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

Abstract

Background: Asthmatic cough is often refractory to standard treatments such as inhaled corticosteroids (ICS) and long-acting β₂ 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.

Keywords: Capsaicin cough reflex sensitivity; Chronic asthmatic cough; Cough severity; Cough-specific quality of life; Tiotropium.