Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, while its association with severe asthma remains unknown.
To determine the clinical impact of C-CS on severe asthma.
We prospectively enrolled 157 asthmatic patients (including 122 severe asthma patients who were in step 4/5 according to the GINA 2015 guideline) between November 2016 and October 2019. Capsaicin cough challenge was performed along with spirometry and assessment of biomarkers. The concentration required to induce at least five coughs by capsaicin (defined as C5) was adopted as an index of C-CS. Asthma control test (ACT) and comorbidities were also evaluated. Associations of biomarkers with 4 clinical features of severe asthma made by the ERS/ATS guideline [poor control (ACT <20, n = 58), frequent exacerbations (≥2 /year, n = 28), admissions (≥1 /year, n = 17), and airflow limitation (%FEV1 <80, n = 30)] were assessed.
Heightened C-CS was associated with poor asthma control, frequent exacerbations and admissions, particularly in non-atopic patients (n = 54). Meanwhile, C-CS was not related to airflow limitation. Multivariate regression analysis has revealed that heightened C-CS (C5 ≤2.44 µM) was a significant risk for poor asthma control, and frequent exacerbations. Regarding general factors and comorbidities, ex-smoking, diabetes mellitus, and chronic rhinosinusitis were associated with clinical features of severe asthma (all p <0.05).
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-type2 severe asthma.

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