Late-Onset Asthma in Obese Individuals Could Be Caused by Amino Acid Imbalance, Holguin-Led Study Reports

A metabolic imbalance—rather than allergy or airway inflammation—may spur increased respiratory symptoms and a quality-of-life loss associated with asthma in obese people, especially those who develop asthma later in life, according to a study led by researchers at the University of Pittsburgh School of Medicine. The findings, published recently in the American Journal of Respiratory and Critical Care Medicine, have prompted a pilot project at the University of Pittsburgh Asthma Institute at UPMC and the University of Pittsburgh School of Medicine to see whether patients’ symptoms improve when they supplement their diet with the deficient agent.

The relationship between asthma and obesity is in many ways a conundrum, said the study’s lead author, Fernando Holguin, a professor in the Division of Pulmonary, Allergy and Critical Care Medicine, Pitt School of Medicine, and codirector of the Asthma Institute. A person who has severe asthma may require frequent steroid treatments and limit his or her activity, resulting in weight gain; in others, obesity seems to aggravate or even initiate asthma symptoms.

“Obese asthma patients tend to have worse symptoms, more frequent episodes of breathing difficulty, and don’t respond as readily to conventional treatments,” Holguin noted. “Our study supports the premise that asthma is a multifactorial condition that can be triggered by a variety of underlying problems.”  Interventions to improve clinically meaningful outcomes may need to be personalized to the type of asthmatic condition that an individual patient has.

Patients who are obese and develop asthma as adults tend to exhale lower levels of nitric oxide, a compound that relaxes blood vessels and is thought to play a similar role in airways. The researchers collected blood samples from 155 adults, nearly half of whom had severe asthma and half were obese. The team found that compared to early-onset asthma patients, late-onset obese asthma patients had lower plasma levels of the amino acid arginine and higher levels of an arginine metabolite called ADMA, which interferes with nitric oxide production.

“In healthy people, a balance is maintained between arginine and ADMA, ensuring normal levels of airway nitrous oxide,” Holguin said. “But in obese, adult-onset asthma, the lower arginine and higher ADMA reduce airway nitrous oxide levels. This finding is promising because it suggests that increasing arginine could restore nitrous oxide levels and its positive effect on airways.” This might translate into patients having less wheezing and shortness of breath.

Arginine is readily available over the counter as a dietary supplement, but it is rapidly metabolized by the body and reduces its practicality as a treatment, he said. Another supplement called citrulline is known to enhance arginine production and can be taken in high doses without ill effects.

“We will soon begin a small pilot study to see whether citrulline supplements can help alleviate symptoms in patients who fit this profile of late-onset asthma, obesity, and decreased exhaled nitrous oxide,” Dr. Holguin said.

Mark Gladwin, chief of the Pitt medical school’s Division of Pulmonary, Allergy and Critical Care Medicine, said, “This research highlights that not everyone with asthma is the same, so our investigators are exploring treatments that work in different ways for specific patients, a concept that we refer to as precision medicine.”

Coauthors of the paper include senior author Sally Wenzel, a professor of medicine within the Pitt medical school’s Division of Pulmonary, Allergy and Critical Care Medicine and director of the Asthma Institute, as well as others from the Pitt School of Medicine. In addition, research was conducted by researchers from the Cleveland Clinic, Wake Forest University, the University of Wisconsin, the University of Texas, Washington University in St. Louis, Emory University, the University of Virginia, Harvard University, and Imperial College London.