At a glance
- The prevalence of obesity and asthma are rising significantly and in parallel.
- One of the richest sources of clues to the nature of the obesity-asthma link is the inflammatory cascade.
- Patient response to inhaled corticosteroid has been shown to decrease with increasing BMI.
- People who are obese have similar but not identical asthma symptoms as those who are thinner.
Physicians at the Canadian Respiratory Conference held April 23-25, 2009, in Toronto, described the factors that make obese individuals prone to asthma. The research also explored why asthma symptoms in the obese are frequently hard to control and why weight loss does not always reduce the symptoms.
Louis-Philippe Boulet, MD, professor of medicine at Laval University in Quebec City, explains that these issues are important because obesity and asthma affect approximately 30% and 10% of the population, respectively.
According to a study Dr. Boulet undertook with a team of researchers, including Shawn Aaron, MD, MSc, associate professor in the Department of Medicine at the University of Ottawa in Ontario, just under one-third of people with asthma who are obese and just over one-fourth of those who are nonobese have been misdiagnosed and do not actually have asthma.
“We are not sure how the relationship between obesity and asthma symptoms works and what the clinical implications are,” says Dr. Boulet.
“Although we know that obesity makes asthma more difficult to control, we still need more data on how obesity leads to the development of the disease itself and exactly what aspects of it are different from asthma in people who are not obese.”
Linking obesity and respiratory pathology
Research supports the presence of intimate interconnections at the molecular and physical levels between obesity and asthma.
A pair of researchers reviewed the literature and concluded that the prevalence of obesity and asthma are rising significantly and in parallel in the United States.1 Overweight and obese individuals are at 38% and 92% higher risk, respectively, for developing asthma than people of normal weight.2
Unfortunately, increased weight also raises the risk for poorly controlled asthma symptoms with medication use. Both fluticasone and the combination of fluticasone and salmeterol were significantly less likely to control asthma in those with a BMI >40 than in less heavy individuals.3
Many factors contribute to the development of asthma symptoms in the obese. Genetics, diet, hormones, allergies, physical mechanics, lifestyle, and medication use all play a role.
In the case of genetics, mutations have been pinpointed in specific regions of chromosomes 5q, 6p, 11q13, and 12q. These regions contain one or more genes for receptors relevant to both asthma and metabolic disorders linked to obesity.4 For example, the beta2-adrenoreceptor gene in the 5q chromosome region controls both airway tone and metabolic rate. Mutations in this gene have been identified in individuals with asthma and obesity. Other relevant gene mutations are in regions coding for the glucocorticoid receptor and for insulinlike growth factor and other inflammatory mediators.
Dietary and environmental factors may also be implicated in the development of asthma among people who have significant excess weight. These factors include reduced intake of vitamin D, antioxidants, and omega-3 fatty acids and possibly increased exposure to environmental pollutants.
“There are very few studies and little evidence in this area. We have to do a lot more research on the effects of these [dietary and environmental] factors on the development of asthma,” says Dr. Boulet.
Changes in estrogen and progesterone related to obesity may also contribute to the development of asthma symptoms.5 These phenomena could explain why more women than men have the combination of obesity and asthma.
In addition, the obese often have comorbidities (e.g., gastroesophageal reflux disease [GERD], hormonal disturbances, atopy, diabetes, and hypertension) that contribute to the development or worsening of asthma.
Inflammation plays a key role
One of the richest sources of clues to the nature of the obesity-asthma link is the inflammatory cascade. Both obesity and asthma are associated with a form of chronic inflammation as well as with elevated levels of such inflammatory markers as lymphocytes.
C-reactive protein (CRP) and fibrinogen, which are strongly associated with inflammation, are present in higher levels in people who are obese than in their nonobese counterparts.5 A significant positive correlation has been found between sputum eosinophil counts and waist circumference.
“Obese patients have evidence of a systemic inflammatory process, but we still do not know how this leads to the classic airway inflammation seen in asthma,” explains Dr. Boulet. “One clue is that the more obese a person with asthma is, the fewer eosinophils are present, suggesting a change in the airway inflammation phenotype.”
Inflammation-related moieties that are implicated include tumor necrosis factor-a, interleukin (IL)-6, insulinlike growth factor-1, adiponectin, and estrogens. One of the members of the IL-6 family produced by fat cells is leptin, and an increase in leptin levels may cause an imbalance between the production of Th1 and Th2 cytokines.5 This imbalance, in turn, is implicated in the development of asthma. Thus, leptin appears to be one of the strongest markers for both asthma and obesity. This fits with the observation that overweight children with asthma have leptin levels twice as high as as overweight children who do not have asthma or normal-weight children who have asthma. Obese individuals also have reduced levels of adiponectin; the absence of adiponectin and its anti-inflammatory properties may contribute to the development of asthma.
Research also indicates that interferon-a may be a mediator of this link between obesity, leptin, adiponectin, and asthma.