Methacholine-induced airway hyper-reactivity phenotypes

Abstract

Objective: The incorporation of airways conductance/resistance is a rare feature in clinical methacholine challenge test (MCT) protocols, and the majority of pulmonary laboratories rely solely on the spirometric parameters. The importance and interpretation of an MCT demonstrating a significant decline in specific airway conductance specific airway conductance (sGaw), but not forced expiratory volume in one second (FEV(1)), remains undefined. This study sought to elucidate the clinical and physiologic phenotypes of individuals with a ≥40% sGaw decline but <20% FEV(1) change.

Methods: All subjects completed the Asthma Quality of Life Questionnaire (AQLQ), followed by standard MCT, with measurements of sGaw and an additional independent measurement of resistance and reactance by impulse oscillation system (IOS) before and after MCT.

Results: Of 201 subjects, 47(23.4%) were in Group 1 (FEV(1) declined by ≥20%), 45(22.4%) were in Group 2 (non-significant FEV(1) drop, sGaw declined ≥40%), and 109(54.2%) were in Group 3 (no significant decline in FEV(1)/sGaw). There was a nearly identical change in all oscillometric parameters and sGaw for Groups 1 and 2 versus Group 3. There were no differences between Groups 1 and 2 in any AQLQ category, and Groups 1 and 2 were statistically different from Group 3.

Conclusions: Our prospective study suggests that patients with a significant sGaw decline alone during MCT are a clinically and physiologically important hyper-reactivity phenotype--whose hyper-reactivity independently was confirmed to be nearly identical to those with an FEV(1) decline. By failing to assess airways conductance/resistance, asthma may be inappropriately "ruled out" in ∼20% of the patients referred for MCT. Based on this, standardized incorporation of body plethysmography and/or IOS to MCT protocols should be considered.