Changes in Small Airway Physiology Measured by Impulse Oscillometry in Subjects with Allergic Asthma Following Methacholine and Inhaled Allergen Challenge.

: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. : To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. : Non-smoking, clinically stable HDM-allergic asthmatic subjects (18-55 years, FEV > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV ≥ 20% (PC) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV from post-diluent baseline during 0-3 h and 3-8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV and IOS parameters. : A total of 47 subjects were included (11 MRs; 36 DRs). FEV % predicted did not differ between MR and DR at baseline, but DR had lower median PCM (0.84 (range 0.07-7.51) vs. MR (2.15 (0.53-11.29)); = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV), the maximal % change from baseline following M and HDM challenge were correlated. PCM was inversely correlated with the % change in FEV and the % change in Xrs5 during the LAR (r= -0.443; = 0.0018 and r= -0.389; = 0.0075, respectively). : During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease.