気道へ浸潤した好酸球の喘息病態における生体内役割

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1327号，学位授与年月日：平成10年9月2日,学位授与年：199

Phosphodiesterase 3 inhibition and cough in elderly asthmatics

AIMS: Cough is a common symptom of bronchial asthma, a chronic inflammatory airway disease. Recently, the therapeutic effects of selective phosphodiesterase (PDE) inhibitors have been focused on bronchial asthma. This study was designed to investigate the clinical effect of PDE 3 inhibition on cough reflex sensitivity in elderly patients with bronchial asthma. METHODS: Effects of cilostazol, a PDE 3 inhibitor, on cough response to inhaled capsaicin were examined in 11 patients over 70 years with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. RESULTS: The cough threshold was significantly (p < 0.05) increased after two-week treatment with cilostazol (100 mg twice a day orally) compared with placebo [48.8 (GSEM 1.4) vs. 29.2 (GSEM 1.3) μM]. CONCLUSION: These findings indicate that PDE 3 inhibition may be a novel therapeutic option for elderly patients with asthma, especially for their cough symptoms

Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway

金沢大学大学院医学系研究科機能再生学Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold was significantly (p < 0.05) decreased after two weeks of treatment with beraprost [17.8 (GSEM 1.20) μM] compared with placebo [30.3 (GSEM 1.21) μM]. PGI2 increases cough reflex sensitivity of the asthmatic airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for patients with asthma, especially cough predominant asthma

Asthma exacerbations after the East Japan Disaster

On March 11, 2011, a 9.0-magnitude earthquake struck east Japan, following tsunami. Many people are forced to live in evacuation shelters without enough life-saving drugs. Asthma control for management of health crisis is required, because asthma exacerbation is a major cause of morbidity, can need acute care and results in death. However, it remains obscure what parameter should be used in primary clinic of evacuation shelters. The objective of this study is to elucidate the practical efficacy of asthma assessment tool in primary clinic for victims of this disaster. Asthma control test (ACT), a brief and patient-based tool to evaluate asthma control, was conducted for 17 patients with asthma in evacuation shelters at Tohoku district. Total sum of ACT scores were significantly decreased after this disaster. Significant decreases were observed for the items ; “Asthma keeps you from getting much done at work”, “Shortness of breath”, “Asthma symptoms wake you up” and “Patient rating of control”. ACT, an easy and practicable tool, clearly demonstrated the asthma exacerbation in evacuation shelters without the use of lung function testing. ACT may contribute to the management of health crisis not only for this East Japan disaster but also for the other forthcoming unavoidable disasters

Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs

BACKGROUND: Late asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs. Although cough reflex sensitivity is increased after antigen challenge in actively sensitized guinea pigs, it is unknown whether the antigen-induced increase in cough reflex sensitivity develops in passively sensitized animals. The aim of this study was to compare the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs. METHODS: Measurement of number of coughs elicited by increasing concentrations of capsaicin (10(-6 )and 10(-4 )M) and bronchial responsiveness to ascending concentrations of methacholine, and analysis of bronchoalveolar lavage fluid (BALF) were separately performed 24 h after an antigen challenge in actively and passively sensitized guinea pigs. RESULTS: Percentage of eosinophils in BALF and bronchial responsiveness to methacholine were increased 24 h after the antigen challenge in both actively and passively sensitized animals compared with saline-challenged actively and passively sensitized animals, respectively. Absolute number of eosinophils in BALF from actively sensitized and antigen-challenged guinea pigs was significantly greater than that from passively sensitized and antigen-challenged animals. Cough response to capsaicin and concentration of substance P in BALF were increased 24 h after the antigen challenge in actively sensitized guinea pigs, but not in passively sensitized guinea pigs. Bronchial responsiveness, cough reflex sensitivity and substance P concentration and total cells in BALF were increased in actively sensitized and saline challenged guinea pigs compared with passively sensitized and saline challenged animals. CONCLUSION: The results suggest that active sensitization per se increases cough reflex sensitivity accompanied by increased inflammatory cells and substance P level in BALF, and antigen challenge further increases them, while simple IgE- and/or IgG-mediated allergic reaction per se or the low intensity of eosinophil infiltration in the airway itself may not affect cough reflex sensitivity in guinea pigs

The measurement of cough response to bronchoconstriction induced by methacholine inhalation in healthy subjects: An examination using the Astograph method

Background: We demonstrated that heightened cough response to bronchoconstriction is a fundamental feature of cough variant asthma (CVA). To evaluate this physiological feature of CVA in daily clinical practice, it is necessary to clarify the cough response to bronchoconstriction in healthy subjects. We evaluated cough response to methacholine (MCh)-induced bronchoconstriction in healthy subjects. A forced oscillometry technique was used to measure airway resistance changes with Mch. Methods: Healthy never-smokers (21 men, 20 women; mean 22.3 ± 3.7 years) participated. None had a >3-week cough history, clinically significant respiratory or cardiovascular disorders, or disorders that might put subjects at risk or influence the study results or the subjects’ ability to participate. Twofold increasing concentrations of Mch chloride diluted in phosphate-buffered saline (0.039 to 160 mg/mL) were inhaled from nebulizers at 1-minute intervals during subjects’ tidal breathing after the baseline respiratory resistance (Rrs) was recorded. Mch inhalation continued until Rrs reached twice the baseline value and forced expiratory volume in 1 second (FEV1) decreased to <90% of baseline value. Spirometry was measured before Mch inhalation and immediately after Rrs had increased twofold. Coughs were counted during and for 30 minutes after Mch inhalation. The cough reflex sensitivity to capsaicin was also examined. Results: The number of coughs was 11.1 ± 14.3 (median, 7.0; range, 0 to 71; reference range, 0 to 39.7). There was no significant difference in the cough response between the sexes. The reproducibility of the cough response to bronchoconstriction was sufficient. No correlation existed between the bronchoconstriction-induced cough response and capsaicin cough-reflex sensitivity. Conclusions: Using the Astograph method, cough response to bronchoconstriction could be measured easily, safely and highly reproducibly in healthy subjects. © 2017 Taylor & FrancisEmbargo Period 12 month