Influence of distinct asthma phenotypes on lung function following weight loss in the obese

Background and objectiveThere appears to be two distinct clinical phenotypes of obese patients with asthmathose with early-onset asthma and high serum IgE (T(H)2-high), and those with late-onset asthma and low serum IgE (T(H)2-low). The aim of the present study was to determine in the two phenotypes of obese asthma the effect of weight loss on small airway function. MethodsT(H)2-low (n=8) and T(H)2-high (n=5) obese asthmatics underwent methacholine challenge before and 12 months following bariatric surgery. Dose-response slopes as measures of sensitivity to airway closure and narrowing were measured as maximum % fall forced vital capacity (FVC) and forced expiratory volume in 1s/FVC, respectively, divided by dose. Resting airway mechanics were measured by forced oscillation technique. ResultsWeight loss reduced sensitivity to airway closure in T(H)2-low but not T(H)2-high obese asthmatics (pre-post mean change95% confidence interval: 1.80.8 doubling doses vs -0.3 +/- 1.7 doubling doses, P=0.04). However, there was no effect of weight loss on the sensitivity to airway narrowing in either group (P=0.8, T(H)2-low: 0.8 +/- 1.0 doubling doses, T(H)2-high: -1.1 +/- 2.5 doubling doses). In contrast, respiratory resistance (20Hz) improved in T(H)2-high but not in T(H)2-low obese asthmatics (pre-post change median interquartile range: 1.5 (1.3-2.8) cmH(2)O/L/s vs 0.6 (-1.8-0.8) cmH(2)O/L/s, P=0.03). ConclusionsT(H)2-low obese asthmatics appear to be characterized by increased small airway responsiveness and abnormalities in resting airway function that may persist following weight loss. However, this was not the case for T(H)2-high obese asthmatics, highlighting the complex interplay between IgE status and asthma pathophysiology in obesity. In obese asthmatic patients with low IgE, weight loss improves airway hyperresponsiveness related to airway closure, but does not improve resting airway resistance. In obese asthmatics with high IgE, weight loss improves resting lung mechanics but does not improve airway hyperresponsiveness.