Can we predict response of refractory asthmatic cough to tiotropium? :a prospective study

Background: Asthmatic cough is often refractory to inhaled corticosteroids and long-acting β2 agonists (ICS/LABA). We preliminary reported tiotropium (Tio) alleviates asthmatic cough refractory to ICS/LABA by modulating cough reflex sensitivity (CRS) but not thorough bronchodilation (JACIP 2018). Rationale: We aimed to evaluate antitussive effects of Tio vs theophylline (Theo) in patients with refractory asthmatic cough in a randomized parallel fashion. Methods: 52 consecutive asthmatics [11 males; aged 51 (16) yrs; ICS dose 702 (251) μg] with chronic cough refractory to ICS/LABA were randomized by 2:1 ratio to additionally receive Tio 5 μg or Theo 400 mg for 4 wks. Spirometry, capsaicin CRS (C2 and C5), and FeNO levels were measured before and after treatments. Cough visual analog scales (VAS), Leicester Cough Questionnaire (LCQ), and Asthma Control Test (ACT) were also repeated. Patients with an improved cough VAS of ≥15 mm were considered responders to treatments. Results: 34 in Tio group and 12 in Theo group were finally analyzed. Both Tio and Theo improved cough VAS (p=0.0001, p=0.04, respectively) and LCQ (p=0.0007, p=0.03, respectively). Only Tio improved ACT scores (p=0.0005). C2 improved in both groups (p=0.003, p=0.02, respectively), but C5 improved only in Tio group (p=0.02). FEV1 and FeNO levels did not change in either group. Changes in each index did not differ between the groups. Changes in cough VAS but not other indices correlated with those in C5 (r=-0.36, p=0.03) in Tio group. 21 responders to Tio were solely predicted by elevated CRS by multivariate analysis. Conclusion: We could replicate our previous study, and newly found that elevated CRS might predict response to Tio.