Asthma
Research has so roundly suggested that metabolic dysfunction contributes to severe, poorly controlled asthma that there’s recent and growing interest in targeting metabolic dysfunction as part of the treatment of obese asthma, said Dr. Dixon, whose own research in obesity and lung disease has focused on asthma.
Data from animal models and some epidemiologic studies have suggested that drugs used to treat type 2 diabetes mellitus, such as glucagon-like peptide receptor-1 (GLPR-1) agonists and metformin, may help control asthma. In one recent study – cited by Dr. Dixon in a 2022 review of obesity and asthma – people with obesity and asthma who were prescribed GLPR-1 agonists for diabetes had fewer asthma exacerbations compared with those who took other medications for diabetes (Semin Respir Crit Care Med. 2022 Feb 17. doi: 10.1055/s-0042-1742384).
There is also research interest in targeting the pro-inflammatory adipokine interleukin 6 (IL-6), since increased circulating levels of IL-6 correlate with asthma severity, and in addressing oxidative stress in asthma through treatment with a mitochondrially targeted antioxidant, she said. Oxidative stress is increased in the airways of people with obesity, and researchers believe it may contribute to the pathophysiology of obese asthma through effects on airway nitric oxide levels.
(Her own research work at the University of Vermont has found associations between poor asthma control and high levels of leptin, and similar associations involving low levels of adiponectin, an anti-inflammatory adipokine that has been shown to downregulate eosinophil recruitment in the airways.)
Weight loss has been shown in mostly small, single-center studies to improve asthma control, but short of weight loss, researchers are also investigating the role of poor dietary quality. Thus far, data suggest that it’s the composition of the diet, and not just its contribution to weight gain, that could be impactful, Dr. Dixon said.
More basic research questions cited by Dr. Dixon include the extent to which adipose tissue inflammation causes inflammation in the lungs. “It’s a little unclear whether all the metabolic dysfunction associated with poor asthma control is causing inflammation in the lungs,” she said, though “we’ve done some work here that shows mediators produced by the adipose tissue could be impacting production of inflammatory mediators by the airway epithelium.”
Overall, she said, “the big questions [in asthma] are, how does adipose tissue affect the airway? Is it through direct effects? Through effects on the immune system? And obesity is affected by diet and the gut microbiome – how can these be [impacting] the airway?”
Obesity “is associated with so many changes – the gut, the immune system, and metabolic dysfunction, in addition to airway mechanics,” she said, “that I no longer think, as I did when I came to this, that it’s just one thing. It’s probably all of these things together.”
In the meantime, questions about potential shared pathways for the development of obesity and asthma remain. “Obesity is a risk factor for developing asthma, but it’s also entirely possible that asthma is a risk factor for developing obesity,” she said. (Some data from pediatric populations, she noted, suggest that nonobese children with asthma are at increased risk of developing obesity.)
Also important, Dr. Dixon said, is “emerging literature in the last 5-10 years” that suggests that people with obesity are more susceptible to the effects of air pollution. Research involving inner-city schoolchildren with asthma, for instance, has shown that those with obesity had worse symptoms with air pollution exposure than did those who were not obese.