Effects of obesity and weight loss on airway physiology and inflammation in asthma

Abstract

Obesity is a major risk factor for asthma, but the mechanisms for the development of asthma in the setting of obesity are not known. The purpose of this article is to review the effects of obesity on airway inflammation in patients with asthma, and to discuss the effects of obesity on airway reactivity in patients with asthma.

Obesity is particularly a risk factor for non-atopic asthma. Airway eosinophilic inflammation is not increased in obesity, in fact the preponderance of the evidence suggests that airway eosinophilia is decreased in obesity. There is some preliminary data suggesting that airway neutrophilia may be increased in obesity, and that this may be particularly related to dietary fats. Obesity also alters adaptive immunity, and may suppress lymphocyte function typically associated with asthmatic airway inflammation.

Population based studies are somewhat inconsistent on the relationship between airway reactivity and asthma, however, recent studies in bariatric surgery show that weight loss surgery in severely obese patients decreases airway reactivity. One study suggested that this was particularly the case for those with low IgE (a marker of a low T_H2 asthma phenotype), suggesting there may be some heterogeneity in asthma in obesity.

There are likely to be two phenotypes of asthma in the obese: one group with early onset disease and asthma complicated by obesity, and a 2nd group with late onset disease with asthma consequent to obesity. Obesity leads to profound changes in airway function, and adaptive and innate immune responses which alter the nature of pre-existing allergic airway disease, and also cause new onset asthmatic disease.

Introduction

Over the past 10 years, unequivocal evidence has emerged implicating obesity as a major risk factor for asthma. The reasons for this are still far from clear. During the same time period, intensive research efforts directed towards understanding the effects of obesity on human physiology and immunology have taken place, many of these studies are pertinent to our understanding of asthma in obesity. At the same time, data are emerging which suggest that asthma in obesity is not a single phenotype, but is likely to occur through the interaction of mechanical factors and altered immunology either interacting with pre-existing airway disease, or leading to de novo disease.

The purpose of this article is to briefly review the epidemiological data linking asthma and obesity, with a particular emphasis on the implications of this data for the phenotype of asthma in obesity. We will discuss the effects of obesity and weight loss on airway inflammation and physiology relevant to asthma, and discuss the relevance of these findings for our current understanding of asthma in obesity.

The prevalence of obesity has been increasing throughout the developed world, as has been discussed in detail in other articles in this issue.

A large number of publications have reported that obesity is a risk factor for asthma. This has been reported in adults and children, men and women, and publications have come from around the world suggesting that this is consistent across diverse ethnic populations [1], [2], [3], [4], [5], [6]. For example, one widely quoted meta-analysis published by Beuther and Sutherland in 2007 pooled data from seven studies, involving over 300 000 subjects: compared with normal weight, overweight and obesity status (body mass index, BMI ≥ 25 kg/m²) increased the odds of incident asthma by 1.51 [1]. There was also a dose–response effect of elevated BMI on the incidence of asthma: there was a higher risk of developing incident asthma for subjects who were obese over and above the risk for those that were merely overweight. Some studies have reported an increased risk for the development of asthma in obese women but not men [7]; in the meta-analysis by Beuther & Sutherland, the risk was elevated for both men and women, with an odds ratio of 1.46 in men, and 1.68 in women. While women may have a slightly higher risk of developing asthma in the setting of obesity, obesity is a risk factor for asthma in both men and women, indeed it is a risk factor for asthma among all demographic groups.

Most studies have reported on the overall risk of developing asthma in the setting of obesity. Some studies have reported on the risk of developing asthma in atopic versus non-atopic individuals (Table 1). An example of this was a cross-sectional survey study of 86 000 adult Canadians asthma published by Chen et al. [3]. These authors reported that non-allergic individuals had a higher risk of asthma in the setting of obesity than allergic individuals: the adjusted odds ratio of having asthma in the setting of obesity was 2.53 in non-allergic and only 1.57 in allergic women. Atopic status similarly affected the risk of asthma in the setting of obesity for men, though the overall risk of reporting asthma in the setting of obesity was a little lower for both allergic and non-allergic men. The preponderance of publications supports the observation that obesity is a risk for asthma particularly among the non-allergic adults, and no publications have reported the reverse [8], [9], [10], [11], [12].