BUFFALO, N.Y. — Genes linked to chronic inflammation in
asthma may be more active in people who are obese, according to new
research that uncovers several biological ties between obesity and
“Our findings point the way to the management of asthma in
the obese through simple weight reduction,” said first author
Paresh Dandona, MD, PhD, SUNY Distinguished Professor and Chief of
Endocrinology, Diabetes and Metabolism at the University at
The research appeared
online June 26 in the journal Obesity and involved two related
studies: A comparative study between obese people and people of
normal weights; and an experiment that looked at how various
biological indicators — including the behavior of
asthma-linked genes — changed when morbidly obese patients
received gastric bypass surgery.
In the comparative study, the scientists found that four genes
associated with chronic inflammation in asthma were more active in
obese and morbidly obese people, by more than 100 percent in some
cases. The highest activity was found in the morbidly obese.
This increased gene expression matters because it can cause
white blood cells called mononuclear cells to produce far greater
amounts of inflammatory factors like interleukin 4, LIGHT and
lymphotoxinβ receptor which contribute to allergic
inflammation and other abnormalities in the bronchial passages in
The scientists also found higher concentrations of two
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
Following gastric bypass surgery in morbidly obese diabetic
patients, MMP-9 and NOM levels dropped, along with the expression
of six asthma-related genes including the key factors, interleukin
4, LIGHT, lymphotoxinβ and interleukin 33 in parallel with
weight loss and improvements in the status of their diabetes.
“Ours is the first study to provide a mechanistic link
between obesity and asthma through biological/immunological
mechanisms,” Dandona said. “There has been, until now,
no biological, mechanistic explanation other than the fact that
obesity may raise the diaphragm and thus reduce lung
Importantly, the research established a connection between Type
2 diabetes, obesity and asthma based on biological mechanisms. This
is important because obesity and Type 2 diabetes are associated
with a more than 100 percent increase in the prevalence of asthma,
The comparative study included:
- 22 patients of normal weights
- 23 obese patients (11 with Type 2 diabetes, and the rest
- and 15 morbidly obese patients with Type 2 diabetes.
The research team reported that obesity was associated with
higher expression of asthma-linked genes and MMP-9 and NOM levels
— whether or not patients had Type 2 diabetes.
None of the research subjects had asthma, which is one of the
strengths of the study, as it provides a level of assurance that
the correlations the researchers saw were not a product of the
The next step, Dandona said, is to conduct clinical studies
examining how weight loss affects asthma in patients who are
“We are embarking on this project now,” he said.
Dandona is also the founder of the Diabetes and Endocrinology
Center of Western New York, which is sponsored by the UB School of
Medicine and Biomedical Sciences and Kaleida Health.
Dandona’s partners on the study included colleagues from
the UB School of Medicine and Biomedical Sciences; Kaleida Health;
UB School of Pharmacy and Pharmaceutical Sciences; and Sisters of
Charity Hospital. His co-authors were: Husam Ghanim, PhD; Scott V.
Monte, PharmD; Joseph A. Caruana, MD; Kelly Green; Sanaa Abuaysheh;
Teekam Lohano, MD; Jerome Schentag, PharmD; Sandeep Dhindsa, MD;
and Ajay Chaudhuri, MD.