Bronchodilator Response Measured by Intrabreath Oscillometry Differentiates Wheezers From Healthy Preschoolers

Abstract

RATIONALE: Oscillometry-based assessments of bronchodilator response (BDR) typically focus on a specific index but rarely compare relative change across indices. This study explored BDR as impedance (Z) vectors incorporating both resistance and reactance from intrabreath oscillometry (IB-OSC) to distinguish asymptomatic wheezy children from healthy children. Methods: BDR was assessed with IB-OSC (10 Hz sinusoid, triplicate trials) during tidal breathing in 3-6-year-olds with recurrent and severe wheezing at recruitment, six weeks, six months, and 12 months. Placebo response and BDR thresholds in health were determined in age-matched healthy children across separate visits. Linear mixed models explored the effects of wheezing phenotype (mild versus severe based on the frequency of wheezy exacerbations during the study period) and height on BDR measured by resistance at end-expiration (ReE), resistance at end-inspiration (ReI), tidal change in resistance (ΔR=ReE-ReI), reactance at end-expiration (XeE), reactance at end-inspiration (XeI), tidal change in reactance (ΔX=XeE-XeI), ΔX normalised by tidal volume (ΔX/VT), and impedance magnitude at end-expiration (ZeE) and end-inspiration (ZeI). Results: In total, 126 wheezy and 57 healthy children were recruited. After adjusting for height in 249 asymptomatic measurements from 138 children, those with severe recurrent wheezing had a ΔR of -0.20 hPaL-1 (95%CI -0.38 to -0.02, p=0.033), XeE of +0.66 hPaL-1 (95%CI +0.27 to +1.05, p=0.001), ΔX of +0.40 hPasL-1 (95%CI +0.20 to +0.60, p<0.001), and ΔX/VT of +1.28 hPasL-2 (95%CI +0.56 to +2.00, p=0.001) compared to healthy children. Plotting BDR as ZeE vectors on a plane of XeE versus ReE (Figure 1) revealed that asymptomatic severe recurrent wheezers (blue arrows) had a ZeE BDR that differed from healthy (green arrows) after adjusting for height (-0.50 hPasL-1, 95%CI -0.98 to -0.01, p=0.048). The arrow direction indicates pre- to post-bronchodilator change. Pink arrows denote the placebo effect in healthy children to outline short-term repeatability. Conclusion: Steeper BDR vector slopes for severe recurrent wheezers suggest a greater BDR for XeE versus ReE. Physiologically this could be explained by predominant improvements in small airway function, improving ventilation inhomogeneity. Greater BDR in ReE versus XeE BDR in mild recurrent wheezers may reflect predominant improvements in conducting airway caliber. This novel expression of BDR as trajectories in the Z plane provides unique physiological insight into the differing mechanical changes between preschool wheeze phenotypes.