Genes Linked to Asthma More Active in Obese Patients

Simple weight reduction may improve the management of asthma in obese patients, according to a new study that links chronic inflammation in obesity to greater activity of asthma-related genes.

“Obese patients have an increased risk of asthma and respiratory problems not only because their lung volumes may be reduced because of obesity but also because the expression and the concentration of various mediators is significantly increased in the obese,” Paresh Dandona, MD, PhD, SUNY Distinguished Professor and Chief of Endocrinology, Diabetes and Metabolism at the University at Buffalo, told ConsultantLive.

Dr Dandona noted that the study is the first to provide a link between obesity and asthma through biological or immunological mechanisms.

Obesity is a chronic proinflammatory state that is associated with an increase in the expression of genes related to asthmatic inflammation, Dr Dandona said. “We hypothesized that rapid weight loss associated with gastric bypass surgery may lead to the reduction in the expression of these genes,” he noted. “The reduction in the expression of these mediators may in turn result in the resolution of clinical asthma.”

In a comparative study, Dr Dandona and colleagues included 22 normal-weight patients, 23 obese patients (11 of whom had type 2 diabetes mellitus [DM]), and 15 morbidly obese patients with type 2 DM. Four genes associated with chronic inflammation in asthma were more active in the obese and morbidly obese patients. The highest activity level was found in the morbidly obese patients.

None of the research subjects had asthma, which is one of the strengths of the study, because a level of assurance is provided that the correlations the researchers saw were not a product of the disease itself, it was noted.

This increased gene expression can cause white blood cells, in particular mononuclear cells, to produce far greater amounts of inflammatory factors, such as interleukin 4, LIGHT, and lymphotoxin-β receptor. These inflammatory factors contribute to allergic inflammation and other abnormalities in the bronchial passages in asthma, Dr Dandona said.

The researchers also found higher concentrations of 2 asthma-related compounds in the plasma of obese and morbidly obese patients: MMP-9, which is associated with inflammation, and nitric oxide metabolites (NOM), which are an indicator of oxidative stress.

After gastric bypass surgery in morbidly obese patients with DM, MMP-9 and NOM levels dropped, along with the expression of 6 asthma-related genes, including the key factors interleukin 4, LIGHT, lymphotoxin-β, and interleukin 33, in parallel with weight loss and improvements in the status of the patients' DM.

Dr Dandona said, “These biological and immunological mediators, which are elevated in asthma and obesity, are likely to contribute to the development of asthma.”

Dr Dandona’s message to primary care physicians: “Pass along information to your patients that will result in greater awareness of obesity as a risk factor of asthma. Also, give them an understanding of how obesity, through its inflammatory mechanisms, may result in asthma. In addition, weight loss may result in the reversal of this risk.”

The study results were published on June 26, 2013, in the journal Obesity.