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

Abstract

Background and objective: There appears to be two distinct clinical phenotypes of obese patients with asthma-those with early-onset asthma and high serum IgE (TH2-high), and those with late-onset asthma and low serum IgE (TH2-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.

Methods: TH2-low (n = 8) and TH2-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 1 s/FVC, respectively, divided by dose. Resting airway mechanics were measured by forced oscillation technique.

Results: Weight loss reduced sensitivity to airway closure in TH 2-low but not TH2-high obese asthmatics (pre-post mean change ± 95% confidence interval: 1.8 ± 0.8 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, TH2-low: 0.8 ± 1.0 doubling doses, TH2-high: -1.1 ± 2.5 doubling doses). In contrast, respiratory resistance (20 Hz) improved in TH2-high but not in TH2-low obese asthmatics (pre-post change median interquartile range: 1.5 (1.3-2.8) cmH₂O/L/s vs 0.6 (-1.8-0.8) cmH₂O/L/s, P = 0.03).

Conclusions: TH2-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 TH2-high obese asthmatics, highlighting the complex interplay between IgE status and asthma pathophysiology in obesity.

Keywords: airway closure; airway hyperresponsiveness; asthma; obesity; weight loss.

© 2014 Asian Pacific Society of Respirology.

Figures

Figure 1. Comparison of the proportion of the fall in FEV1 during methacholine challenge that is due to airway closure prior to bariatric surgery

The Closing Index, calculated as the % fall in FVC/ % fall in FEV1 at the highest dose of the methacholine challenge, was compared between obese non-asthmatic, obese asthmatics with elevated serum IgE (TH2-high) and obese asthmatics with normal serum IgE (TH2-low). A larger closing index represents a greater proportion of overall bronchoconstriction attributed to airway closure. The mean± SEM closing index in normal weight non-asthmatics is 0.54 ± 0.03 (9). ns = non-significant ANOVA.

Figure 2. Comparison of resting respiratory system resistance (Rrs20Hz, A) and reactance (Xrs5Hz, B) in obese asthmatic subjects before (pre) and 12 months following bariatric surgery (post)

Obese asthmatic subjects were grouped into those with elevated IgE (TH2-high) and those with normal IgE (TH2-low). The p-values shown are for the TH2-status × surgery interaction factor p = 0.05 (A) and 0.01 (B) for effect of surgery

Figure 3. Comparison of the proportion of the fall in FEV1 during methacholine challenge that is due to airway closure prior to and 12 months following bariatric surgery in obese asthmatic subjects

Obese asthmatic subjects were grouped into those with elevated IgE (TH2-high) and those with normal IgE (TH2-low). The Closing Index, calculated as the % fall in FVC/% fall in FEV1 at the highest dose of the methacholine challenge, was compared prior to and 12 month following bariatric surgery in obese asthmatic subjects. A larger closing index represents a greater proportion of overall bronchoconstriction attributed to airway closure. The p-value shown is for the TH2-status × surgery interaction factor p = 0.03 for effect of surgery

Figure 4. Comparison of the sensitivity to airway narrowing (a) and airway closure (b) in obese asthmatic subjects before (pre) and 12 months following bariatric surgery (post)

Obese asthmatic subjects were grouped into those with elevated IgE (TH2-high) and those with normal IgE (TH2-high). Sensitivity to methacholine was measured as the dose response slope (DRS), calculated as the two point slope from the fall in lung function at the end of challenge divided by the dose of methacholine (MCh) in µmoles. The sensitivity to airway narrowing and airway closure was determined by calculating a DRS using % fall in FEV1/FVC (DRS(FEV1/FVC)) and % fall in FVC (DRSFVC). DRS is log-normally distributed and is thus plotted on a log-scale The p-values shown are for the TH2-status × surgery interaction factor .p = 0.79 (A) and 0.11 (B) for effect of surgery