Obesity and asthma

Abstract

Asthma and obesity are prevalent disorders, each with a significant public health impact, and a large and growing body of literature suggests an association between the two. The systemic inflammatory milieu in obesity leads to metabolic and cardiovascular complications, but whether this environment alters asthma risk or phenotype is not yet known. Animal experiments have evaluated the effects of leptin and obesity on airway inflammation in response to both allergic and nonallergic exposures and suggest that airway inflammatory response is enhanced by both endogenous and exogenous leptin. Cross-sectional and prospective cohort studies of humans have shown a modest overall increase in asthma incidence and prevalence in the obese, although body mass index does not appear be a significant modifier of asthma severity. Studying the obesity-asthma relationship in large cohorts, in which self-reports are frequently used to ascertain the diagnosis of asthma, has been complicated by alterations in pulmonary physiology caused by obesity, which may lead to dyspnea or other respiratory symptoms but do not fulfill accepted physiologic criteria for asthma. Recent investigations toward elucidating a shared genetic basis for these two disorders have identified polymorphisms in specific regions of chromosomes 5q, 6p, 11q13, and 12q, each of which contains one or more genes encoding receptors relevant to asthma, inflammation, and metabolic disorders, including the beta(2)-adrenergic receptor gene ADRB2 and the glucocorticoid receptor gene NR3C1. Further research is warranted to synthesize these disparate observations into a cohesive understanding of the relationship between obesity and asthma.

Figure 1.

In obesity, visceral adiposity is correlated with circulating levels of proinflammatory cytokines, and adipose tissue propagates inflammation both locally and systemically, in part through recruitment of macrophages via chemokines such as monocyte chemoattractant protein-1 (MCP-1) and in part via elaboration of cytokines and chemokines such as (but not limited to) leptin, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1), and eotaxin. Although the precise relationship between obesity and asthma remains to be determined, modifications of atopy, lung development, Th1–Th2 balance, immune responsiveness, and airway smooth muscle have been hypothesized to be mechanisms by which obesity might increase asthma risk or modify asthma phenotype. CRP = C-reactive protein.

Figure 2.

Obesity leads to alterations of lung volumes (top), particularly expiratory reserve volume (ERV) and FRC, leading to a rapid, shallow breathing pattern that occurs close to closing volume. Obesity also causes reduced peripheral airway diameter (middle), which can lead to increased airway hyperresponsiveness due to alterations of smooth muscle structure and function (59).