Allergen challenge increases capsaicin evoked cough responses in allergic asthma

Publication date: Available online 17 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Imran Satia, Richard Watson, Tara Scime, Rachel J. Dockry, Shilpi Sen, James W. Ford, Patrick D. Mitchell, Stephen J. Fowler, Gail M. Gauvreau, Paul M. O'Byrne, Jaclyn A. Smith

Abstract

Background

Cough is a common and troublesome symptom in asthma but little is known about the neuronal pathways that trigger cough. The mechanisms by which airway inflammation, airway hyper-responsiveness and variable airflow obstruction cause cough are unclear.

Objective

To investigate the effects of allergen exposure on cough reflex sensitivity.

Methods

We performed a nine visit, randomised, single-blind, placebo-controlled, two-way cross-over study comparing cough responses to inhaled capsaicin in mild atopic asthmatics after allergen challenge compared with diluent control. Full dose capsaicin challenge was performed at screening to determine the excitatory dose evoking half the maximum cough response (ED₅₀), which was subsequently administered at 30mins and 24-hours after inhaled allergen/diluent challenge. Spontaneous coughing was measured for 24-hours after allergen/diluent. Methacholine challenge and induced sputum was performed before and after allergen/diluent challenge.

Results

Twelve steroid naïve subjects completed the study (6 female, mean age 34.8yrs) Allergen inhalation caused both an early (mean 38.2±S.D.13.0%) and late (23.7±13.2%) fall in FEV₁ and an increase in sputum eosinophils 24-hours later [median 1.9(IQR 0.8-5.8) % post-diluent to 14.9(8.9-37.3) % post-allergen, p=0.005]. There was also an increase in capsaicin evoked coughs after allergen exposure compared to diluent at both 30 mins [geometric mean coughs 21.9(95% C.I 16.5-29.20) versus 12.1(8.3-17.7), p<0.001], and at 24hrs [geometric mean coughs 16.1(95% C.I 11.3-23.0) versus 9.8(6.1-15.8), p=0.001]. Allergen exposure was also associated with an increase in spontaneous coughs over 24-hours.

Conclusion

Allergen induced bronchoconstriction and airway eosinophilia results in increased cough reflex sensitivity to capsaicin associated with an increase in 24-hour spontaneous coughing.

Graphical abstract

http://bit.ly/2RYBAda