Allergen challenge increases capsaicin-evoked cough responses in patients with allergic asthma

Background: Cough is a common and troublesome symptom in asthmatic patients, but little is known about the neuronal pathways that trigger cough. The mechanisms by which airway inflammation, airway hyperresponsiveness, and variable airflow obstruction cause cough are unclear. Objective: We sought to investigate the effects of allergen exposure on cough reflex sensitivity. Methods: We performed a 9-visit, randomized, single-blind, placebo-controlled, 2-way crossover study comparing cough responses to inhaled capsaicin in patients with mild atopic asthma after allergen challenge compared with diluent control. Full-dose capsaicin challenge was performed at screening to determine the capsaicin dose inducing a half-maximal response, which was subsequently administered at 30 minutes and 24 hours after inhaled allergen/diluent challenge. Spontaneous coughing was measured for 24 hours after allergen/diluent. Methacholine challenge and sputum induction were performed before and after allergen/diluent challenge. Results: Twelve steroid-naive subjects completed the study (6 female subjects; mean age, 34.8 years). Allergen inhalation caused both an early (mean +/- SD, 38.2% +/- 13.0%) and late (mean +/- SD, 23.7% +/- 13.2%) decrease in FEV1 and an increase in sputum eosinophil counts 24 hours later (after diluent: median, 1.9% left perpendicularinterquartile range, 0.8% to 5.8%right perpendicular; after allergen: median, 14.9% [interquartile range, 8.9% to 37.3%]; P =.005). There was also an increase in capsaicin-evoked coughs after allergen exposure compared with diluent at both 30 minutes (geometric mean coughs, 21.9 [95% CI, 16.5-29.20] vs 12.1 [95% CI, 8.3-17.7]; P <.001) and 24 hours (geometric mean coughs, 16.1 [95% CI, 11.3-23.0] vs 9.8 [95% CI, 6.1-15.8]; P =.001). Allergen exposure was also associated with an increase in spontaneous coughs over 24 hours. Conclusion: Allergen-induced bronchoconstriction and airway eosinophilia result in increased cough reflex sensitivity to capsaicin associated with an increase in 24-hour spontaneous coughing.