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論文
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Hara, Johsuke ; Fujimura, Masaki ; Ohkura, Noriyuki ; Sakai, Tamami ; Yamamura, Kenta ; Abo, Miki ; Koba, Hayato ; Watanabe, Satoshi ; Yoneda, Taro ; Nishikawa, Shingo ; Sone, Takashi ; Kimura, Hideharu ; Ishiura, Yoshihisa
概要:
Background: We demonstrated that heightened cough response to bronchoconstriction is a fundamental feature of cough vari
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ant 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 & Francis<br />Embargo Period 12 months
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論文
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Nakade, Yusuke ; Fujimura, Masaki ; Ohkura, Noriyuki ; Nakata, Masako ; Nanbu, Yuko ; Oe, Hiroyasu ; Horita, Hiroshi ; Sakai, Yoshio ; Wada, Takashi
概要:
Objective Partial expiratory flow-volume curves have the potential to detect mild bronchoconstriction because they are n
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ot affected by the modulatory effects of deep inspiration. The aim of this study was to investigate the relationship between the efficacy of bronchodilator therapy (BDT) in treating the cough and to assess the increase in the expiratory flow of the partial flow-volume curve at 40% above the residual volume level (PEF40) caused by treatment with a short-acting beta-2 agonist (SABA) in patients with chronic nonproductive cough. Methods We measured the reversibility of PEF40 caused by a SABA in 42 patients with chronic nonproductive cough at visit 1 (day 0). The patients received BDT for six days. The visual analogue scale (VAS) was used to assess the efficacy of BDT in treating coughing at visit 2 (day 7) (0 mm, 'no cough;' 100 mm, 'no change in coughing'). Results Reversibility of the PEF40 was correlated (r=0.690, p<0.001) with the VAS score determined at visit 2 and was higher in the patients with cough variant asthma (CVA) (44.9±18.3%) than in those with atopic cough (13.4±10.4%) (p<0.01). Conclusion Reversibility of the PEF40 predicted the efficacy of BDT in patients with chronic nonproductive cough and helped to identify patients with CVA.
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論文
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藤村, 政樹 ; Fujimura, Masaki
概要:
I.基礎的研究1.モルモットを用いてアトピー咳嗽と咳喘息それぞれの動物モデルの作成に成功した。1)アトピー咳嗽モデルに関する研究によって、咳感受性の亢進には、ニュートラルエンドペプチダーゼ活性の阻害によるサブスタンスPが重要な役割を担ってお
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り、ヒスタミンがサブスタンスPとの相互作用によって関与することが解明された。2)咳喘息モデルに関する研究によって、本モデルの抗原誘発咳嗽は気管支平滑筋収縮によって発生し、ロイコトリエンが関与するも、タキキニンは関与しないことが解明された。2.咳感受性に与える気道への機械的圧ストレスの影響咳発作を想定した気道への定量的圧負荷装置を開発し、気道への圧負荷が咳感受性を亢進させ、さらに気道への好中球浸潤を引き起こすことを発見した。すなわち、咳嗽発作が咳感受性性をさらに亢進し、好中球性気道炎症を惹起することによって、咳嗽と咳感受性亢進に増幅回路(悪循環回路)が形成されることが明かとなった。II.臨床的研究1.アトピー咳嗽と咳喘息は、生理学的および病理学的基本病態が異なることに加えて、予後も異なることを明らかにした。すなわち、咳喘息は数年の内に約30%の患者が喘息を発症するが、アトピー咳嗽は喘息を発症しないことが明かとなった。2.咳喘息から喘息を発症する危険因子が、気道過敏性亢進と長期吸入ステロイド療法を実施しないことの2つであることがわかった。3.慢性咳嗽の原因疾患の頻度多施設共同前向き研究によって検討した結果、慢性咳嗽の三大原因疾患は咳喘息、アトピー咳嗽、副鼻腔気管支症候群であることが明かとなり、本邦におけるアトピー咳嗽の重要性が確認された。<br />I. Basic research1. guinea pig models for atopic cough and cough variant asthma have been developed.1) Using the atopic cough model, it has been disclosure d that increased level of substance P resulted from antigen-induced inactivation of neutral endopeptidase is important in the antigen-induced increase in cough sensitivity, and that there may bean interaction between histamine and substance P.2) Using the cough variant asthma model, It is clarified that cough is elicited via antigen-induced bronchoconstridion, and that leukotrienes, but not tachykinins, are involved in the cough.2. We developed a apparatus to give quantitative mechanical pressure stress to guinea pig airway. The Mechanical pressure stress to airway induced cough reflex hypersensitivity associated with airway neutrophilic inflammation., suggesting self-perpetuating cycle between cough and cough hypersensitivity.II. Clinical research1. In addition to the difference of pathophysiologic feature between atopic cough and cough variant astluna, we elucidated the long-term outcome is also different between these two condition.: Nearly 30% patients with cough variant asthma develops typical asthma within several years but no patient with atopic cough does.2. Bronchial hyperresponsiveness and no use of long-tern inhaled corticosteroids were risk factors of typical asthma onset from cough variant asthma.3. Our prospective study confirmed that cough variant asthma, atopic cough and sinobronchial syndrome are common causes of chronic cough in Japan.<br />研究課題/領域番号:14570546, 研究期間(年度):2002-2004<br />出典：「慢性咳嗽の病態解明に基づく診断・治療法の開発」研究成果報告書 課題番号14570546 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）) 本文データは著者版報告書より作成
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