On the Road to Better Treatments for Obese Asthmatics

By Nancy McCann

Ten year-old Jack looks longingly out his living room window, yearning to play kickball with his friends. But mom doesn’t want his asthma to flare up, which it tends to do when he runs around. As much as he wants to go outside, he won’t, because he knows how uncomfortable he gets when his chest starts to tighten. Instead, Jack spends hours on the couch in front of the television, playing video games.

This reinforcing cycle keeps churning — exercise and outdoor play are great for combatting Jack’s obesity, but they’re bad for his asthma. Sitting around begets more weight troubles, but it doesn’t cause him breathing discomfort. Around and around it goes.

Sarah Henrickson, MD, PhD, an attending physician with the Division of Allergy at Children’s Hospital of Philadelphia, wants to help. With a new grant from the National Institute of Allergy and Infectious Diseases, she’s searching for what causes obese asthmatics to respond poorly to standard asthma medications and to have a higher rate of more severe viral asthma flares. Her ultimate goal: Get Jack outside and playing with his friends.

“In the clinic, we tell families, ‘We want your kids to be as active as can be,’” Dr. Henrickson said. “Our job is to support them medically so they can be active and do those things. We don’t want their asthma to hold them back, and we don’t want the disease to be a reinforcing cycle with obesity either.”

Chronic Childhood Diseases

Obesity and asthma are among the most common chronic childhood diseases, and, unfortunately, are growing in prevalence in this country and worldwide. These two illnesses are linked: As body mass index increases, the risk of asthma also increases.

“Obese asthmatics have a very severe disease that doesn’t respond as well to our baseline preventative medicines, and when they get their flares, they tend to do worse with those flares,” Dr. Henrickson said. “But we don’t know why. Is there something being released from the fat that’s changing how the immune cells work and that sets them up to be asthmatic? That’s what we’re trying to understand.”

In her search for answers, Dr. Henrickson plans to use a combination of advanced experimental methods and cutting-edge data analysis tools to uncover possible causes of immune system dysfunction in obese asthma that may play important roles in the poor anti-viral responses. This NIH grant is focused on validating hypotheses formed from a human pilot study she conducted during her fellowship here at CHOP. For example, could a difference in metabolites in the blood be partially underlying the obese asthmatic’s T cell dysfunction?

“What we know is these T cells don’t look like the healthy ones,” Dr. Henrickson said. “So can we help these patients fight viruses more effectively by increasing the level of function at baseline of their anti-viral T cell? It may be a pathway to alternate therapeutic strategies in these hard to treat kids.We think we know what’s going on, but we need to test these ideas working with  mouse models and in human cells in vitro.”

Mechanistically Speaking

Asthma and obesity — which are complex diseases for both children and adults — are not always addressed mechanistically, Dr. Henrickson said.

“It’s really tough to get at the core mechanisms and different mechanisms,” she said. “So it’s important to tackle this obese asthma group of patients because they tend to be harder to control and have more severe flares. We don’t understand what is different about that mechanism, and if we did, we could treat them more successfully and keep them healthier.”

And get Jack outside, playing ball again.