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

Rationale: 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.

Tiotropium Attenuates Refractory Cough and Capsaicin Cough Reflex Sensitivity in Patients with Asthma.

BACKGROUND: Asthmatic cough is often refractory to standard treatments such as inhaled corticosteroids (ICS) and long-acting ß2 agonists (LABA). Tiotropium may modulate cough reflex sensitivity of acute viral cough, but its efficacy in asthmatic cough remains unknown. OBJECTIVE: To evaluate whether tiotropium improves cough and cough reflex sensitivity in patients with asthma refractory to ICS/LABA. METHODS: Seventeen consecutive patients with asthma with chronic cough despite the use of ICS/LABA (13 women; 43.4 ± 19.0 years; average ICS dose, 651 ± 189 µg/d; fluticasone equivalent) were additionally treated with tiotropium (5 µg/d) for 4 to 8 weeks to examine its effects on pulmonary function and capsaicin cough reflex sensitivity (cough thresholds C2 and C5). Cough severity, cough-specific quality of life, and asthma control were also evaluated using cough visual analog scales (VASs), the Japanese version of Leicester Cough Questionnaire (J-LCQ), and Asthma Control Test (ACT), respectively. Patients with an improved cough VAS score of 15 mm or more were considered responders to tiotropium. RESULTS: Tiotropium significantly improved cough VAS, J-LCQ, and ACT scores, but not FEV1. Changes in cough VAS score correlated with those in C2 (r = -0.58; P = .03), C5 (r = -0.58; P = .03), and ACT scores (r = -0.62; P = .02), but not in FEV1 in the overall patients. When analyses were confined to the 11 responders, tiotropium significantly improved capsaicin cough reflex sensitivity within the subgroup (C2: P = .01 and C5: P = .02) and versus the nonresponders (C2: P = .004 and C5: P = .02). CONCLUSION: Tiotropium may alleviate asthmatic cough refractory to ICS/LABA by modulating cough reflex sensitivity but not through bronchodilation.