with omalizumab were assessed. RESULTS: GETE assessment showed 19 responders (61.3%) and 12 non-responders (38.7%). Responders showed significantly higher levels of CXCL10 and IL-12 at baseline compared to non-responders (CXCL10: responders, 1530.0 ± 315.2 pg/ml vs. non-responders, 1066.0 ± 396.8 pg/ml, P = 0.001; IL-12: responders, 60.2 ± 39.2 pg/ml vs. non-responders, 32.2 ± 26.3 pg/ml, P = 0.04). ROC curves to distinguish responders from non-responders using the baseline serum CXCL10 level showed a good AUC of 0.83. At 32 weeks of omalizumab therapy, serum CXCL10 tended to be increased (1350 ± 412.3 pg/ml at baseline vs. 1529 ± 637.6 pg/ml at 32 weeks, P = 0.16) and serum IL-12 tended to be decreased (49.4 ± 37.0 pg/ml at baseline vs. 43.9 ± 30.9 pg/ml at 32 weeks, P = 0.05). On the other hand, serum IL-5 and PDGF were significantly decreased (IL-5: 54.2 ± 13.8 pg/ml at baseline vs. 49.1 ± 12.5 pg/ml at 32 weeks, P = 0.008; PDGF: 4821 ± 2458 pg/ml at baseline vs. 4219 ± 1951 pg/ml at 32 weeks, P = 0.048). CONCLUSIONS: High baseline serum CXCL10 and IL-12 levels may be useful in predicting a good omalizumab response in severe asthmatics.
  • Matsumoto H
    Arerugi = [Allergy] 67 7 891 - 900 2018年 [査読有り]
  • オルガノイド形成下におけるヒトiPS細胞由来肺胞幹細胞の長期培養とその細胞不均一性
    山本 佑樹; 後藤 慎平; 興梠 陽平; 関 真秀; 小西 聡史; 池尾 聡; 曽根 尚之; 長崎 忠雄; 松本 久子; 室 繁郎; 伊藤 功朗; 平井 豊博; 河野 隆志; 鈴木 穣; 三嶋 理晃
    生命科学系学会合同年次大会 2017年度 [2LBA - 085] 生命科学系学会合同年次大会運営事務局 2017年12月
  • Yuki Yamamoto; Shimpei Gotoh; Yohei Korogi; Masahide Seki; Satoshi Konishi; Satoshi Ikeo; Naoyuki Sone; Tadao Nagasaki; Hisako Matsumoto; Shigeo Muro; Isao Ito; Toyohiro Hirai; Takashi Kohno; Yutaka Suzuki; Michiaki Mishima
    Nature methods 14 11 1097 - 1106 2017年11月 [査読有り]
     
    The stable expansion of tissue-specific stem cells in vitro has contributed to research on several organs. Alveolar epithelial type II (AT2) cells function as tissue stem cells in the lung, but robust models for studying human AT2 cells are lacking. Here we report a method for the efficient generation and long-term expansion of alveolar organoids (AOs) harboring SFTPC+ alveolar stem cells derived from human induced pluripotent stem cells (hiPSCs). hiPSC-derived SFTPC+ cells self-renewed, with transcriptomes and morphology consistent with those of AT2 cells, and were able to differentiate into alveolar epithelial type I (AT1)-like cells. Single-cell RNA-seq of SFTPC+ cells and their progenitors demonstrated that their differentiation process and cellular heterogeneity resembled those of developing AT2 cells in vivo. AOs were applicable to drug toxicology studies recapitulating AT2-cell-specific phenotypes. Our methods can help scientists overcome the limitations of current approaches to the modeling of human alveoli and should be useful for disease modeling and regenerative medicine.
  • Tadao Nagasaki; Hisako Matsumoto; Tsuyoshi Oguma; Isao Ito; Hideki Inoue; Toshiyuki Iwata; Tomoko Tajiri; Yoshihiro Kanemitsu; Yumi Izuhara; Chie Morimoto; Yumi Ishiyama; Hironobu Sunadome; Akio Niimi; Toyohiro Hirai
    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 119 5 408 - 414 2017年11月 [査読有り]
     
    BACKGROUND: Sensitization to Staphylococcus aureus enterotoxins (SEs) augments eosinophilic inflammation in asthma. Recent epidemiologic studies demonstrate that sensitization to SEs is increased in healthy smokers; however, there is no evidence on the association between sensitization to SEs and eosinophilic inflammation in smokers with asthma. OBJECTIVE: To clarify the role of SEs on clinical indexes, including eosinophilic inflammation and lung function in smokers with asthma. METHODS: The frequency of atopic sensitization to SEs was examined in adult patients with asthma. In current or ex-smokers with asthma, the association of sensitization to SEs with eosinophilic inflammation, airflow limitation, or treatment steps was determined. Clinical indexes were examined at the first visit, and treatment steps were assessed 6 months after enrollment. RESULTS: Overall, 23 current smokers, 40 ex-smokers, and 118 never smokers with asthma were enrolled. The frequency of sensitization to SEs, but not to other aeroallergens, was significantly higher in current, ex-, and never smokers, in decreasing order. In current or ex-smokers with asthma, patients with sensitization to SEs exhibited higher serum levels of total and specific IgE to aeroallergens, higher blood eosinophil counts, greater airflow limitation, and more severe disease 6 months later than those without sensitization to SE. A longer smoking abstinence period was associated with serum specific IgE levels to SEs, and 3 years was the best cutoff of abstinence period to predict the absence of sensitization to SEs. CONCLUSION: Sensitization to SEs is increased in smokers with asthma, and it may be a marker of eosinophilic inflammation and severe asthma in smokers with asthma. TRIAL REGISTRATION: umin.ac.jp Identifier: UMIN000007818.
  • Hideki Inoue; Isao Ito; Akio Niimi; Hisako Matsumoto; Tsuyoshi Oguma; Tomoko Tajiri; Toshiyuki Iwata; Tadao Nagasaki; Yoshihiro Kanemitsu; Toshitaka Morishima; Tomomitsu Hirota; Mayumi Tamari; Sally E Wenzel; Michiaki Mishima
    Respiratory investigation 55 6 338 - 347 2017年11月 [査読有り]
     
    BACKGROUND: IL1RL1 (ST2) is involved in Th2 inflammation including eosinophil activation. Single nucleotide polymorphisms (SNPs) of the IL1RL1 gene are associated with asthma development and increased peripheral blood eosinophil counts. However, the association between IL1RL1 SNPs and eosinophilic phenotype among adults with asthma remains unexplored. METHODS: In a primary cohort of 110 adult Japanese patients with stable asthma, we examined the associations between IL1RL1 SNPs and clinical measurements including forced expiratory volume (FEV1), airway reversibility of FEV1, exhaled nitric oxide (FeNO), serum soluble-ST2 (sST2) levels, peripheral blood eosinophil differentials and serum total IgE level. The findings in the primary cohort were confirmed in a validation cohort of 126 adult Japanese patients with stable asthma. RESULTS: Patients with minor alleles in 3 SNPs (rs17026974, rs1420101, and rs1921622) had high FeNO, blood eosinophil differentials, and reversibility of FEV1, but low levels of serum sST2 and FEV1. Minor alleles of rs1041973 were associated with low serum sST2 levels alone. In the validation cohort, minor alleles of rs1420101 were associated with high FeNO and blood eosinophil differentials, whereas minor alleles of rs17026974 and rs1921622 were associated with high blood eosinophil differentials and FeNO, respectively. Multivariate analyses revealed that the minor allele of rs1420101 additively contributed to the FeNO, blood eosinophil differentials, and reversibility of FEV1. CONCLUSIONS: The minor alleles of IL1RL1 SNPs were associated with high FeNO and peripheral blood eosinophilia among adult Japanese patients with stable asthma. IL1RL1 SNPs may characterize the eosinophilic phenotype with greater eosinophilic inflammation in the Japanese asthma cohort.
  • Satoshi Hamada; Shuji Tatsumi; Yoshiki Kobayashi; Hisako Matsumoto; Hirotaka Yasuba
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 5 6 1657 - 1662 2017年11月 [査読有り]
     
    BACKGROUND: Sinonasal inflammation on both clinical examinations and imaging significantly impacts both asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVE: The objective of this study was to examine the association between sinonasal inflammation and asthma-COPD overlap syndrome (ACOS). METHODS: A total of 112 patients with a ratio of forced expiratory volume in 1 s to forced vital capacity of less than 70% were enrolled. COPD, asthma, and ACOS were clinically diagnosed according to the 2014 Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Sinonasal inflammatory condition was evaluated using sinus computed tomography, and its severity was assessed according to the Lund-Mackay staging (LMS) system. Ethmoid sinus-dominant shadow was defined as the presence of greater LMS scores for the anterior and posterior ethmoid sinuses than for the maxillary sinus. RESULTS: COPD, asthma, and ACOS were diagnosed in 55 (49.1%), 39 (34.8%), and 18 patients (16.1%), respectively. The frequency of radiographic evidence of sinonasal inflammation in patients with COPD, asthma, ACOS was 60.0%, 94.9%, and 72.2%, respectively. Patients with ACOS and COPD had only mild radiographic evidence of sinonasal inflammation (LMS score, 1-7), whereas moderate (LMS score, 8-11) and severe (LMS score, >= 12) radiographic evidence of sinonasal inflammation were detected only in patients with asthma. Furthermore, the frequency of ethmoid sinus-dominant shadow was significantly higher in patients with asthma than in those with COPD and ACOS. CONCLUSIONS: Radiographic evidence of sinonasal inflammation was a common comorbidity in ACOS. Future studies are required to examine the role of sinonasal inflammation in ACOS. (C) 2017 American Academy of Allergy, Asthma & Immunology
  • Sunadome H; Matsumoto H; Petrova G; Kanemitsu Y; Tohda Y; Horiguchi T; Kita H; Kuwabara K; Tomii K; Otsuka K; Fujimura M; Ohkura N; Tomita K; Yokoyama A; Ohnishi H; Nakano Y; Oguma T; Hozawa S; Nagasaki T; Ito I; Inoue H; Tajiri T; Iwata T; Izuhara Y; Ono J; Ohta S; Hirota T; Tamari M; Yokoyama T; Niimi A; Izuhara K; Mishima M
    Clin Exp Allergy 47 8 998 - 1006 2017年08月 [査読有り]
     
    Background: Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. Objective: To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. Methods: In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor a (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (>= 95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. Results: Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (% FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin >= 95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. Conclusions and Clinical Relevance: IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.
  • Tadao Nagasaki; Hisako Matsumoto; Kenji Izuhara
    Allergology international : official journal of the Japanese Society of Allergology 66 3 404 - 410 2017年07月 [査読有り]
     
    Type-2/eosinophilic inflammation plays a pivotal role in asthma. The identification of severe type-2/eosinophilic asthma is important for improving the management of patients with asthma. Therefore, efforts to develop non-invasive biomarkers for type-2/eosinophilic airway inflammation have been made during this decade. Currently, fraction of exhaled nitric oxide (FeNO) and serum periostin levels are considered markers of type-2/eosinophilic inflammation in asthma. However, a single-marker approach has limited the ability to diagnose severe type-2/eosinophilic asthma accurately and predict disease outcomes precisely. The present article reviews the utility of FeNO and serum periostin levels in a single-marker approach and in a multiple-marker approach in identifying patients with severe type-2/eosinophilic asthma. Furthermore, based on a sub-analysis of the Kinki Hokuriku Airway disease Conference (KiHAC), geno-endo-phenotypes of patients were stratified into four groups according to the FeNO and serum periostin levels.
  • Matsumoto H; Nagasaki T; Kanemitsu Y; Niimi A; Tabara Y
    Annals of the American Thoracic Society 14 7 1232 - 1233 2017年07月 [査読有り]
  • 一般人口における末梢血好酸球数とBMI、遺伝子多型との関係 ながはま疫学研究
    砂留 広伸; 松本 久子; 長崎 忠雄; 金光 禎寛; 小熊 毅; 伊藤 功朗; 田原 康玄; 室 繁郎; 陳 和夫; 平井 豊博
    日本職業・環境アレルギー学会雑誌 25 1 92 - 92 日本職業・環境アレルギー学会 2017年06月
  • 砂留 広伸; 松本 久子; 出原 裕美; 長崎 忠雄; 金光 禎寛; 石山 祐美; 森本 千絵; 小熊 毅; 伊藤 功朗; 田原 康玄; 松田 文彦; 新実 彰男; 室 繁郎; 三嶋 理晃
    アレルギー 66 4-5 589 - 589 (一社)日本アレルギー学会 2017年05月
  • Hisako Matsumoto; Yumi Izuhara; Akio Niimi; Yasuharu Tabara; Tadao Nagasaki; Yoshihiro Kanemitsu; Kimihiko Murase; Tsuyoshi Oguma; Isao Ito; Shigeo Muro; Akihiro Sekine; Fumihiko Matsuda; Shinji Kosugi; Takeo Nakayama; Kazuo Chin; Michiaki Mishima
    ANNALS OF THE AMERICAN THORACIC SOCIETY 14 5 698 - 705 2017年05月 [査読有り]
     
    Rationale: Chronic cough hypersensitivity, a potentially important concept of chronic or prolonged cough, is featured by heightened cough response to low-intensity stimuli, which may be generated in the absence of airflow limitations or allergic conditions. However, there is little epidemiological evidence to support this.Objectives: In this large-scale community survey, we aimed to determine risks and cough-aggravating factors of prolonged cough while focusing on serum IgE levels.Methods: Prevalence of prolonged cough, defined as cough lasting 3 weeks or longer, was determined in 9,804 residents from a baseline measurement of the Nagahama Cohort Study, conducted from 2008 to 2010. Risk assessment of prolonged cough was confined to subjects without asthma (n = 9,402). Afollow-up measurement of the Nagahama Studywas successively conducted from 2013 to 2015, recruiting the same residents living inNagahamaCity, Japan (n = 8,292). Validation analysis was performed in the follow-up measurement.Results: In a baseline measurement, prolonged cough was reported by 9.5% of subjects without asthma and 32.3% of subjects with asthma. In subjects without asthma, various cough-aggravating factors were associated with prolonged cough. On the multivariate analysis, several cough-aggravating factors, including nighttime or early morning, weather, pollen season, and common cold, were associated with prolonged cough, independent of female sex, younger age, chronic obstructive pulmonary disease, postnasal drip, daytime sputum, and lower serum total IgE. Serum-specific IgE levels against Japanese cedar pollen were significantly higher in subjects who responded "yes" to " cough in the pollen season" than in those who did not respond, whereas, among subjects who responded "yes" to "cough in the pollen season," prolonged coughers showed lower serum IgE levels against Japanese cedar pollen than temporal coughers. Validation analysis in a follow-up measurement confirmed the associations between prolonged cough and cough-aggravating factors observed in the baseline measurement.Conclusions: The presence of several cough-aggravating factors in the absence of severe allergic conditions may support the presence of cough hypersensitivity.
  • Hisako Matsumoto; Yumi Izuhara; Akio Niimi; Yasuharu Tabara; Tadao Nagasaki; Yoshihiro Kanemitsu; Kimihiko Murase; Tsuyoshi Oguma; Isao Ito; Shigeo Muro; Akihiro Sekine; Fumihiko Matsuda; Shinji Kosugi; Takeo Nakayama; Kazuo Chin; Michiaki Mishima
    Annals of the American Thoracic Society 14 5 698 - 705 2017年05月 [査読有り]
     
    RATIONALE: Chronic cough hypersensitivity, a potentially important concept of chronic or prolonged cough, is featured by heightened cough response to low-intensity stimuli, which may be generated in the absence of airflow limitations or allergic conditions. However, there is little epidemiological evidence to support this. OBJECTIVES: In this large-scale community survey, we aimed to determine risks and cough-aggravating factors of prolonged cough while focusing on serum IgE levels. METHODS: Prevalence of prolonged cough, defined as cough lasting 3 weeks or longer, was determined in 9,804 residents from a baseline measurement of the Nagahama Cohort Study, conducted from 2008 to 2010. Risk assessment of prolonged cough was confined to subjects without asthma (n = 9,402). A follow-up measurement of the Nagahama Study was successively conducted from 2013 to 2015, recruiting the same residents living in Nagahama City, Japan (n = 8,292). Validation analysis was performed in the follow-up measurement. RESULTS: In a baseline measurement, prolonged cough was reported by 9.5% of subjects without asthma and 32.3% of subjects with asthma. In subjects without asthma, various cough-aggravating factors were associated with prolonged cough. On the multivariate analysis, several cough-aggravating factors, including nighttime or early morning, weather, pollen season, and common cold, were associated with prolonged cough, independent of female sex, younger age, chronic obstructive pulmonary disease, postnasal drip, daytime sputum, and lower serum total IgE. Serum-specific IgE levels against Japanese cedar pollen were significantly higher in subjects who responded "yes" to "cough in the pollen season" than in those who did not respond, whereas, among subjects who responded "yes" to "cough in the pollen season," prolonged coughers showed lower serum IgE levels against Japanese cedar pollen than temporal coughers. Validation analysis in a follow-up measurement confirmed the associations between prolonged cough and cough-aggravating factors observed in the baseline measurement. CONCLUSIONS: The presence of several cough-aggravating factors in the absence of severe allergic conditions may support the presence of cough hypersensitivity.
  • 砂留 広伸; 松本 久子; 出原 裕美; 長崎 忠雄; 金光 禎寛; 石山 祐美; 森本 千絵; 小熊 毅; 伊藤 功朗; 田原 康玄; 室 繁郎; 陳 和夫; 三嶋 理晃
    日本呼吸器学会誌 6 増刊 115 - 115 (一社)日本呼吸器学会 2017年03月
  • 森本 千絵; 松本 久子; 出原 裕美; 長崎 忠雄; 金光 禎寛; 石山 祐美; 砂留 広伸; 小熊 毅; 伊藤 功朗; 田原 康玄; 新実 彰男; 室 繁郎; 三嶋 理晃
    日本呼吸器学会誌 6 増刊 240 - 240 (一社)日本呼吸器学会 2017年03月
  • Hisako Matsumoto; Yoshihiro Kanemitsu; Tadao Nagasaki; Yuji Tohda; Takahiko Horiguchi; Hideo Kita; Kazunobu Kuwabara; Keisuke Tomii; Kojiro Otsuka; Masaki Fujimura; Noriyuki Ohkura; Katsuyuki Tomita; Akihito Yokoyama; Hiroshi Ohnishi; Yasutaka Nakano; Tetsuya Oguma; Soichiro Hozawa; Yumi Izuhara; Isao Ito; Tsuyoshi Oguma; Hideki Inoue; Tomoko Tajiri; Toshiyuki Iwata; Junya Ono; Shoichiro Ohta; Tomomitsu Hirota; Takahisa Kawaguchi; Mayumi Tamari; Tetsuji Yokoyama; Yasuharu Tabara; Fumihiko Matsuda; Kenji Izuhara; Akio Niimi; Michiaki Mishima
    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 118 2 197 - 203 2017年02月 [査読有り]
     
    BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. OBJECTIVE: To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. METHODS: We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. RESULTS: A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. CONCLUSION: SE sensitization contributes to TH2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.
  • Hideki Inoue; Akio Niimi; Hisako Matsumoto; Isao Ito; Tsuyoshi Oguma; Kojiro Otsuka; Tomoshi Takeda; Hitoshi Nakaji; Tomoko Tajiri; Toshiyuki Iwata; Tadao Nagasaki; Michiaki Mishima
    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 44 1 21 - 29 2017年01月 [査読有り]
     
    Patch formulation of tulobuterol has been used in asthma treatment as a long-acting (2)-agonist (LABA) through sustained skin absorption. Its treatment efficacy, especially in small airways, remains poorly understood. The study aim was to investigate LABA add-on effects of tulobuterol patch (TP) and salmeterol inhaler (SA) on pulmonary function, asthma control and health status. Patients who had adult-onset under-control asthma, despite taking inhaled corticosteroids, were enrolled in a randomized, open-label, parallel-group, proof-of-concept study of 12-week add-on treatment with TP (n=16) or SA (n=17). Spirometry, impulse oscillometry (IOS), exhaled nitric oxide levels, and clinical questionnaires of asthma control, health status (St. George's Respiratory Questionnaire: SGRQ), and symptoms were evaluated every 4weeks. Add-on treatment of SA significantly improved the spirometric indices of small airway obstruction (forced expiratory flow between 25% and 75% of FVC: FEF25-75, and maximum expiratory flow at 25% of FVC: MEF25) and IOS indices of whole respiratory resistance (resistance at 5Hz) as compared to TP. In intra-group comparisons, add-on treatment of TP improved the scores of the asthma control test and the total SGRQ, as well as the symptom and impact components of the SGRQ. SA add-on treatment improved FEV1 and IOS parameters of resistance at 20Hz and reactance at 5Hz. Neither of the treatments improved exhaled nitric oxide levels. In conclusion, add-on treatment of TP improved asthma control and health status, whereas SA improved pulmonary function measures associated with large and small airway involvement among patients with adult-onset mild-to-moderate asthma.
  • Masaya Takemura; Akio Niimi; Hisako Matsumoto; Tetsuya Ueda; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Kian Fan Chung; Michiaki Mishima
    Allergology international : official journal of the Japanese Society of Allergology 66 1 83 - 88 2017年01月 [査読有り]
     
    BACKGROUND: Inhalation studies suggested "protective" roles of exogenous prostaglandin E2, but the clinical relevance of endogenous prostanoids in asthma is poorly known. The objective of this study is to measure sputum levels of prostanoids in asthmatic patients to correlate with clinical indices. METHODS: Mild (n = 41) or moderate-to-severe (19) asthmatics and 27 normal controls were examined for pulmonary function (FEV1 and mid-forced expiratory flow), sputum cell differentials, and sputum levels of prostaglandins D2, E2, F2α, and thromboxane B2 measured by sandwich enzyme immunoassay. RESULTS: Each prostanoid level did not differ among the three groups. Sputum number of bronchial epithelial cells was greater in moderate-to-severe asthmatics than in the other two groups, suggesting epithelial desquamation. Levels of prostaglandin F2α, D2, and thromboxane B2 positively correlated with the severity of airflow obstruction in the 60 asthmatic patients, whereas prostaglandin E2 levels were unrelated to pulmonary function. The ratio of combined "contractile" prostanoids (prostaglandin D2/prostaglandin F2α/thromboxane B2) to prostaglandin E2 was 2.5-fold greater in moderate-to-severe asthmatics than in controls (p = 0.001) or in mild asthmatics (p = 0.0002) but did not differ between the latter two groups. In the two asthmatic groups combined, this ratio positively correlated with the sputum number of epithelial cells. The combined "contractile" prostanoids levels positively correlated with prostaglandin E2 levels in controls and in mild asthmatics but not in moderate-to-severe asthmatics. CONCLUSIONS: An imbalance in production, breakdown, or both between prostaglandin E2 and other prostanoids possibly due to epithelial damage may be involved in the pathogenesis of moderate-to-severe asthma.
  • Hideki Inoue; Akio Niimi; Hisako Matsumoto; Isao Ito; Tsuyoshi Oguma; Kojiro Otsuka; Tomoshi Takeda; Hitoshi Nakaji; Tomoko Tajiri; Toshiyuki Iwata; Tadao Nagasaki; Michiaki Mishima
    Clinical and experimental pharmacology & physiology 44 1 21 - 29 2017年01月 [査読有り]
     
    Patch formulation of tulobuterol has been used in asthma treatment as a long-acting β2 -agonist (LABA) through sustained skin absorption. Its treatment efficacy, especially in small airways, remains poorly understood. The study aim was to investigate LABA add-on effects of tulobuterol patch (TP) and salmeterol inhaler (SA) on pulmonary function, asthma control and health status. Patients who had adult-onset under-control asthma, despite taking inhaled corticosteroids, were enrolled in a randomized, open-label, parallel-group, proof-of-concept study of 12-week add-on treatment with TP (n=16) or SA (n=17). Spirometry, impulse oscillometry (IOS), exhaled nitric oxide levels, and clinical questionnaires of asthma control, health status (St. George's Respiratory Questionnaire: SGRQ), and symptoms were evaluated every 4 weeks. Add-on treatment of SA significantly improved the spirometric indices of small airway obstruction (forced expiratory flow between 25% and 75% of FVC: FEF25-75 , and maximum expiratory flow at 25% of FVC: MEF25 ) and IOS indices of whole respiratory resistance (resistance at 5 Hz) as compared to TP. In intra-group comparisons, add-on treatment of TP improved the scores of the asthma control test and the total SGRQ, as well as the symptom and impact components of the SGRQ. SA add-on treatment improved FEV1 and IOS parameters of resistance at 20 Hz and reactance at 5 Hz. Neither of the treatments improved exhaled nitric oxide levels. In conclusion, add-on treatment of TP improved asthma control and health status, whereas SA improved pulmonary function measures associated with large and small airway involvement among patients with adult-onset mild-to-moderate asthma.
  • Yuji Tohda; Takashi Iwanaga; Hiroyuki Sano; Hiroaki Kume; Kazuto Hirata; Noriyuki Ohkura; Isao Tachibana; Yoshihiro Nishimura; Hisako Matsumoto; Yoshiaki Minakata; Masanori Yoshikawa; Masaki Fujimura
    International journal of clinical practice 71 1 2017年01月 [査読有り]
     
    BACKGROUND AND OBJECTIVES: Assessment of the effects of long-term management on patient quality of life (QOL) would be extremely useful for determining asthma treatment strategies. However, no studies have evaluated QOL over an extended period of time. This study evaluated the changes in QOL, drug management and disease severity in the same asthma patients at an interval of approximately 9 years. METHODS: We re-surveyed asthma patients enrolled in a survey conducted in 2004 to evaluate the effects of approximately a decade of treatment on disease severity and QOL assessed by the Japanese Asthma Health Questionnaire (AHQ-JAPAN). RESULTS: A total of 2179 patients were enrolled in the study from 93 centres, and 1332 patients were included in the per-protocol analysis. Usage rates of inhaled corticosteroids (ICS) for treatment of stable asthma were over 90% at both time points. The AHQ-JAPAN total score improved significantly from 22.2±19.7 in 2004 to 19.7±19.9 in 2013 (P<.001). Significant improvements were also observed in 5 of 6 subscales of AHQ-JAPAN, with Social Activity constituting the sole exception. CONCLUSIONS: Asthma severity declined and QOL assessed by AHQ-JAPAN improved, which is considered as a reflection of improved asthma control at least partly attributable to widespread use of anti-inflammatory drugs as represented by ICS. The study also revealed the presence of those with poor QOL, especially in patients with concomitant respiratory diseases, and an increase in severe persistent asthma cases, warranting further long-term efforts at improving QOL. TRIAL REGISTRATION NUMBER: UMIN 000010483.
  • Takahiro Kamada; Isao Ito; Yoshihiro Kanemitsu; Susumu Sato; Hisako Matsumoto; Akio Niimi; Michiaki Mishima
    Respiratory investigation 55 1 69 - 73 2017年01月 [査読有り]
     
    Relapsing polychondritis (RP) is characterized by recurrent systemic inflammation of the cartilages and is accompanied by central airway collapse. We report a case wherein three-dimensional imaging of respiratory system resistance (Rrs) and respiratory system reactance (Xrs) by using MostGraph (CHEST M.I., Tokyo, Japan), a forced oscillation system, revealed that Rrs and Xrs in the inspiratory and expiratory phases correlated with proximal airway collapse. The degree of difference in Rrs and Xrs between the supine and sitting positions reflected airway collapse more closely than did the pulmonary function test. MostGraph could be a useful tool for assessing airway collapse in RP.
  • Kiminobu Tanizawa; Tomohiro Handa; Sonoko Nagai; Akio Niimi; Tsuyoshi Oguma; Takeshi Kubo; Yutaka Ito; Kensaku Aihara; Kohei Ikezoe; Hisako Matsumoto; Toyohiro Hirai; Kazuo Chin; Michiaki Mishima
    ERJ Open Research 3 1 2017年01月 [査読有り]
  • Shoichiro Ohta; Masaki Okamoto; Kiminori Fujimoto; Noriho Sakamoto; Koichiro Takahashi; Hiroshi Yamamoto; Hisako Kushima; Hiroshi Ishii; Keiichi Akasaka; Junya Ono; Ayami Kamei; Yoshinori Azuma; Hisako Matsumoto; Yukie Yamaguchi; Michiko Aihara; Takeshi Johkoh; Atsushi Kawaguchi; Masao Ichiki; Hironori Sagara; Jun-Ichi Kadota; Masayuki Hanaoka; Shin-Ichiro Hayashi; Shigeru Kohno; Tomoaki Hoshino; Kenji Izuhara
    PloS one 12 3 e0174547  2017年 [査読有り]
     
    The natural course of idiopathic pulmonary fibrosis (IPF) is variable. Predicting disease progression and survival in IPF is important for treatment. We previously demonstrated that serum periostin has the potential to be a prognostic biomarker for IPF. Our aim was to use monomeric periostin in a multicenter study to evaluate its efficacy in diagnosing IPF and predicting its progression. To do so, we developed a new periostin kit to detect only monomeric periostin. The subjects consisted of 60 IPF patients in a multicenter cohort study. We applied monomeric periostin, total periostin detected by a conventional kit, and the conventional biomarkers-KL-6, SP-D, and LDH-to diagnose IPF and to predict its short-term progression as estimated by short-term changes of %VC and % DL, CO. Moreover, we compared the fraction ratios of monomeric periostin to total periostin in IPF with those in other periostin-high diseases: atopic dermatitis, systemic scleroderma, and asthma. Monomeric periostin showed the greatest ability to identify IPF comparable with KL-6 and SP-D. Both monomeric and total periostin were well correlated with the decline of %VC and % DL, CO. Clustering of IPF patients into high and low periostin groups proved useful for predicting the short-term progression of IPF. Moreover, the relative ratio of monomeric periostin was higher in IPF than in other periostin-high diseases. Measuring monomeric periostin is useful for diagnosing IPF and predicting its short-term progression. Moreover, the ratio of monomeric periostin to total periostin is elevated in IPF compared to other periostin-high diseases.
  • Hitoshi Nakaji; Akio Niimi; Hirofumi Matsuoka; Toshiyuki Iwata; Shilei Cui; Hisako Matsumoto; Isao Ito; Tsuyoshi Oguma; Kojiro Otsuka; Tomoshi Takeda; Hideki Inoue; Tomoko Tajiri; Tadao Nagasaki; Yoshihiro Kanemitsu; Kazuo Chin; Michiaki Mishima
    Respiratory investigation 54 6 419 - 427 2016年11月 [査読有り]
     
    BACKGROUND: Chronic cough involves airway remodeling associated with cough reflex hypersensitivity. Whether cough itself induces these features remains unknown. METHODS: Guinea pigs were assigned to receive treatment with citric acid (CA), saline (SA), or CA+dextromethorphan (DEX). All animals were exposed to 0.5M CA on days 1 and 22. On days 4-20, the CA and CA+DEX groups were exposed to CA, and the SA group to saline thrice weekly, during which the CA+DEX group was administered DEX pretreatment to inhibit cough. The number of coughs was counted during each 10-min CA or SA exposure. Terbutaline premedication was started to prevent bronchoconstriction. Bronchoalveolar lavage and pathology were examined on day 25. Average cough number for 10 CA exposures was examined as "cough index" in the CA group, which was divided into frequent (cough index>5) and infrequent (<5) cough subgroups for lavage and pathology analysis. RESULTS: The number of coughs significantly increased in the CA group from day 13 onwards. In the CA+DEX and SA groups, the number of coughs did not differ between days 1 and 22, while average number of coughs during days 4-20 was significantly lower than at days 1 and 22. Bronchoalveolar cell profiles were similar among the four groups. The smooth muscle area of small airways was significantly greater in the frequent-cough subgroup than in the other groups (in which it was similar), and highly correlated with cough index in CA group. CONCLUSION: Repeated cough induces airway smooth muscle remodeling associated with cough reflex hypersensitivity.
  • Yoshihiro Kanemitsu; Hisako Matsumoto; Nuriamina Osman; Tsuyoshi Oguma; Tadao Nagasaki; Yumi Izuhara; Isao Ito; Tomoko Tajiri; Toshiyuki Iwata; Akio Niimi; Michiaki Mishima
    Respiratory investigation 54 6 413 - 418 2016年11月 [査読有り]
     
    BACKGROUND: Fractional exhaled nitric oxide (FeNO) is considered an alternative marker of eosinophilic airway inflammation and is sometimes incorporated in the diagnosis of asthma. However, many patients with cough variant asthma (CVA) demonstrate an FeNO in the normal range. Therefore, additional information is needed to confirm the diagnosis of CVA, particularly in patients with low FeNO levels. We aimed to investigate the feasibility of using cough triggers to help diagnose CVA. METHODS: We studied 163 patients presenting with prolonged/chronic cough alone (including 104 CVA patients) who underwent FeNO measurements and an airway responsiveness test, and answered a questionnaire listing 18 cough triggers. The sensitivity and specificity of FeNO levels and cough triggers for the diagnosis of CVA were determined. RESULTS: CVA patients showed higher FeNO levels than non-CVA patients. When the cut-off value of FeNO levels for the diagnosis of CVA was set at 22ppb, its sensitivity was 57%. CVA patients more frequently responded to "cold air" and "talking" as cough triggers than non-CVA patients. When the analysis was confined to those with a low FeNO (<22ppb) group, the sensitivity and positive predictive values of "cold air" and "talking" for the diagnosis of CVA were 36% and 70% for "cold air", and 44% and 74% for "talking", respectively. Their specificity was 81%. "Cold air" was associated with airway hyperresponsiveness in all patients with an emphasis on those with low FeNO levels. CONCLUSION: "Cold air" and/or "talking" as cough triggers could be signs for the diagnosis of CVA, particularly when FeNO levels are low.
  • Hideki Inoue; Isao Ito; Akio Niimi; Hisako Matsumoto; Hirofumi Matsuoka; Makiko Jinnai; Tomoshi Takeda; Tsuyoshi Oguma; Kojiro Otsuka; Hitoshi Nakaji; Tomoko Tajiri; Toshiyuki Iwata; Tadao Nagasaki; Yoshihiro Kanemitsu; Michiaki Mishima
    The Journal of asthma : official journal of the Association for the Care of Asthma 53 9 914 - 21 2016年11月 [査読有り]
     
    OBJECTIVES: Eosinophilic asthma (EA) is a distinct clinical phenotype characterized by eosinophilic airway inflammation and airway remodeling. Few studies have used computed tomography (CT) scanning to assess the association between sputum eosinophil differential counts and airway involvement. We aimed to investigate the clinical characteristics and airway involvement of EA, and to examine the correlation between induced sputum eosinophil differential counts and CT-assessed airway remodeling. METHODS: We retrospectively divided 63 patients with stable asthma receiving inhaled corticosteroids into 2 groups: 26 patients with EA (sputum eosinophil >3%) and 37 patients with non-eosinophilic asthma (NEA). Clinical measurements such as spirometry, fractional exhaled nitric oxide levels (FeNO), and CT-assessed indices of airway involvement were compared between the groups. Multivariate analysis was performed to identify determinants of the percentage of wall area (WA%). RESULTS: The EA group had significantly longer asthma duration, lower pulmonary function, and higher FeNO than the NEA group. Also, the EA group had higher WA% and smaller airway luminal area than the NEA group. Sputum eosinophil differential counts and WA% were positively correlated. The multivariate linear regression analysis showed that the factors associated with WA% included sputum eosinophil differential counts, age, and body mass index. However, asthma duration was not associated with WA%. Our CT-assessed findings demonstrated large airway involvement in EA, and we observed a positive association between induced sputum eosinophil differential counts and WA%. CONCLUSIONS: The findings indicate that induced sputum eosinophil differential counts may be associated with airway remodeling in patients with stable asthma.
  • T. Tajiri; H. Matsumoto; Y. Gon; R. Ito; S. Hashimoto; K. Izuhara; M. Suzukawa; K. Ohta; J. Ono; S. Ohta; I. Ito; T. Oguma; H. Inoue; T. Iwata; Y. Kanemitsu; T. Nagasaki; A. Niimi; M. Mishima
    ALLERGY 71 10 1472 - 1479 2016年10月 [査読有り]
     
    Background: Omalizumab, a humanized anti-IgE monoclonal antibody, has demonstrated efficacy in patients with severe allergic asthma. However, treatment responses vary widely among individuals. Despite a lack of data, free serum IgE levels following omalizumab treatment have been proposed as a marker of treatment responsiveness. Methods: In this prospective, observational study, we assessed the utility of biomarkers of type 2 inflammation in predicting omalizumab treatment responses, as determined by the absence of asthma exacerbation during the first year of treatment. Free serum IgE levels were monitored for 2 years to examine their association with baseline biomarker levels and the number of exacerbations. Results: We enrolled thirty patients who had been treated with omalizumab for at least 1 year, of whom 27 were treated for 2 years. Baseline serum periostin levels and blood eosinophil counts were significantly higher in patients without exacerbations during the first year of treatment than in patients with exacerbations. Baseline serum periostin levels, but not eosinophil counts, were negatively associated with free serum IgE levels after 16 or 32 weeks of treatment. Reduced free serum IgE levels during treatment from those at baseline were associated with reduced exacerbation numbers at 2 years. In 14 patients who continued to have exacerbations during the first year of treatment, exacerbation numbers gradually and significantly decreased over the 2-year study period, with concurrent significant reductions in free serum IgE levels. Conclusion: Baseline serum periostin levels and serum free IgE levels during treatment follow-up may be useful in evaluating responses to omalizumab treatment.
  • Daiki Hira; Yuko Komase; Setsuko Koshiyama; Tetsuya Oguma; Tetsuo Hiramatsu; Akira Shiraki; Masanori Nishikawa; Masanori Nakanishi; Takao Tsuji; Hisako Matsumoto; Koichi Ichimura; Takashi Iwanaga; Miwa Morikawa; Hirotaka Yasuba; Fumiko Sugaya; Yukako Arakawa; Yoshiki Kobayashi; Toshiyuki Kato; Yutaka Futamura; Fumio Tsuji; Tomohiro Terada
    Allergology international : official journal of the Japanese Society of Allergology 65 4 444 - 449 2016年10月 [査読有り]
     
    BACKGROUND: There is no systematic analysis to identify problems involved with instruction on inhalation therapy for elderly patients. We conducted a nationwide questionnaire survey for patients and medical professionals. METHODS: A questionnaire survey was conducted of adult patients on inhaled drugs (ages 18-92 years, 820 individuals) and medical professionals (pharmacists or nurses) who provided instruction on inhalation therapy to these patients in 23 institutions in Japan to investigate the technique and the level of understanding (knowledge) of the inhalation therapy. Changes in the recognition of performance of inhalation technique and inhalation knowledge with increasing age were analyzed. RESULTS: According to patients' subjective assessment, there was no deterioration in the performance of the inhalation technique or loss of the knowledge with increasing age. On the other hand, medical professionals' objective assessment revealed a significant loss of both inhalation technique and knowledge with increasing age. Not many elderly patients noticed their own problems themselves, revealing a great perception gap between elderly patients and medical professionals. Thus, there was concern that patients would unconsciously practice the inhalation procedure improperly. On the other hand, in comparison with non-elderly patients, elderly patients were less resistant to continuation of therapy, suggesting that they would be more likely to accept instruction on inhalation therapy. CONCLUSIONS: Elderly patients are apt to assume that they "understand well", therefore, in order to recognize and close the perception gap between elderly patients and medical professionals, it is necessary to provide them with more aggressive (frequent) instructions on inhalation therapy.
  • Satoshi Hamada; Hisako Matsumoto; Yoshiki Kobayashi; Mikiya Asako; Hirotaka Yasuba
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 4 4 751 - 752 2016年08月 [査読有り]
  • Yoshihiro Kanemitsu; Akio Niimi; Hisako Matsumoto; Toshiyuki Iwata; Isao Ito; Tsuyoshi Oguma; Hideki Inoue; Tomoko Tajiri; Tadao Nagasaki; Yumi Izuhara; Guergana Petrova; Surinder S Birring; Michiaki Mishima
    Allergology international : official journal of the Japanese Society of Allergology 65 3 320 - 6 2016年07月 [査読有り]
     
    BACKGROUND: Gastroesophageal reflux disease (GERD) is known as a common comorbidity of asthma and chronic cough. The impact of GERD symptoms on cough-specific quality of life (QoL) in patients with asthmatic cough is poorly understood. The aim of this study is to determine the association of GERD symptoms with cough-specific quality of life in patients with cough variant asthma (CVA) using the Leicester Cough Questionnaire (LCQ). METHODS: A total of 172 consecutive patients (121 females) with mean cough duration of 45.1 months (range 2-480 months) completed the Japanese version of the LCQ. The Frequency Scale for the Symptoms of Gastroesophageal reflux was administered to assess symptoms of acid-reflux and dysmotility. A range of clinical variables that may determine cough-specific QoL (LCQ) were estimated. RESULTS: The mean LCQ scores was 12.9 (SD 3.5), consistent with severe impairment in QoL. Female gender, symptoms of gastroesophageal dysmotility, sensitization to allergens (house dust and Japanese cedar pollen) and the number of sensitized allergens were associated with lower LCQ scores (i.e. impaired cough-specific QoL) in univariate regression analysis. Acid-reflux symptoms, airway hyperresponsiveness, fractional exhaled nitric oxide, and sensitization to molds were unrelated to the LCQ score. After adjustment for gender, symptoms of gastroesophageal dysmotility was the only significant determinant of impaired cough-specific QoL accounting for 23% of the variance. CONCLUSIONS: Cough-specific QoL is severely impaired in patients with CVA. Symptoms of gastroesophageal dysmotility are an independent predictor of cough-specific QoL of patients with CVA.
  • Y. Izuhara; H. Matsumoto; T. Nagasaki; Y. Kanemitsu; K. Murase; I. Ito; T. Oguma; S. Muro; K. Asai; Y. Tabara; K. Takahashi; K. Bessho; A. Sekine; S. Kosugi; R. Yamada; T. Nakayama; F. Matsuda; A. Niimi; K. Chin; M. Mishima
    ALLERGY 71 7 1031 - 1036 2016年07月 [査読有り]
     
    Background: Allergic rhinitis, a known risk factor for asthma onset, often accompanies mouth breathing. Mouth breathing may bypass the protective function of the nose and is anecdotally considered to increase asthma morbidity. However, there is no epidemiological evidence that mouth breathing is independently associated with asthma morbidity and sensitization to allergens. In this study, we aimed to clarify the association between mouth breathing and asthma morbidity and allergic/eosinophilic inflammation, while considering the effect of allergic rhinitis. Methods: This community-based cohort study, the Nagahama Study, contained a self-reporting questionnaire on mouth breathing and medical history, blood tests, and pulmonary function testing. We enrolled 9804 general citizens of Nagahama City in the Shiga Prefecture, Japan. Results: Mouth breathing was reported by 17% of the population and was independently associated with asthma morbidity. The odds ratio for asthma morbidity was 1.85 (95% CI, 1.27-2.62) and 2.20 (95% CI, 1.72-2.80) in subjects with mouth breathing alone and allergic rhinitis alone, which additively increased to 4.09 (95% CI, 3.01-5.52) when mouth breathing and allergic rhinitis coexisted. Mouth breathing in nonasthmatics was a risk for house dust mite sensitization, higher blood eosinophil counts, and lower pulmonary function after adjusting for allergic rhinitis. Conclusion: Mouth breathing may increase asthma morbidity, potentially through increased sensitization to inhaled allergens, which highlights the risk of mouthbypass breathing in the ` one airway, one disease' concept. The risk of mouth breathing should be well recognized in subjects with allergic rhinitis and in the general population.
  • 金光 禎寛; 松本 久子; 小熊 毅; 長崎 忠雄; 出原 裕美; 伊藤 功朗; 田尻 智子; 岩田 敏之; 草田 修; 青山 典仁; 佐々木 一彦; 三嶋 理晃; 新実 彰男
    アレルギー 65 4-5 548 - 548 (一社)日本アレルギー学会 2016年05月
  • 田尻 智子; 松本 久子; 権 寧博; 伊藤 玲子; 橋本 修; 出原 賢治; 鈴川 真穂; 大田 健; 金光 禎寛; 長崎 忠雄; 岩田 敏之; 小熊 毅; 伊藤 功朗; 新実 彰男; 三嶋 理晃
    アレルギー 65 4-5 574 - 574 (一社)日本アレルギー学会 2016年05月
  • 小熊 毅; 松本 久子; 砂留 広伸; 出原 裕美; 長崎 忠雄; 佐藤 晋; 新実 彰男; 三嶋 理晃
    アレルギー 65 4-5 654 - 654 (一社)日本アレルギー学会 2016年05月
  • 砂留 広伸; 松本 久子; 金光 禎寛; 東田 有智; 堀口 高彦; 北 英夫; 富井 啓介; 藤村 政樹; 横山 彰仁; 中野 恭幸; 保澤 総一郎; 新実 彰男; 小熊 毅; 田尻 智子; 伊藤 功朗; 出原 裕美; 長崎 忠雄; 出原 賢治; 三嶋 理晃
    アレルギー 65 4-5 547 - 547 (一社)日本アレルギー学会 2016年05月 [査読有り]
  • Kenji Izuhara; Simon J Conway; Bethany B Moore; Hisako Matsumoto; Cecile T J Holweg; John G Matthews; Joseph R Arron
    American journal of respiratory and critical care medicine 193 9 949 - 56 2016年05月 [査読有り]
     
    Periostin is a matricellular protein that has been implicated in many disease states. It interacts with multiple signaling cascades to modulate the expression of downstream genes that regulate cellular interactions within the extracellular matrix. This review focuses on the role of periostin in respiratory diseases, including asthma and idiopathic pulmonary fibrosis, and its potential to help guide treatment or assess prognosis. Epithelial injury is a common feature of many respiratory diseases, resulting in the secretion, among others, of periostin, which is subsequently involved in airway remodeling and other aspects of pulmonary pathophysiology. In asthma, periostin is recognized as a biomarker of type 2 inflammation; POSTN gene expression is up-regulated in bronchial epithelial cells by IL-13 and IL-4. Serum periostin has been evaluated for the identification of patients with increased clinical benefit from treatment with anti-IL-13 (lebrikizumab, tralokinumab) and anti-IgE (omalizumab) therapy and may be prognostic for increased risk of asthma exacerbations and progressive lung function decline. Furthermore, in asthma, periostin may regulate subepithelial fibrosis and mucus production and may serve as a systemic biomarker of eosinophilic airway inflammation. Periostin is also highly expressed in the lungs of patients with idiopathic pulmonary fibrosis, and its serum levels may predict clinical progression. Overall, periostin contributes to multiple pathogenic processes across respiratory diseases, and peripheral blood levels of periostin may have utility as a biomarker of treatment response and disease progression.
  • Shigeo Muro; Yasuharu Tabara; Hisako Matsumoto; Kazuya Setoh; Takahisa Kawaguchi; Meiko Takahashi; Isao Ito; Yutaka Ito; Kimihiko Murase; Chikashi Terao; Shinji Kosugi; Ryo Yamada; Akihiro Sekine; Takeo Nakayama; Kazuo Chin; Michiaki Mishima; Fumihiko Matsuda
    Medicine 95 15 e3371  2016年04月 [査読有り]
     
    Chronic obstructive pulmonary disease (COPD) is a possible risk factor for cardiovascular disease. The association of COPD with the pathogenicity of infection with Chlamydia pneumoniae and Mycoplasma pneumoniae is controversial. We conducted a cross-sectional study to clarify the association between atypical pneumoniae seropositivity and COPD in a general population. We also investigated genetic polymorphisms conferring susceptibility to a pneumonia titer. The study included 9040 Japanese subjects (54 ± 13 years). COPD was defined as a ratio of forced expiratory volume in 1 second to forced vital capacity of less than 70%. Serum levels of IgA and IgG antibodies to C pneumoniae were determined using an enzyme-linked immunoassay, and M pneumoniae seropositivity was assessed by a particle agglutination test. Subjects seropositive for C pneumoniae (26.1%) had a higher prevalence of COPD (seropositive, 5.8%; seronegative, 3.1%; P < 0.001) after adjustment for age, sex, height, weight, and smoking status. The association between M pneumoniae seropositivity (20.4%) and COPD was also significant in covariate-adjusted analysis (P < 0.001). A genome-wide association analysis of the C pneumoniae IgA index identified a susceptible genotype (rs17634369) near the IKZF1 gene, and the seropositive rate of C pneumoniae significantly differed among genotypes (AA, 22.5; AG, 25.3; GG, 29.7%, P < 0.001). On multiple regression analysis, seropositivity for both C pneumoniae (odds ratio = 1.41, P = 0.004) and M pneumoniae (odds ratio = 1.60, P = 0.002) was an independent determinant for COPD, while no direct association was found with the rs17634369 genotype. Seropositivity for both C pneumoniae and M pneumoniae is an independent risk factor for COPD in the general population.
  • 田尻 智子; 松本 久子; 権 寧博; 伊藤 玲子; 橋本 修; 鈴川 真穂; 大田 健; 金光 禎寛; 長崎 忠雄; 小熊 毅; 伊藤 功朗; 新実 彰男; 三嶋 理晃
    日本呼吸器学会誌 5 増刊 163 - 163 (一社)日本呼吸器学会 2016年03月
  • 長崎 忠雄; 松本 久子; 小熊 毅; 砂留 広伸; 出原 裕美; 金光 禎寛; 伊藤 功朗; 岩田 敏之; 田尻 智子; 新実 彰男; 三嶋 理晃
    日本呼吸器学会誌 5 増刊 325 - 325 (一社)日本呼吸器学会 2016年03月
  • 出原 裕美; 松本 久子; 長崎 忠雄; 金光 禎寛; 伊藤 功朗; 小熊 毅; 室 繁郎; 別所 和久; 田原 康玄; 松田 文彦; 中山 健夫; 新実 彰男; 陳 和夫; 三嶋 理晃
    日本呼吸器学会誌 5 増刊 251 - 251 (一社)日本呼吸器学会 2016年03月 [査読有り]
  • 小西聡史; 後藤慎平; 立石和博; 山本佑樹; 興梠陽平; 長崎忠雄; 松本久子; 室 繁郎; 平井豊博; 伊藤功朗; 月田早智子; 三嶋理晃
    日本呼吸器学会誌 5 増刊号 143  2016年03月
  • Satoshi Konishi; Shimpei Gotoh; Kazuhiro Tateishi; Yuki Yamamoto; Yohei Korogi; Tadao Nagasaki; Hisako Matsumoto; Shigeo Muro; Toyohiro Hirai; Isao Ito; Sachiko Tsukita; Michiaki Mishima
    Stem cell reports 6 1 18 - 25 2016年01月 [査読有り]
     
    Multi-ciliated airway cells (MCACs) play a role in mucociliary clearance of the lung. However, the efficient induction of functional MCACs from human pluripotent stem cells has not yet been reported. Using carboxypeptidase M (CPM) as a surface marker of NKX2-1(+)-ventralized anterior foregut endoderm cells (VAFECs), we report a three-dimensional differentiation protocol for generating proximal airway epithelial progenitor cell spheroids from CPM(+) VAFECs. These spheroids could be induced to generate MCACs and other airway lineage cells without alveolar epithelial cells. Furthermore, the directed induction of MCACs and of pulmonary neuroendocrine lineage cells was promoted by adding DAPT, a Notch pathway inhibitor. The induced MCACs demonstrated motile cilia with a "9 + 2" microtubule arrangement and dynein arms capable of beating and generating flow for mucociliary transport. This method is expected to be useful for future studies on human airway disease modeling and regenerative medicine.
  • T. Tajiri; H. Matsumoto; Y. Gon; R. Ito; S. Hashimoto; K. Izuhara; M. Suzukawa; K. Ohta; J. Ono; S. Ohta; I. Ito; T. Oguma; H. Inoue; T. Iwata; T. Nagasaki; Y. Kanemitsu; A. Niimi; M. Mishima
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 193 e Pub ahead of print  2016年 [査読有り]
  • ヒトiPS細胞から気道線毛上皮細胞への分化誘導
    小西 聡史; 後藤 慎平; 立石 和博; 山本 佑樹; 興梠 陽平; 長崎 忠雄; 松本 久子; 室 繁郎; 平井 豊博; 伊藤 功朗; 月田 早智子; 三嶋 理晃
    日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回 [2LBA024] - [2LBA024] (公社)日本生化学会 2015年12月
  • Shinsaku Tokuda; Young Hak Kim; Hisako Matsumoto; Shigeo Muro; Toyohiro Hirai; Michiaki Mishima; Mikio Furuse
    PLOS ONE 10 12 e0145522  2015年12月 [査読有り]
     
    The relationship between chronic inflammation and cancer is well known. The inflammation increases the permeability of blood vessels and consequently elevates pressure in the interstitial tissues. However, there have been only a few reports on the effects of hydrostatic pressure on cultured cells, and the relationship between elevated hydrostatic pressure and cell properties related to malignant tumors is less well understood. Therefore, we investigated the effects of hydrostatic pressure on the cultured epithelial cells seeded on permeable filters. Surprisingly, hydrostatic pressure from basal to apical side induced epithelial stratification in Madin-Darby canine kidney (MDCK) I and Caco-2 cells, and cavities with microvilli and tight junctions around their surfaces were formed within the multi-layered epithelia. The hydrostatic pressure gradient also promoted cell proliferation, suppressed cell apoptosis, and increased transepithelial ion permeability. The inhibition of protein kinase A (PKA) promoted epithelial stratification by the hydrostatic pressure whereas the activation of PKA led to suppressed epithelial stratification. These results indicate the role of the hydrostatic pressure gradient in the regulation of various epithelial cell functions. The findings in this study may provide clues for the development of a novel strategy for the treatment of the carcinoma.
  • Toshiyuki Iwata; Isao Ito; Akio Niimi; Koji Ikegami; Satoshi Marumo; Naoya Tanabe; Hitoshi Nakaji; Yoshihiro Kanemitsu; Hisako Matsumoto; Junzo Kamei; Mitsutoshi Setou; Michiaki Mishima
    PLOS ONE 10 11 e0141823  2015年11月 [査読有り]
     
    Cough affects all individuals at different times, and its economic burden is substantial. Despite these widespread adverse effects, cough research relies on animal models, which hampers our understanding of the fundamental cause of cough. Postnasal drip is speculated to be one of the most frequent causes of chronic cough; however, this is a matter of debate. Here we show that mechanical stimuli by postnasal drip cause chronic cough. We distinguished human cough from sneezes and expiration reflexes by airflow patterns. Cough and sneeze exhibited one-peak and two-peak patterns, respectively, in expiratory airflow, which were also confirmed by animal models of cough and sneeze. Transgenic mice with ciliary dyskinesia coughed substantially and showed postnasal drip in the pharynx; furthermore, their cough was completely inhibited by nasal airway blockade of postnasal drip. We successfully reproduced cough observed in these mice by injecting artificial postnasal drip in wild-type mice. These results demonstrated that mechanical stimulation by postnasal drip evoked cough. The findings of our study can therefore be used to develop new antitussive drugs that prevent the root cause of cough.
  • 保険薬局と協働で行う吸入指導とその評価
    寺尾 真琴; 杉本 充弘; 萱野 勇一郎; 木村 嘉彦; 山嶋 仁実; 今井 哲司; 佐藤 晋; 松本 久子; 室 繁郎; 松原 和夫
    日本呼吸ケア・リハビリテーション学会誌 25 Suppl. 243s - 243s (一社)日本呼吸ケア・リハビリテーション学会 2015年09月
  • Kenji Izuhara; Hisako Matsumoto; Shoichiro Ohta; Junya Ono; Kazuhiko Arima; Masahiro Ogawa
    ALLERGOLOGY INTERNATIONAL 64 S3 - S10 2015年09月 [査読有り]
     
    Although it is currently recognized that bronchial asthma is not a single disease but a syndrome, we have not yet made use of our new understanding of this heterogeneity as we treat asthma patients. To increase the efficacy of anti-asthma drugs and to decrease costs, it is important to stratify asthma patients into subgroups and to develop therapeutic strategies for each subgroup. Periostin has recently emerged as a biomarker for bronchial asthma, unique in that it is useful not in diagnosis but in categorizing asthma patients. We first found that periostin is a novel component of subepithelial fibrosis in bronchial asthma downstream of IL-13 signals. Thereafter, it was shown that periostin can be a surrogate biomarker of type 2 immune responses, the basis of the notion that a detection system of serum periostin is potentially a companion diagnostic for type 2 antagonists. Furthermore, we have recently shown that serum periostin can predict resistance or hyporesponsiveness to inhaled corticosteroids, based on its contribution to tissue remodeling or fibrosis in bronchial asthma. Thus, serum periostin has two characteristics as a biomarker for bronchial asthma: it is both a surrogate biomarker of type 2 immune responses and a biomarker reflecting tissue remodeling or fibrosis. We can take advantage of these characteristics to develop stratified medicine in bronchial asthma. Copyright (C) 2015, Japanese Society of Allergology. Production and hosting by Elsevier B.V.
  • Tsuyoshi Oguma; Toyohiro Hirai; Motonari Fukui; Naoya Tanabe; Satoshi Marumo; Hajime Nakamura; Hisao Ito; Susumu Sato; Akio Niimi; Isao Ito; Hisako Matsumoto; Shigeo Muro; Michiaki Mishima
    THORAX 70 8 719 - 724 2015年08月 [査読有り]
     
    Background Airway remodelling in bronchial asthma (BA) and COPD has been quantitatively assessed by analysing the airway wall area and the luminal area on cross-sectional CT images. To date, there have been no reports on assessment of the longitudinal structure of the airway lumen. Methods Quantitative airway analysis using CT was performed on three groups consisting of 29 patients with BA, 58 patients with COPD and 59 healthy controls. To assess the longitudinal shape irregularity of the airway lumen, new quantitative CT parameters, validated by a phantom study, were established. The internal radii of imaginary inscribed spheres in the airway lumen were measured as a function of distance from the level of the carina to the fifth-order branches of the right posterior basal bronchus. The gaps of these radii from the regression line were calculated as parameters to reflect the longitudinal airway lumen shape irregularity. These new parameters were compared among the study groups as well as with the conventional parameters of airway wall thickening and luminal area. Results Longitudinal airway lumen shape irregularity was significantly greater in patients with COPD than in those with BA and healthy controls. Wall thickening was significantly greater, and luminal area smaller, in patients with BA than in those with COPD and healthy controls. These results were consistent even among the BA and COPD subgroups with similar airflow limitation. Conclusions The combination of cross-sectional and longitudinal airway structure analyses using CT images may suggest differences in the characteristics of airway remodelling between COPD and asthma.
  • ヒト多能性幹細胞から呼吸器上皮細胞への分化誘導
    後藤 慎平; 小西 聡史; 山本 佑樹; 興梠 陽平; 長崎 忠雄; 松本 久子; 室 繁郎; 平井 豊博; 伊藤 功朗; 三嶋 理晃
    日本細胞生物学会大会講演要旨集 67回 145 - 145 (一社)日本細胞生物学会 2015年06月
  • 松本久子
    呼吸と循環 63 4 291 - 297 2015年04月
  • Nagasaki Tadao; Matsumoto Hisako; Kanemitsu Yoshihiro; Izuhara Kenji; Tohda Yuji; Horiguchi Takahiko; Kita Hideo; Tomii Keisuke; Fujimura Masaki; Yokoyama Akihito; Nakano Yasutaka; Hozawa Soichiro; Ito Isao; Oguma Tsuyoshi; Izuhara Yumi; Tajiri Tomoko; Iwata Toshiyuki; Ono Junya; Ohta Shoichiro; Yokoyama Tetsuji; Niimi Akio; Mishima Michiaki; Kinki Hokuriku Airway Disease Conference
    アレルギー 64 3-4 404 - 404 2015年04月 [査読有り]
  • 呼吸器 ヒトでの肺切除後代償性肺成長は起こるのか 生体肺移植ドナー術後同側残存肺での画像検討
    志熊 啓; 陳 豊史; 大畑 恵資; 久保 武; 小熊 毅; 松本 久子; 室 繁郎; 山田 徹; 佐藤 雅昭; 毛受 暁史; 青山 晃博; 佐藤 寿彦; 園部 誠; 大政 貢; 伊達 洋至
    日本外科学会定期学術集会抄録集 115回 OP - 075 (一社)日本外科学会 2015年04月
  • Tsuyoshi Oguma; Akio Niimi; Toyohiro Hirai; Makiko Jinnai; Hisako Matsumoto; Isao Ito; Masafumi Yamaguchi; Hirofumi Matsuoka; Kojiro Otsuka; Tomoshi Takeda; Hitoshi Nakaji; Kazuo Chin; Michiaki Mishima
    RESPIRATION 89 6 539 - 549 2015年 [査読有り]
     
    Background: Computed tomography (CT) assessment of air trapping has been considered useful as a measure of small airway disease. Mean lung density (MLD) and the percentage of the lung field occupied by low attenuation area (LAA%) can be evaluated automatically, and their expiratory/inspiratory (E/I) ratios correlate with asthma severity and spirometry parameters. However, mosaic attenuation, another indicator of air trapping, has been assessed visually, and its functional relevance remains controversial. Objectives: This retrospective study was conducted to correlate mosaic attenuation, which was assessed visually and automatically, and the E/I ratios of MLD and LAA% (defined as areas <-960 Hounsfield units) with clinical and physiological variables, including impulse oscillometry (IOS) indices. Material and Methods: In 36 nonsmoking patients with stable asthma, the lungs were scanned at full inspiration and full expiration. Mosaic attenuation was measured visually and automatically, by counting areas with CT values higher than the surrounding areas. MLD and LAA% were measured using our validated method. Spirometry, IOS, exhaled NO and the sputum eosinophil count were evaluated. Results: The automatic results and visual scores of mosaic attenuation correlated well on expiratory scans (r = 0.894) and to a lesser degree on inspiratory scans (r = 0.629; p < 0.0001 for both). However, only the E/I ratios of MLD and LAA% correlated with forced expiratory volume in 1 s/forced vital capacity of spirometry and the IOS indices of resistance from 5 to 20 Hz and the integrated area of low-frequency reactance. Conclusions: Our automatic method for analysis of mosaic attenuation is likely useful, but the results themselves may not be reflecting small airway involvement of asthma, unlike the E/I ratios of MLD and LAA%. (C) 2015 S. Karger AG, Basel
  • Tadao Nagasaki; Hisako Matsumoto; Yoshihiro Kanemitsu; Kenji Izuhara; Yuji Tohda; Takahiko Horiguchi; Hideo Kita; Keisuke Tomii; Masaki Fujimura; Akihito Yokoyama; Yasutaka Nakano; Soichiro Hozawa; Isao Ito; Tsuyoshi Oguma; Yumi Izuhara; Tomoko Tajiri; Toshiyuki Iwata; Junya Ono; Shoichiro Ohta; Tetsuji Yokoyama; Akio Niimi; Michiaki Mishima
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 190 12 1449 - 1452 2014年12月 [査読有り]
  • Hideki Inoue; Akio Niimi; Tomoshi Takeda; Hisako Matsumoto; Isao Ito; Hirofumi Matsuoka; Makiko Jinnai; Kojiro Otsuka; Tsuyoshi Oguma; Hitoshi Nakaji; Tomoko Tajiri; Toshiyuki Iwata; Tadao Nagasaki; Yoshihiro Kanemitsu; Kazuo Chin; Michiaki Mishima
    ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY 113 5 527 - 533 2014年11月 [査読有り]
     
    Background: Comprehensive studies of the pathophysiologic characteristics of elderly asthma, including predominant site of disease, airway inflammation profiles, and airway hyperresponsiveness, are scarce despite their clinical importance. Objective: To clarify the pathophysiologic characteristics of elderly patients with asthma. Methods: Patients older than 65 years (elderly; n = 45) vs those no older than 65 years (nonelderly; n = 67) were retrospectively analyzed by spirometry, computed tomographic indices of large airway wall thickness and small airway involvement (air trapping), impulse oscillation measurements, exhaled nitric oxide levels, blood and induced sputum cell differentials, methacholine airway responsiveness, and total and specific serum IgE levels. Results: Elderly patients with asthma had significantly lower values for forced expiration volume in 1 second, mid-forced expiratory flow (percentage predicted), and ratio of forced expiration volume in 1 second to forced vital capacity than nonelderly patients with asthma (median 81.2% vs 88.8%, P = .02; 50.9% vs 78.6%, P = .03; 0.72 vs 0.78, P = .001, respectively). In computed tomographic measurements, elderly patients with asthma had significantly greater airway wall thickening and air trapping than nonelderly patients. Impulse oscillation measurements indicated that elderly patients with asthma showed significantly greater resistance at 5 Hz (used as an index of total airway resistance), greater decrease in resistance from 5 to 20 Hz, a higher ratio of decrease in resistance from 5 to 20 Hz to resistance at 5 Hz, higher integrated area between 5 Hz and frequency of resonance, greater frequency of resonance, and lower reactance at a frequency of 5 Hz (potential markers of small airway disease) than nonelderly patients. There were no significant differences in blood or sputum cell differentials, exhaled nitric oxide, or methacholine airway responsiveness between the 2 groups. Total serum IgE levels and positive rates of specific IgE antibodies against several allergens were significantly lower in elderly than in nonelderly patients with asthma. Conclusion: Based on spirometric, computed tomographic, and impulse oscillation analyses, elderly patients with asthma have greater involvement of small and large airways than nonelderly patients with asthma. (C) 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
  • Tomoko Tajiri; Akio Niimi; Hisako Matsumoto; Isao Ito; Tsuyoshi Oguma; Kojiro Otsuka; Tomoshi Takeda; Hitoshi Nakaji; Hideki Inoue; Toshiyuki Iwata; Tadao Nagasaki; Yoshihiro Kanemitsu; Yumi Izuhara; Michiaki Mishima
    ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY 113 4 470 - U282 2014年10月 [査読有り]
     
    Background: Omalizumab, a humanized anti-IgE monoclonal antibody, is reportedly an effective treatment for severe allergic asthma. However, there have been few comprehensive analyses of its efficacy, including assessments of small airways or airway remodeling. Objective: To comprehensively evaluate the efficacy of omalizumab, including its effects on small airways and airway remodeling, in adult patients with severe refractory asthma. Methods: In this prospective, time-series, single-arm observational study, 31 adult patients with severe refractory asthma despite the use of multiple controller medications, including high-dose inhaled corticosteroids (1,432 +/- 581 mu g/d of fluticasone propionate equivalent), were enrolled. Clinical variables, including Asthma Quality of Life Questionnaire, asthma exacerbations, exhaled nitric oxide, pulmonary function, methacholine airway responsiveness, induced sputum, and chest computed tomogram, were assessed at baseline and after 16 and 48 weeks of treatment with omalizumab. Results: Twenty-six of the 31 patients completed 48 weeks of treatment. For these patients, Asthma Quality of Life Questionnaire scores and peak expiratory flow values significantly and continuously improved throughout the 48 weeks (P < .001 for all comparisons). Unscheduled physician visits, asthma exacerbations requiring systemic corticosteroids, fractional exhaled nitric oxide at 50 mL/s and alveolar nitric oxide levels, sputum eosinophil proportions, and airway-wall thickness as assessed by computed tomography significantly decreased at 48 weeks (P < .05 for all comparisons). Conclusion: Omalizumab was effective for adult patients with severe refractory asthma. Omalizumab may have anti-inflammatory effects on small airways and reverse airway remodeling. (C) 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
  • 松本久子
    呼吸 33 9 875 - 881 2014年09月
  • Yoshihiro Kanemitsu; Isar Ito; Akio Niimi; Kenji Izuhara; Shoichiro Ohta; Junya Ono; Toshiyuki Iwata; Tsuyoshi Oguma; Tomoko Tajiri; Tadao Nagasaki; Yumi Izuhara; Hisako Matsumoto; Michiaki Mishima
    EUROPEAN RESPIRATORY JOURNAL 44 2014年09月 [査読有り]
  • Shimpei Gotoh; Isao Ito; Tadao Nagasaki; Yuki Yamamoto; Satoshi Konishi; Yohei Korogi; Hisako Matsumoto; Shigeo Muro; Toyohiro Hirai; Michinori Funato; Shin-Ichi Mae; Taro Toyoda; Aiko Sato-Otsubo; Seishi Ogawa; Kenji Osafune; Michiaki Mishima
    STEM CELL REPORTS 3 3 394 - 403 2014年09月 [査読有り]
     
    No methods for isolating induced alveolar epithelial progenitor cells (AEPCs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) have been reported. Based on a study of the stepwise induction of alveolar epithelial cells (AECs), we identified carboxypeptidase M (CPM) as a surface marker of NKX2-1(+) "ventralized" anterior foregut endoderm cells (VAFECs) in vitro and in fetal human and murine lungs. Using SFTPC-GFP reporter hPSCs and a 3D coculture system with fetal human lung fibroblasts, we showed that CPM+ cells isolated from VAFECs differentiate into AECs, demonstrating that CPM is a marker of AEPCs. Moreover, 3D coculture differentiation of CPM+ cells formed spheroids with lamellar-body-like structures and an increased expression of surfactant proteins compared with 2D differentiation. Methods to induce and isolate AEPCs using CPM and consequently generate alveolar epithelial spheroids would aid human pulmonary disease modeling and regenerative medicine.
  • Yumi Izuhara; Hisako Matsumoto; Yoshihiro Kanemitsu; Kenji Izuhara; Yuji Tohda; Takahiko Horiguchi; Hideo Kita; Kazunobu Kuwabara; Tomii Keisuke; Kojiro Otsuka; Masaki Fujimura; Noriyuki Okura; Katsuyuki Tomita; Akihito Yokoyama; Hiroshi Onishi; Yasutaka Nakano; Tetsuya Oguma; Soichiro Hozawa; Tadao Nagasaki; Isao Ito; Tsuyoshi Oguma; Hideki Inoue; Tomoko Tajiri; Toshiyuki Iwata; Junya Ono; Shoichiro Ohta; Mayumi Tamari; Tomomitsu Hirota; Tetsuji Yokoyama; Akio Niimi; Michiaki Mishima
    EUROPEAN RESPIRATORY JOURNAL 44 668 - 673 2014年09月 [査読有り]
  • Yoshihiro Kanemitsu; Isao Ito; Akio Niimi; Kenji Izuhara; Shoichiro Ohta; Junya Ono; Toshiyuki Iwata; Hisako Matsumoto; Michiaki Mishima
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 190 4 472 - 474 2014年08月 [査読有り]
  • 松本久子
    日本胸部臨床 73 7 779 - 790 克誠堂出版 2014年07月
  • Yoshihiro Kanemitsu; Hisako Matsumoto; Michiaki Mishima
    ALLERGOLOGY INTERNATIONAL 63 2 181 - 188 2014年06月 [査読有り]
     
    Patients with asthma show a steeper age-related decline in pulmonary function than healthy subjects, which is often alleviated after the initiation of treatment with inhaled corticosteroids (ICS). However, there still are patients who develop irreversible airflow limitations despite receiving adequate ICS treatment. The identification of the characteristics of such patients and biomarkers of progression for airflow limitation, a functional consequence of airway remodeling, is considered important in the management of asthma. A variety of biomarkers are associated with the forced expiratory volume in 1 S (FEV1) in asthma in a cross-sectional fashion. However, few biomarkers are known to reflect the decline in pulmonary function, particularly in patients with asthma who receive ICS treatment. Recently periostin, a matricellular protein that prolongs Th2/eosinophilic inflammation and reflects airway remodeling, was reported to be detected in serum. In a Kinki Hokuriku Airway disease Conference multicenter cohort study, we demonstrated that among several serum markers, high serum periostin level, particularly >= 95 ng/mL, was the only marker associated with a greater annual decline in FEV1 and a decline in FEV1 of mL.yr(-1). A variant (rs9603226) of the POSTN gene that encodes periostin was also involved in the frequency of a decline in FEV1 of 30 mL.yr(-1). Our results suggest that the serum periostin level is a useful marker reflecting pulmonary function decline in patients with asthma receiving ICS.
  • Hisako Matsumoto
    ALLERGOLOGY INTERNATIONAL 63 2 153 - 160 2014年06月 [査読有り]
     
    Chronic airway inflammation and remodeling are fundamental features of asthma. Even with adequate inhaled corticosteroid (ICS) treatment, there are still patients who exhibit Th2/eosinophilic inflammation and develop airflow limitation, a functional consequence of airway remodeling. There are few biomarkers that are applicable in the clinical setting that reflect refractory Th2/eosinophilic inflammation and remodeling of the asthmatic airways. Therefore, establishing such biomarkers is essential for managing patients who suffer from these conditions. This review addresses the importance of serum periostin measurements by describing observations made in a KiHAC multicenter cohort with periostin used as a marker of pulmonary function decline and refractory Th2/eosinophilic inflammation in patients with asthma receiving long-term ICS treatment. Furthermore, serum periostin could be a companion diagnostic for targeted therapy against refractory Th2/eosinophilic inflammation. Finally, the distinct characteristics of serum periostin as compared to conventional biomarkers are addressed.
  • Y. Izuhara; H. Matsumoto; Y. Kanemitsu; K. Izuhara; Y. Tohda; T. Horiguchi; H. Kita; K. Kuwabara; K. Tomii; K. Otsuka; M. Fujimura; N. Ohkura; K. Tomita; A. Yokoyama; H. Ohnishi; Y. Nakano; T. Oguma; S. Hozawa; T. Nagasaki; I. Ito; T. Oguma; H. Inoue; T. Tajiri; T. Iwata; J. Ono; S. Ohta; M. Tamari; T. Hirota; T. Yokoyama; A. Niimi; M. Mishima
    ALLERGY 69 5 668 - 673 2014年05月 
    Background In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. Methods In this study, 224 patients with asthma receiving ICS treatment for at least 4years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30ml/year or greater were determined. Results Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (>= 95ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (>= 250/mu l) in the high serum periostin group. Conclusions A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
  • Tadao Nagasaki; Hisako Matsumoto; Yoshihiro Kanemitsu; Kenji Izuhara; Yuji Tohda; Hideo Kita; Takahiko Horiguchi; Kazunobu Kuwabara; Keisuke Tomii; Kojiro Otsuka; Masaki Fujimura; Noriyuki Ohkura; Katsuyuki Tomita; Akihito Yokoyama; Hiroshi Ohnishi; Yasutaka Nakano; Tetsuya Oguma; Soichiro Hozawa; Isao Ito; Tsuyoshi Oguma; Hideki Inoue; Tomoko Tajiri; Toshiyuki Iwata; Yumi Izuhara; Junya Ono; Shoichiro Ohta; Tetsuji Yokoyama; Akio Niimi; Michiaki Mishima
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 133 5 1474 - U406 2014年05月 [査読有り]
  • 松本久子
    月刊薬事 56 3 315 - 319 2014年03月
  • Fumihiro Mizokami; Katsunori Furuta; Hisako Matsumoto; Atsushi Utani; Zenzo Isogai
    International Wound Journal 11 1 106 - 107 2014年02月 [査読有り]
  • 松本久子; 室繁郎
    医薬ジャーナル 50 476 - 479 2014年01月
  • Tomoko Tajiri; Akio Niimi; Hisako Matsumoto; Isao Ito; Tsuyoshi Oguma; Kojiro Otsuka; Tomoshi Takeda; Hitoshi Nakaji; Hideki Inoue; Toshiyuki Iwata; Tadao Nagasaki; Michiaki Mishima
    RESPIRATION 87 3 211 - 218 2014年 [査読有り]
     
    Background: A clinically relevant relationship between classic asthma and allergic rhinitis has been reported. However, the possible link between cough variant asthma (CVA) and allergic rhinitis remains unknown. Objectives: To clarify the prevalence and clinical relevance of perennial allergic rhinitis or seasonal allergic rhinitis in CVA patients compared to classic asthma patients. Methods: We retrospectively studied adult patients with classic asthma (n = 190) and those with CVA (n = 83). The prevalence of perennial allergic rhinitis or seasonal allergic rhinitis and associations of concomitant perennial or seasonal allergic rhinitis with asthma severity, forced expiratory volume in 1 s (% predicted), fractional exhaled nitric oxide (FeNO) levels, and eosinophil proportions in sputum and blood were analyzed in the two groups. Results: The prevalence of perennial allergic rhinitis and/or seasonal allergic rhinitis was significantly higher in classic asthma patients than in CVA patients (all p < 0.05). Concomitant perennial allergic rhinitis was associated with higher FeNO levels and eosinophil proportions in sputum and blood in classic asthma patients (p = 0.035, p = 0.036, and p = 0.008, respectively) and with higher asthma severity, FeNO levels, and sputum eosinophil proportions in CVA patients (p = 0.031, p = 0.007, and p = 0.010, respectively). Concomitant seasonal allergic rhinitis was only associated with higher sputum eosinophil proportions in CVA patients with active rhinitis symptoms during the sensitized pollen season (p = 0.025). Conclusions: Perennial allergic rhinitis may be relevant for CVA patients as well as classic asthma patients by consistently augmenting eosinophilic lower airway inflammation. (C) 2013 S. Karger AG, Basel
  • Hidenao Kayawake; Hiroaki Sakai; Hisako Matsumoto; Hiroshi Date
    Respirology Case Reports 2 4 150 - 153 2014年 [査読有り]
     
    Swyer-James syndrome was first described in 1953 as unilateral pulmonary emphysema in a 6-year-old boy. The characteristic feature of this syndrome is unilateral pulmonary hyperlucency on a chest X-ray film. Typical symptoms include recurrent chest infections, chronic cough, wheezing, and exertional dyspnea. Although there have been a few reports of pneumothorax in patients with Swyer-James syndrome, there have been no reports about an association with giant bullae. Here, we report a case of Swyer-James syndrome associated with a giant bulla and asthma, in which surgery achieved marked improvement of dyspnea.
  • 松本久子
    ぜん息 26 2 134 - 138 2013年11月
  • Hisako Matsumoto
    Calcium Signaling In Airway Smooth Muscle Cells 359 - 379 2013年11月 [査読有り]
     
    Crosstalk between airway inflammation and airway smooth muscle cells (ASMCs) contributes to airway hyperresponsiveness, a cardinal feature of asthma. The main putative mechanism underlying the agonist-induced intracellular Ca< sup> 2+< /sup> ([Ca< sup> 2+< /sup> ]< inf> i< /inf> ) transients in ASMCs is Ca< sup> 2+< /sup> release from the sarcoplasmic reticulum (SR) via the inositol 1,4,5-trisphosphate (IP< inf> 3< /inf> ) receptor and ryanodine receptor (RyR). Ca< sup> 2+< /sup> depletion in SR then triggers store-operated Ca< sup> 2+< /sup> entry (SOCE), Ca< sup> 2+< /sup> influx from extracellular space. These mechanisms are modulated by inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-13, which have pivotal roles in asthma and chronic obstructive pulmonary disease (COPD). TNF-α upregulates Gq and Gi protein expression, and interleukin (IL)-13 enhances histamine H1 receptor and cysteinyl leukotriene receptor 1, which enhances agonist-induced IP< inf> 3< /inf> /IP< inf> 3< /inf> receptor signaling. Expression of CD38, which affects Ca< sup> 2+< /sup> release from the SR via RyR, is upregulated with TNF-α, IL-13, and, to a lesser extent, interferon-γ and IL-1β pretreatment. TNF-α and IL-13 also augment SOCE and expression of caveolin-1, a scaffolding protein in caveolae, flask-shaped plasma membrane invaginations, which play a key role in Ca< sup> 2+< /sup> signaling. Furthermore, both TNF-α and IL-13 decrease the expression of sarcoendoplasmic reticulum Ca< sup> 2+< /sup> ATPase SERCA2, which transfers Ca< sup> 2+< /sup> from the cytosol of the cell to the lumen of the SR to replenish Ca< sup> 2+< /sup> in the SR. The downregulation of SERCA2 mimics altered Ca< sup> 2+< /sup> homeostasis observed in asthma. This chapter describes the mechanisms that underlie the inflammatory cytokine-mediated modulation of [Ca< sup> 2+< /sup> ]< inf> i< /inf> in ASMCs.
  • Nagasaki Tadao; Matsumoto Hisako; Kanemitsu Yoshihiro; Izuhara Kenji; Tohda Yuji; Kita Hideo; Horiguchi Takahiko; Kuwahara Kazunobu; Tomii Keisuke; Otsuka Kojiro; Fujimura Masaki; Ohkura Noriyuki; Tomita Katsuyuki; Yokoyama Akihito; Ohnishi Hiroshi; Nakano Yasutaka; Oguma Tetsuya; Hozawa Soichiro; Niimi Akio; Mishima Michiaki
    RESPIROLOGY 18 35  2013年11月 [査読有り]
  • Masafumi Yamaguchi; Akio Niimi; Hisako Matsumoto; Isao Ito; Tetsuya Oguma; Taishi Nagao; Yasutaka Nakano
    RESPIROLOGY 18 154 - 154 2013年11月 [査読有り]
  • Tsuyoshi Oguma; Toyohiro Hirai; Akio Niimi; Hisako Matsumoto; Shigeo Muro; Michio Shigematsu; Takashi Nishimura; Yoshiro Kubo; Michiaki Mishima
    PLOS ONE 8 10 e76381  2013年10月 [査読有り]
     
    Objectives: (a) To assess the effects of computed tomography (CT) scanners, scanning conditions, airway size, and phantom composition on airway dimension measurement and (b) to investigate the limitations of accurate quantitative assessment of small airways using CT images. Methods: An airway phantom, which was constructed using various types of material and with various tube sizes, was scanned using four CT scanner types under different conditions to calculate airway dimensions, luminal area (Ai), and the wall area percentage (WA%). To investigate the limitations of accurate airway dimension measurement, we then developed a second airway phantom with a thinner tube wall, and compared the clinical CT images of healthy subjects with the phantom images scanned using the same CT scanner. The study using clinical CT images was approved by the local ethics committee, and written informed consent was obtained from all subjects. Data were statistically analyzed using one-way ANOVA. Results: Errors noted in airway dimension measurement were greater in the tube of small inner radius made of material with a high CT density and on images reconstructed by body algorithm (p<0.001), and there was some variation in error among CT scanners under different fields of view. Airway wall thickness had the maximum effect on the accuracy of measurements with all CT scanners under all scanning conditions, and the magnitude of errors for WA% and Ai varied depending on wall thickness when airways of <1.0-mm wall thickness were measured. Conclusions: The parameters of airway dimensions measured were affected by airway size, reconstruction algorithm, composition of the airway phantom, and CT scanner types. In dimension measurement of small airways with wall thickness of <1.0 mm, the accuracy of measurement according to quantitative CT parameters can decrease as the walls become thinner.
  • Nagasaki Tadao; Matsumoto Hisako; Kanemitsu Yoshihiro; Izuhara Kneji; Tohda Yuji; Kita Hideo; Horiguchi Takahiko; Kuwabara Kazunobu; Tomii Keisuke; Otsuka Kojiro; Fujimura Masaki; Ohkura Noriyuki; Tomita Katsuyuki; Yokoyama Akihito; Ohnishi Hiroshi; Nakano Yasutaka; Oguma Tetsuya; Hozawa Soichiro; Petrova Guergana; Ito Isao; Oguma Tsuyoshi; Inoue Hideki; Tajiri Tomoko; Iwata Toshiyuki; Izuhara Yumi; Ono Junya; Ohta Shoichiro; Niimi Akio; Mishima Michiaki
    EUROPEAN RESPIRATORY JOURNAL 42 2013年09月 [査読有り]
  • Guergana Petrova; Hisako Matsumoto; Yoshihiro Kanemitsu; Kenji Izuhara; Yuji Tohda; Hideo Kita; Takahiko Horiguchi; Kazunobu Kuwabara; Keisuke Tomii; Kojiro Otsuka; Masaki Fujimura; Noriyuki Ohkura; Katsuyuki Tomita; Akihito Yokoyama; Hiroshi Ohnishi; Yasutaka Nakano; Tetsuya Oguma; Soichiro Hozaqa; Tadao Nagasaki; Isao Ito; Tsuyoshi Oguma; Hideki Inoue; Tomoko Tajiri; Toshiyuki Iwata; Yumi Izuhara; Junya Ono; Shoichiro Ohta; Akio Niimi; Michiaki Mishima
    EUROPEAN RESPIRATORY JOURNAL 42 2013年09月 [査読有り]
  • Hideki Inoue; Akio Niimi; Hisako Matsumoto; Isao Ito; Tsuyoshi Oguma; Kojiro Otsuka; Tomoshi Takeda; Hitoshi Nakaji; Tomoko Tajiri; Toshiyuki Iwata; Tadao Nagasaki; Michiaki Mishima
    EUROPEAN RESPIRATORY JOURNAL 42 2013年09月 [査読有り]
  • 松本久子
    日本医師会雑誌 142 6 1255 - 1259 2013年09月
  • Yoshihiro Kanemitsu; Hisako Matsumoto; Kenji Izuhara; Yuji Tohda; Hideo Kita; Takahiko Horiguchi; Kazunobu Kuwabara; Keisuke Tomii; Kojiro Otsuka; Masaki Fujimura; Noriyuki Ohkura; Katsuyuki Tomita; Akihito Yokoyama; Hiroshi Ohnishi; Yasutaka Nakano; Tetsuya Oguma; Soichiro Hozawa; Tadao Nagasaki; Isao Ito; Tsuyoshi Oguma; Hideki Inoue; Tomoko Tajiri; Toshiyuki Iwata; Yumi Izuhara; Junya Ono; Shoichiro Ohta; Mayumi Tamari; Tomomitsu Hirota; Tetsuji Yokoyama; Akio Niimi; Michiaki Mishima
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 132 2 305 - + 2013年08月 [査読有り]
     
    Background: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. Objective: We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. Methods: Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. Results: High serum periostin levels (>= 95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). Conclusions: Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.
  • Tomoko Tajiri; Hisako Matsumoto; Akio Niimi; Isao Ito; Tsuyoshi Oguma; Hitoshi Nakaji; Hideki Inoue; Toshiyuki Iwata; Tadao Nagasaki; Yoshihiro Kanemitsu; Guergana Petrova; Michiaki Mishima
    PLOS ONE 8 6 e65284  2013年06月 [査読有り]
     
    Background: Airway eosinophilia is a predictor of steroid responsiveness in steroid-naive asthma. However, the relationship between airway eosinophilia and the expression of FK506-binding protein 51 (FKBP51), a glucocorticoid receptor cochaperone that plays a role in steroid insensitivity in asthma, remains unknown. Objective: To evaluate the relationship between eosinophilic inflammation and FKBP51 expression in sputum cells in asthma. Methods: The FKBP51 mRNA levels in sputum cells from steroid-naive patients with asthma (n = 31) and stable asthmatic patients on inhaled corticosteroid (ICS) (n = 28) were cross-sectionally examined using real-time PCR. Associations between FKBP51 levels and clinical indices were analyzed. Results: In steroid-naive patients, the FKBP51 levels were negatively correlated with eosinophil proportions in blood (r = -0.52) and sputum (r = -0.57), and exhaled nitric oxide levels (r = -0.42) (all p<0.05). No such associations were observed in patients on ICS. In steroid-naive patients, improvement in forced expiratory volume in one second after ICS initiation was correlated with baseline eosinophil proportions in blood (r = 0.74) and sputum (r = 0.76) and negatively correlated with FKBP51 levels (r = -0.73) (all p<0.0001) (n = 20). Lastly, the FKBP51 levels were the lowest in steroid-naive asthmatic patients, followed by mild to moderate persistent asthmatic patients on ICS, and the highest in severe persistent asthmatic patients on ICS (p<0.0001). Conclusions: Lower FKBP51 expression in sputum cells may reflect eosinophilic inflammation and glucocorticoid responsiveness in steroid-naive asthmatic patients.
  • T. Nagasaki; H. Matsumoto; H. Nakaji; A. Niimi; I. Ito; T. Oguma; S. Muro; H. Inoue; T. Iwata; T. Tajiri; Y. Kanemitsu; M. Mishima
    CLINICAL AND EXPERIMENTAL ALLERGY 43 6 608 - 615 2013年06月 [査読有り]
     
    Background Epidemiological studies have shown that smoking increases the propensity for atopy and asthma. However, the effects of smoking on atopy and eosinophilic inflammation in asthmatics, including the elderly, remain unknown. Objective To determine the effects of smoking on serum immunoglobulin E (IgE) levels and eosinophilic inflammation in asthmatics of all ages. Methods The associations of serum IgE levels, blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels with smoking and age in steroid-naive asthmatics were cross-sectionally assessed (n=307). Levels of sputum eosinophil and thymic stromal lymphopoietin (TSLP) that promotes Th2 inflammation were also analysed. Current smokers were excluded when analysing contributing factors of FeNO. Results Levels of serum IgE, blood eosinophil and FeNO decreased with increasing age in never-smokers, whereas decrease in serum IgE levels with increasing age was not observed in current smokers. In addition, current smoking was associated with higher blood eosinophil counts. In atopic asthmatics, age-related declines in serum IgE levels were less steep in ex-smokers than in never-smokers, and atopic ex-smokers with asthma showed higher blood eosinophil counts and higher FeNO irrespective of age. Lastly, sputum TSLP levels were associated with sputum eosinophil proportions and pack-years. Current and ex-smokers had higher TSLP levels than never-smokers. Conclusions and Clinical Relevance In steroid-naive asthmatics, smoking may attenuate the age-related decrease in IgE levels and maintain eosinophilic inflammation, in which TSLP may be involved.
  • Tomoko Tajiri; Hisako Matsumoto; Harukazu Hiraumi; Hiroki Ikeda; Kyohei Morita; Kenji Izuhara; Junya Ono; Shoichiro Ohta; Isao Ito; Tsuyoshi Oguma; Hitoshi Nakaji; Hideki Inoue; Toshiyuki Iwata; Tadao Nagasaki; Yoshihiro Kanemitsu; Juichi Ito; Akio Niimi; Michiaki Mishima
    Annals of Allergy, Asthma and Immunology 110 5 387 - 388 2013年05月 [査読有り]
  • 松本久子; 三嶋理晃
    月刊医学と薬学 69 3 391 - 398 2013年03月
  • Hitoshi Nakaji; Guergana Petrova; Hisako Matsumoto; Toshiyuki Iwata; Isao Ito; Tsuyoshi Oguma; Hideki Inoue; Tomoko Tajiri; Tadao Nagasaki; Yoshihiro Kanemitsu; Akio Niimi; Michiaki Mishima
    ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY 110 3 198 - + 2013年03月 [査読有り]
     
    Background: Eosinophilic inflammation of the small airways is a key process in asthma that often smolders in treated patients. The long-term effects of add-on therapy on the persistent inflammation in the small airways remain unknown. Objective: To examine the effects of add-on therapy with either ciclesonide, an inhaled corticosteroid with extrafine particles, or montelukast on small airway inflammation. Methods: Sixty patients with stable asthma receiving inhaled corticosteroid treatment were enrolled in a randomized, open-label, parallel comparison study of 24-week add-on treatment with ciclesonide or montelukast. Patients were randomly assigned to 3 groups: ciclesonide (n = 19), montelukast (n = 22), or no add-on as controls (n = 19). At baseline and at weeks 4, 12, and 24, extended nitric oxide analysis; pulmonary function tests, including impulse oscillometry; blood eosinophil counts; and asthma control tests (ACTs) were performed. Results: A total of 18 patients in the ciclesonide group, 19 in the montelukast group, and 15 in the control group completed the study and were analyzed. With repeated-measures analysis of variance, ciclesonide produced a significant decrease in alveolar nitric oxide and a significant improvement in ACT scores over time. Montelukast produced significant decreases in alveolar nitric oxide concentrations and blood eosinophil counts over time and slightly improved ACT scores, whereas no such changes were observed in the control group. Alveolar nitric oxide concentrations with ciclesonide and reactance area at low frequencies with montelukast produced greater improvements over time compared with control. Conclusion: Ciclesonide add-on therapy and montelukast add-on therapy may act differently, but both separately can improve small airway abnormalities and provide better asthma control. Trial Registration: umin.ac.jp/ctr Identifier: UMIN000001083 (C) 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
  • 松本久子
    薬局 64 1 60 - 64 2013年01月
  • Tadao Nagasaki; Hisako Matsumoto
    Allergology International 62 2 171 - 179 2013年 [査読有り]
     
    Asthma is a heterogeneous disease with varying phenotypes and numerous risk factors. This condition results from complex interactions between genetic and environmental factors, and active smoking is one of these risk factors. The effects of aging should also be taken into account in these interactions. From an epidemiological standpoint, smokers and/or elderly patients with asthma are not small part in the total population with asthma. Furthermore, both smoking and aging are important risk factors for severe asthma. This review discusses the potential effects of smoking and aging on healthy subjects and patients with asthma, particularly from the perspective of inflammatory changes. First we show evidence that smokers and the elderly have increased neutrophil counts in their airways, which may have impacts on their clinical characteristics of elderly smokers with asthma. Secondly, on the basis of our recent findings on the interactions between smoking and aging in patients with asthma, we propose that IgE/eosinophilic inflammation should not be underestimated in elderly smokers with asthma, particularly those who are atopic. This review may expand our understanding of the effects of smoking and aging on asthma with a new perspective of an old issue. © 2013 Japanese Society of Allergology.
  • 松本久子
    アレルギー 61 6 760 - 769 一般社団法人 日本アレルギー学会 2012年06月
  • 伊藤穣; 平井豊博; 前川晃一; 藤田浩平; 今井誠一郎; 辰巳秀爾; 半田知宏; 松本久子; 室繁郎; 新実彰男; 三嶋理晃
    日本呼吸器学会誌 1 増刊 149 - 149 (一社)日本呼吸器学会 2012年03月
  • Y. Ito; T. Hirai; K. Maekawa; K. Fujita; S. Imai; S. Tatsumi; T. Handa; H. Matsumoto; S. Muro; A. Niimi; M. Mishima
    INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE 16 3 408 - 414 2012年03月 [査読有り]
     
    SETTING: Kyoto, Japan. OBJECTIVE: To determine predictors of 5-year mortality in pulmonary Mycobacterium avium-intracellulare complex (MAC) disease. DESIGN: Retrospective study of 164 patients diagnosed with pulmonary MAC disease between 1999 and 2005 and followed for 5 years. RESULTS: Overall 5-year mortality was 28.0%. Among 117 patients with microbiological outcomes, 54 were treated (treated MAC patients) and 24 were not treated and did not experience sputum culture conversion during follow-up (untreated chronic MAC patients); 39 patients were not treated and experienced sputum culture conversion. Five-year all-cause overall mortality among the 78 patients with definite MAC disease (including treated and untreated chronic MAC patients) was 25.6%. The mortality rate was 33.3% for untreated chronic MAC patients only vs. 22.2% for treated MAC patients (P = 0.30). After adjustment for clinical, microbiological and radiological confounders, independent factors for 5-year mortality were a high Charlson comorbidity index in cases with definite MAC disease (hazard ratio [HR] 1.76) and untreated chronic MAC (HR 3.08), and presence of cavitary lesions in cases with definite MAC disease (HR 1.82) and treated MAC patients (HR 3.91). CONCLUSION: Patients with cavitary lesions require immediate treatment for sputum culture conversion and to improve their chances of survival.
  • Hisako Matsumoto; Rollin P. Tabuena; Akio Niimi; Hideki Inoue; Isao Ito; Masafumi Yamaguchi; Kojiro Otsuka; Tomoshi Takeda; Tsuyoshi Oguma; Hitoshi Nakaji; Tomoko Tajiri; Toshiyuki Iwata; Tadao Nagasaki; Makiko Jinnai; Hirofumi Matsuoka; Michiaki Mishima
    ALLERGOLOGY INTERNATIONAL 61 1 123 - 132 2012年03月 [査読有り]
     
    Background: The character or timing of chronic cough is considered to be unpredictable for diagnosing its cause. However, the associations of cough triggers with cough pathophysiology remains unknown. Methods: We developed a closed questionnaire listing 18 triggers that were reported by >= 1% of 213 patients in a retrospective survey. Using this questionnaire, patients with cough-predominant or cough-variant asthma (n = 140) and those with non-asthmatic cough (54) were asked whether their cough was induced by the listed triggers. Associations of triggers with causes of cough, airway sensitivity to inhaled methacholine, exhaled nitric oxide (NO) levels, number of sensitizing allergens, and scores from gastroesophageal reflux (GER) questionnaires were examined. Factor analysis was used to categorize variables, including the 12 most common cough triggers, diagnosis of asthmatic cough, airway sensitivity, and exhaled NO levels. Results: "Cold air" and "fatigue/stress" induced cough more often in asthmatic coughers than in non-asthmatic coughers. "Spices" and "meals" induced cough more frequently in GER-coughers (n = 19). Patients who marked "cold air" as the trigger were more sensitive to inhaled methacholine and showed higher exhaled NO levels than those who did not mark this trigger. The "post-nasal drip" trigger was associated with elevated exhaled NO levels, and this association was mainly exhibited by patients with cough-predominant asthma. The triggers "pollen" and "mold smell" were associated with a number of sensitizing allergens. The number of triggers was weakly associated with GER scores. By factor analysis, "cold air," "fatigue/stress," asthmatic cough, airway hypersensitivity, and elevated NO levels were categorized into the same factor. Conclusions: Several cough triggers may reflect the pathophysiology of prolonged or chronic cough.
  • 中治 仁志; 松本 久子; 新実 彰男; 伊藤 功朗; 小熊 毅; 井上 英樹; 岩田 敏之; 田尻 智子; 長崎 忠雄; 三嶋 理晃
    日本呼吸器学会誌 1 増刊 116 - 116 (一社)日本呼吸器学会 2012年03月
  • 田尻 智子; 松本 久子; 新実 彰男; 伊藤 功朗; 小熊 毅; 金光 禎寛; 長崎 忠雄; 岩田 敏之; 井上 英樹; 中治 仁志; 大塚 浩二郎; 竹田 知史; 三嶋 理晃
    日本呼吸器学会誌 1 増刊 232 - 232 (一社)日本呼吸器学会 2012年03月
  • 長崎 忠雄; 松本 久子; 中治 仁志; 新実 彰男; 伊藤 功朗; 小熊 毅; 井上 英樹; 岩田 敏之; 田尻 智子; 金光 禎寛; 三嶋 理晃
    日本呼吸器学会誌 1 増刊 232 - 232 (一社)日本呼吸器学会 2012年03月
  • Hisako Matsumoto; Yutaka Hirata; Kojiro Otsuka; Toshiyuki Iwata; Aya Inazumi; Akio Niimi; Isao Ito; Emiko Ogawa; Shigeo Muro; Hiroaki Sakai; Kazuo Chin; Yoshitaka Oku; Michiaki Mishima
    CYTOKINE 57 1 19 - 24 2012年01月 [査読有り]
     
    Physiological mechanisms associated with interleukin-13 (IL-13), a key cytokine in asthma, in intracellular Ca2+ signaling in airway smooth muscle cells (ASMCs) remain unclear. The aim of this study was to assess effects of IL-13 on Ca2+ oscillations in response to leukotriene D4 (LTD4) in human cultured ASMCs. LTD4-induced Ca2+ oscillations in ASMCs pretreated with IL-13 were imaged by confocal microscopy. mRNA expressions of cysteinyl leukotriene 1 receptors (CysLT1R), CD38, involved with the ryanodine receptors (RyR) system, and transient receptor potential canonical (TRPC), involved with store-operated Ca2+ entry (SOCE), were determined by real-time PCR. In IL-13-pretreated ASMCs, frequency of LTD4-induced Ca2+ oscillations and number of oscillating cells were significantly increased compared with untreated ASMCs. Both xestospongin C, a specific inhibitor of inositol 1,4,5-triphosphate receptors (IP3R), and ryanodine or ruthenium red, inhibitors of RyR, partially blocked LTD4-induced Ca2+ oscillations. Ca2+ oscillations were almost completely inhibited by 50 AM of 2-aminoethoxydiphenyl borate (2-APB), which dominantly blocks SOCE but not IP3R at this concentration. Pretreatment with IL-13 increased the mRNA expressions of CysLT1R and CD38, but not of TRPC1 and TRPC3. We conclude that IL-13 enhances frequency of LTD4-induced Ca2+ oscillations in human ASMCs, which may be cooperatively modulated by IP3R, RyR systems and possibly by SOCE. (C) 2011 Elsevier Ltd. All rights reserved.
  • Hisako Matsumoto
    Japanese Journal of Allergology 61 6 760 - 769 2012年 [査読有り]
  • Masaya Takemura; Akio Niimi; Hisako Matsumoto; Tetsuya Ueda; Hirofumi Matsuoka; Masafumi Yamaguchi; Makiko Jinnai; Kazuo Chin; Michiaki Mishima
    RESPIRATION 83 4 308 - 315 2012年 [査読有り]
     
    Background: Cough variant asthma (CVA) is a phenotype of asthma presenting solely with coughing, characterized by airway hyperresponsiveness, eosinophilic inflammation and a cough response to bronchodilators. Leukotriene receptor antagonists (LTRAs) are antiasthma medications with anti-inflammatory and bronchodilatory properties. Although LTRAs exert antitussive effects in CVA, the mechanisms involved are unknown. Objectives: This study aimed to clarify the antitussive mechanisms of LTRAs in CVA patients. Methods: We prospectively observed the effect of montelukast (10 mg) daily for 4 weeks in 23 consecutive nonsmoking adults with anti-inflammatory treatment-naive CVA. We evaluated, before and after treatment, the cough visual analogue scale (VAS), pulmonary function (spirometry and impulse oscillation), methacholine airway responsiveness, cough receptor sensitivity, expressed by the concentration of capsaicin inducing 2 or more (C2) and 5 or more (C5) coughs, sputum eosinophil counts and levels of inflammatory mediators, including cysteinyl leukotrienes, leukotriene B-4, pros taglandin (PG) D-2, PGE(2), PGF(2 alpha) and thromboxane B-2. We compared the baseline characteristics of the patients based on the symptomatic response to montelukast, defined as a decrease in the cough VAS of >25% (n = 15) or <= 25% (n = 8). Results: Montelukast significantly decreased the cough VAS (p = 0.0008), sputum eosinophil count (p = 0.013) and cough sensitivity (C2: p = 0.007; C5: p = 0.039), whereas pulmonary function, airway responsiveness and sputum mediator levels remained unchanged. Multivariate analysis showed that a better response to montelukast was associated solely with younger age (p = 0.032). Conclusion: The antitussive effect of montelukast in CVA may be attributed to the attenuation of eosinophilic inflammation rather than its bronchodilatory properties. Copyright (C) 2011 S. Karger AG, Basel
  • Kojiro Otsuka; Hisako Matsumoto; Akio Niimi; Shigeo Muro; Isao Ito; Tomoshi Takeda; Kunihiko Terada; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Tsuyoshi Oguma; Hitoshi Nakaji; Hideki Inoue; Tomoko Tajiri; Toshiyuki Iwata; Kazuo Chin; Michiaki Mishima
    RESPIRATION 83 6 507 - 519 2012年 [査読有り]
     
    Background: Recent evidence suggests that YKL-40, also called chitinase-3-like-1 protein, is involved in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Details of sputum YKL-40 in asthma and COPD, however, remain unknown. Objectives: To clarify associations of sputum YKL-40 levels with clinical indices in asthma and COPD. Methods: Thirty-nine patients with asthma, 14 age-matched never-smokers as controls, 45 patients with COPD, and 7 age-matched smokers as controls were recuited for this study. Sputum YKL-40 levels were measured and YKL-40 expression in sputum cells was evaluated by immunocytochemistry. Results: Sputum YKL-40 levels were higher in patients with COPD (346 +/- 325 ng/ml) than in their smoker controls (125 +/- 122 ng/ml; p < 0.05), but were not significantly different between patients with asthma (117 +/- 170 ng/ml) and their controls (94 +/- 44 ng/ml; p = 0.15). In patients with asthma only, sputum YKL-40 levels were positively correlated with disease severity (r = 0.34, p = 0.034) and negatively correlated with pre- and postbronchodilator % FEV1 (r = -0.47 and -0.42, respectively; p < 0.01) and forced mid-expiratory flow (r = -0.48 and -0.46, respectively, p < 0.01). Sputum YKL-40 levels were positively correlated with sputum neutrophil counts in asthma (r = 0.55, p < 0.001) and with neutrophil and macrophage counts in COPD (r = 0.45 and 0.65, respectively, p < 0.01). YKL-40 was expressed in the cytoplasm of sputum neutrophils and macrophages in all groups. Conclusions: Elevated sputum YKL-40 reflects airflow obstruction in asthma whereas the roles of YKL-40 in the proximal airways in COPD remain to be elucidated. Copyright (C) 2011 S. Karger AG, Basel
  • 中治 仁志; 松本 久子; 新実 彰男; 伊藤 功朗; 小熊 毅; 井上 英樹; 岩田 敏之; 田尻 智子; 長崎 忠雄; 三嶋 理晃
    アレルギー 60 9-10 1325 - 1325 (一社)日本アレルギー学会 2011年10月
  • 金光 禎寛; 新実 彰男; 松本 久子; 伊藤 功朗; 小熊 毅; 井上 英樹; 田尻 智子; 岩田 敏之; 長崎 忠雄; 三嶋 理晃
    アレルギー 60 9-10 1341 - 1341 (一社)日本アレルギー学会 2011年10月
  • 田尻 智子; 松本 久子; 新実 彰男; 伊藤 功朗; 小熊 毅; 金光 禎寛; 長崎 忠雄; 岩田 敏之; 井上 英樹; 三嶋 理晃
    アレルギー 60 9-10 1361 - 1361 (一社)日本アレルギー学会 2011年10月
  • 長崎 忠雄; 松本 久子; 中治 仁志; 新実 彰男; 伊藤 功朗; 小熊 毅; 井上 英樹; 岩田 敏之; 田尻 智子; 金光 禎寛; 三嶋 理晃
    アレルギー 60 9-10 1377 - 1377 (一社)日本アレルギー学会 2011年10月
  • Tomomitsu Hirota; Atsushi Takahashi; Michiaki Kubo; Tatsuhiko Tsunoda; Kaori Tomita; Satoru Doi; Kimie Fujita; Akihiko Miyatake; Tadao Enomoto; Takehiko Miyagawa; Mitsuru Adachi; Hiroshi Tanaka; Akio Niimi; Hisako Matsumoto; Isao Ito; Hironori Masuko; Tohru Sakamoto; Nobuyuki Hizawa; Masami Taniguchi; John J. Lima; Charles G. Irvin; Stephen P. Peters; Blanca E. Himes; Augusto A. Litonjua; Kelan G. Tantisira; Scott T. Weiss; Naoyuki Kamatani; Yusuke Nakamura; Mayumi Tamari
    NATURE GENETICS 43 9 893 - U108 2011年09月 [査読有り]
     
    Bronchial asthma is a common inflammatory disease caused by the interaction of genetic and environmental factors(1,2). Through a genome-wide association study and a replication study consisting of a total of 7,171 individuals with adult asthma (cases) and 27,912 controls in the Japanese population, we identified five loci associated with susceptibility to adult asthma. In addition to the major histocompatibility complex and TSLP-WDR36 loci previously reported, we identified three additional loci: a USP38-GAB1 locus on chromosome 4q31 (combined P = 1.87 x 10(-12)), a locus on chromosome 10p14 (P = 1.79 x 10(-15)) and a gene-rich region on chromosome 12q13 (P = 2.33 x 10(-13)). We observed the most significant association with adult asthma at rs404860 in the major histocompatiblity complex region (P = 4.07 x 10(-23)), which is close to rs2070600, a SNP previously reported for association with FEV(1)/FVC in genome-wide association studies for lung function. Our findings offer a better understanding of the genetic contribution to asthma susceptibility.
  • Hitoshi Nakaji; Hisako Matsumoto; Akio Niimi; Tomohiro Handa; Isao Ito; Makiko Kanai; Hisako Tabata; Hiroaki Sakai; Yoichiro Kobashi; Yoshiro Mochizuki; Kazuo Chin; Michiaki Mishima
    NITRIC OXIDE-BIOLOGY AND CHEMISTRY 24 4 173 - 175 2011年05月 [査読有り]
  • 井上 英樹; 伊藤 功朗; 新実 彰男; 松本 久子; 小熊 毅; 中治 仁志; 田尻 智子; 岩田 敏之; 長崎 忠雄; 三嶋 理晃
    アレルギー 60 3-4 420 - 420 (一社)日本アレルギー学会 2011年04月
  • 田尻 智子; 新実 彰男; 松本 久子; 伊藤 功朗; 長崎 忠雄; 岩田 敏之; 井上 英樹; 中治 仁志; 小熊 毅; 三嶋 理晃
    アレルギー 60 3-4 491 - 491 (一社)日本アレルギー学会 2011年04月
  • 長崎 忠雄; 新実 彰男; 松本 久子; 伊藤 功朗; 小熊 毅; 中治 仁志; 井上 英樹; 岩田 敏之; 田尻 智子; 三嶋 理晃
    アレルギー 60 3-4 497 - 497 (一社)日本アレルギー学会 2011年04月
  • 竹田 知史; 新実 彰男; 松本 久子; 伊藤 功朗; 山口 将史; 松岡 弘典; 陣内 牧子; 大塚 浩二郎; 小熊 毅; 中治 仁志; 井上 英樹; 田尻 智子; 岩田 敏之; 三嶋 理晃; 宮木 幸一; 中山 健夫; 久保 武; 富樫 かおり
    日本呼吸器学会雑誌 49 増刊 214 - 214 (一社)日本呼吸器学会 2011年03月
  • 小熊 毅; 新実 彰男; 松本 久子; 伊藤 功朗; 中治 仁志; 井上 英樹; 岩田 敏之; 田尻 智子; 長崎 忠雄; 三嶋 理晃
    日本呼吸器学会雑誌 49 増刊 125 - 125 (一社)日本呼吸器学会 2011年03月
  • 田尻 智子; 新実 彰男; 松本 久子; 伊藤 功朗; 長崎 忠雄; 岩田 敏之; 井上 英樹; 中治 仁志; 小熊 毅; 大塚 浩二郎; 竹田 知史; 三嶋 理晃
    日本呼吸器学会雑誌 49 増刊 179 - 179 (一社)日本呼吸器学会 2011年03月
  • 中治 仁志; 新実 彰男; 松岡 弘典; 松本 久子; 伊藤 功朗; 井上 英樹; 岩田 敏之; 田尻 智子; 長崎 忠雄; 三嶋 理晃
    日本呼吸器学会雑誌 49 増刊 277 - 277 (一社)日本呼吸器学会 2011年03月
  • Hirofumi Kiyokawa; Hisako Matsumoto; Hitoshi Nakaji; Akio Niimi; Isao Ito; Kikuko Ono; Tomoshi Takeda; Tsuyoshi Oguma; Kojiro Otsuka; Michiaki Mishima
    Allergology International 60 3 381 - 385 2011年 [査読有り]
     
    Background: Despite the fact that bronchioles are involved in asthma, there have been limited asthmatic cases showing marked centrilobular opacities on computed tomography (CT) chest scans. Systemic corticosteroids have been administered in such cases, but the efficacy of extra-fine particle inhaled corticosteroids has not been assessed. Case Summary: A previously healthy 64-year-old man presented with a four-month history of productive cough and progressive dyspnea despite a combination therapy with inhaled salmeterol (50 μg bid) and fluticasone (500 μg bid), sustained-release theophylline, and pranlukast because of suspicion of asthma. Physical examination revealed wheezing at the end of forced expiration. High resolution CT chest scan showed diffuse centrilobular opacities, bronchiectatic changes, and bronchial wall thickening. Transbronchial lung biopsy, bronchoalveolar lavage fluid, and transbronchial biopsy all showed predominant eosinophil infiltrates, suggesting that eosinophilic inflammation across the entire airway tree caused the abnormal CT findings. Alveolar fraction of exhaled nitric oxide level, a non-invasive marker of eosinophilic peripheral airway inflammation, was also elevated. Because he refused systemic corticosteroids, inhaled ciclesonide (400 μg bid) and inhaled tiotropium were added on to his current medication under careful observation. His symptoms, pulmonary function and CT findings promptly improved, and he had fully recovered at follow-up. Discussion: Extra-fine particle inhaled corticosteroids could be an alternative approach in centrilobular opacities caused by eosinophilic peripheral airway inflammation. © 2011 Japanese Society of Allergology.
  • Kojiro Otsuka; Akio Niimi; Hisako Matsumoto; Isao Ito; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Tsuyoshi Oguma; Tomoshi Takeda; Hitoshi Nakaji; Kazuo Chin; Kazuhiko Sasaki; Norihito Aoyama; Michiaki Mishima
    RESPIRATION 82 5 431 - 438 2011年 [査読有り]
     
    Background: Substance P (SP) is involved in the pathogenesis of cough in animal models. However, few studies in humans have been reported and the roles of SP in clinical cough remain obscure. Objectives: To clarify the relevance of plasma levels of SP in patients with persistent cough. Methods: We studied 82 patients with cough persisting for at least 3 weeks and 15 healthy controls. Patients were classified as having asthmatic cough (cough-variant asthma and cough-predominant asthma; n = 61) or nonasthmatic cough (n = 21; postinfectious cough, n = 6; gastroesophageal reflux disease, n = 5; idiopathic cough, n = 5, and others, n = 5). Correlations were evaluated between plasma SP levels as measured with ELISA and methacholine airway hyperresponsiveness (airway sensitivity and airway reactivity), capsaicin cough sensitivity, sputum eosinophil and neutrophil counts, and pulmonary function. Results: Plasma SP levels were significantly elevated in patients with both asthmatic and nonasthmatic cough compared with controls [31.1 pg/ml (range 18.0-52.2) and 30.0 pg/ml (range 15.1-50.3) vs. 15.4 pg/ml (range 11.3-23.7); p = 0.003 and p = 0.038, respectively] but did not differ between the two patient groups (p = 0.90). Plasma SP levels correlated with airway sensitivity (threshold dose of methacholine) in the patients with asthmatic cough (r = -0.37, p = 0.005) but not with airway reactivity, cough sensitivity, FEV(1) values, or sputum eosinophil and neutrophil counts in either group. Conclusions: Increased levels of SP in plasma are associated with persistent cough in humans and might be related to airway sensitivity in asthmatic cough. Copyright (C) 2011 S. Karger AG, Basel
  • H. Matsumoto; A. Niimi; M. Takemura; T. Ueda; M. Yamaguchi; H. Matsuoka; M. Jinnai; T. Takeda; K. Otsuka; T. Oguma; T. Handa; T. Hirai; K. Chin; M. Mishima
    JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY 21 2 113 - 119 2011年 [査読有り]
     
    Background: Effects of long-term treatment with inhaled corticosteroids (ICSs) on airway-wall thickness in patients with asthma remain unknown. Objectives: To determine whether airway-wall thickness consistently decreases after long-term ICS treatment, and to analyze factors contributing to long-term airway-wall changes in asthmatics. Methods: A retrospective analysis of long-term changes in airway-wall thickness using computed tomography was performed in 14 patients with asthma. Wall area corrected by body surface area (WA/BSA) was examined at baseline, 12 weeks after the commencement of ICSs (second measurement), and at least 2 years (mean +/- SEM. 4.2 +/- 0.5) after the second measurement (third measurement). Mean +/- SEM changes in WA/BSA from the second to the third measurements were analyzed. Results: The mean change in WA/BSA was not significant between the second and the third measurements (-0.27 +/- 0.59 mm(2)/m(2)/y). Overall, the changes were significantly associated with disease duration but not with other clinical indices. When the 14 patients were divided into 2 groups using a cutoff value of 0.32 mm(2)/m(2)/y for the mean change in WA/BSA, for the 5 patients whose WA/BSA exceeded this cutoff, daily ICS doses were not reduced and both forced expiratory volume in the first second (FEV(1)) and forced vital capacity decreased significantly. For the remaining 9 patients, daily ICS doses were reduced and long-term FEV(1) values did not change. Conclusions: Despite long-term treatment with ICSs, airway-wall thickness did not consistently decrease. One possible mechanism underlying poor response to long-term treatment may be long-standing asthma.
  • Hisako Matsumoto; Akio Niimi; Makiko Jinnai; Hitoshi Nakaji; Tomoshi Takeda; Tsuyoshi Oguma; Kojiro Otsuka; Hideki Inoue; Masafumi Yamaguchi; Hirofumi Matsuoka; Isao Ito; Toyohiro Hirai; Kazuo Chin; Michiaki Mishima
    RESPIRATION 81 4 311 - 317 2011年 [査読有り]
     
    Background: Inflammation of peripheral airways is implicated in the pathophysiology of severe asthma. However, contributions of peripheral airway inflammation to airway caliber/function in patients with stable asthma, including those with mild to moderate disease, remain to be confirmed. Objectives: To determine whether peripheral airway inflammation affects airway function in patients with asthma. Methods: In 70 patients with mild to severe asthma, alveolar nitric oxide [CANO(TMAD)] levels were examined as a noninvasive biomarker of peripheral airway/alveolar inflammation. CANO(TMAD) and maximal nitric oxide (NO) flux in the airway compartment, J'awNO, were estimated with a model that incorporated trumpet-shaped airways and axial diffusion using exhaled NO output at different flow rates. Measures of pulmonary function were then assessed by spirometry and an impulse oscillometry system, and their bronchodilator reversibility was examined. Results: CANO(TMAD) levels were not correlated with pre- or postbronchodilator spirometric values, but were significantly associated with prebronchodilator reactance at low frequency (Xrs5) (rho = -0.31, p = 0.011), integrated area of low-frequency Xrs (AX) (rho = 0.35, p = 0.003) and negative frequency dependence of resistance (Rrs5-Rrs20) (rho = 0.35, p = 0.004). Furthermore, CANO(TMAD) levels were associated with bronchodilator reversibility of FEV(1), FEF(25-75%), Xrs5 and AX (rho = 0.35, 0.31, -0.24 and -0.31, respectively; p <= 0.05 for all). No variables were related to J'awNO. Conclusions: Elevated CANO(TMAD), but not J'awNO, partly reflects reversible airway obstruction originating in the peripheral airway. These findings indicate the involvement of peripheral airway inflammation in physiological abnormalities in asthma. Copyright (C) 2010 S. Karger AG, Basel
  • Hirofumi Matsuoka; Akio Niimi; Hisako Matsumoto; Masaya Takemura; Tetsuya Ueda; Masafumi Yamaguchi; Makiko Jinnai; Hideki Inoue; Isao Ito; Kazuo Chin; Michiaki Mishima
    CHEST 138 6 1418 - 1425 2010年12月 [査読有り]
     
    Background Sputum cell-subtype profiles in cough-variant asthma (CVA) are unknown Methods Ninety-eight inhaled corticosteroid (ICS)-naive CVA patients were classified according to sputum eosinophil (eos)/neutrophil (neu) counts, as reported in subjects with asthma, as eosinophilic (E) (eos >= 1 0%, neu <61%, n = 28), neutrophilic (N) (eos <1 0%, neu >= 61%, n = 31), mixed granulocytic (M) (eos >= 1 0%, neu >= 61%, n = 12), and paucigranulocytic (P) (eos < 1 0%, neu < 61%, n = 27) subtypes Patient characteristics, sputum levels of eosinophil cationic protein (ECP), IL-8, and neutrophil elastase (NE), and daily ICS doses required to maintain control during follow-up (6, 12, 18, and 24 months) were compared, retrospectively Results Subtype N patients, predominantly women, were marginally older than the other subtypes, but FEV1, airway responsiveness, and total and specific IgE results did not differ ECP levels were higher in M and E than in N and P subtypes, being similar between M and E or N and P subtypes Levels of IL-8 and NE were higher in M than in other subtypes, being similar among the latter ICS doses were initially similar in all subtypes (800 mu g equivalent of beclomethasone) but were higher in M than in N and P subtypes throughout follow-up, with E being intermediate between M and N or P subtypes ICS doses decreased (halved or quartered) in E, N, and P patients followed for 24 months (P < 0001 for all) but remained unchanged m M subjects IL-8 and NE levels correlated positively with ECP levels Conclusions In addition to eosinophils, neutrophils, which are possibly activated in the presence of eosinophils, may participate in the pathophysiology of CVA CHEST 2010, 138(6) 1418-1425
  • Isao Ito; Seizo Kadowaki; Naoya Tanabe; Akane Haruna; Masahito Kase; Yoshiro Yasutomo; Mitsuhiro Tsukino; Asako Nakai; Hisako Matsumoto; Akio Niimi; Kazuo Chin; Satoshi Ichiyama; Michiaki Mishima
    PULMONARY PHARMACOLOGY & THERAPEUTICS 23 5 403 - 410 2010年10月 [査読有り]
     
    Background: Treatment of aspiration pneumonia is becoming an important issue due to aging of populations worldwide. Effectiveness of tazobactam/piperacillin (TAZ/PIPC) in aspiration pneumonia is not clear. Purpose: To compare clinical efficacy between TAZ/PIPC (1:4 compound) and imipenem/cilastatin (IPM/CS) in patients with moderate-to-severe aspiration pneumonia. Patients and methods: In this open-label, randomized study either TAZ/PIPC 5 g or IPM/CS 1 g was intravenously administered every 12 h to patients with moderate-to-severe community-acquired aspiration pneumonia or nursing home-acquired pneumonia with risk for aspiration pneumonia for average 11 days. The primary outcome was clinical response rate at the end of treatment (EOT) in validated perprotocol (VPP) population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EDS) in VPP population, and survival at day 30 in modified intention-to-treat (MITI) population. Results: There was no difference between the groups in primary or secondary outcome. However, significantly faster improvement as measured by axillary temperature (p < 0.05) and WBC count (p = 0.01) was observed under TAZ/PIPC treatment. In patients with gram-positive bacterial infection, TAZ/PIPC was more effective at EOT in VPP population (p = 0.03). Conclusion: TAZ/PIPC is as effective and safe as IPM/CS in the treatment of moderate-to-severe aspiration pneumonia. (C) 2010 Elsevier Ltd. All rights reserved.
  • Makiko Jinnai; Akio Niimi; Tetsuya Ueda; Hirofumi Matsuoka; Masaya Takemura; Masafumi Yamaguchi; Kojiro Otsuka; Tsuyoshi Oguma; Tomoshi Takeda; Isao Ito; Hisako Matsumoto; Michiaki Mishima
    CHEST 137 5 1122 - 1129 2010年05月 [査読有り]
     
    Background: Mucus hypersecretion is an important pathophysiologic index of airway disease. Measurement of secreted mucin in sputum has been reported in asthma, but not in chronic cough with or without increased sputum production. Methods: We studied 49 patients with classic asthma (CA), 39 with cough-variant asthma (CVA), nine and five with chronic cough associated with sinobronchial syndrome (SBS) and gastroesophageal reflux disease (GERD), respectively, and 11 healthy controls. Seventeen patients with CA, but none from the other groups, were taking antiinflammatory medications. Mucin levels in induced sputum supernatants were measured by enzyme-linked immunosorbent assay, which detects airway mucin, probably including MUC5AC and MUC5B. Results: Mucin levels were higher in patients with CA (674.2 +/- 548.8 mu g/mL) and SBS (638.4 +/- 650.7 mu g/mL) than in controls (212.0 +/- 167.1 mu g/mL) (P = .0037 and .044). They were also higher in patients with CA than in those with CVA (350.4 +/- 374.0 mu g/mL) and GERD (134.3 +/- 93.1 mu g/mL) (P = .0016 and 0.015), but results did not differ between the latter groups and controls. When the four disease groups were combined, patients with frequent sputum production had greater mucin levels than those with occasional (P = .0023) or no sputum production (P < .0001). Patients with CA showed negative correlations of mucin levels with respiratory resistance indices on impulse oscillation and with airway sensitivity to methacholine. Conclusions: Sputum mucin levels differ in various respiratory conditions when compared with controls, primarily reflecting the degree of sputum production. Airway mucin might possibly exert protective effects in asthma, at least between exacerbations, but this issue needs to be further clarified by future studies. CHEST 2010; 137(5):1122-1129
  • Michiyoshi Nishioka; Emiko Ogawa; Daisuke Kinose; Akane Haruna; Tadashi Ohara; Isao Ito; Yuma Hoshino; Yutaka Ito; Hisako Matsumoto; Akio Niimi; Tadashi Mio; Kazuo Chin; Toyohiro Hirai; Shigeo Muro; Michiaki Mishima
    RESPIROLOGY 15 4 669 - 676 2010年05月 [査読有り]
     
    Background and objective: Connective tissue growth factor (CTGF) is up-regulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke and repeated bacterial infections, both of which are rich sources of LPS, are major causes of COPD. The high levels of LPS in lung epithelial lining fluid also suggest that it may have a considerable impact on the airway epithelium, in terms of cytokine and growth factor production. The aim of this study was to clarify the mechanism of LPS-induced CTGF expression in bronchial epithelial cells. Methods: The expression and transcriptional regulation of the CTGF gene were assessed using the cultured human bronchial epithelial cell line, BEAS-2B. Results: LPS significantly up-regulated CTGF mRNA expression in a dose-dependent fashion, with 100 mu g/mL LPS causing a twofold increase after 2 h. CTGF protein expression was also up-regulated by LPS after 8 h. Transforming growth factor-beta 1 mRNA expression was not changed by LPS treatment. A pharmacological inhibitor of nuclear factor (NF)-kappa B, MG132, inhibited LPS-induced CTGF mRNA expression. Furthermore, luciferase assays demonstrated that deletion of base pairs -253 to -53 from the CTGF promoter, where the Smad and proximal NF-kappa B binding sites are located, decreased the induction of CTGF by LPS. After stimulation with LPS, the p65 subunit of NF-kappa B was shown to be bound to the CTGF promoter in vitro and in situ. Conclusions: LPS directly induced CTGF expression in bronchial epithelial cells, independently of transforming growth factor-beta 1, suggesting a possible mechanism for airway remodelling in COPD that is induced by smoking and repeated bacterial infections.
  • Tomoshi Takeda; Toru Oga; Akio Niimi; Hisako Matsumoto; Isao Ito; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Kojiro Otsuka; Tsuyoshi Oguma; Hitoshi Nakaji; Kazuo Chin; Michiaki Mishima
    RESPIRATION 80 2 120 - 126 2010年 [査読有り]
     
    Background: Small airways play important roles in the pathophysiology of asthma. However, relationships between small airway involvement and health status and dyspnea have not been investigated. Objectives: It was the aim of this study to assess the relationships between proximal and peripheral airway functions and health status, dyspnea and disease control in patients with asthma, using impulse oscillometry (IOS). Methods: We performed IOS, spirometry and assessment of health status (Asthma Quality of Life Questionnaire and St. George's Respiratory Questionnaire), dyspnea (Baseline Dyspnea Index) and disease control (Asthma Control Questionnaire) in 65 asthmatics and evaluated their relationships. Results: Peripheral airway function as evaluated by IOS [R5-R20 (the fall in resistance from 5 to 20 Hz) and X5 (reactance at 5 Hz)], in addition to the proximal airway index (R20), significantly correlated with health status, dyspnea and disease control. Multiple regression analyses revealed that peripheral airway function significantly contributes to these, independently of the proximal airway index. In contrast, forced expiratory volume in 1 s did not significantly contribute to health status or dyspnea. Conclusions: IOS correlated better with clinical symptoms and asthma control than spirometry in patients with asthma. Peripheral and proximal airway functions as assessed separately by IOS independently contribute to health status, dyspnea and disease control, indicating that peripheral airways also represent an important therapeutic target. Copyright (C) 2009 S. Karger AG, Basel
  • 松岡 弘典; 新実 彰男; 松本 久子; 伊藤 功朗; 大塚 浩二郎; 小熊 毅; 竹田 知史; 中治 仁志; 三嶋 理晃
    アレルギー 59 3 408 - 408 一般社団法人 日本アレルギー学会 2010年
  • Yoshitaka Oku; Yutaka Hirata; Hisako Matsumoto; Michiaki Mishima
    JOURNAL OF PHYSIOLOGICAL SCIENCES 60 S25 - S25 2010年 [査読有り]
  • Tomomasa Tsuboi; Toru Oga; Kazuko Machida; Yuichi Chihara; Hisako Matsumoto; Akio Niimi; Kensuke Sumi; Motoharu Ohi; Michiaki Mishima; Kazuo Chin
    RESPIRATORY MEDICINE 103 12 1854 - 1861 2009年12月 [査読有り]
     
    Background: Long-term noninvasive positive pressure ventilation (NPPV) is associated with an excellent survival rate, especially in post-tuberculosis patients. Nothing is currently known on which method of ventilatory support is associated with a better continuation of tong-term NPPV, which itself might lead to longer survival. Methods: One hundred and eighty four post-tuberculosis patients, who started NPPV at the Kyoto University Hospital group and the National Tokyo Hospital from June 1990 to August 2007, were examined retrospectively. Ventilator mode (an assisted mode or a pure controlled mode) and potential confounders were examined with the discontinuation of NPPV as the primary outcome. Results: Patients treated with a pure controlled mode had significantly better continuation rates (hazard ratio, 3.09; 95% confidential interval, 1.75-5.47; p = 0.0001) and better survival rates (Log-rank test; p = 0.0031) than those treated with an assisted mode. Female gender and no pulmonary lesions were also associated with a significantly better probability of continuing NPPV. The five- and ten-year probabilities of continuing NPPV for 106 patients with a pure controlled mode were 68.3% and 41.4%, respectively, while those for 76 patients with an assisted mode were 46.7% and 12.7%, respectively. Conclusions: Patients treated with pure controlled ventilation had significantly better continuation rates and survival rates than those treated with assisted ventilation. Prospective randomized controlled trials are needed to verify the effectiveness of a pure controlled mode in patients with not only restrictive thoracic disease but also other diseases including chronic obstructive pulmonary disease. (C) 2009 Elsevier Ltd. All rights reserved.
  • Masafumi Yamaguchi; Akio Niimi; Tetsuya Ueda; Masaya Takemura; Hirofumi Matsuoka; Makiko Jinnai; Kojiro Otsuka; Tsuyoshi Oguma; Tomoshi Takeda; Isao Ito; Hisako Matsumoto; Toyohiro Hirai; Kazuo Chin; Michiaki Mishima
    PULMONARY PHARMACOLOGY & THERAPEUTICS 22 4 326 - 332 2009年08月 [査読有り]
     
    Background: Small airways appear to have an important role in asthma. Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) has ultrafine particles and accordingly greater deposition in the small airways than chlorofluorocarbon (CFC)-BDP Impulse oscillometry systems (IOS), a new and non-invasive measure of pulmonary function, can examine the resistance of total (R5), large (R20), and small airways (R5-R20) separately, and low-frequency reactance area (AX), also considered a measure of small airways dysfunction. Methods: Mild-to-moderate asthmatics who were inhaled corticosteroid naive were randomized to receive 200 mcg HFA-BDP bid (n = 26) or 400 mcg CFC-BDP bid (n = 12) for 12 weeks in an open-label manner. Following baseline measurements, IOS and spirometry were repeated every 4 weeks, and methacholine challenge to separately assess airway sensitivity and airway reactivity and lung volumes at 12 weeks. Results: Moderate correlations were found between R5-R20 or AX and spirometry and lung volume indices of small airways, and between R20 and peak expiratory flow at baseline. The two groups did not significantly differ in baseline clinical or functional parameters. At 12 weeks, all IOS indices improved in the HFA-BDP group, whereas all but R5-R20 improved with CFC-BDP. R5-R20 and AX progressively improved with HFA-BDP; these changes achieved statistical significance at 12 weeks versus the CFC-BDP group. Other IOS and spirometry indices failed to show such trends. HFA-BDP significantly attenuated methacholine airway sensitivity; the degree of this attenuation strongly correlated with R5-R20 and AX baseline values, and with improvement of AX with treatment. Conclusion: HFA-BDP is an effective treatment of small airways in asthma. Prolonged treatment provides a progressive effect over time, which is associated with an attenuation of airway responsiveness. (C) 2009 Elsevier Ltd. All rights reserved.
  • 松本久子
    臨床研修プラクティス 6 7 13 - 18 2009年06月
  • Hirofumi Matsuoka; Akio Niimi; Hisako Matsumoto; Tetsuya Ueda; Masaya Takemura; Masafumi Yamaguchi; Makiko Jinnai; Kojiro Otsuka; Tsuyoshi Oguma; Tomoshi Takeda; Isao Ito; Kazuo Chin; Ryoichi Amitani; Michiaki Mishima
    CHEST 135 4 898 - 903 2009年04月 [査読有り]
     
    Background: Sensitization to Trichophyton, a major dermatophyte, has been associated with asthma. Whether such sensitization is generally associated with the severity of asthma, like other molds such as Alternaria, is unknown. Methods: We compared 258 patients with asthma, which was classified by severity as mild (n = 123), moderate (101), or severe (34), and 114 healthy control subjects, with regard to specific IgE titers against Trichophyton rubrum and other common allergens such as mixed molds, house-dust mite, cat dander, dog dander, Japanese cedar pollen, mixed Graminea pollens and mixed weed pollens. Results: Positive rate of Trichophyton-specific IgE was higher in the patients with moderate asthma (15.8%) than in the-control subjects (7.0%, p = 0.04) and patients with mild asthma (4.9%, p < 0.006), and it was also higher in the patients with severe asthma (32.4%) than in control subjects (p = 0.0001), and patients with mild asthma (p < 0.0001) and moderate asthma (p = 0.04), but it did not differ between the control subjects and patients with mild asthma. The positive rates of mixed molds, cat dander, and dog dander were almost invariably higher in patients in all asthma subgroups than in the control subjects but did not differ among patients in the three asthma subgroups. The positive rates of other allergens were not different in all groups. Reanalysis of positive rate of Trichophyton-specific IgE after excluding 52 subjects with positive results for mixed molds showed a similar statistical trend to that of the original cohort. This may negate the potential effect of cross-reactivity to these molds. Multivariate analysis of asthma subgroups identified positive IgE results for Trichophyton as an independent determinant of asthma severity. Conclusions: Specific IgE response to Trichophyton may be associated with more severe asthma.
  • Akio Niimi; Hisako Matsumoto; Michiaki Mishima
    PULMONARY PHARMACOLOGY & THERAPEUTICS 22 2 114 - 120 2009年04月 [査読有り]
     
    Chronic cough is a major clinical problem. The causes of chronic cough can be categorized into eosinophilic and noneosinophilic disorders, the former being comprised of asthma, cough variant asthma (CVA), atopic cough (AC) and non-asthmatic eosinophilic bronchitis (NAEB). Cough is one of the major symptoms of asthma. Cough in asthma can be classified into three categories; 1) CVA: asthma presenting solely with coughing, 2) cough-predominant asthma: asthma predominantly presenting with coughing but also with dyspnea and/or wheezing, and 3) cough remaining after treatment with inhaled corticosteroid (ICS) and beta 2-agonists in patients with classical asthma, despite control of other symptoms. There may be two subtypes in the last category; one is cough responsive to anti-mediator drugs such as leukotriene receptor antagonists and histamine H1 receptor antagonists, and the other is cough due to co-morbid conditions such as gastroesophageal reflux. CVA is one of the commonest causes of chronic isolated cough. It shares a number of pathophysiological features with classical asthma with wheezing such as atopy, airway hyperresponsiveness (AHR), eosinophilic airway inflammation and various features of airway remodeling. One third of adult patients may develop wheezing and progress to classical asthma. As established in classical asthma, ICS is considered the first-line treatment, which improves cough and may also reduce the risk of progression to classical asthma. AC proposed by Fujimura et al. presents with bronchodilator-resistant dry cough associated with an atopic constitution. It involves eosinophilic tracheobronchitis and cough hypersensitivity and responds to ICS treatment, while lacking in AHR and variable airflow obstruction. These features are shared by non-asthmatic eosinophilic bronchitis (NAEB). However, atopic cough does not involve bronchoalveolar eosinophilia, has no evidence of airway remodeling, and rarely progresses to classical asthma, unlike CVA and NAEB. Histamine H1 antagonists are effective in atopic cough, but their efficacy in NAEB is unknown. AHR of NAEB may improve with ICS within the normal range. Taken together, NAEB significantly overlaps with atopic cough, but might also include milder cases of CVA with very modest AHR. The similarity and difference of these related entities presenting with chronic cough and characterized by airway eosinophilia will be discussed. (c) 2008 Elsevier Ltd. All rights reserved.
  • Hisako Matsumoto; Akio Niimi; Masaya Takemura; Tetsuya Ueda; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Kazuo Chin; Michiaki Mishima
    Cough 5 1 3  2009年 [査読有り]
     
    Background. Little is known regarding mechanistic and phenotypic differences between cough variant asthma (CVA), presenting with a chronic cough as the sole symptom that responds to bronchodilators, and classic asthma with wheezing during methacholine inhalation. Here we reported airway sensitivity, airway reactivity, and as the main concern, the appearance of cough and wheezes during methacholine inhalation in patients with CVA or classic asthma. Methods. We cross-sectionally examined the degrees of airway sensitivity, the point where resistance started to increase, and reactivity, the slope of the methacholine-resistance curve, and the appearance of cough and wheezes in steroid-naïve adult patients with classic asthma (n = 58) or CVA (n = 55) while they were continuously inhaling methacholine during simultaneous measurement of respiratory resistance. Results. Patients with CVA were less sensitive and less reactive to inhaled methacholine and wheezed less frequently but coughed more frequently during methacholine-induced bronchoconstriction than did patients with classic asthma. Multivariate analysis revealed that airway hypersensitivity and lower baseline FEV1/FVC were associated with the appearance of wheezes, whereas a diagnosis of CVA was associated with coughing. Conclusion. There are mechanistic and phenotypic differences between CVA and classic asthma during methacholine inhalation. Frequent coughing during bronchoconstriction may be a distinctive feature of CVA. © 2009 Matsumoto et al licensee BioMed Central Ltd.
  • Tomohiro Handa; Sonoko Nagai; Toyohiro Hirai; Kazuo Chin; Takeshi Kubo; Toru Oga; Akio Niimi; Hisako Matsumoto; Yutaka Ito; Kenichi Takahashi; Kizuku Watanabe; Takateru Izumi; Michiaki Mishima
    RESPIRATION 77 3 273 - 281 2009年 [査読有り]
     
    Background: It was previously reported that visual scores of the lung opacities were associated with lung function in patients with sarcoidosis. However, there are no reports on the evaluation of airway dimensions or lung density by computed tomography (CT) in sarcoidosis patients. Objectives: The aim of this study was to investigate whether airway dimensions and lung densities assessed by CT associate with pulmonary function in patients with sarcoidosis. Methods: CT scanning was performed in 43 sarcoidosis patients and lung densities were measured using in-house software. Means and standard deviations of lung density, kurtosis and skewness of lung density histograms were calculated. Tracheal area and airway wall area/total airway area (WA%) of the right apical bronchus were also measured. Pulmonary function tests were performed on the same day. Results: Increased standard deviation of lung density and decreased kurtosis and skewness of lung density histograms were all associated with decreased total lung capacity, vital capacity and diffusion capacity. Increased standard deviation of lung density was also associated with decreased percentages of forced expiratory volume in 1 s and peak expiratory flow (%PEF). There was a positive correlation between tracheal area corrected by body surface area and %PEF, and negative correlation between WA% and %PEF. Stepwise regression analysis showed that increased standard deviation of lung density and decreased tracheal area were independently associated with lower %PEF. Conclusions: Thus, in sarcoidosis, densitometric parameters reflect restrictive lung function impairment. In addition to parenchymal lesions, it is concluded that the luminal area of the central airways also affects PEF. Copyright (C) 2008 S. Karger AG, Basel
  • Yutaka Hirata; Hisako Matsumoto; Kojiro Otsuka; Isao Ito; Emiko Ogawa; Shigeo Muro; Hiroaki Sakai; Akio Niimi; Michiaki Mishima; Yoshitaka Oku
    JOURNAL OF PHYSIOLOGICAL SCIENCES 59 225 - 225 2009年 [査読有り]
  • 半田知宏; 長井苑子; 平井豊博; 陳和夫; 久保武; 小賀徹; 新実彰男; 松本久子; 伊藤穣; 高橋憲一; 渡辺創; 泉孝英; 三嶋理晃
    サルコイドーシス/肉芽腫性疾患 28 1 33 - 40 2008年10月
  • Ken-ichi Takahashi; Kazuo Chin; Takashi Akamizu; Satoshi Morita; Kensuke Sumi; Toru Oga; Hisako Matsumoto; Akio Niimi; Tomomasa Tsuboi; Shunichi Fukuhara; Kenji Kangawa; Michiaki Mishima
    RESPIROLOGY 13 6 810 - 816 2008年09月 [査読有り]
     
    Background and objectives: Patients with newly diagnosed OSA have been reported to have recent weight gain prior to diagnosis. Ghrelin stimulates food intake and increases weight gain. Plasma ghrelin is decreased in obese and increased in lean individuals. Of the two circulating forms of ghrelin, acylated and unacylated, the former is thought to be essential for the biological activity of ghrelin. Methods: The plasma levels of the two forms of ghrelin were measured in 21 OSA patients (with a mean of 46.2 sleep-disordered events/h) before and after 1 month of nasal CPAP (nCPAP) treatment, and were compared with those in 14 untreated OSA patients and 13 individuals without OSA. Results: The BMI was significantly higher in the 21 OSA patients than in the non-OSA group as were the baseline acylated (11.4 +/- 5.86 vs 7.19 +/- 3.80 fmol/mL, P = 0.03) and unacylated (84.2 +/- 50.6 vs 48.3 +/- 23.2 fmol/mL, P = 0.02) ghrelin levels. The total ghrelin level was positively correlated with the number of sleep-disordered breathings (P = 0.002). After 1 month of nCPAP treatment, the acylated ghrelin level significantly decreased (P = 0.02) while the unacylated ghrelin level did not (P = 0.09). Conclusions: Treatment of OSA may play an important role in the management of obesity in these patients by reducing the acylated ghrelin level.
  • Hisako Matsumoto
    MULTIDISCIPLINARY RESPIRATORY MEDICINE 3 3 217 - 222 2008年06月 [査読有り]
     
    Cough variant asthma (CVA), a variant form or a precursor of asthma, is one of the most common causes of chronic cough. The mechanisms of coughing in CVA have not been fully explained but airway inflammation may be responsible for the coughing. Studies using the sputum induction technique have revealed that eosinophils, mast cells, possibly lymphocytes, mediators derived from these cells, and neuropeptides may be involved in the airway inflammation and coughing in CVA. Some of these markers in sputum, such as eosinophil counts or eosinophilic cationic protein levels, may reflect the response to therapeutic intervention.
  • Tadashi Ohara; Toyohiro Hirai; Susumu Sato; Kunihiko Terada; Daisuke Kinose; Akane Haruna; Satoshi Marumo; Michiyoshi Nishioka; Emiko Ogawa; Yasutaka Nakano; Yuma Hoshino; Yutaka Ito; Hisako Matsumoto; Akio Niimi; Tadashi Mio; Kazuo Chin; Shigeo Muro; Michiaki Mishima
    RESPIROLOGY 13 3 372 - 378 2008年05月 [査読有り]
     
    Background and objective: Chest CT has been widely used for the evaluation of structural changes in lung parenchyma and airways in cross-sectional studies. There has been no report on the annual changes in airway dimensions as assessed by CT in COPD patients. The objective of this study was to investigate the annual changes in airway dimensions and lung attenuation using CT in patients with COPD and to evaluate the correlations among annual changes in CT measurements and pulmonary function. Methods: Eighty-three men with COPD had completed five annual assessments of CT scans and pulmonary function tests over 4 years. Airway dimensions of the basal segment bronchi and lung attenuation on CT images were analysed in 38 subjects in whom the same airway could be measured at least three times, including at entry and at the end of the study. Results: Mean annual decline in FEV1 was 21 mL/year. Annual changes in the percentage of low attenuation areas were not significantly correlated with decline in FEV1. On the other hand, annual changes in the percentage of wall area (WA%/year) were significantly inversely correlated with annual changes in FEV1 (r = -0.363, P = 0.025), whereas WA%/year did not differ among severity stages at entry and did not correlate with baseline FEV1. Conclusions: The results showing that annual changes in airway thickening correlated with annual decline in air flow limitation suggests the importance of treatment of airway inflammation in COPD. CT is a useful tool for quantitative estimation not only of emphysema but also of airway lesions in longitudinal studies.
  • Ken-Ichi Takahashi; Kazuo Chin; Hajime Nakamura; Satoshi Morita; Kensuke Sumi; Toru Oga; Hisako Matsumoto; Akio Niimi; Shunichi Fukuhara; Junji Yodoi; Michiaki Mishima
    ANTIOXIDANTS & REDOX SIGNALING 10 4 715 - 726 2008年04月 [査読有り]
     
    Obstructive sleep apnea (OSA) is associated with increased cardiovascular mortality, and oxidative stress was suggested to play an important role. We hypothesized that the plasma TRX level, a novel oxidative stress marker, is elevated in OSA patients. Plasma TRX and adiponectin levels, which are significantly associated with cardiovascular mortality, were measured in 41 patients with severe OSA before (n = 41) and after (n = 27) nasal continuous positive airway pressure therapy (nCPAP) for 1 month and in 12 subjects without OSA (non-OSA group). The TRX level was significantly higher (p = 0.02) and the adiponectin level was significantly lower (p = 0.02) in the OSA group than in the non-OSA group. After I month of nCPAP (n = 27), the TRX level significantly decreased (p = 0.03), and the adiponectin level significantly increased (p = 0.03). Among the 14 patients with untreated OSA, the TRX and adiponectin levels did not significantly change over a 1-month interval. Among the 53 (41 OSA + 12 non-OSA) subjects, the TRX level was positively correlated with the respiratory disturbance index (p = 0.001) and percentage of time with SaO(2) <90% (p = 0.0002). The adiponectin level, but not the TRX level, was correlated with the BMI (n = 53; p = 0.02). Plasma TRX may be a unique marker for evaluating oxidative stress and monitoring the effectiveness of nCPAP in OSA patients.
  • Tetsuya Ueda; Akio Niimi; Hisako Matsumoto; Masaya Takemura; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Kazuo Chin; Masayoshi Minakuchi; Lei Cheng; Taro Shirakawa; Michiaki Mishima
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 121 3 659 - 664 2008年03月 [査読有り]
     
    Background: TGF-beta 1 can modulate airway inflammation and exaggerate airway remodeling. A polymorphism of a promoter region of TGFBI, C-509T, might be associated with the development of asthma, but its pathophysiologic relevance remains poorly understood. Objective: We investigated relations of the C-509T polymorphism to airflow obstruction, sputum eosinophilia, and airway wall thickening, as assessed by means of computed tomography, in 85 patients with stable asthma. Methods: The CC, CT, and TT genotypes were examined by means of PCR and restriction enzyme fragment length polymorphism. At a selected bronchus, 3 indices of airway wall thickness were measured with an automatic method. Results: The CC, CT, and TT genotypes were found in 22,46, and 17 patients, respectively. Serum TGF-beta 1 levels were significantly associated with the polymorphism and were increased in the CT/TT genotypes. FEV1 and sputum eosinophil percentages were also significantly associated with the polymorphism and were both decreased in the CT/TT genotypes. The polymorphism was unrelated to airway wall thickness. Conclusion: In addition to increased serum TGF-beta 1 levels, the T allele of the C-509T polymorphism is related to increased airflow obstruction but attenuated eosinophilic inflammation. The former relation is not attributed to thickening of the central airway walls. The latter relation might reflect the anti-inflammatory effect of TGF-beta 1. The C-509T polymorphism has a complex role in asthma pathophysiology, presumably because of the diverse functions of TGF-beta 1 and its various interactions with cells and humoral factors in vivo.
  • Hirofumi Matsuoka; Akio Niimi; Hisako Matsumoto; Tetsuya Ueda; Masaya Takemura; Mosafumi Yamaguchi; Makiko Jinnai; Liang Chang; Kojiro Otsuka; Tsuyoshi Ogunia; Tomoshi Takeda; Kazuo Chin; Michiaki Mishima
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 121 3 774 - 776 2008年03月 [査読有り]
  • Kumiya Sugiyama; Hironori Sagara; Mitsuru Adachi; Kenji Minoguchi; Akihiko Tanaka; Hiroshi Inoue; Kouhei Yamauchi; Hitoshi Kobayashi; Kazuo Akiyama; Naomi Tsurikisawa; Masami Taniguchi; Mitsuru Munakata; Junpei Saito; Suguru Sato; Michiaki Mishima; Akio Niimi; Hisako Matsumoto; Ken Ohta; Tetsuya Adachi; Hiroyuki Nagase; Hiroshi Nakajima; Shin-Ichiro Kagami; Itsuo Iwamoto; Takeshi Fukuda
    Japanese Journal of Allergology 57 12 1275 - 1283 2008年 [査読有り]
     
    Background: In asthmatic patients, first asthmatic symptoms are not often typical. In those cases, it takes long time before asthma diagnosis, and the severities are progressed in some patients. For early intervention, we tried to make the diagnostic criteria for asthma, which are useful to diagnose as early stage of asthma. Methods: Three hundred and eighty eight of asthmatic patients, who were recorded first their symptoms in asthma, were enrolled. Their first symptoms and examinations were analyzed. Results: In first asthmatic symptoms, 79% of patients had cough, 68% patients had wheezing, 49% patients had dyspnoea, and 15% of patients did not have typical asthmatic symptoms in the early stage. The percentages of abnormal in first examinations were 99% in airway hypersensitivity, 92% of low %V25, 82% of eosinophila in sputum and 77% of low %V50. Low FEV1% and reversible airway obstruction were not seen in a lot of patients. Conclusion: We advocate that the diagnostic criteria for early stage of asthma are the following three elements. First criterion is spasmodic cough, wheezing and dyspnoea. Second criterion is airway hypersensitivity, or over 3% of eosinophils in sputum, or under 70% of % V̇50, or under 50% of % V̇25, or effect of bronchodilator. Effect of bronchodilator will be required, when the symptom is cough only. Third criterion is the exclusion of other lung and heart diseases. © 2008 Japanese Society of Allergology.
  • Makiko Jinnai; Akio Niimi; Masaya Takemura; Hisako Matsumoto; Yoshitaka Konda; Michiaki Mishima
    Cough 4 1 5  2008年 [査読有り]
     
    A 15-year-old girl was referred with a 2-year history of perennial non-productive cough, which had been preceded by Mycoplasma pneumoniae pneumonia and subsequent asthma. Symptoms were only partially responsive to anti-asthma treatment including an inhaled corticosteroid and a leukotriene receptor antagonist. The patient's BMI was 27.8 she had gained over 10 kg in the previous two years. Typical symptoms of gastroesophageal reflux disease were not evident except for belch. Coughing worsened on eating and rising from bed. Although esophagography failed to disclose reflux esophagitis, esophageal pH monitoring revealed significant acid reflux. Asthma was considered well controlled. Treatment with the proton-pump inhibitor rabeprazole resulted in disappearance of cough. Frequency Scale for the Symptoms of Gastroesophageal reflux disease (FSSG) score, a questionnaire evaluating the symptoms of gastroesophageal reflux disease, was initially high but normalized after treatment. Capsaicin cough sensitivity also diminished with treatment. Chronic cough due to gastroesophageal reflux disease has been considered rare in adolescents, but this condition might be increasing in line with the recent trend in adults. Clinical features of gastroesophageal reflux disease-associated cough typical for adult patients and a specific questionnaire for evaluating gastroesophageal reflux disease validated in adults may also be useful diagnostic clues in adolescents.
  • M. Yamaguchi; A. Niimi; H. Matsumoto; T. Ueda; M. Takemura; H. Matsuoka; M. Jinnai; K. Otsuka; T. Oguma; T. Takeda; I. Ito; K. Chin; M. Mishima
    JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY 18 3 202 - 206 2008年 [査読有り]
     
    Background: Transforming growth factor (TGF)beta(1) is considered to play central roles in the pathogenesis of airway remodeling in asthma. This notion is based primarily on the results of experimental studies; clinical evidence is limited. Objectives: To ascertain the involvement of TGF-beta(1) in asthma. Methods: We studied 27 patients with moderate-to-severe, but stable, asthma treated with inhaled corticosteroids and 8 healthy controls. Helical computed tomography scans were acquired at full inspiration. Airway wall thickness (WT) was assessed on the basis of wall area corrected for body surface area (WA/BSA) and absolute WT corrected for BSA (WT root BSA) according to a validated method. Induced sputum concentrations of TGF-beta(1) were measured by enzyme-linked immunosorbent assay. Pulmonary function was evaluated. Results: Indices of expiratory airflow were significantly lower in the asthmatic patients than in the controls. WA/BSA, WT/root BSA, and sputum concentrations of TGF-beta(1), were significantly higher in the asthmatic patients. Sputum TGF-beta(1), concentrations correlated positively with WA/BSA and WT/root BSA and negatively with forced expiratory volume in 1 second in both asthmatic and control subjects. Conclusions: Levels of TGF-beta(1) in induced sputum are elevated in asthmatic patients despite treatment with inhaled corticosteroids and are associated with airflow obstruction and airway wall thickening. TGF-beta(1) is involved in the pathogenesis of airway remodeling and resultant functional impairment and it may be a target for specific medical treatment.
  • M. Takemura; A. Niimi; H. Matsumoto; T. Ueda; M. Yamaguchi; H. Matsuoka; M. Jinnai; K. Chin; M. Mishima
    CLINICAL AND EXPERIMENTAL ALLERGY 37 12 1833 - 1839 2007年12月 [査読有り]
     
    Background Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear. Objective To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group. Methods Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment. Results Patients with classic asthma had higher total IgE (P < 0.0001), larger numbers of sensitized allergens (P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P < 0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens (P=0.02) and had higher rates of sensitization to HDM (P=0.01) and dog dander (P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease (n=60) and the subgroup with moderate-to-severe disease (n=55), as reported previously. Conclusions Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential.
  • Masafumi Yamaguchi; Akio Niimi; Masayoshi Minakuchi; Hisako Matsumoto; Koichi Shimizu; Kazuo Chin; Michiaki Mishima
    ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY 99 4 371 - 374 2007年10月 [査読有り]
     
    Background: Therapy-resistant asthma is an important clinical problem. However, before considering asthma truly therapy resistant, it is essential to exclude diagnoses that may masquerade as therapy-resistant asthma, such as vocal cord dysfunction and recurrent aspiration, as well as factors related to loss of asthma control, including poor compliance, exposure to allergens, and sinusitis. Corticosteroid-induced myopathy may be an unrecognized but potentially important consideration in both settings. Objectives: To describe a patient with corticosteroid-induced myopathy complicating recurrent exacerbations of asthma, which presented with persistently reduced airflow that mimicked therapy-resistant asthma. Methods: A 20-year-old Japanese woman with severe intractable asthma who had a history of near-fatal attacks was admitted with recurrent asthma exacerbations that required long-term systemic corticosteroids. Results: Wheezing episodes decreased but airflow limitation persisted, which was due to not only uncontrolled asthma but also corticosteroid-induced myopathy. Myopathy prevented the adequate use of inhalers, which in turn complicated the tapering of corticosteroids, leading to a vicious cycle. Careful and gradual reduction of corticosteroid dose, while continuing systemic administration of nonsteroidal antiasthma medications, resulted in a resolution of clinical and electromyographic signs of myopathy and pulmonary function abnormalities. Conclusions: Corticosteroid-induced myopathy can masquerade as therapy-resistant asthma and can cause poor asthma control.
  • Hisako Matsumoto; Lyn M. Moir; Brian G. G. Oliver; Janette K. Burgess; Michael Roth; Judith L. Black; Brent E. McParland
    THORAX 62 10 848 - 854 2007年10月 [査読有り]
     
    Backgrounds: Exaggerated bronchial constriction is the most significant and life threatening response of patients with asthma to inhaled stimuli. However, few studies have investigated the contractility of airway smooth muscle (ASM) from these patients. The purpose of this study was to establish a method to measure contraction of ASM cells by embedding them into a collagen gel, and to compare the contraction between subjects with and without asthma. Methods: Gel contraction to histamine was examined in floating gels containing cultured ASM cells from subjects with and without asthma following overnight incubation while unattached (method 1) or attached (method 2) to casting plates. Smooth muscle myosin light chain kinase protein levels were also examined. Results: Collagen gels containing ASM cells reduced in size when stimulated with histamine in a concentration-dependent manner and reached a maximum at a mean (SE) of 15.7 (1.2) min. This gel contraction was decreased by inhibitors for phospholipase C (U73122), myosin light chain kinase (ML-7) and Rho kinase (Y27632). When comparing the two patient groups, the maximal decreased area of gels containing ASM cells from patients with asthma was 19 (2)% (n = 8) using method 1 and 22 (3)% (n = 6) using method 2, both of which were greater than that of cells from patients without asthma: 13 (2)% (n = 9, p = 0.05) and 10 (4)% (n = 5, p = 0.024), respectively. Smooth muscle myosin light chain kinase levels were not different between the two groups. Conclusion: The increased contraction of asthmatic ASM cells may be responsible for exaggerated bronchial constriction in asthma.
  • 松本久子
    治療 89 9 2599 - 2603 2007年09月
  • Kazuo Chin; Ken-ichi Takahashi; Kazufumi Ohmori; Iwasa Toru; Hisako Matsumoto; Akio Niimi; Hiraku Doi; Tadashi Ikeda; Tatsutoshi Nakahata; Masashi Komeda; Michiaki Mishima
    JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 134 1 260 - 261 2007年07月 [査読有り]
  • Hisako Matsumoto; Akio Niimi; Rollin P. Tabuena; Masaya Takemura; Tetsuya Ueda; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Kazuo Chin; Michiaki Mishima
    CHEST 131 4 1042 - 1049 2007年04月 [査読有り]
     
    Background: Chronic cough, which may be of asthmatic or nonasthmatic origin, is an important clinical issue. Airway inflammation, and remodeling demonstrated by subbasement membrane thickening has been associated with cough variant asthma (CVA) as well as with nonasthmatic chronic cough (NAC). CT studies have shown airway wall thickening in patients with asthma who wheeze. We examined airway wall thickness by CT in adult patients with chronic cough and examined its pathophysiologic implication. Methods: Nonsmoking, steroid-naive patients with CVA (n = 27), NAC (n = 26), and healthy control subjects (n = 15) were studied. Airway dimensions were assessed by a validated CT technique, in which we measured airway wall area (WA) corrected by body surface area (BSA), the ratio of WA to outer wall area (percentage of wall area [WA%]) absolute wall thickness (T)/root BSA, and airway luminal area/BSA of a segmental bronchus. Correlations between CT parameters and clinical indexes such as disease duration and cough sensitivity were examined. Results: In patients with CVA, WA/BSA, WA%, and T/root BSA were all significantly greater than those in control subjects. In patients with NAC, WA/BSA and T/root BSA were significantly greater than in control subjects. The increase of WA/BSA and T/root BSA of NAC patients was less than that of CVA patients. In a subset of patients with NAC, WA% correlated with capsaicin cough sensitivity (n = 9, r = 0.75, p = 0.034). Conclusions: Walls of central airways are thickened in patients with CVA, and also to a lesser degree in patients with NAC. Airway wall thickening in NAC may be associated with cough hypersensitivity.
  • Hisako Matsumoto; Akio Niimi; Masaya Takemura; Tetsuya Ueda; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Kazuo Chin; Michiaki Mishima
    Cough 3 1 1  2007年 [査読有り]
     
    Gastro-oesophageal reflux (GOR) is one of the most common causes of chronic cough in Western countries, responsible for 10 to 40% of cases. In Japan, however, GOR-associated chronic cough (GOR-CC) has been rarely reported and its clinical manifestation including frequency of concomitant reflux laryngitis is poorly known. We have analyzed prevalence and clinical characteristics of patients who were diagnosed as having GOR-CC among adult patients with chronic cough (≥ 8 weeks) who visited our asthma and cough clinic over a period of 19 months. Diagnosis of GOR-CC was based on the response of coughing to a proton-pump inhibitor (lansoprazole™) and/or positive results of 24 h ambulatory esophageal pH monitoring. Laryngeal involvement was based on symptoms or objective diagnosis by specialists. GOR-associated chronic cough was diagnosed in 7.1% (8 of 112) of chronic cough patients. In addition to the demographic data which were consistent with the characteristics of patients with GOR-CC in the Western populations, including gender (6 females), age (mean ±SE, 56.9 ± 5.8 years), duration of cough (9.9 ± 3.3 months), lack of gastrointestinal symptoms (3 of 8) and complication with other causes of cough (5 of 8), we found the standard range of body mass index (23.9 ± 1.5 kg/m2) and high incidence of concomitant reflux laryngitis (5 of 8) in the present 8 patients. Among 4 patients who could stop treatment with temporal resolution of cough, cough recurred in 3 patients, 1 week to 8 months after the discontinuation. In conclusion, GOR-CC is a less frequent cause of chronic cough in Japan than in Western countries. Signs or symptoms of laryngitis may be important as clues to suspicion of GOR-CC.
  • Peter Borger; Hisako Matsumoto; Sarah Boustany; Mikael M. C. Gencay; Janette K. Burgess; Greg G. King; Judith L. Black; Michael Tamm; Michael Roth
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 119 1 98 - 105 2007年01月 [査読有り]
     
    Background: CCAAT/enhancer-binding proteins (C/EBPs) control cell proliferation; lack of C/EBP alpha correlates with increased proliferation of bronchial smooth muscle cells (BSMCs) of asthmatic patients. Objective: We sought to assess disease-specific expression of C/EBP alpha, beta, delta, and epsilon and the effects of budesonide (10(-8) mol/L) and formoterol (10(-8) mol/L). Methods: Expression and function of C/EBP alpha, beta, delta, and epsilon BSMCs of control subjects (n = 9), asthmatic patients (n = 12), and patients with chronic obstructive pulmonary disease (COPD; n = 10) were determined. Results: The control group expressed C/EBP alpha, beta, delta, and epsilon, which were upregulated by serum (5%). Budesonide completely inhibited C/EBP alpha and beta expression; formoterol increased C/EBP alpha expression (2-fold). C/EBP delta and epsilon expression were not affected by the drugs. The asthmatic group did not appropriately express C/EBP alpha. Basal levels of C/EBP beta, delta, and epsilon were upregulated by serum (5%). Budesonide and formoterol increased C/EBP beta levels (3.4-fold and 2.5-fold, respectively), leaving C/EBP alpha, delta, and epsilon levels unaffected. The COPD group normally expressed C/EBP alpha, beta, and epsilon, which were upregulated by serum treatment (5%). Basal levels of C/EBP,5 were downregulated by serum in 7 of 10 BSMC lines. Budesonide inhibited C/EBPa and P expression, upregulated C/EBP delta (3.2-fold), and had no effect on C/EBP epsilon. Formoterol upregulated C/EBP alpha expression (3-fold) but not the other C/EBPs. Protein analysis and electrophoretic mobility shift assay confirmed the disease-specific expression pattern of C/EBP alpha in asthmatic patients and C/EBP delta in patients with COPD. Conclusions: The expression and regulation of C/EBPs in BSMCs of asthmatic patients and patients with COPD seems disease specific. Budesonide and formoterol modulate C/EBP expression in a drug- and disease-specific pattern. Clinical implications: The data could provide a method to discriminate between asthma and COPD at an early disease stage.
  • 松本久子
    月刊アレルギーの臨床 354 1088 - 1093 2006年12月
  • Tetsuya Ueda; Akio Niimi; Hisako Matsumoto; Masaya Takemura; Toyohiro Hirai; Masafumi Yamaguchi; Hirofumi Matsuoka; Makiko Jinnai; Shigeo Muro; Kazuo Chin; Michiaki Mishima
    JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 118 5 1019 - 1025 2006年11月 [査読有り]
     
    Background: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. Objective: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. Methods: Both lungs were scanned at full-inspiratory and fullexpiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. Results: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV1/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV1/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV1 and FEV1/FVC) and peripheral airflow obstruction. Conclusion: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. Clinical implications: Small airways are an important therapeutic target in asthma.
  • 松本久子
    月刊アレルギーの臨床 351 895  2006年10月
  • Kazuo Chin; Takaya Nakamura; Ken-ichi Takahashi; Kensuke Sumi; Hisako Matsumoto; Akio Niimi; Shunichi Fukuhara; Michiaki Mishima; Takashi Nakamura
    JOURNAL OF HYPERTENSION 24 10 2091 - 2099 2006年10月 [査読有り]
     
    Objectives Effective treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (nCPAP) lowers blood pressure (BP). The long-term effects of nCPAP treatment on BP in OSA patients are not well known. The time period of such treatment sufficient to lower BP in OSA patients is also not known. We investigated compliance with long-term nCPAP therapy and its effects on BP. Methods This observational study involved 66 OSA patients [59 men, seven women; mean age, 51 (48-54) years; body mass index (BMI), 28.7 (27.7-29.7) kg/m(2); apnoea and hypopnoea, 50.3 (45.6-55.0)/h; 95% confidence intervals]. BP and BMI were measured before the study and at two checkpoints after usage of nCPAP [620 (552-688) and 1071 (1000-1143) days]. Results The different times between the first and second checkpoints for detecting objective compliance were 17 (4-30) min (P = 0.003). Diastolic BP decreased by 5.9 (3.1-8.7) mmHg after 600 days nCPAP treatment and by 4.6 (2.0-7.2) mmHg after 1000 days (P = 0.0006). Systolic BP and BMI did not change significantly. Usage of nCPAP treatment for a daily average of 3 h was needed to achieve a significant decrease in diastolic BP [7.4 (4.3-10.6) mmHg, P < 0.0001]. Diastolic BP of normotensive OSA patient did not change significantly by nCPAP treatment, but that of hypertensive OSA patients decreased significantly within 1 month-3 years of nCPAP treatment whether or not medication was used. Conclusions In patients with severe OSA, the use of nCPAP for a daily average of 3 h would be sufficient to decrease the diastolic BP of hypertensive OSA patients.
  • 松本久子
    薬局 57 8 2622 - 2627 2006年08月
  • K. Sumi; K. Chin; K. Takahashi; T. Nakamura; H. Matsumoto; A. Niimi; M. Mishima
    QJM-AN INTERNATIONAL JOURNAL OF MEDICINE 99 8 545 - 553 2006年08月 [査読有り]
     
    Background: Elevated heart rate (HR) is a risk factor for cardiovascular disease. The effects of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) on HR are controversial. Aim: To investigate the effect of nasal continuous positive airway pressure (nCPAP) therapy on HR in OSAHS patients. Methods: Sixty-two OSAHS patients underwent 24-h electrocardiographic recording, both before and 3 or 4 days after instigation of nCPAP. Results: After nCPAP was started, HR significantly decreased (mean +/- SD 71.8 +/- 10.6 vs. 67.5 +/- 9.4 bpm, p < 0.0001), both in the daytime (0600-2200 h, 76.3 +/- 12.2 vs. 72.2 +/- 10.2 bpm, p < 0.0001) and at night-time (2200-0600 h, 64.5 +/- 9.1 vs. 60.0 +/- 8.9 bpm, p < 0.0001). HR was significantly reduced in both periods in the 44 patients with hypertension and/or diabetes mellitus, but only during the night-time in the 18 with neither condition. Before nCPAP treatment, HR was positively correlated with percentage time of arterial O-2 saturation < 90% during sleep (p = 0.008) and with the apnoea-hypopnoea index during sleep (p = 0.003). In 15 patients undergoing HR for 2 days before starting nCPAP, the mean HRs for the two periods were similar (p = 0.95). Discussion: nCPAP therapy appears to decrease HR in OSAHS patients, and may thereby reduce their risk of cardiovascular disease.
  • K. Sumi; K. Chin; K. Takahashi; T. Nakamura; H. Matsumoto; A. Niimi; M. Mishima
    QJM-AN INTERNATIONAL JOURNAL OF MEDICINE 99 8 545 - 553 2006年08月 [査読有り]
     
    Background: Elevated heart rate (HR) is a risk factor for cardiovascular disease. The effects of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) on HR are controversial. Aim: To investigate the effect of nasal continuous positive airway pressure (nCPAP) therapy on HR in OSAHS patients. Methods: Sixty-two OSAHS patients underwent 24-h electrocardiographic recording, both before and 3 or 4 days after instigation of nCPAP. Results: After nCPAP was started, HR significantly decreased (mean +/- SD 71.8 +/- 10.6 vs. 67.5 +/- 9.4 bpm, p < 0.0001), both in the daytime (0600-2200 h, 76.3 +/- 12.2 vs. 72.2 +/- 10.2 bpm, p < 0.0001) and at night-time (2200-0600 h, 64.5 +/- 9.1 vs. 60.0 +/- 8.9 bpm, p < 0.0001). HR was significantly reduced in both periods in the 44 patients with hypertension and/or diabetes mellitus, but only during the night-time in the 18 with neither condition. Before nCPAP treatment, HR was positively correlated with percentage time of arterial O-2 saturation < 90% during sleep (p = 0.008) and with the apnoea-hypopnoea index during sleep (p = 0.003). In 15 patients undergoing HR for 2 days before starting nCPAP, the mean HRs for the two periods were similar (p = 0.95). Discussion: nCPAP therapy appears to decrease HR in OSAHS patients, and may thereby reduce their risk of cardiovascular disease.
  • M Takemura; H Matsumoto; A Niimi; T Ueda; H Matsuoka; M Yamaguchi; M Jinnai; S Muro; T Hirai; Y Ito; T Nakamura; T Mio; K Chin; M Mishima
    EUROPEAN RESPIRATORY JOURNAL 27 5 908 - 912 2006年05月 [査読有り]
     
    Asthma is characterised by chronic inflammation of the airways, but the relevance of high-sensitivity assays for C-reactive protein (hs-CRP), which are known to be a sensitive marker of low-grade systemic inflammation, has not been fully studied in asthma. The objective was to examine serum hs-CRP levels in patients with asthma and their relationship to clinical characteristics and degree of airway inflammation. Serum hs-CRP levels were cross-sectionally examined in steroid-naive (n=22) and steroid-inhaling (n=23) adult patients with asthma and healthy controls (n=14). All were nonsmokers. Serum hs-CRP levels were significantly increased in steroid-naive patients (mean +/- SD 1.33 +/- 1.48 mg.L-1) compared with controls (0.21 +/- 0.30 mg.L-1), but not in patients on inhaled corticosteroid. Among steroid-naive patients, serum hs-CRP levels significantly negatively correlated with indices of pulmonary function (forced expiratory volume in one second/forced vital capacity and forced mid-expiratory flow) and positively with sputum eosinophil count. Among patients on inhaled corticosteroid, hs-CRP levels did not correlate with any indices. In conclusion, an increase in serum C-reactive protein levels measured by high-sensitivity assays may be associated with airflow obstruction and airway inflammation, and may serve as a surrogate marker of airway inflammation in asthma.
  • 咳喘息の診断におけるImpulse Oscillometry System(IOS)の有用性の検討
    上田 哲也; 新実 彰男; 松本 久子; 竹村 昌也; 山口 将史; 松岡 弘典; 陣内 牧子; 常 亮; 三嶋 理晃
    呼吸 25 2Suppl. S40 - S41 (一社)呼吸研究 2006年02月
  • H Matsumoto; A Niimi; M Takemura; T Ueda; R Tabuena; M Yamaguchi; H Matsuoka; T Hirai; S Muro; Y Ito; T Mio; K Chin; H Nishiyama; M Mishima
    JOURNAL OF ASTHMA 43 2 131 - 135 2006年 [査読有り]
     
    Patients with cough variant asthma, a common cause of chronic cough, may develop wheezing. We examined the determinants of this phenomenon and achievement of remission in 42 patients. During 4 years after diagnosis, wheezing developed in 13 of the patients. Early inhaled corticosteroid treatment was inhibitory against the development of wheezing by univariate analysis and by multivariate analysis with an odds ratio of 0.12 (95% confidence interval, 0.02 to 0.87, p = 0.037). Remission was achieved in 7 patients, who were younger than those without remission by univariate analysis ( p = 0.048). Early treatment with inhaled corticosteroid may prevent the progression of cough variant asthma to classic asthma.
  • 松岡 弘典; 新実 彰男; 松本 久子; 上田 哲也; 竹村 昌也; 山口 将史; 陣内 牧子; 大塚 浩二郎; 小熊 毅; 竹田 知史
    アレルギー 55 8 1110 - 1110 一般社団法人 日本アレルギー学会 2006年
  • Shigeaki Muto; Kiyoko Sebata; Hitomi Watanabe; Fumie Shoji; Yoshie Yamamoto; Michie Ohashi; Takako Yamada; Hisako Matsumoto; Tomoko Mukouyama; Takekazu Yonekura; Sachiko Namiki; Eiji Kusano
    American Journal of Kidney Diseases 46 4 697 - 705 2005年10月 [査読有り]
     
    •Background: Extrarenal potassium disposal is particularly critical in patients with end-stage renal disease. Exogenous insulin stimulates this disposal by enhancing potassium uptake into cells in hemodialysis (HD) patients and healthy subjects. However, the effect of physiological levels of endogenous insulin on this disposal in these patients or healthy subjects is unknown. Methods: Effects of an oral glucose tolerance test (37.5, 75, and 150 g) on serum potassium levels were determined in 13 HD patients and 7 healthy controls. Serum potassium and insulin levels and plasma aldosterone and epinephrine levels were measured before and after glucose loads. Results: In HD patients and controls, serum insulin levels increased to a similar magnitude in parallel with increased serum glucose levels, but serum potassium levels decreased significantly only in HD patients. In HD patients, plasma aldosterone or epinephrine levels were not changed significantly after a glucose load. In HD patients, the decrease in serum potassium levels was dependent on the increase in serum insulin levels and was more prominent when 150 g of glucose was administered. In HD patients, the decrease in serum potassium levels correlated negatively (r = -0.45 P < 0.001) with the increase in serum insulin levels, and maximal decrease in serum potassium levels correlated negatively (r = -0.54 P < 0.001) with maximal increase in serum insulin levels. Conclusion: Endogenous production of physiological concentrations of insulin in response to exogenous glucose administration decreases serum potassium levels only in HD patients, independently of plasma aldosterone and epinephrine levels. © 2005 by the National Kidney Foundation, Inc.
  • 松本久子; 新実彰男
    月刊アレルギーの臨床 331 370 - 374 2005年05月
  • H Matsumoto; A Niimi; M Takemura; T Ueda; M Minakuchi; R Tabuena; K Chin; T Mio; Y Ito; S Muro; T Hirai; S Morita; S Fukuhara; M Mishima
    THORAX 60 4 277 - 281 2005年04月 [査読有り]
     
    Background: The balance between matrix metalloproteinase- 9 ( MMP- 9) and tissue inhibitor of metalloproteinase- 1 ( TIMP- 1) may be critical in extracellular matrix remodelling, a characteristic of asthmatic airways. An excess of TIMP- 1 over MMP- 9 has been associated with chronic airflow obstruction but the mechanisms underlying this association remain unknown. Recent computed tomographic ( CT) studies indicate that airway wall thickening is associated with chronic airflow obstruction. Methods: Sputum levels of MMP- 9, TIMP- 1, and their molar ratio were examined in 26 patients with stable asthma and their relationship with pulmonary function and airway wall thickness, assessed by a validated CT technique which measured wall area corrected by body surface area ( WA/ BSA), the ratio of WA to outer wall area ( WA%), and the absolute wall thickness corrected by root BSA of a segmental bronchus ( T/ ! BSA), was examined. Results: Sputum MMP- 9 levels were inversely correlated with WA% and TIMP- 1 levels were positively correlated with WA/ BSA and T/ root BSA. The MMP- 9/ TIMP- 1 molar ratio was inversely correlated with WA% and T/! BSA and positively correlated with post- bronchodilator values of mid- forced expiratory flow and maximum expiratory flow at the quartile of lung volume. Conclusion: Excess TIMP- 1 may have a pathogenetic role in airway wall thickening in asthmatic patients which may result in chronic airflow obstruction.
  • 松本久子
    アレルギー科 19 3 192 - 199 2005年03月
  • K Takahashi; K Chin; K Sumi; T Nakamura; H Matsumoto; A Niimi; Ikai, I; M Mishima
    RESPIRATORY MEDICINE 99 3 262 - 264 2005年03月 [査読有り]
     
    Hepatic hydrothorax is defined as pleural effusion with liver cirrhosis but no primary cardiopulmonary disease. Hepatic hydrothorax is often resistant to various therapeutic interventions. The most likely cause is the transfer of ascites fluid from the abdomen to the pleural space via the diaphragm because of a negative intrathoracic pressure gradient. A 62-year-otd man was diagnosed with hepatoma and cirrhosis. After a partial hepatectomy, he suffered with hepatic hydrothorax. He had snoring without obvious steep apnea. The patient's hepatic hydrothorax markedly improved following nasal continuous positive airway pressure (nCPAP) treatment during steep. The mechanism for the improvement may have been the intrathoracic positive pressure during steep induced by the nCPAP treatment during steep. nCPAP treatment may provide a new therapy for resistant hepatic hydrothorax. (C) 2004 Elsevier Ltd. All rights reserved.
  • 松本 久子; 新実 彰男; 上田 哲也; 竹村 昌也; 山口 将史; 松岡 弘典; 常 亮; 三嶋 理晃
    アレルギー 54 8 958 - 958 一般社団法人 日本アレルギー学会 2005年
  • 松本久子
    月刊アレルギーの臨床 325 1027 - 1030 2004年12月
  • T Ueda; R Tabuena; H Matsumoto; M Takemura; A Niimi; K Chin; M Mishima
    INTERNAL MEDICINE 43 11 1060 - 1062 2004年11月 [査読有り]
     
    In the treatment of severe asthma attack, acute application of non-invasive positive pressure ventilation is shown to be beneficial in some selected patients, while endotracheal intubation and mechanical ventilation is required in the remaining cases. Management with invasive ventilation in status asthmaticus is often associated with complications such as excessive mucus production and atelectasis, which may lead to prolonged hypoxemia and may increase mortality. We present a case of status asthmaticus who developed refractory atelectasis during invasive mechanical ventilation but had a dramatic resolution as well as successful weaning when non-invasive positive pressure ventilation was instituted.
  • 松本久子; 三嶋理晃
    医学のあゆみ 210 10 851 - 855 2004年09月
  • A Niimi; H Matsumoto; M Takemura; T Ueda; Y Nakano; M Mishima
    CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY 27 1 45 - 57 2004年08月 [査読有り]
     
    Airway remodeling is an established feature of asthma. Histologic examination is essential in the assessment of remodeling that is a pathologic concept. Examinations of autopsied or resected lung have enabled detailed morphologic and morphometric studies and have provided fundamental knowledge of airway remodeling in asthma. However, such materials are only accidentally available, and clinical information may often be insufficient in autopsied cases. Bronchoscopic mucosal biopsy has been widely used since the 1980s, and has contributed substantially to basic investigations of inflammation and remodeling. However such specimens are limited in size and depth, limited to central airways, and the procedure might be too invasive to be repeated. Remodeling can also be assessed indirectly. Pulmonary function tests to evaluate chronic airflow obstruction are available in clinical settings and suitable for screening or mass studies, but they may be affected by concomitant diseases or short-term asthma control. Computed tomography (CT) has recently been utilized to assess remodeling. It cannot discern pathologic details but provides a broader range of airway/lung morphology and may be less invasive compared to biopsy. In addition to classic subjective evaluations, quantitative assessment has been reported for central airway dimensions, such as airway wall area, luminal area and wall thickness, and for peripheral airway abnormality or air trapping as measured by decreased lung attenuation or increased mosaic perfusion. This article summarizes the merits and limitations of various methods to assess airway remodeling, and describes the details of methodologies, interpretations, pathophysiologic relevance, and future directions of asthmatic airway remodeling assessed by CT.
  • A Niimi; H Matsumoto; R Amitani; Y Nakano; H Sakai; M Takemura; T Ueda; K Chin; H Itoh; EP Ingenito; M Mishima
    AMERICAN JOURNAL OF MEDICINE 116 11 725 - 731 2004年06月 [査読有り]
     
    PURPOSE: Computed tomography studies demonstrate thickening of the asthmatic airway wall and its relation to disease severity. We evaluated the effect of inhaled corticosteroid on this phenomenon. METHODS: Cross-sectional images of the right upper lobe apical segmental bronchus were obtained by helical computed tomography in 45 corticosteroid-naive patients with persistent asthma and 28 healthy controls. Airway wall thickness was measured as airway wall area normalized to body surface area. Computed tomogaphy, pulmonary function, and serum levels of eosinophil cationic protein were examined before and after treatment with beclomethasone (800 mug/d for 12 weeks). RESULTS: Before treatment, airway wall thickness was greater in asthma patients than in controls (P < 0.0001). After treatment, it decreased by 11% (P < 0.001) but remained high (P < 0.0001 vs. control); the serum level of eosinophil cationic protein decreased, and airflow obstruction was reduced, but not to the level in controls. The decrease in wall thickness was associated with a decrease in the serum level of eosinophil cationic protein (r = 0.39, P = 0.009) and an increase in the forced expiratory volume in 1 second (r = 0.45, P = 0.003) and was inversely related to disease duration at entry (r = -0.38, P = 0.009). Post-treatment wall thickness was related to disease duration (r = 0.45, P = 0.003) and remaining airflow obstruction. CONCLUSION: Wall thickening of asthmatic central airways responds partially to inhaled corticosteroid therapy and may reflect an overall reduction in airway inflammation. "Unresponsive components," possibly involving structural changes, may increase in the absence of inhaled corticosteroid treatment, potentially leading to chronic airflow obstruction. Am J Med. 2004;116:725-731. (C)2004 by Excerpta Medica Inc.
  • K Chin; S Fukuhara; K Takahashi; K Sumi; T Nakamura; H Matsumoto; A Niimi; N Hattori; M Mishima; T Nakamura
    SLEEP 27 3 490 - 493 2004年05月 [査読有り]
     
    Study Objectives: After nasal continuous positive airway pressure (nCPAP) treatment, several symptoms such as hypersomnolence, daytime fatigue, and impaired concentration improve in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). A variability of perception of pretreatment sleepiness (response-shift phenomenon) experienced in OSAHS patients before and after nCPAP treatment may reflect informative shifts in an individual's internal standards, in values and priorities, or in the conceptualization of perceived sleepiness. The objective of this study is to determine whether there is a response shift in perceptions of pretreatment sleepiness before and after nCPAP treatment in patients with OSAHS. We investigated the response shift in Epworth Sleepiness Scale scores before and after nCPAP. Design: Thirty-one consecutive OSAHS patients filled out the subjective ESS before nCPAP treatment (Pre-ESS). After a mean of about 10 months of nCPAP treatment, the patients filled out the ESS again, which was designated as the Post-ESS. Then they were asked to complete the scale again, recalling sleepiness before nCPAP treatment (Response Shift-Pre-ESS). The control group consisted of 11 patients with OSAHS who had not yet received nCPAP treatments and were matched for age, body mass index, and respiratory disturbance index. Setting: University Hospital in, Japan. Interventions: N/A. Measurements and Results: There was a significant response shift in ESS scores before and after nCPAP treatment (Pre-ESS: 8.5 [95% Confidence interval (CI), 7.1-9.9] vs Response Shift-Pre-ESS: 11.1 [95% Cl, 9.5-12.8], P < .002). A significant number of patients (P < .02) had not recognized the degree of sleepiness experienced before treatment until after they had received nCPAP treatment. Eight had pretreatment ESS scores greater than or equal to11 and 18 had posttreatment ESS scores greater than or equal to11 on the Response Shift-Pre-ESS. In the control group, ESS did not change significantly from the first to the second testing performed before nCPAP treatment (first ESS, 8.8 [95% Cl, 5.3-12.3]; second ESS, 8.3 [95% Cl, 4.7-11.8]: P = .95). Conclusions: Response shifts should be taken into consideration when explaining factors underlying individual differences in susceptibility to daytime sleepiness.
  • RP Tabuena; H Matsumoto; T Mio; Y Nagata; M Mishima
    INTERNAL MEDICINE 43 5 445 - 446 2004年05月 [査読有り]
  • 松本久子
    ぜん息 17 2 27 - 31 2004年04月
  • M Takemura; A Niimi; M Minakuchi; H Matsumoto; T Ueda; K Chin; M Mishima
    CHEST 125 4 1352 - 1358 2004年04月 [査読有り]
     
    Background: Investigations using high-resolution CT (HRCT) show that bronchial dilatation (BD) is found in many patients with asthma. However, the pathogenesis and pathophysiologic relevance of BD in asthma are poorly understood. A balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may control the remodeling of extracellular matrix, and excess MMPs have been associated with destruction or dilatation of airways in patients with bronchiectasis. Objectives: To study the prevalence of BD as assessed by HRCT according to standard subjective criteria in 37 patients with stable asthma and 10 healthy control subjects, and to examine the relation of BD in asthmatic patients to clinical characteristics and sputum indices, including MMP-9 and TIMP-1 levels. Design: A prospective cohort study. Results: At least one dilated bronchus was present in 23 asthmatic subjects (62%) and 2 control subjects (20%) [p = 0.030]. The ratio of dilated bronchi to all eligible bronchi in each subject (individual BD%) was higher in the asthmatic patients than in the control subjects (11.4 +/- 16.1% vs 1.3 +/- 3.0%, p = 0.011) [mean +/- SD]. Asthmatic patients with (n = 23) and those without BD (n = 14) were similar with regard to age, duration and severity of asthma, atopy, pulmonary function, sputum eosinophil or neutrophil count, and sputum levels of MMP-9 or TIMP-1 and their molar ratio. Individual BD% of asthmatic patients was also unrelated to these clinical and sputum variables. When analysis was confined to the 23 patients with BD, however, individual BD% correlated with the severity score of asthma (r = 0.49, p = 0.023). The results of follow-up HRCT obtained from 19 patients suggested that BD was a fixed rather than transient phenomenon. Conclusion: BD is more prevalent in asthmatic patients than in normal subjects and might be associated with the severity of asthma. Cellular inflammation or possible imbalance between MMP-9 and TIMP-I was not demonstrated in this study to be related to BD in asthma.
  • 松本久子
    アレルギー・免疫 11 2 246 - 252 2004年02月
  • 松本 久子; 新実 彰男; 竹村 昌也; 上田 哲也; 松岡 弘典; 山口 将史; 三嶋 理晃
    アレルギー 53 8 860 - 860 一般社団法人 日本アレルギー学会 2004年
  • Shigeaki Muto; Kiyoko Sebata; Michie Ohashi; Takako Yamada; Hisako Matsumoto; Tomoko Mukouyama; Sachiko Namiki; Eiji Kusano; Yasushi Asano
    ASAIO Journal 49 6 660 - 666 2003年11月 [査読有り]
     
    The current study simultaneously measured serum and red blood cell (RBC) K+ as well as plasma pH, bicarbonate, serum insulin, and aldosterone at pre-, end-, and at 5, 11, and 19 hours posthemodialysis in 25 patients with end-stage renal disease and evaluated the factors influencing serum K + levels during those periods. Our patients were studied under their current dietary conditions. At end-dialysis, serum K+ levels decreased, but RBC K+ levels were not changed. At this time point, the decrease in serum K+ levels was exclusively caused by removal of K+ by dialysis. At 5 hours postdialysis, serum K+ rapidly increased, whereas RBC K+ decreased. The 5 hour postdialysis serum K+ increase negatively correlated with the decrease in serum insulin levels. At 11 hours postdialysis, serum K+ slowly but significantly increased, and RBC K+ increased to those levels at pre- and end-dialysis. At 19 hours postdialysis, serum K+ further increased, but RBC K+ remained stable. From 5 to 19 hours postdialysis, the increase in serum K+ was independent of changes in plasma pH, bicarbonate, insulin, and aldosterone but was associated with both the predialysis serum K+ levels and the magnitude of the decrease in serum K+ at end-dialysis.
  • A Niimi; H Matsumoto; M Takemura; T Ueda; K Chin; M Mishima
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 168 8 983 - 988 2003年10月 [査読有り]
     
    Airway wall thickening has been assumed to cause airway hyperresponsiveness, but a protective effect against airway narrowing has also been suggested. We investigated the relationship between airway wall thickness as assessed by helical computed tomography and two components of airway responsiveness, airway sensitivity and reactivity, in patients with stable asthma with (n = 23) and without (n = 22) inhaled steroid treatment. A cross-section of the apical bronchus of the right upper lobe was obtained. Airway wall area corrected by body surface area was measured as an index of wall thickness. Airway sensitivity and reactivity were measured by continuous inhalation of methacholine, on the basis of the methacholine respiratory resistance dose-response curve. The eosinophil count in sputum was determined in 16 patients [steroid (+) group] and 14 patients [steroid (-) group]. In both groups of patients, airway sensitivity was not related to airway reactivity. Airway sensitivity was related to eosinophil count [r = 0.57 in the steroid (+) group and r = 0.49 in the steroid (-) group], but not to airway wall thickness. In contrast, airway reactivity negatively correlated with airway wall thickness [r = -0.56 in the steroid (+) group and r = -0.55 in the steroid (-) group] but not with eosinophil count. Our results suggest that airway wall thickening attenuates airway reactivity in patients with asthma. These findings may have important implications in pathophysiology and in the treatment of airway remodeling.
  • M Minakuchi; A Niimi; H Matsumoto; R Amitani; M Mishima
    RESPIRATION 70 4 362 - 366 2003年07月 [査読有り]
     
    Background: Chronic eosinophilic pneumonia (CEP) is highly sensitive to systemic corticosteroids, but frequently relapses if the dose is tapered or treatment discontinued. Long-term usage of systemic corticosteroids may cause side effects. Alternative treatments are therefore desired. Objectives: We evaluated the response of CEP to monotherapy with inhaled corticosteroids (ICS). Methods: Four patients who had CEP without spontaneous resolution were studied. Patients received inhaled beclomethasone dipropionate (BDP) at a dose of 0.8 mg/day in 1 patient and 1.6 mg/day in 3 patients for 2 weeks. Treatment was continued if a patient showed improvement in at least 1 of the following indices: radiological findings, symptoms, and blood eosinophilia. Results: After the initial 2 weeks of treatment with BDP, the blood eosinophil count increased in 2 patients and decreased in 2. Symptoms worsened in 2 and improved in 2. Infiltrates on chest radiography increased in 3 and showed little change in 1. In the 2 patients with worsening of all 3 outcome indices, oral prednisolone was started; the indices improved. In the remaining 2 patients, BDP alone was continued. One patient had worsening of CEP after 2 months of treatment, and another had relapse of CEP at 3.5 years while receiving 1.6 mg/day of BDP. All patients thus finally had worsening or relapse of CEP during treatment with BDP. Conclusions: ICS may not be effective when given as monotherapy in patients with CEP. Copyright (C) 2003 S. Karger AG, Basel.
  • M Minakuchi; A Niimi; H Matsumoto; R Amitani; M Mishima
    RESPIRATION 70 4 362 - 366 2003年07月 [査読有り]
     
    Background: Chronic eosinophilic pneumonia (CEP) is highly sensitive to systemic corticosteroids, but frequently relapses if the dose is tapered or treatment discontinued. Long-term usage of systemic corticosteroids may cause side effects. Alternative treatments are therefore desired. Objectives: We evaluated the response of CEP to monotherapy with inhaled corticosteroids (ICS). Methods: Four patients who had CEP without spontaneous resolution were studied. Patients received inhaled beclomethasone dipropionate (BDP) at a dose of 0.8 mg/day in 1 patient and 1.6 mg/day in 3 patients for 2 weeks. Treatment was continued if a patient showed improvement in at least 1 of the following indices: radiological findings, symptoms, and blood eosinophilia. Results: After the initial 2 weeks of treatment with BDP, the blood eosinophil count increased in 2 patients and decreased in 2. Symptoms worsened in 2 and improved in 2. Infiltrates on chest radiography increased in 3 and showed little change in 1. In the 2 patients with worsening of all 3 outcome indices, oral prednisolone was started; the indices improved. In the remaining 2 patients, BDP alone was continued. One patient had worsening of CEP after 2 months of treatment, and another had relapse of CEP at 3.5 years while receiving 1.6 mg/day of BDP. All patients thus finally had worsening or relapse of CEP during treatment with BDP. Conclusions: ICS may not be effective when given as monotherapy in patients with CEP. Copyright (C) 2003 S. Karger AG, Basel.
  • 松本久子; 新実彰男
    ぜん息 16 2 51 - 54 2003年04月
  • K Chin; T Nakamura; K Takahashi; K Sumi; Y Ogawa; H Masuzaki; S Muro; N Hattori; H Matsumoto; A Niimi; T Chiba; K Nakao; M Mishima; M Ohi; T Nakamura
    AMERICAN JOURNAL OF MEDICINE 114 5 370 - 376 2003年04月 [査読有り]
     
    PURPOSE: Obesity has been associated with obstructive sleep apnea and hepatic steatosis. We investigated the effects of obstructive sleep apnea and treatment with nasal continuous positive airway pressure (CPAP) on serum aminotransferase levels in obese patients. METHODS: We studied 40 obese men with obstructive sleep apnea syndrome. None had hepatitis B antigen or C antibody, autoimmune disease, or an excessive intake of alcohol. Serum levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, glucose, insulin, and-leptin were determined in the afternoon and in the morning immediately after sleep, before and after nasal CPAP treatment. RESULTS: Aminotransferase levels were abnormal in j5% (n = 14) of patients. Before treatment, mean (+/- SD) aspartate aminotransferase levels were higher in the morning than in the previous afternoon (presleep, 34 +/- 20 IU/L; postsleep, 39 +/- 28 IU/L; P = 0.006). The overnight mean increases in aminotransferase levels were less marked after the first night of nasal CPAP treatment (aspartate aminotransferase: from 6 +/- 11 IU/L to 2 +/- 6 IU/L, P = 0.0003; alanine aminotransferase: from 5 9 IU/L to 2 +/- 6 IU/L, P = 0.006). Leptin levels (n = 23) decreased significantly after treatment (P = 0.0002), whereas insulin resistance (calculated by the homeostasis model assessment method) and triglyceride levels were unchanged. Improvements in aspartate and alanine aminotransferase levels were maintained after 1 and 6 months of nasal CPAP treatment. CONCLUSION: Nasal CPAP therapy may have beneficial effects on serum aminotransferase abnormalities in obese patients who have obstructive sleep apnea. (C) 2003 by Excerpta Medica Inc.
  • A Niimi; H Matsumoto; T Ueda; M Takemura; K Suzuki; E Tanaka; K Chin; M Mishima; R Amitani
    THORAX 58 2 152 - 153 2003年02月 [査読有り]
     
    Background: A substantial proportion of patients with recurrent pneumonia do not have an apparent underlying condition, but they may have unknown defects in host defence mechanisms such as cough reflex. Methods: Capsaicin cough sensitivity was measured in seven patients with recurrent pneumonia but no underlying condition. Recurrent pneumonia was defined as at least two episodes of pneumonia in 1 year, or three or more episodes at any time. After remission of pneumonia, 10 doubling concentrations of capsaicin (1.22-625 muM) were inhaled until five or more coughs were induced (cough threshold). Mucociliary clearance was assessed on the basis of nasal ciliary beat frequency and nasal clearance time. Twenty one age and sex matched healthy subjects were studied as controls. Results: Each patient had 2-6 episodes of pneumonia. Most episodes developed in dependent lung segments, suggesting the involvement of silent aspiration. Log transformed cough threshold was significantly higher in patients than in controls (mean 2.37 M (95% Cl 1.84 to 2.90) v 1.29 muM (95% Cl 1.11 to 1.47); p<0.0001). The effect of pneumonia per se on cough reflex seemed unlikely since the cough threshold showed little change when re-examined after 3 months. The patients and controls did not differ with respect to the indices of mucociliary clearance. Conclusions: Impaired cough reflex may be involved in the pathogenesis of recurrent pneumonia.
  • Peripheral airway lesions in asthma: Assessment by HRCT
    A. Niimi; H. Matsumoto; T. Ueda; M. Takemura; M. Mishima
    Respiration and Circulation 51 3 241 - 248 2003年 [査読有り]
  • 新実 彰男; 松本 久子; 竹村 昌也; 三嶋 理晃
    アレルギー 51 2 227 - 227 一般社団法人 日本アレルギー学会 2002年
  • 新実 彰男; 松本 久子; 竹村 昌也; 上田 哲也; 三嶋 理晃
    アレルギー 51 9 863 - 863 一般社団法人 日本アレルギー学会 2002年
  • H Matsumoto; K Ishihara; T Hasegawa; B Umeda; A Niimi; M Hino
    CHEST 120 5 1468 - 1473 2001年11月 [査読有り]
     
    Background: It is not certain whether inhaled corticosteroid (ICS) therapy-reduces bone mineral density (BMD) in asthmatic patients. In addition, the potential risk of osteoporosis associated with the rescue use of short courses of oral corticosteroids (SC-OCS) is unclear. Objective: To evaluate the effect of inhaled beclomethasone dipropionate (BDP) and SC-OCS on 0MID in asthmatic patients. Design: A 4-year longitudinal study. Method: Lumbar BMD was measured twice by dual-energy x-ray absorptiometry at a mean (+/- SD) interval of 4.2 +/-0.1years in 35 asthmatic adults (15 men and 20 postmenopausal women; mean age at the second evaluation, 60.6 +/- 11.5 years) who had been treated with BDP and SC-OCS. Results: The average period of BDP treatment was 7.7 +/-2.2 years (range, 4.8 to 13.0 years) at the second evaluation. During the study period, the daily dose of BDP was 765 +/- 389 mug (range, 100 to 1,730 mug), and the frequency of SC-OCS was 1.9 +/-2.7 courses per year (range, 0.0 to 8.9 courses per year). As a whole, lumbar BMD was unchanged during the course of the study, whereas the Z score (ie, the percentage of normal value predicted from age and sex) increased significantly. Changes in BMD and Z scores in patients receiving high doses of BDP (ie, >1,000 mug/d; n=9) were not significantly different from those of patients receiving lower doses (ie, less than or equal to1,000 mug/d; n=26). However, patients receiving frequent SC-OCS (ie, >2.5 courses per year; n=9) showed a significantly greater loss in BMD and Z score compared with those receiving sporadic courses (ie, less than or equal to2.5 courses per year; n=26) (p=0.002 and p=0.035, respectively). Conclusions: ICS therapy per se does not affect BMD, whereas frequent SC-OCS may do so.
  • H Matsumoto; K Ishihara; T Hasegawa; B Umeda; A Niimi; M Hino
    CHEST 120 5 1468 - 1473 2001年11月 [査読有り]
     
    Background: It is not certain whether inhaled corticosteroid (ICS) therapy-reduces bone mineral density (BMD) in asthmatic patients. In addition, the potential risk of osteoporosis associated with the rescue use of short courses of oral corticosteroids (SC-OCS) is unclear. Objective: To evaluate the effect of inhaled beclomethasone dipropionate (BDP) and SC-OCS on 0MID in asthmatic patients. Design: A 4-year longitudinal study. Method: Lumbar BMD was measured twice by dual-energy x-ray absorptiometry at a mean (+/- SD) interval of 4.2 +/-0.1years in 35 asthmatic adults (15 men and 20 postmenopausal women; mean age at the second evaluation, 60.6 +/- 11.5 years) who had been treated with BDP and SC-OCS. Results: The average period of BDP treatment was 7.7 +/-2.2 years (range, 4.8 to 13.0 years) at the second evaluation. During the study period, the daily dose of BDP was 765 +/- 389 mug (range, 100 to 1,730 mug), and the frequency of SC-OCS was 1.9 +/-2.7 courses per year (range, 0.0 to 8.9 courses per year). As a whole, lumbar BMD was unchanged during the course of the study, whereas the Z score (ie, the percentage of normal value predicted from age and sex) increased significantly. Changes in BMD and Z scores in patients receiving high doses of BDP (ie, >1,000 mug/d; n=9) were not significantly different from those of patients receiving lower doses (ie, less than or equal to1,000 mug/d; n=26). However, patients receiving frequent SC-OCS (ie, >2.5 courses per year; n=9) showed a significantly greater loss in BMD and Z score compared with those receiving sporadic courses (ie, less than or equal to2.5 courses per year; n=26) (p=0.002 and p=0.035, respectively). Conclusions: ICS therapy per se does not affect BMD, whereas frequent SC-OCS may do so.
  • H Matsumoto; A Niimi; M Minakuchi; T Izumi
    CLINICAL AND EXPERIMENTAL ALLERGY 31 4 637 - 643 2001年04月 [査読有り]
     
    Background Serum eosinophil cationic protein (ECP) levels reflect ongoing eosinophilic airway inflammation and are used as a marker for asthma activity. ECP levels, however, may not be elevated in some asthmatic patients, even when they are symptomatic. Objective To clarify the characteristics of patients with 'low' ECP titres despite asthma exacerbation. Methods Serum ECP levels were measured in 113 asthmatic patients during exacerbation. Patients were divided into two groups according to ECP titre: a high ECP group (H; ECP greater than or equal to 16.0 mug/L) and a low ECP group (L; ECP < 16.0 mug/L). Twenty-two patients who had recently received systemic steroids were excluded and the clinical features of the remaining patients in H (n = 54) and L (n = 37 were compared. Results Gender, atopic or smoking status, disease severity, inhaled steroid or theophylline usage, peak expiratory flow (% personal best) and forced expiratory volume in 1 s (FEV1) (% predicted) did not significantly differ between the two groups. Patients in L were significantly older and had longer disease duration and lower serum IgE levels than those in H. Multivariate analysis combining age, disease duration and IgE levels showed that age and disease duration were independently associated with ECP level. Airway wall thickness, assessed in a subset of patients using computed tomography, was significantly larger in L. Conclusion Serum ECP levels in asthmatic patients may not be elevated during exacerbation and thus may not be a useful marker in patients who are older, have longer disease duration or possibly have thicker airway walls. Mechanisms other than eosinophilic inflammation, such as airway remodelling, may be involved in asthma exacerbation in these patients.
  • K Tsuyuguchi; K Suzuki; H Matsumoto; E Tanaka; R Amitani; F Kuze
    CLINICAL AND EXPERIMENTAL IMMUNOLOGY 123 3 428 - 434 2001年03月 [査読有り]
     
    The purpose of the present study was to elucidate the role of oestrogen in the pathogenesis of Mycobacterium avium complex (MAC) pulmonary disease, which occurs most frequently in postmenopausal women. The study was carried out in a murine infectious model using ovariectomized DBA/2 female mice. Infection with MAC was established by intratracheal administration of bacilli. In some experiments, ovariectomized mice were treated with exogenous 17 beta -estradiol (E2). The number of bacilli in the lungs of infected mice which received ovariectomy was significantly larger than that in the lungs of sham-operated control mice, and treatment of ovariectomized mice with exogenous E2 restored the burden of bacilli to the same level as that in the sham-operated control mice. We next examined the effect of E2 in vitro using bone marrow-derived macrophages obtained from DBA/2 female mice. The macrophages showed bacteriostatic activity against MAC after treatment with interferon-gamma (IFN-gamma) and this activity was further enhanced by the exogenous addition of E2 to the culture medium. In parallel with these findings, E2 augmented the production of reactive nitrogen intermediates (RNI) by macrophages pretreated with IFN-gamma and stimulated with MAC, as shown by evaluating nitrite production and inducible nitric oxide synthase mRNA expression. These findings taken together suggest that absence of endogenous oestrogen appears to be responsible for the development of MAC pulmonary disease in this mouse model and that the enhancement by E2 of anti-MAC activity of murine macrophages induced through increased RNI production may play some role in resistance to MAC infection.
  • A Niimi; H Matsumoto; R Amitani; Y Nakano; M Mishima; M Minakuchi; K Nishimura; H Itoh; T Izumi
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 162 4 1518 - 1523 2000年10月 [査読有り]
     
    Postmortem studies have shown that airway wall thickening is present in asthmatic patients and may play a pathophysiologic role. We investigated the presence and characteristics of airway wall thickening in patients with asthma, using helical computed tomography. Eighty-one asthmatic patients and 28 healthy control subjects were studied cross-sectionally. Airway wall thickness was assessed by a validated method on the basis of wall area (WA), WA corrected by body surface area (WA/BSA), and WA%, defined as (WA/total area) x 100 at the apical bronchus of the right upper lobe. Airway luminal area (Ai) and Ai/BSA were also examined. Asthma duration and severity, pulmonary function, and serum eosinophil cationic protein levels were evaluated. Intraobserver and interobserver reproducibility of WA, WA%, and Ai measurements were good. As compared with control, WA, WA/BSA, and WA% were significantly increased in patients with mild (n = 13), moderate (39), and severe persistent (22) asthma but not in patients with intermittent asthma (7). Comparison of the four asthmatic subgroups demonstrated thicker airways in more severe disease, but no difference in Ai or Ai/BSA. When all asthmatic patients were analyzed together, WA and WA/BSA correlated with the duration, although weakly, and severity of asthma. WA and WA/BSA negatively correlated with FEV1 (percentage of predicted), FEV1/FVC (%), and FEF25-75% (percentage of predicted), whereas WA% negatively correlated with only FEV1. We conclude that airway wall thickening occurs in patients with asthma and is not limited to those with severe disease. The degree of airway wall thickening may relate to the duration and severity of disease and the degree of airflow obstruction.
  • H Matsumoto; A Niimi; K Suzuki; M Kawai; Y Matsui; R Amitani
    RESPIRATION 67 5 577 - 579 2000年09月 [査読有り]
     
    We describe a case of Churg-Strauss syndrome (CSS) associated with allergic bronchopulmonary candidiasis (ABPC). A 61-year-old man who had been given a diagnosis of ABPC based on serologic and radiographic findings experienced pain and purpuric rash on the left leg accompanied with motor weakness. The diagnosis of CSS was made from skin, nerve and muscle biopsies. Although immunosuppressant and prednisolone were administered and resulted in transient improvement, candidal pneumonia was suspected to have developed 60 days after the administration and the patient finally died of respiratory failure. To our knowledge, this is the first case of CSS associated with ABPC. Copyright (C) 2000 S. Karger AG. Basel.
  • A Niimi; H Matsumoto; M Minakuchi; M Kitaichi; R Amitani
    LANCET 356 9229 564 - 565 2000年08月 [査読有り]
     
    Subepithelial-layer thickening, a pathological feature of airway remodelling, is present in cough-variant asthma. In bronchial biopsy samples we found mean subepithelial-layer thickness was 7.1 (SE 0.4) mu m in patients with cough-variant asthma, 8.6 (0.4) mu m in patients with classic asthma with wheezing, and 5.0 (0.2) mu m in healthy controls. Thickness was significantly higher in patients with asthma than in controls, and was significantly greater in those with classic asthma than in those with cough-variant asthma. Early anti-inflammatory treatment might, therefore, be beneficial in cough-variant asthma, as recommended in classic asthma.
  • E Tanaka; T Kimoto; H Matsumoto; K Tsuyuguchi; K Suzuki; S Nagai; M Shimadzu; H Ishibatake; T Murayama; R Amitani
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 161 5 1643 - 1647 2000年05月 [査読有り]
     
    We report two Japanese families affected by pulmonary Mycobacterium avium complex (MAC) disease, involving an older brother and younger sister in one family and two brothers in the second family. We investigated whether defects in the natural resistance-associated macrophage protein gene (NRAMP1) underlay susceptibility to MAC in these cases. All of the patients had computed tomographic findings of peripheral nodules and bronchiectasis. Pulse-field gel electrophoresis patterns of mycobacterial genomic DNA restriction fragments revealed that none of the MAC strains isolated from the patients was epidemiologically related to any of the others. Direct sequencing of the complementary DNA of the patients' NRAMP1 revealed a nonconservative missense mutation at codon 419 in one patient, which was heterozygous and was not seen in his affected sibling. No variations similar to those found in mice that show susceptibility to MAC were found. The results suggest an underlying genetic defect in host defense rather than exposure to an unusually virulent strain of MAC as the pathogenetic factor in MAC disease; however, alterations in the coding region of NRAMP1 do not appear to explain the susceptibility to MAC.
  • H Matsumoto; K Suzuki; Watanabe, I; T Kimoto; K Tsuyuguchi; A Niimi; E Tanaka; T Murayama; R Amitani
    INTERNAL MEDICINE 39 1 63 - 65 2000年01月 [査読有り]
     
    Hemoptysis in patients with tuberculosis is usually associated with smear-positive and cavitary lung disease. The present case describes a patient suffering from recurrent hemoptysis associated with tuberculosis who had smear-negative and non-cavitary lung disease, and who was subsequently diagnosed as having mild hemophilia A. Although mild hemophilia A sometimes escapes detection until adolescence, there has been no reported case of mild hemophilia A detected by recurrent hemoptysis due to pulmonary tuberculosis. Here, we report a rare case of recurrent hemoptysis in a patient with tuberculosis who had smear-negative and non-cavitary lung disease and who was finally shown to have hemophilia A.
  • K Suzuki; K Tsuyuguchi; H Matsumoto; A Niimi; E Tanaka; R Amitani
    FEMS MICROBIOLOGY LETTERS 182 1 69 - 72 2000年01月 [査読有り]
     
    The effect of omeprazole, a clinically used proton pump inhibitor, alone or in combination with clarithromycin was evaluated against Mycobacterium avium, Mycobacterium intracellulare and Mycobacterium tuberculosis, using a human alveolar macrophage model of infection. Omeprazole exhibited no significant effect on the growth of the two M. avium complex strains or on the mycobactericidal activity of clarithromycin against them. In contrast, omeprazole significantly promoted the growth of Mycobacterium tuberculosis and the antimycobacterial activity of clarithromycin against it in human alveolar macrophages. It was speculated that intracellular acidic milieu around M. tuberculosis might be one reason for the lower activity of clarithromycin in the treatment of human tuberculosis. (C) 2000 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
  • H Matsumoto; K Suzuki; Watanabe, I; T Kimoto; K Tsuyuguchi; A Niimi; E Tanaka; T Murayama; R Amitani
    INTERNAL MEDICINE 39 1 63 - 65 2000年01月 [査読有り]
     
    Hemoptysis in patients with tuberculosis is usually associated with smear-positive and cavitary lung disease. The present case describes a patient suffering from recurrent hemoptysis associated with tuberculosis who had smear-negative and non-cavitary lung disease, and who was subsequently diagnosed as having mild hemophilia A. Although mild hemophilia A sometimes escapes detection until adolescence, there has been no reported case of mild hemophilia A detected by recurrent hemoptysis due to pulmonary tuberculosis. Here, we report a rare case of recurrent hemoptysis in a patient with tuberculosis who had smear-negative and non-cavitary lung disease and who was finally shown to have hemophilia A.
  • H. Matsumoto; A. Niimi; S. Satou; K. Kishi
    Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society 38 6 461 - 465 2000年 [査読有り]
  • E Tanaka; T Kimoto; K Tsuyuguchi; Watanabe, I; H Matsumoto; A Niimi; K Suzuki; T Murayama; R Amitani; F Kuze
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE 160 3 866 - 872 1999年09月 [査読有り]
     
    We have investigated the efficacy of a clarithromycin-containing four-drug regimen for Mycobacterium avium complex (MAC) pulmonary disease in 46 patients without acquired immunodeficiency syndrome (AIDS). The patients were 14 males and 32 females with a mean age of 60.9 +/- 11.5 yr. Patients received 10 mg/kg/d of clarithromycin plus ethambutol, rifampin, and initial kanamycin and subsequent quinolone for 24 mo. Seven patients (15.2%) were dropped in the first 6 mo. Among 39 patients who received more than 6 mo of therapy, 28 patients (71.8%) converted their sputa to negative: 26 of 31 patients (83.9%) infected with clarithromycin-susceptible strains and two of eight patients (25.0%) with resistant or intermediate strains. The timing of sputum conversion was 3.6 +/- 1.9 mo, with a range of 2 to 9 mo. The conversion rate was significantly lower in patients who were infected with clarithromycin-resistant or intermediate strains, who had had prior therapy (55.0% versus 89.5%), or who were acid-fast bacilli (AFB) smear-positive at entry (60.7% versus 100%). The age and sex of patients, the species of pathogen (M. avium or M. intracellulare), type and extent of the disease, and the use of kanamycin did not significantly affect the conversion rate. Although the regimen was efficacious for newly treated patients, frequent adverse reactions and a low conversion rate of sputum in retreated patients are problems that remain to be solved.
  • Serum measurement of eosinophil cationic protein in the management of asthma
    Niimi A; Matsumoto H
    Curr Opin Pulm Med 1999年 [査読有り]
  • 新実 彰男; 松本 久子; 水口 正義; 網谷 良一; 泉 孝英
    アレルギー 48 8 1068 - 1068 一般社団法人 日本アレルギー学会 1999年
  • 新実 彰男; 松本 久子
    アレルギー 48 2 265 - 265 一般社団法人 日本アレルギー学会 1999年
  • 松本 久子; 新実 彰男; 水口 正義; 泉 孝英
    アレルギー 48 8 947 - 947 一般社団法人 日本アレルギー学会 1999年
  • 松本 久子; 新実 彰男; 泉 孝英
    アレルギー 48 2 326 - 326 一般社団法人 日本アレルギー学会 1999年
  • 松本久子; 長井苑子; 北市正則; 泉孝英
    Lung Perspect 7 1 46 - 49 1999年01月
  • H Matsumoto; K Tsuyuguchi; K Suzuki; E Tanaka; R Amitani; F Kuze
    INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE 2 11 935 - 940 1998年11月 [査読有り]
     
    SETTING: A commercially available polymerase chain reaction (PCR) test (Roche Amplicor(TM) Mycobacterium avium and M. intracellulare assay-MAC-PCR) designed to detect M. avium complex (MAC) in bronchial washing was evaluated. DESIGN: A total of 141 specimens from 127 patients with various pulmonary conditions were examined. Results were compared with acid-fast smears, cultures with Ogawa egg medium, as is still commonly used in Japan, and final diagnoses. RESULTS AND CONCLUSIONS: A total of 14 bronchial washing specimens yielded MAC. Six smear-negative and culture-positive specimens were all MAC-PCR positive. In eight smear-negative and culture-positive specimens, six were MAC-PCR positive. The overall sensitivity versus culture was 85.7% (12/14). However, sensitivity might be over-estimated, as there is a lower recovery rate of MAC with egg-based medium compared with liquid media. In 127 patients, 15 were identified as having pulmonary MAC disease, of whom 13 had positive MAC-PCR in bronchial washing. In the remaining 112 patients, MAC-PCR was negative, which suggests that positive MAC-PCR was not a contaminated result. However, in terms of sensitivity and speed, we were unable to show any additional clinical benefit for using MAC-PCR as opposed to liquid media, in which MAC can frequently be detected in 7 to 14 days.
  • K Suzuki; T Kimoto; K Tsuyuguchi; H Matsumoto; A Niimi; E Tanaka; T Murayama; R Amitani
    JOURNAL OF CLINICAL MICROBIOLOGY 36 9 2745 - 2747 1998年09月 [査読有り]
     
    We report on a patient whose sputum contained both Mycobacterium tuberculosis and Mycobacterium avium complex (MAC). The MAC failed to be detected by the PCR-based AMPLICOR test. The unrecognized coexistence of MAC in the sample modified the results of drug susceptibility tests. Experiments revealed that the presence of both M. tuberculosis and MAC was not detected by the AMPLICOR test under certain conditions.
  • 新実彰男; 松本久子; 泉孝英
    Pharma Med 16 5 17 - 24 1998年05月
  • 松本久子; 石原享介
    月刊アレルギーの臨床 231 277 - 280 1998年04月
  • K Tsuyuguchi; R Amitani; H Matsumoto; E Tanaka; K Suzuki; K Yanagihara; H Mizuno; S Hitomi; F Kuze
    INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE 2 3 258 - 260 1998年03月 [査読有り]
     
    We present the first reported case of Mycobacterium szulgai pulmonary disease that needed surgical resection due to unsuccessful antimycobacterial chemotherapy. The patient was a non-immunocompromised 48-year-old male who presented with hemoptysis and whose sputum cultures repeatedly yielded M. szulgai. Antimycobacterial chemotherapy with isoniazid (INH) and rifampin (RMP)/ethambutol (EMB) for three years had been unsuccessful, and subsequent chemotherapy with RMP, EMB, ethionamide and kanamycin had to be discontinued due to liver dysfunction. Surgical resection was finally performed, and resulted in a favorable outcome. Although M. szulgai pulmonary disease is usually well controlled by antimycobacterial chemotherapy alone, surgical treatment may be necessary in some cases.
  • 久世文幸; 新実彰男; 松本久子; 田中栄作; 渡辺勇夫; 木本てるみ; 鈴木克洋; 高倉俊二; 露口一成
    結核 73 10 591 - 597 1998年 [査読有り]
     
    A 52-year-old woman with visual loss of her left eye consulted a opthalmology clinic. She was conducted left vitrectomy and administered corticosteroid under the diagnosis of uveitis of unknown cause. But her visual activity was not improved. Although re-surgery was planned, pus retention was found in her left eye. After her left eye was resected, fever and general malaise appeared suddenly. Her chest X-ray film revealed diffuse micronodular opacities. Acid-fast bacilli were detected from her sputum and identified to be Mycobacterium tuberculosis. She was diagnosed miliary tuberculosis, and then antituberculous chemotherapy consisting of 4 drugs was started. Granulomatous inflammation destructing retina and numerous acid- fact bacilli were found in histologic examination of the resected eye. This case was thought to be miliary tuberculosis disseminated from intraocular tuberculosis. After 2 months of therapy, neurologic symptoms which might be caused by brain tuberculoma appeared and deteriorated rapidly. But by adding corticosteroid to antituberculous therapy, symptoms were diminished gradually.
  • 新実 彰男; 松本 久子; 網谷 良一; 泉 孝秀
    アレルギー 47 2 260 - 260 一般社団法人 日本アレルギー学会 1998年
  • 松本 久子; 石原 享介; 長谷川 幹; 梅田 文一
    アレルギー 47 9 1036 - 1036 一般社団法人 日本アレルギー学会 1998年
  • 新実 彰男; 松本 久子; 網谷 良一; 西村 浩一; 泉 孝英
    アレルギー 47 9 948 - 948 一般社団法人 日本アレルギー学会 1998年
  • H Matsumoto; K Suzuki; K Tsuyuguchi; E Tanaka; R Amitani; A Maeda; K Yamamoto; M Sasada; F Kuze
    INFECTION AND IMMUNITY 65 11 4405 - 4410 1997年11月 [査読有り]
     
    Macrophage-derived interleukin-12 (IL-12) is essential for the activation of a protective immune response against intracellular pathogens. In this study, we examined the regulation of lL-12 mRNA expression by monocyte-derived macrophages (MDM) in response to Mycobacterium bovis BCG stimulation. A reverse transcription-PCR assay detected p40 mRNA of IL-12 at 3 h and showed a peak at 6 to 12 h with a subsequent decline. Semiquantitation of mRNA levels by competitive PCR revealed that pretreatment with gamma interferon (IFN-gamma) amplified the expression approximately 100-fold, while pretreatment with tumor necrosis factor alpha (TNF-alpha) or granulocyte-macrophage colony-stimulating factor augmented this expression about 10-fold. In contrast, pretreatment with IL-10 and IL-4 inhibited IL-12 mRNA expression, These results were further confirmed by measuring the p70 bioactive protein level in each conditioned medium by an enzyme-linked immunosorbent assay. Since IL-12 mRNA expression was weak without cytokine pretreatment and IFN-gamma strongly augmented production, we speculated that IFN-gamma might have a role in BCG stimulation of IL-12 mRNA expression. Unexpectedly, the addition of three different kinds of anti-IFN-gamma antibodies and anti-IFN-gamma receptor antibody and the coaddition of anti-TNF-alpha antibody with anti-IFN-gamma receptor antibody all failed to inhibit IL-12 mRNA expression, However, the MiniMACS method used to remove NK cells from a mononuclear cell suspension inhibited the expression of p40 mRNA but not the expression of mRNA of TNF-alpha or IL-1 beta. We concluded that the coexistence of MC cells was essential for the induction of IL-12 in MDM stimulated with BCG rather than through the secretion of IFN-gamma.
  • K Suzuki; K Tsuyuguchi; H Matsumoto; T Yamamoto; T Hashimoto; E Tanaka; R Amitani; F Kuze
    INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE 1 5 460 - 467 1997年10月 [査読有り]
     
    SETTING: The activity of KRM 1648 (KRM), a new benzoxazinorifamycin, and rifabutin (RBT), alone or in combination with clarithromycin (CLA), was evaluated against Mycobacterium avium complex (MAC) that multiplied in human alveolar macrophages (AM). DESIGN: AM were recovered by bronchoalveolar lavage, incubated in RPMI 1640 medium with 10% human AB serum, infected with four strains of MAC (of non-acquired immune deficiency syndrome [AIDS] origin), and then treated with each drug alone or in combination. After incubation for 7 days, colony forming units in each well were counted on 7H10 agar. RESULTS: Although concentrations between 0.2 mu g/ml and 20 mu g/ml of both rifamycins showed clear dose-dependent activities against all MAC strains tested, only 20 mu g/ml of each drug had modest bactericidal effect. In combination with 2.0 mu g/ml of CLA, however, 0.2 mu g/ml of both drugs caused a bactericidal response against two of the four MAC strains examined. CONCLUSION: According to this human alveolar macrophage model of MAC infection, KRM and RBT in combination with CLA was found to be a premising candidate against human pulmonary MAC infection, and deserves clinical evaluation.
  • 鈴木克洋; 露口一成; 松本久子; 新実彰男; 田中栄作; 村山尚子; 網谷良一; 久世文幸
    結核 72 4 187 - 192 1997年04月 [査読有り]
     
    Fifty six clinical isolates of Mycobacterium tuberculosis were tested for drug susceptibility in Mycobacteria Growth Indicator Tube (MGIT) containing 0.1μg/ml of INH, 1.0 μg/ml of RFP, 3.5μg/ml of EB and 0.8μg/ml of SM. These results were compared with those obtained by testing the same M. tuberculosis isolates by the absolute concentration method using 1% Ogawa egg slant containing 0.1μg/ml of INH, 10μg/ml of REP, 2.5 μg/ml of EB and 20μg/ml of SM. Fifty six isolates consisted of 18 pansensitive strains, 27 multidrug resistant strains and 11 single drug resistant strains. The results for individual drugs showed excellent agreement between the MGIT and the Ogawa methods, and overall agreement rate of the two methods were 96.4%. The results were just the same for all drugs in 48 out of 56 strains studied. The drug resistance could be observed much earlier by the MGIT method (mean 5.9 days) than by the Ogawa method (more than 21 days). In conclusion, the MGIT system could be a promising new drug susceptibility test which might become available in Japan replacing the Ogawa method.
  • 高倉俊二; 田中栄作; LEE W J; 松本久子; 露口一成; 新実彰男; 鈴木克洋; 村山尚子; 久世文幸
    結核 72 1 15 - 20 1997年01月 [査読有り]
     
    We reported 2 cases of Mycobacterium avium complex lung disease occurred in middle-aged women without underlying disorders, which we could observe for more than 30 years. One case was a 42-year-old woman started with bloody sputum, and the other was a 43-year-old woman with cough and sputum. In both cases, chest X ray films were normal on their first visit. More than 15 years after their first visit, Mycobacterium avium complex was isolated from their sputum or bronchial washing. During the observation, a cluster of small nodules in the periphery of the lung and bronchiectasis appeared and deteriolated, and excretion of the bacilli increased gradually. Their past history and family history were normal. Since lung disease caused by Mycobacterium avium complex progresses very slowly, long time observation would be necessary to consider its pathogenesis.
  • 新実 彰男; 網谷 良一; 松本 久子; 久世 文幸
    気管支学 19 6 500 - 501 特定非営利活動法人 日本呼吸器内視鏡学会 1997年
  • 松本久子; 長谷川幹; 石原享介
    日本臨床 54 11 2998 - 3003 1996年11月
  • 冨岡洋海; 石原享介; 松本久子; 長谷川幹; 岡崎美樹; 片上信之; 坂本広子; 三浦昌生; 梅田文一
    呼吸 15 4 455 - 460 1996年04月
  • H. Matsumoto; R. Amitani; S. Watanabe; Woon Joo Lee; A. Niimi; T. Tsuboi; K. Chin; M. Ohi; S. Nakamura; H. Kuze
    Japanese Journal of Thoracic Diseases 34 9 997 - 1002 1996年 [査読有り]
     
    A 52-year-old man have been asymptomatic except for nasal speech since his third decade of life. A chest roentgenogram obtained during a health screening one year before admission revealed elevation of the right hemidiaphragm and infiltrates in the right lower lung field. Because the pulmonary shadows had gradually increased, he was admitted to the hospital, for further examination. Based on physiological findings and on the results of electromyography, myotonic dystrophy was diagnosed. The chest roentgenographic abnormalities were regarded as resulting from complications of this disease. Arterial blood gas analysis showed hypercapnic hypoxia and a spirogram showed that the vital capacity and maximum voluntary ventilation were about half of their respective predicted values. The hypercapnic ventilatory response was also abnormally low. An overnight study of oxygen saturation showed episodes of marked desaturation, and polysomnography revealed central sleep apnea. Inhalation of capsaicin showed an abnormally high cough threshold. Patients with undiagnosed myotonic dystrophy rarely present with chest roentgenographic abnormalities.
  • 松本久子; 石原享介; 藤井宏; 羽白高; 渡辺勇夫; 西村尚志; 岡崎美樹; 長谷川幹; 梅田文一
    日本胸部疾患学会雑誌 34 8 937 - 942 1996年 [査読有り]
     
    A 73-year-old woman with diabetes mellitus and hypothyroidism had been well until 4 days before she presented with fever, productive coughing, and general malaise. Dyspnea gradually worsened, and she was admitted to Kobe City General Hospital. She appeared toxic and was in moderate respiratory distress on admission. There were scattered rales in both lung fields. The abdomen was soft with no tenderness. A chest roentgenogram showed peripheral infiltrates in both lung fields. Arterial blood gas analysis showed a PO2 of 48.6 Torr and a PCO2 of 27.2 Torr. A blood culture on admission showed Escherichia coli. Computerized tomography of the chest showed multiple nodules of various sizes in the peripheral lung fields. Some nodules had necrotic centers and feeding vessels. Wedge-shaped lesions abutting the pleura were also seen. These findings strongly suggested septic pulmonary emboli. An abscess in the left kidney, which was considered to be source of the septic pulmonary emboli, was found with Ga scintigraphy, ultrasonography, and computerized tomography of the abdomen. Treatment with antibacterial drugs was effective against the lung lesions but not the renal abscess. A left nephrectomy was done. In the proper clinical setting, characteristic CT features emboli can contribute to early diagnosis of this disease.
  • 松本久子; 石原享介; 渡辺勇夫; 羽白高; 西村尚志; 岡崎美樹; 長谷川幹; 片上信之; 梅田文一
    月刊アレルギーの臨床 191 416 - 419 1995年06月
  • 松本久子; 片上信之; 渡辺勇夫; 羽白高; 西村尚志; 長谷川幹; 岡崎美樹; 石原享介; 梅田文一
    日本胸部疾患学会雑誌 33 11 1319 - 1324 1995年 [査読有り]
     
    From 1983 to 1993, we performed ultrasonically guided percutaneous needle biopsies on 320 thoracic tumors. Of those, 77 tumors were smaller than 3 cm in diameter and were peripherally located adjacent to the chest wall (n = 71) or in the posterior mediastinum (n = 6). We evaluated the efficacy and safety of UGNB for diagnosing these small lesions. The mean tumor size was 2.0 ± 0.7 cm. Nine nodules were less than 1.0 cm in diameter, 38 were between 1.1 and 2.0 cm, and 30 were between 2.1 and 3.0 cm. Biopsies were done with a 17- gauge Trucut needle a 21-gauge needle was used to aspirate specimens for cytological study. A definitive diagnosis was made in 31 (77%) of 40 malignant lesions and in 19 (51%) of 37 benign lesions. Complications included pneumothorax (n = 5) and hemoptysis (n = 3), but no special medications were needed. Thus, real-time sonographic guidance is a safe, easy, and reliable biopsy method for small pulmonary and mediastinal nodules adjacent to the chest wall.
  • 長谷川 幹; 石原 享介; 西村 尚志; 松本 久子; 梅田 文一
    アレルギー 44 3 371 - 371 一般社団法人 日本アレルギー学会 1995年
  • 片上信之; 松本久子; 冨岡洋海; 岡崎美樹; 長谷川幹; 坂本広子; 西山秀樹; 乾宏行; 坂東憲司
    癌と化学療法 22 4 531 - 537 1995年 
    Forty-two patients with stage IIIA (bronchoscopically T3 and/or bulky N2) and stage IIIB NSCLC were treated with concurrent chemoradiotherapy (CRT). Treatment consisted of CDDP, 20 mg/m2 and etoposide, 40 mg/m2 by continuous infusion (day 1-5) of weeks 1 and 5 simultaneously with chest radiotherapy (RT), 50 Gy, 2 Gy/Fx, 5 Fx/week. Surgery was attempted 3-5 weeks after RT in pts clinically downstaged. Between 10/90 and 12/92, 43 previously untreated pts were enrolled and 42 were eligible. Pts characteristics were: male/female = 37/5 mean age, 61 yrs (range, 31-74 yrs) stage IIIA/IIIB = 10/32 15 adenocarcinoma, 24 squamous cell, 2 large cell, 1 unclassified PS 0/1/2 = 11/24/7. Excluding 1 ineligible pts, 42 pts were evaluated for CRT response. The response rate was 81% (1 CR, 33 PR, 5 NC, 1 PD, 2 NE). Clinical downstaging was achieved in 20 pts (48%). Twenty-one pts (50%) received surgery and 19 of them were completely resected. In 7 resection specimens, no tumor was observed. Toxicity of CRT was well tolerable (Grade 4 leukopenia, 15% Grade 2-3 esophagitis, 15%). We conclude that this intensive combined modality therapy is acceptable and appears to increase the response rate as well as resectability. Prospective randomized studies should be conducted for further evaluation of this treatment modality.
  • 岡崎美樹; 渡辺勇夫; 羽白高; 松本久子; 片上信之; 石原享介; 梅田文一; 坂東憲司; 西山秀樹
    癌と化学療法 22 13 1987 - 1989 1995年
  • 片上信之; 松本久子; 石原享介; 梅田文一
    日本胸部疾患学会雑誌 33 11 1313 - 1318 1995年 
    We encountered two patients with typical bronchial carcinoid and metastases to the liver who presented with typical carcinoid syndrome. In typical bronchial carcinoid without metastases to regional lymph nodes, recurrence and distant metastasis after curative resection are generally thought to be rare. The first patient was a 62-year-old woman who was admitted to our hospital because of facial flushing and diarrhea. She had undergone curative resection of a typical bronchial carcinoid 9 years earlier, and the postsurgical pathological stage was I. On the second admission, she was found to have multiple liver metastases. The second patient was a 59-year-old woman who was admitted to our hospital because of facial flushing, dyspnea, and dehydration due to diarrhea. She had undergone curative resection of a typical bronchial carcinoid 21 months earlier, and the postsurgical pathological stage was I. On the second admission, she was found to have multiple intrabronchial, bone, and liver metastases. Both patients were treated with subcutaneous injections of octreotide, and with transhepatic arterial chemoembolization. In addition, the second patient underwent percutaneous ethanol injection under ultrasonic guidance. Signs and symptoms disappeared soon after therapy began and the patients survived longer than expected. Hepatic artery chemoembolization and simultaneous chemotherapy can relieve symptoms in patients with carcinoid syndrome and multiple liver metastases, and self-administration of octreotide is the treatment of choice for immediate relief.
  • 松本久子; 石原享介; 羽白高; 冨岡洋海; 岡崎美樹; 長谷川幹; 片上信之; 坂本広子; 高塚勝哉
    日本胸部臨床 53 9 764 - 768 1994年09月
  • 松本 久子; 石原 享介; 岡崎 美樹; 長谷川 幹; 坂本 廣子; 梅田 文一
    アレルギー 43 8 1051 - 1051 一般社団法人 日本アレルギー学会 1994年
  • 長谷川 幹; 石原 享介; 松本 久子; 坂本 廣子; 梅田 文一
    アレルギー 43 2 348 - 348 一般社団法人 日本アレルギー学会 1994年
  • 坂本広子; 石原享介; 羽白高; 松本久子; 冨岡洋海; 岡崎美樹; 長谷川幹; 片上信之; 梅田文一
    日本胸部疾患学会雑誌 32 6 561 - 565 1994年 
    As an initial investigation to determine whether or not inhaled corticosteroids can be discontinued, we evaluated the results of discontinuation in patients who had been well controlled with inhaled corticosteroids for more than one year prior to this study. The average dose of BDP which the patients had been inhaling at the start of this study was 365 μg/day. To determine the effect of discontinuing inhaled corticosteroids, we compared the patients' peak expiratory flow rates and the frequency of beta-agonist use between the 4-week observation period and follow-up periods of varying duration. Only three out of twenty patients enrolled were able to maintain their discontinuation of BDP, while the remaining seventeen patients restarted after a mean period of 30.8 days. Mean peak flow values began to fall during the first week after discontinuation, and decreased morning peak flow values became significant in the 2nd, 3rd and 4th weeks. The mean peak flow value during the observation period was 85.2% of each patient's personal best, but had dropped to 68.8% of this level just before restarting inhaled corticosteroid. The frequency of beta-agonist use during the study period (2.99 ± 3.39 times a day) was significantly higher than during the observation period (1.94 ± 2.95 times a day). This finding strongly suggests that the patients' asthmatic conditions had become unstable during the study period. These results suggest that any decision to discontinue the use of inhaled corticosteroid, even in well controlled patients with chronic asthma, should be taken with great care.
  • 長谷川幹; 石原享介; 松本久子; 冨岡洋海; 岡崎美樹; 片上信之; 坂本広子; 梅田文一; 片山覚
    日本胸部疾患学会雑誌 32 8 757 - 762 1994年 
    We examined HPA axis function using a short tetracosactrin test in 94 asthmatics treated with three different modalities. The first group, (B+S), consisted of 41 patients taking BDP (910±320 μg, daily) plus a short term burst of oral steroids (20-40 mg daily, 3-7 days/course, 1-18 courses/year). The second group, (B+R), consisted of 19 patients taking BDP (1076±410 μg, daily) plus continuous oral steroids (2.5-20 mg/day for 1.8-24 years). The third group, (B alone), consisted of 34 patients taking BDP only (615±258 μg, daily). All patients had been inhaling BDP for more than 1 year. The rise in cortisol in response to tetracosactrin in B+S, B+R, and B alone was 12±4.3 μg/dl, 7.0±5.0 μg/dl and 14±4.5 μg/dl, respectively, and achieved cortisol was 21±4.5 μg/dl, 12±7.2 μg/dl and 23±4.2 μg/dl, respectively. Both values were significantly lower in the B+R group than in either B+S or B alone. However, there was no difference between B+S and B alone, although the BDP dose was significantly larger in the B+S group. Significant HPA axis suppression (rise in cortisol < 7 μg/dl and achieved cortisol < 18 μg/dl) was seen in 7 patients. Although HPA axis suppression was more frequently seen in B+R (10/19), no significant difference was seen between B+S and B alone (4/41 and 1/34, respectively). There was no correlation between response to ACTH and frequency of a short term burst of oral steroids. In conclusion, BDP plus a short term burst of oral steroids is as safe as BDP alone, and is a useful treatment strategy for patients with chronic asthma.
  • 杉田孝和; 松永和人; 岡崎美樹; 松本久子; 縄田隆平; 坂東憲司; 望月吉郎; 乾宏行; 南方良章
    癌と化学療法 21 14 2479 - 2483 1994年 
    The efficacy of continuous five-day intravenous infusion of cisplatin (CDDP) and etoposide with concurrent chest radiation therapy was evaluated in patients with limited stage small cell lung cancer. The first group of patients registered from February 1989 to September 1990 received three courses of chemotherapy (CDDP 20 mg/m2/day x 5 days, etoposide 40 mg/m2/day x 5 days) and concurrent chest radiation therapy on the third course with dose reduction of etoposide. The second group of patients registered after February 1991 received four courses of chemotherapy (CDDP 20 mg/m2/day x 5 days, etoposide 50 mg/m2/day x 5 days) and concurrent chest radiation therapy on the first and second courses with dose reduction of etoposide. The response rates were 91.7% and 93.3% respectively. The median duration of survival was 32.0 months and 20.1 months, respectively. Major toxicity was leukocytopenia and 64% and 80% of patients encountered leukocytopenia of Grade 3 or 4. In conclusion these regimens show remarkable efficacy with acceptable toxicity.
  • 岡崎美樹; 松本久子; 冨岡洋海; 長谷川幹; 片上信之; 坂本広子; 石原享介; 梅田文一; 日野恵
    日本胸部疾患学会雑誌 32 11 1104 - 1108 1994年 
    Chest radiography of a 73-year-old man with upper abdominal pain showed hypercalcemia and an upper mediastinal mass. Functional mediastinal parathyroid adenoma was diagnosed, because of abnormally high levels of PTH in his serum and in fluid collected by transtracheal needle aspiration from the mediastinal mass. We resected the adenoma operatively. It is a cystic tumor located behind the superior vena cava and the trachea. The inferior end of the tumor was as low as the aortic arch, and superiorly the tumor was attached to the inferior pole of the thyroid gland by a vascular pedicle. Histologically adenoma cells were predominant. This tumor was a mediastinal parathyroid adenoma by location, but because it was attached to the thyroid gland superiorly, it may have originated from the superior parathyroid gland and then descended because of its weight into the posterior superior mediastinum. Thus, it cannot be considered an ectopic parathyroid adenoma in origin. Mediastinal parathyroid adenoma is a rare disease, and these tumors are usually so small that correct localization ot the adenoma is often difficult even by CT scan or scintigram. This is the first reported case of a mediastinal parathyroid adenoma that appeared as a mediastinal mass on a plain chest radiography and in which the level of PTH in the fluid collected from the mass by transtracheal needle aspiration was high.
  • 長谷川幹; 松本久子; 冨岡洋海; 岡崎美樹; 片上信之; 坂本広子; 石原享介; 梅田文一
    日本胸部疾患学会雑誌 32 11 1125 - 1130 1994年 
    We report a case of sarcoidosis with mediastinal and abdominal lymph node involvement presenting as multiple high-density masses on chest and abdominal CT. The patient was a 43-year-old housewife who came to our hospital because of a dry cough and exertional dyspnea. A chest radiograph showed bilateral diffuse reticulo-nodular shadows and widening of the mediastinum. On CT of the chest and the abdomen, lymph nodes were swollen throughout the mediastinum and the para-aortic area of the abdomen. They appeared as very-high-density masses on plain CT. Bronchoscopy revealed involvement of the bronchial walls. Punch biopsy of the bronchial wall, TBLB, and biopsy of the anterior mediastinal lymph node all revealed non-caseous epithelioid cell granulomas. These granulomas contained lamellated, irregularly shaped and darkly-stained structures (Schaumann bodies) that caused the high density of the involved lymph nodes on CT. This case shows at least a part of the mechanism of calcification of lymph node lesions in patients with sarcoidosis.
  • 松本久子; 石原享介; 羽白高; 冨岡洋海; 岡崎美樹; 長谷川幹; 坂本広子; 梅田文一; 日野恵
    日本胸部疾患学会雑誌 32 10 970 - 976 1994年 
    Inhaled steroids are currently the first-line treatment of chronic asthma. Because each metered dose of beclomethasone dipropionate (BDP) is small (50 μg), short term burst or continuous use of oral steroids are combined in moderately to severely asthmatic patients. The effect of these treatments on bone metabolism remains unclear. Bone mineral density (BMD), osteocalcin (OC), PTH, Ca, and ALP were assessed in 130 asthmatic patients. There were 3 groups: the first group [B + R] consisted of 17 patients taking BDP (1190±536 μg/day) and also taking oral steroids (8.0±3.8 mg/day, 8.11±5.52 years), the second group [B + S] had 35 patients taking BDP (885±320 ±g/day) and short-term bursts of oral steroids (PSL 20-40 mg/day, 3-7 days/course, 7.51±4.54 courses/year) and the third group [B alone] consisted of patients who were taking BDP (480±260 μg/day) alone. BMD was measured by dual energy X-ray absorptiometry (DEXA). In the [B + R], [B + S], and [B alone] groups, the BMD of vertebra (L 1-4) was 0.75, 0.86, and 0.90 g/cm2, respectively. The percentages of predicted values based on age and sex were 92.0, 102.7, and 106.9% respectively. BMD and percent decrease were significantly lower in the [B + R] group than in the [B + S] or [B alone] group. It is likely that this phenomenon is caused by long-term use of oral steroids rather than by BDP inhalation but there is no significant difference between the [B + S] and the [B alone] groups. Daily BDP dose did not correlate with BMD by multiple regression analysis. There were no significant differences in OC, PTH, Ca or ALP among the three groups. The results show that BDP and short-term bursts of oral steroids can be used safely, though longitudinal studies are needed.
  • 長谷川幹; 石原享介; 坂本広子; 松本久子; 冨岡洋海; 岡崎美樹; 片上信之; 石井昌生; 五十嵐哲也
    日本呼吸管理学会誌 3 2 85 - 90 1993年12月
  • 石原享介; 長谷川幹; 松本久子; 岡崎美樹; 片上信之; 坂本広子; 梅田文一; 楠由美子; 竹下勇雄
    日本呼吸管理学会誌 3 2 106 - 108 1993年12月

書籍

  • Periostin
    Hisako Matsumoto (担当:分担執筆範囲:Roles of periostin in asthma)Springer 2019年
  • Advances in Asthma-pathophysiology, diagnosis and treatment
    Hisako Matsumoto (担当:分担執筆範囲:Treatment with Anti-IgE monoclonal antibody and free IgE. How effective is the treatment with anti-IgE antibody for asthma?)Springer 2018年
  • Calcium Signaling In Airway Smooth Muscle Cells
    Hisako Matsumoto (担当:分担執筆範囲:Effects of inflammatory cytokines on Ca2+ homeostasis in airway smooth muscle cells)Springer 2013年

講演・口頭発表等

  • 重症喘息におけるIgEの役割  [招待講演]
    松本久子
    第62回日本呼吸器学会中国・四国地方会 2019年11月
  • Moving toward precision medicine in severe difficult asthma; a role of serum periostin  [招待講演]
    Hisako Matsumoto
    Korean Academy of Tuberculosis nad Respiratory Diseases (KATRD) Internatinal Conference 2019 2019年11月 口頭発表（招待・特別）
  • 軽症～重症喘息患者の病態・診断・治療について  [招待講演]
    松本久子
    第93回日本呼吸器学会近畿地方会 2019年07月
  • Establishment of precision medicine for asthma using its endotypes.  [招待講演]
    松本 久子
    European Academy of Allergy and Clinical Immunology 2019年06月 シンポジウム・ワークショップパネル（指名）
  • Management of seveasthma using biologics with greater precision.  [招待講演]
    松本 久子
    Asian Pacific Society of Respirology 2018年11月 シンポジウム・ワークショップパネル（指名）
  • 成人喘息と関連疾患の管理  [招待講演]
    松本 久子
    第53回日本アレルギー学会専門医認定教育セミナー 2018年06月 公開講演，セミナー，チュートリアル，講習，講義等
  • 喘息の病態と治療～眼科疾患との関わりを含めて～  [招待講演]
    松本 久子
    第6回日本眼科アレルギー講習会 2017年09月 公開講演，セミナー，チュートリアル，講習，講義等
  • 重症難治性喘息への挑戦～病態解析から得られたもの、そうでないもの～  [招待講演]
    松本 久子
    第79回日本呼吸器学会・日本結核病学会・日本サルコイドーシス/肉芽腫性疾患学会 九州支部秋季学術講演会 2017年09月 公開講演，セミナー，チュートリアル，講習，講義等
  • 2型炎症反応を中心とした成人喘息におけるバイオマーカー  [通常講演]
    松本 久子
    第66回日本アレルギー学会学術大会 2017年06月 シンポジウム・ワークショップパネル（指名）
  • 慢性咳嗽の治療戦略  [通常講演]
    松本 久子
    第65回日本アレルギー学会 2016年06月 シンポジウム・ワークショップパネル（指名）
  • 喘息患者の層別化管理  [通常講演]
    松本 久子
    第65回日本アレルギー学会 2016年06月 公開講演，セミナー，チュートリアル，講習，講義等
  • Serum Periostin: A Key Marker to Dissect the Pathophysiology of Type-2 Predominant Asthma  [通常講演]
    松本 久子
    American Thoracic Society 2016 2016年05月 シンポジウム・ワークショップパネル（指名）
  • 難治性喘息の個別化治療：新規抗喘息薬の有用性と展望 抗IgE抗体  [通常講演]
    松本 久子
    第56回日本呼吸器学会学術講演会 2016年04月 シンポジウム・ワークショップパネル（指名）
  • 成人喘息治療の現状と課題 ～重症喘息から咳喘息まで～  [通常講演]
    松本 久子
    第86回日本呼吸器学会地方会教育講演 2015年12月 公開講演，セミナー，チュートリアル，講習，講義等
  • 喘息のバイオマーカー 血液中の指標  [招待講演]
    松本 久子
    第2回総合アレルギー講習会 2015年12月 公開講演，セミナー，チュートリアル，講習，講義等
  • Roles of biomarkers of type 2 inflammation in the management of asthma  [招待講演]
    松本 久子
    The 25th Congress of Interasma Japan/North Asia 2015年09月 シンポジウム・ワークショップパネル（指名）
  • 重症喘息の病態と治療 基礎から最新の知見まで  [招待講演]
    松本 久子
    第55回臨床呼吸機能講習会ランチョンセミナー 2015年08月 公開講演，セミナー，チュートリアル，講習，講義等
  • Anti-IgE antibody against severe allergic asthma: effectiveness and its predictive markers  [招待講演]
    松本 久子
    The 43rd Hakone Symposium on Respiration 2015年06月 シンポジウム・ワークショップパネル（指名）
  • 松本久子
    第64回日本アレルギー学会学術大会 2015年05月 シンポジウム・ワークショップパネル（指名）
  • 松本久子
    第55回日本呼吸器学会学術講演会 2015年04月 シンポジウム・ワークショップパネル（指名）
  • 成人喘息発症の機序-咳喘息からの移行を含めて  [招待講演]
    松本 久子
    小児気道アレルギーフォーラム 2014年06月 口頭発表（招待・特別）
  • 松本久子
    第26回日本アレルギー学会春季臨床大会 2014年05月 シンポジウム・ワークショップパネル（指名）
  • 松本久子
    第26回日本アレルギー学会春季臨床大会 2014年05月 シンポジウム・ワークショップパネル（指名）
  • 気管支喘息における呼吸機能イメージング  [通常講演]
    松本 久子
    第6回呼吸機能イメージング研究会学術集会 2014年01月 シンポジウム・ワークショップパネル（指名）
  • 喘息管理における血清ぺリオスチン測定の有用性について-KiHAC多施設共同研究結果を含めて  [通常講演]
    松本 久子
    第63回日本アレルギー学会秋季学術大会 2013年11月 シンポジウム・ワークショップパネル（指名）
  • 松本久子
    第63回日本アレルギー学会秋季学術大会 2013年11月 シンポジウム・ワークショップパネル（指名）
  • Serum periostin, a promising biomarker, in the management of asthma-Observations from KiHAC multicenter study-  [通常講演]
    松本 久子
    第23回国際喘息学会日本・北アジア部会 2013年09月 シンポジウム・ワークショップパネル（指名）
  • 金光禎寛; 松本久子
    日本小児アレルギー学会 2013年09月 シンポジウム・ワークショップパネル（指名）
  • 松本久子
    第53回日本呼吸器学会学術講演会 2013年04月 シンポジウム・ワークショップパネル（指名）
  • Allergenとasthmagen:咳喘息から高齢者喘息まで  [通常講演]
    松本 久子
    第38回佐島シンポジウム 2011年06月 シンポジウム・ワークショップパネル（指名）
  • Therapeutic strategies targeting inflammatory cells- Altered properties of airway smooth muscle in asthma.  [通常講演]
    松本 久子
    第59回日本アレルギー学会秋季学術大会 international symposium 2009年10月 シンポジウム・ワークショップパネル（指名）
  • 松本久子
    第59回日本アレルギー学会秋季学術大会 2009年10月 シンポジウム・ワークショップパネル（指名）
  • 咳喘息における吸入アレルゲンへの感作について-咳喘息、典型的喘息間での比較  [通常講演]
    松本 久子
    第54回日本アレルギー学会秋季学術大会 2004年11月 シンポジウム・ワークショップパネル（指名）
  • 咳喘息から喘息への移行に対する早期導入  [通常講演]
    松本 久子
    第16回日本アレルギー学会春季臨床大会 2004年05月 シンポジウム・ワークショップパネル（指名）
  • Step downはどうするか  [通常講演]
    松本 久子
    第15回日本アレルギー学会春季臨床大会 2003年05月 シンポジウム・ワークショップパネル（指名）

作品等

  • 気管支喘息の病態に関連する遺伝子の研究
    2002年

MISC

受賞

  • 2022年 Best Doctors in Japan 2022-2023 Best Doctors, Inc.
     
    受賞者: 松本久子
  • 2020年 Best Doctors, Inc. Best Doctors in Japan 2020-2021
     
    受賞者: 松本久子
  • 2019年 日本呼吸器学会 平成30年度日本呼吸器学会熊谷賞
     
    受賞者: 松本久子
  • 2015年 日本内科学会 第112回医学生・研修医の“日本内科学会ことはじめ” 指導教官賞
     
    受賞者: 松本久子
  • 2013年 第22回Pneumo Forum賞
     
    受賞者: 松本久子
  • 2011年 臨床喘息研究会 第19回臨床喘息研究会最優秀賞
     
    受賞者: 松本久子
  • 2011年 藤原記念財団 平成23年度少壮研究者奨励金
     
    受賞者: 松本久子
  • 2010年 日本アレルギー学会 第6回日本アレルギー学会学術大会賞
     
    受賞者: 松本久子
  • 2001年 ２００１年度アストラゼネカ喘息研究奨励助成
     JPN

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2022年04月 -2025年03月 
    代表者 : 松本 久子; 田辺 直也; 佐藤 晋; 西山 理; 佐野 安希子
     
    令和5年度は、喘息例での胸部CT所見（気管支拡張・細気管支炎像の有無，進展度）等と遺伝子多型との関係を中心に解析した。候補遺伝子としてびまん性汎細気管支炎や非若齢発症喘息のリスク遺伝子であり、分泌型ムチンをコードするHCG22遺伝子の一塩基多型（SNP）rs2523870に着目した。喘息106例において、rs2523870のgenotypeはTT 37名、CT 45名、CC 24名であった。リスクアレルのホモ接合体であるCC型と他との２群比較で、喘息発症年齢、呼吸機能、mReiff score(気管支拡張像の進展度)との関係はなかったが、CC型で好酸球性副鼻腔炎併存率、過去の血液好酸球数、過去の吸入ステロイド量、過去及び直近の胸部CTで細気管支炎罹患葉数が有意に多かった。IL4RA rs8832、IL13 rs20541についても解析を行ったが、mReiff scoreや細気管支炎の罹患葉数との関連は認めなかった。本研究でCC型での細気管支病変が、好酸球性か否かは確認できなかったが、好酸球性副鼻腔炎の併存率から推察すると一定の割合で好酸球性細気管支炎も存在すると考えられる。喘息の細気管支病変例で、好中球性気道炎症を呈するびまん性汎細気管支炎と同様のリスク多型が確認されたことは、分泌型ムチンの異常、気道クリアランスの障害が、炎症型を問わず細気管支病変の形成に寄与する可能性が推察される（J Allergy Clin Immunol 2023 Epub ahead of print）。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2019年04月 -2022年03月 
    代表者 : 松本 久子; 伊藤 功朗; 小熊 毅
     
    喘息合併を含む気管支拡張症例における喀痰中黄色ブドウ球菌の検出は、菌由来エンテロトキシン感作を中心としたアレルギー性炎症や好酸球性炎症と関連した。一方でアレルギー性炎症と好酸球性炎症の分布は同一でないことも示された。重症喘息を含む閉塞性気道疾患例において、γ-Proteobacteria綱、Haemophilus属の喀痰内高占有は、好中球性炎症のみならず中等度までの好酸球性/2型炎症（混合性炎症）や喀痰症状と関連した。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2018年04月 -2021年03月 
    代表者 : 平田 豊; 松本 久子
     
    IL-33は障害を受けた気道上皮から放出され、喘息における2型/好酸球性気道炎症において重要な役割を果たすが、IL-33の生理・病態的な産生メカニズムは不明な点が多い。 真菌・Alternariaの刺激によりPAR-2を介してIL-33を放出するin vivoの報告はあるが、その発現機序は不明である。YKL-40は喘息患者の喀痰中濃度が重症度、気道リモデリング、非2型気道炎症と相関することが自他の検討で報告されている。 本研究では、IL-33発現抑制を、レクチン・YKL-40の作用機序の観点から解明することを目的とする。得られた結果より、IL-33の産生メカニズムの解明、喘息での2型・非2型炎症の決定に重要な知見をもたらし、創薬につながると考えられる。 今年度、我々は、microRNAiにてYKL-40発現を抑制した気道上皮細胞において、IL-33発現の上昇を見出した。 更に、PAR-2を活性化する真菌・alternaria extractによるIL-33発現の増加をYKL-40が著しく抑制したことを見出した。これは、microRNAiにてPAR-2発現を抑制した気道上皮細胞ではIL-33の発現が増加した結果に一致した。従って、YKL-40によるIL-33発現抑制にPAR-2を介している経路が関与することが示唆された。この研究成果をWCP2018にて発表した。今後、PAR-2を介したIL-33発現抑制の経路にYKL-40がどのように関与するか等を検討する。
  • 日本学術振興会：科学研究費助成事業 基盤研究(B)
    研究期間 : 2017年04月 -2020年03月 
    代表者 : 陳 和夫; 松田 文彦; 田原 康玄; 松本 久子; 若村 智子
     
    1) ながはまコホートにおいて、肺機能と動脈硬化の指標である上腕-足首脈速度(baPWV)の継時的な情報（初回調査[I期]から再調査[II期]）を取得可能であった7523人を対象に、一秒量（FEV1）とbaPWVの経年的変化の関連を検討した。経年的FEV1の変化量は、%ΔFEV1= (II期FEV1 - I期FEV1)/追跡期間/I期FEV1×100として、経年的baPWVの変化量はΔbaPWV = II期baPWV-I期baPWVとして算出した。平均追跡期間は、1815±135日であった。平均経年的FEV1変化量は-34.0 ± 0.6 ml/年であった。%ΔFEV1とΔbaPWVは年齢・性別・喫煙・高血圧・糖尿病などの既知の動脈硬化に関与する因子で補正後も負の相関関係を認めた(β = -0.035、p = 0.0027) 2)コホートで得られた客観的な睡眠障害関連データを含む各種の臨床データと、質量分析による99種の代謝産物血中濃度(メタボローム)のデータを解析した(n = 6417)。正常群と中等症以上の睡眠呼吸障害合併群の比較でfold change>1.1かつP<0.05であった代謝産物は32種であった。これらの因子でKEGG pathway解析を行った結果、プリン代謝及びデンプン・ショ糖代謝経路の有意なenrichmentを認めた。これらの経路にある因子のうち、フルクトース・尿酸・ヒポキサンチンは、年齢・性別・合併症を補正した重回帰分析でも中等症以上のSAS合併と血中濃度上昇に有意な相関を認めた。中等症以上の睡眠呼吸障害はフルクトース代謝とプリン代謝経路に影響する可能性がある。 １）２）の結果を日本呼吸器学会にて報告した。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 松本 久子; 長崎 忠雄; 小熊 毅
     
    近年2型炎症喘息群のgeno-endo-phenotypeの解析は進んできたが、非2型炎症群についての知見は乏しい。本研究ではIL4RA, POSTNの遺伝子多型の一定の組み合わせにおいては、血清ペリオスチンが低値となること、そこにORMDL3のリスク遺伝子多型が加わることで、喘息増悪リスクがあがることを示した。増悪リスクのある非2型炎症群のgeno-endo-phenotypeを反映すると考えられる。
  • 日本学術振興会：科学研究費助成事業 基盤研究(A)
    研究期間 : 2015年04月 -2018年03月 
    代表者 : 三嶋 理晃; 瀬山 邦明; 半田 知宏; 平井 豊博; 金 永学; 佐藤 篤靖; 佐藤 晋; 伊藤 功朗; 長崎 忠雄; 堀田 秋津; 小熊 毅; 後藤 慎平; 室 繁郎; 松本 久子; 小笹 裕晃; 永井 宏樹; 陳 和夫; 浅香 勲; 谷澤 公伸
     
    ヒトiPS細胞は細胞株によって分化効率が異なり、応用研究における大きなハードルだったが、表面抗原Carboxypeptidase Mを利用して呼吸器上皮幹細胞を単離し、三次元培養を行なって分化促進することで、気道や肺胞上皮細胞に安定して効率よく分化誘導が可能となった。II型肺胞上皮細胞については長期培養も可能になり、線維芽細胞との共培養なしでも分化誘導が可能となった。これを用いて、iPS細胞由来のII型肺胞上皮細胞を免疫不全マウスにオルガノイドとして移植する方法の開発を進め、疾患モデリングについては薬剤性肺障害、気道疾患、肺線維症、肺がんに対する領域別の応用研究を進めた。
  • 気道細菌叢と感作に着目した閉塞性気道疾患の病態解析
    平成30年 日本呼吸器財団助成
    研究期間 : 2018年
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2013年04月 -2016年03月 
    代表者 : 松本 久子; 室 繁郎; 佐藤 篤靖
     
    喫煙喘息例の特徴である好酸球・2型炎症/好中球性炎症を惹起しうる因子に着目し、ブドウ球菌由来スーパー抗原（SE）への感作と禁煙後の炎症遷延との関係を臨床検体で明らかにした。一方SE刺激下気道平滑筋細胞でのサイトカイン発現に有意な変化はなく、この系でのエピゲノム解析候補サイトカイン同定は困難であった。次に2型炎症喘息例において、IL4Rα とADAM33 の多型が各々独立して高いodds比で増悪に寄与することが示された。特に後者は喫煙喘息に特徴的な混合性炎症と関連することが示された。臨床的寄与度の高いゲノム変化部位を同定し、効率的なエピゲノム解析の基盤形成に寄与したと言える。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2011年04月 -2016年03月 
    代表者 : 新實 彰男; 松本 久子; 伊藤 功朗; 小栗 鉄也
     
    典型的喘息と咳喘息という表現型を規定する因子の追求を目的とした。両疾患が全国のアレルギー専門施設で慢性咳嗽患者の70%以上を占めること(J Asthma 2013)、典型的喘息で咳喘息に比しアレルギー性鼻炎の合併頻度が有意に高いが、気道炎症や重症度への鼻炎の寄与は同様であること(Respiration 2014)、咳喘息における抗ロイコトリエン薬の有用性(Respiration 2012)と咳を生じるトリガーの特徴(Allergol Int 2012)、喘息性咳嗽における好酸球性炎症の重要性(Lung 2014)と消化管運動不全の寄与(Allergol Int 2016)について成果を挙げた。
  • 日本学術振興会：科学研究費助成事業 基盤研究(A)
    研究期間 : 2010年04月 -2015年03月 
    代表者 : 三嶋 理晃; 小川 恵美子; 瀬山 邦明; 半田 知宏; 平井 豊博; 伊藤 功朗; 室 繁郎; 松本 久子; 平家 俊男; 陳 和夫; 星野 勇馬; 新実 彰男
     
    ヒトiPS/ES細胞を分化させ肺胞前駆細胞を誘導しその過程でCarboxypeptidase M (CPM)が有用な表面蛋白質であることを見出した。また肺胞を作るのに不可欠なII型肺胞上皮細胞の分化誘導のため、この細胞に特異性の高いSurfactant Protein C(SPC)のレポーターiPS細胞を作成した。さらにCPMを使って単離した肺胞前駆細胞を3次元培養することでSPC陽性かつ電顕でlamellar body様構造がみられる肺胞上皮細胞を分化誘導しレポーター細胞用いてこれらの細胞を単離できた。また複数種の疾患患者細胞から疾患特異的iPS細胞を作成した。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2010年 -2012年 
    代表者 : 松本 久子; 伊藤 穣; 平田 豊; 越久 仁敬
     
    非好酸球性気道炎症下での気道リモデリング形成の機序には不明な点が多い。気道上皮細胞、好中球・マクロファージから産生されるキチナーゼ関連蛋白質 YKL-40は、加齢関連蛋白質としても知られるが、本検討において、気道平滑筋細胞増殖を促進し、細胞外基質の組成を変化させる可能性が示された。 高齢喘息や COPD の気道病態、特にステロイド低感受性の非好酸球性気道炎症下リモデリング形成において YKL-40 の関与が示唆された。
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2003年 -2004年 
    代表者 : 三尾 直士; 松本 久子
     
    呼気凝集液は非侵襲的に得られる臨床検体であり、近年喘息・COPDなど多くの呼吸器疾患において研究および臨床上の有用性が検討されつつある。本研究では呼気凝集液の肺癌患者の診療における有用性を検討することを目的として、呼気凝集液中の腫瘍マーカー、サイトカイン、Prostanoidsの測定を試みた。 また、呼気凝集液をベッドサイドにおいても採取できるように採集器を開発した。それを用いて、23例の肺癌担癌患者より採取した。また健常ボランティア10名からも同様に採取して対照とした。腫瘍マーカーとしてはCEA, SLX, CA19-9, CYFRA, ProGRP, NSEを血清中の値が上昇している患者よりの検体で検出を試みたが検出できなかった。サイトカインとしては炎症・線維化に関与すると考えられるIL-1β, IL-6, IL-8, TGFβを測定したが、同様に測定できなかった。ProstanoidsとしてはPGE_2, LTB_4の測定を試み、一部の症例で測定可能であったが、測定値は測定限度下限程度であり、臨床上の所見との比較が行える程度ではなかった。 以上から呼気凝集液中の高分子量の腫瘍マーカー物質・サイトカインなどの測定は通常の方法では難しいと考えられた。より低分子量のProstanoidsに関してはより高感度な検出法をもちたり、検体を濃縮することにより測定ができる可能性が考えられる。今後は低分子量物質を中心に臨床検体として同様に非侵襲的に得られる誘発喀痰などとの臨床症状の有用性に関する比較が必要であると考えられた。
  • 日本学術振興会：科学研究費助成事業 若手研究(B)
    研究期間 : 2003年 -2004年 
    代表者 : 松本 久子
     
    本研究は慢性咳嗽例において、誘発痰上清、呼気凝集液中のヒスタミンを含む炎症性メディエーター、神経ペプチドの濃度を測定し、原因疾患、治療への反応性などの臨床所見との関係を検討するとともに、気道上皮内、直下の肥満細胞について検討を加え、慢性咳嗽の病態解明を目指すものである。 平成16年度は慢性咳嗽31例において、最も侵襲が少なく、全例で検体採取可能な呼気凝集液を用いてヒスタミン、神経ペプチド、炎症性メディエーターなどの測定を行った。ヒスタミン、PGE2は測定可能であり、健常人と比べ高値をとる傾向はみられたが、現在のところ原因疾患別での差、治療への反応性等との関連は検出されていない。今後症例数を加え検討を続ける予定である。また咳喘息6例において、気管支粘膜組織(4μm厚)の上皮内、直下の肥満細胞、及び誘発喀痰中肥満細胞をAntimast cell tryptase monoclonal antibodyを用いて染色し定量化を試みたが、いずれも陽性細胞が少なく、他の病理所見、カプサイシン咳閾値等の臨床パラメーターとの関連の検討は不能であった。尚、気道粘膜組織は得られていないが、咳喘息21例、非喘息性慢性咳嗽18例、健常人15例において、ヘリカルCTを用いて中枢気道壁厚を定量解析し、気道過敏性、カプサイシン咳閾値との関連を検討したところ、慢性咳嗽例では健常人に比し有意に気道壁が肥厚していた。また咳喘息では気道感受性と肥厚の程度が有意な正の相関を示し、非喘息性慢性咳嗽では咳閾値と肥厚の程度が正の相関をとる傾向が示されており、気道壁肥厚が咳嗽の病態に関連していることが明らかになった。肥厚の程度と呼気凝集液中のヒスタミン濃度などとの関連を検討中である。
  • 感作ラットの気道に対する長期抗原暴露と喫煙の影響
    2004 AstraZeneca Research Grant
    研究期間 : 2004年 
    代表者 : 松本久子
  • 動的CT撮影により評価した気道壁肥厚の質と喘息の病態の関連
    2001年度アストラゼネカ喘息研究奨励助成
    研究期間 : 2001年 
    代表者 : 松本久子
  • 気管支喘息の気道壁ﾘﾓﾃﾞﾘﾝｸﾞにおけるマトリックスメタロプロテアーゼおよびその阻害因子の関与
    2000年度アストラゼネカ喘息研究奨励助成
    研究期間 : 2000年 
    代表者 : 松本久子
  • 喘息、咳嗽
    民間学術研究振興費補助金
    研究期間 : 1999年
  • 日本の重症喘息患者における疾病負担および疫学研究
    代表者 : 松本久子

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