Mannitol-evoked cough response is reduced by inhaled salbutamol

Background: Mannitol inhalation induces bronchoconstriction and coughing in asthmatic patients. Salbutamol causes smooth muscle relaxation in acute asthma, but its effects on airway nerves are unclear. We conducted mannitol cough challenges in allergic asthmatic patients (AAs) and healthy controls (HCs) to determine whether salbutamol would reduce mannitol-evoked coughs independent of changes in airway calibre. Methods: A double-blind, randomised, placebo-controlled, two-way crossover study included 20 mild steroid-naïve AAs and 20 HCs. The maximum number of coughs (Emax) evoked by mannitol was compared between salbutamol and placebo. Results: HCs and AAs were matched for age, lung function and sex. Mannitol-evoked cough dose ratio (CDR) in HCs was significantly lower than in AAs (5.63±1.84 versus 7.32±3.67 coughs, p=0.023). Both groups had similar Emax, C2 and C5 (dose causing two and five coughs, respectively). In AAs mannitol decreased forced expiratory volume in 1 s (FEV₁) by 8.11±2.32% with placebo, which was attenuated to 3.19±1.16% with salbutamol (p=0.03). In HCs, FEV₁ reduction was not significant. Emax in AAs for placebo and salbutamol was 8.90 (8.09-9.80) coughs and 7.07 (6.28-8.00) coughs, respectively (p<0.001) and in HCs 8.19 (7.08-9.61) coughs and 4.95 (4.38-5.66) coughs, respectively (p<0.001). The effect of salbutamol on Emax between groups was significantly different (p<0.001). Salbutamol improved CDR, C2 and C5 in AAs (p<0.05) but without effect between groups. Conclusion: Salbutamol reduced mannitol Emax in AAs and HCs. The reduced mannitol-evoked cough response by salbutamol in HCs was independent of changes in airway calibre measured by FEV₁, suggesting mechanisms of salbutamol extend beyond smooth muscle relaxation.