Bronchodilating and Bronchoprotective Effects of Deep Inspirations in Asthma, Cough Variant Asthma, and Methacholine-induced Cough but Normal Airway Sensitivity

Abstract

Rationale: The pathophysiologic differences between classic asthma (CA), cough variant asthma (CVA), and methacholine (MCh)-induced cough but normal airway sensitivity (COUGH) are poorly understood and may relate to differences in small airway function. We hypothesized that the bronchodilating and bronchoprotective effects of DIs are: (a) absent or impaired in individuals with CA; (b) impaired in individuals with CVA; and (c) preserved in those with COUGH. Purpose: To compare the effect of DIs in individuals with CA, CVA and COUGH using high-dose methacholine (MCh). Methods: Individuals aged 18-65 years with CA, or suspected CVA attended 3 visits. On visit 1, subjects performed body plethysmography and high-dose MCh testing to a maximum change (Δ) in FEV1 of 50% from baseline (MAX). On visits 2 and 3, subjects performed one of two modified single-dose MCh challenge tests with or without DIs prior to MCh administration. Partial and maximal-flow volume curves (used to calculated a DI index), impulse oscillometry (IOS) measurements and breathlessness (Borg scale) were recorded at baseline and at each dose of MCh. Lung volumes were measured by body plethysmography at baseline and MAX. Responses from baseline to a 20% decline in FEV1 (PC20) or MAX, and between visits with or without DIs were compared using paired t-tests. Between group differences were assessed by analysis of variance. Results: 19 subjects (14 female; 45.1±13.1 years (MEAN±SD)) completed the protocol (n=8 CA, n=7 CVA, and n=4 COUGH). At the dose nearest to PC20, the DI index was positive in all 3 groups, indicating preserved bronchodilation (CA: 0.88±0.67; CVA: 0.33±0.39; COUGH: 0.016±0.46; P=.0.076). There were no significant differences in: the Δs in spirometry, lung volumes, airway resistance, IOS measurements, closing indices, the DI index, or dyspnea when the single dose of MCh was preceded either by five DIs or by DI avoidance in CVA and COUGH. DIs in CA resulted in greater Δs in mid-to-late flows. Conclusion: The bronchodilating effect of DIs is preserved in CA, CVA and COUGH. The bronchoprotective effect may fall along a continuum. A larger study including subjects with more severe CA is required to definitively test the hypotheses.