The Nonallergic Asthma of Obesity. A Matter of Distal Lung Compliance

Abstract

Rationale: The pathogenesis of asthma in obesity is poorly understood, but may be related to breathing at low lung volumes.Objectives: To determine if lung function in obese patients with asthma and control subjects would respond differently to weight loss.Methods: Lung function was evaluated by conventional clinical tests and by impulse oscillometry in female late-onset, nonallergic patients with asthma and control subjects before, and 12 months after, bariatric surgery. Measurements and Main Results:Patients with asthma (n = 10) had significantly lower FEV 1 (79.8 6 10.6 vs. 95.5 6 7.0%) and FVC (82.4 6 13.2 vs. 93.7 6 8.9%) compared with control subjects (n = 13). There were no significant differences in FRC or TLC at baseline. Twelve months after surgery, control subjects had significant increases in FEV 1 (95.5 6 7.0 to 100.7 6 5.9), FVC (93.6 6 8.9 to 98.6 6 8.3%), FRC (45.4 6 18.5 to 62.1 6 15.3%), and TLC (84.8 6 15.0 to 103.1 6 15.3%), whereas patients with asthma had improvement only in FEV 1 (79.8 6 10.6 to 87.2 6 11.5). Control subjects and patients with asthma had a significantly different change in respiratory system resistance with weight loss: control subjects exhibited a uniform decrease in respiratory system resistance at all frequencies, whereas patients with asthma exhibited a decrease in frequency dependence of resistance. Fits of a mathematical model of lung mechanics to these impedance spectra suggest that the lung periphery was more collapsed by obesity in patients with asthma compared with control subjects.Conclusions: Weight loss decompresses the lung in both obese control subjects and patients with asthma, but the more pronounced effects of weight loss on lung elastance suggest that the distal lung is inherently more collapsible in people with asthma.

Physiological Mechanisms of Airway Hyperresponsiveness in Obese Asthma

“…Impedance from 5 to 35 Hz (Figures 2A and 2B) was fit with a two-compartment model featuring the compliance of both the peripheral lung and the central airways ( Figure 2C). The individuals with asthma started out before weight loss with larger values of peripheral elastance compared with the control subjects, and weight loss caused peripheral elastance to decrease by 60% in the those with asthma but only by 27% in the control subjects (51). The implication of these findings is that those with LONA obese asthma are distinguished from obese control subjects by having unusually collapsible airways that cause their lung functions to become especially compromised when lung volumes are reduced by obesity.…”

“…This being the case, that which distinguishes those with LONA obese asthma and those with EOS obese asthma may be the way in which they respond to reduced lung volume. We recently uncovered a clue as to what this might be by measuring respiratory system impedance in individuals with LONA obese asthma and obese control subjects both before and after major weight loss achieved through bariatric surgery (51). Impedance from 5 to 35 Hz (Figures 2A and 2B) was fit with a two-compartment model featuring the compliance of both the peripheral lung and the central airways ( Figure 2C).…”

The Asthma–Obesity Epidemic

“…49,50 Decreased lung volumes increase airway reactivity, 51 perhaps through effects on airway smooth muscle. 52 The tendency toward early airway closure may also manifest during bronchoconstriction 53,54 and contribute to the increased dyspnea symptoms reported by obese asthmatics in comparison to their lean counterparts. We have found that obese asthmatics tend to have a less compliant lung periphery, which improves with weight loss.…”

“…We have found that obese asthmatics tend to have a less compliant lung periphery, which improves with weight loss. 54 The cause of this stiff periphery is not known, but could be related to airway closure, as sensitivity to airway closure decreases with weight loss. 55 Changes in lung function with decreased lung volumes and increased airway closure likely contribute significantly to the development of poorly controlled asthma in obesity.…”

“…A significant improvement was observed in individuals in the intervention group in lung function (FEV 1 , FVC), symptoms, morbidity, and health status. 54 Bafadhel et al examined 151 adults with severe asthma in an one-year observational study. After 12 months, 23% of the patients had lost weight (an average of 2.8 kg), and a significant correlation was observed between weight loss and increased FEV 1 , whereas no significant association was found between weight change and self-reported asthma control and exacerbations.…”