In obesity-related asthma, a new hormonal target



– A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.

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“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.

“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.

Asthma affects 10% of the world population, and it’s becoming increasingly understood that obesity-related, adult-onset asthma is a separate disease entity from allergic asthma, which usually begins in childhood, said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.

“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”

The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.

Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”

Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”

A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.

Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.

Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.

Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.

These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.

Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.

The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”

Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.

SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.

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