Small-airway obstruction, dynamic hyperinflation, and gas trapping despite normal airway sensitivity to methacholine in adults with chronic cough

Abstract

The clinical relevance of cough during methacholine challenge in individuals with normal airway sensitivity is unknown. We compared responses of individuals with chronic cough who cough during high-dose methacholine bronchoprovocation and have normal versus increased airway sensitivity to healthy controls. Fifteen healthy participants (CONTROL) aged 26 ± 7 yr (mean ± SD) and 32 participants aged 42 ± 14 yr with chronic cough and suspected asthma completed high-dose methacholine challenge testing. Three participants who did not cough and had normal airway sensitivity were excluded. Spirometry and lung volumes were compared at the maximum response (MAX) among 1) ASTHMA [ n = 15, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (FEV 1 ) from baseline (PC 20 ) 4.71 ± 1.37 mg/ml], 2) methacholine-induced cough with normal airway sensitivity (COUGH, n = 14, PC 20 41.2 ± 18.7 mg/ml for 3 participants with a measurable PC 20 ), and 3) CONTROL ( n = 15; PC 20 93.4 ± 95.4 mg/ml for 4 participants with a measurable PC 20 ). Esophageal pressure-derived pulmonary mechanics were compared at MAX for the ASTHMA and COUGH groups. From baseline to MAX, FEV 1 and forced expiratory flow between 25% and 75% of forced vital capacity decreased more in ASTHMA (−36.2 ± 3.8 %pr; −47.1 ± 6.9 %pr, respectively) than COUGH (−12.2 ± 3.0 %pr ( P < 0.001); −24.7 ± 6.5 %pr ( P < 0.001), respectively) and CONTROL (−13.7 ± 2.0 %pr ( P < 0.001); −32.8 ± 5.4 %pr ( P < 0.017), respectively). In both ASTHMA and COUGH, inspiratory capacity decreased by 500–800 ml, and functional residual capacity and residual volume increased by ~800 ml. Individuals with COUGH develop dynamic hyperinflation and gas trapping comparable to individuals with ASTHMA despite less bronchoconstriction and smaller reductions in mid-to-late expiratory flows, which leads us to believe that COUGH is a distinct phenotype. NEW & NOTEWORTHY Healthy individuals and individuals with chronic cough who demonstrate normal airway sensitivity but cough during methacholine bronchoprovocation bronchoconstrict less than individuals with mild asthma. However, those who cough and have normal airway sensitivity develop dynamic hyperinflation and gas trapping comparable to individuals with mild asthma. Thus, methacholine-induced cough with normal airway sensitivity may be clinically relevant, related to reversible small airway obstruction and preservation of the bronchodilating and/or bronchoprotective effects of deep inspirations.