Studies Find Biological Links between Obesity, Asthma

Two interrelated studies found that genes linked to chronic inflammation in asthma may be more active in obese people.

Although obesity and Type 2 diabetes are associated with a more than 100 percent increase in the prevalence of asthma, the UB studies are “the first to find biological or immunological connections,” says Paresh Dandona, MD, PhD, SUNY Distinguished Professor of medicine and chief of endocrinology, diabetes and metabolism.

Until now, the only explanation has been that obesity may raise the diaphragm and thus reduce lung volumes, he says.

The new findings suggest that simple weight reduction could be used to manage asthma in obese patients, notes Dandona, who founded the Diabetes and Endocrinology Center of Western New York, sponsored by UB and Kaleida Health.

A comparative study assessed differences among 23 obese patients (including 11 with Type 2 diabetes), 15 morbidly obese patients with Type 2 diabetes and 22 normal-weight individuals.

Another study involving the morbidly obese patients explored the effect of gastric bypass surgery on various biological indicators—including the behavior of asthma-linked genes.

To help ensure that the correlations found were not a product of existing disease, none of the study participants had asthma.

In the comparative study, the researchers found that obese people—whether or not they had Type 2 diabetes—exhibited a higher expression of asthma-linked genes as well as higher levels of asthma-related compounds.

Four genes associated with chronic inflammation in asthma were more active in obese people.

This activity increased by more than 100 percent in some cases and was highest in the morbidly obese.

This increased gene expression can cause mononuclear or white blood cells to produce far greater amounts of key inflammatory factors, including interleukin 4, LIGHT, lymphotoxinβ receptor and chemokine receptor-2 (CCR-2).

With asthma, these factors contribute to allergic inflammation and other abnormalities in bronchial passages.

The researchers also found higher concentrations of two asthma-related mediators in the plasma of obese patients: MMP-9, associated with inflammation, and nitric oxide metabolites (NOM), which indicate oxidative stress.

After gastric bypass surgery, the morbidly obese patients saw decreases in the expression of six asthma-related genes, including those mentioned above, as well as plasma MMP-9 and NOM levels.

They also lost weight and improved their diabetes status.

Dandona and his team now plan to conduct clinical studies to learn how weight loss affects asthma in patients who are obese.

With Dandona as first author, the resulting paper, “Increase in the Mediators of Asthma in Obesity and Obesity with Type 2 Diabetes: Reduction with Weight Loss,” has been published in Obesity.

Co-authors include Ajay Chaudhuri, MD, clinical associate professor of medicine; Husam Ghanim, PhD, research assistant professor of medicine; and others in the UB School of Medicine and Biomedical Sciences.

Additional collaborators are from Kaleida Health, the UB School of Pharmacy and Pharmaceutical Sciences and Sisters of Charity Hospital.