• Am. J. Respir. Crit. Care Med. · May 2020

    Comparative Study

    Increased Capsaicin Sensitivity in Severe Asthmatics Associated with Worse Clinical Outcome.

    • Yoshihiro Kanemitsu, Kensuke Fukumitsu, Ryota Kurokawa, Norihisa Takeda, Motohiko Suzuki, Jennifer Yap, Hirono Nishiyama, Tomoko Tajiri, Satoshi Fukuda, Takehiro Uemura, Hirotsugu Ohkubo, Ken Maeno, Yutaka Ito, Tetsuya Oguri, Masaya Takemura, and Akio Niimi.
    • Department of Respiratory Medicine, Allergy, and Clinical Immunology and.
    • Am. J. Respir. Crit. Care Med. 2020 May 1; 201 (9): 1068-1077.

    AbstractRationale: Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, although its association with severe asthma remains unknown.Objectives: To determine the clinical impact of C-CS on severe asthma.Methods: We prospectively enrolled 157 patients with asthma (including 122 patients with severe asthma who were in step 4 or 5 according to the Global Initiative for Asthma 2015 guidelines) between November 2016 and October 2019. A capsaicin cough challenge was performed along with spirometry and assessment of biomarkers. The concentration required to induce at least five coughs by capsaicin was adopted as an index of C-CS. An Asthma Control Test and comorbidities were also evaluated. Associations of biomarkers with four clinical features of severe asthma made by the European Respiratory Society/American Thoracic Society guidelines (poor control [Asthma Control Test < 20; n = 58], frequent exacerbations [≥2/yr; n = 28], admissions [≥1/yr; n = 17], and airflow limitation [FEV1% predicted < 80%; n = 30]) were assessed.Measurements and Main Results: Heightened C-CS was associated with poor asthma control, frequent exacerbations, and admissions, particularly in patients without atopy (n = 54). Meanwhile, C-CS was not related to airflow limitation. Multivariate regression analysis has revealed that heightened C-CS (at least five coughs by capsaicin ≤ 2.44 μM) was a significant risk for poor asthma control and frequent exacerbations. Regarding general factors and comorbidities, ex-smoking status, diabetes mellitus, and chronic rhinosinusitis were associated with clinical features of severe asthma (all P < 0.05).Conclusions: Heightened C-CS is a risk factor for severe asthma. The present study suggests the association of airway neuronal dysfunction with the pathophysiology of non-type 2 severe asthma.

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