Increased Capsaicin Sensitivity in Patients with Severe Asthma Is Associated with Worse Clinical Outcome

Abstract

<b>Rationale:</b> Capsaicin cough reflex sensitivity (C-CS) is associated with poorly controlled asthma, although its association with severe asthma remains unknown.<b>Objectives:</b> To determine the clinical impact of C-CS on severe asthma.<b>Methods:</b> 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; <i>n</i> = 58], frequent exacerbations [≥2/yr; <i>n</i> = 28], admissions [≥1/yr; <i>n</i> = 17], and airflow limitation [FEV₁% predicted < 80%; <i>n</i> = 30]) were assessed.<b>Measurements and Main Results:</b> Heightened C-CS was associated with poor asthma control, frequent exacerbations, and admissions, particularly in patients without atopy (<i>n</i> = 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 <i>P</i> < 0.05).<b>Conclusions:</b> 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.