Urban children with obesity-related asthma exhibit significant metabolic changes
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Key takeaways:
- The study analyzed 906 metabolites with less than 50% missing values.
- Androgenic steroids, fatty acids and sphingomyelins were statistically significantly elevated in children with overweight or obesity.
SAN DIEGO — Urban children with asthma and overweight or obesity exhibited significant metabolic changes compared with other urban children with asthma, according to a presentation at the American Thoracic Society International Conference.
As a heterogeneous childhood asthma phenotype, obesity-related asthma is increasing in prevalence, particularly in inner cities, Perdita Permaul, MD, pediatric allergist and immunologist, Weill Cornell Medicine, and colleagues wrote.
“This heterogeneity is likely due to various underlying pathogenetic mechanisms,” Permaul told Healio.
Children who have obesity-related asthma experience greater asthma symptoms as well as loss of asthma control, higher asthma-related health care use and poor response to inhaled corticosteroids and other standard therapy, she continued.
“Metabolomic profiling may potentially link a child’s genetic background and environmental exposures such as diet to disease endotypes, which could ultimately allow for better targeted treatments,” Permaul said.
Over the past 2 decades, obesity and asthma, which both are chronic childhood diseases, have seen a striking surge in prevalence, Permaul said, especially in inner cities.
“In addition to environmental exposures known to trigger asthma in the inner city such as mouse and cockroach allergen, there is a paucity of supermarkets and healthy fresh food, a high number of fast-food restaurants, and lack of green spaces and parks, all contributing to the childhood obesity epidemic,” she explained.
Also, she said, epidemiologic studies have shown that early obesity or weight gain is a risk factor for childhood asthma development.
Study results, next steps
The study included 191 participants (age range, 2-20 years; 21% Black, 51% Hispanic) from the ongoing prospective observational New York-Presbyterian Pediatric Asthma Cohort Study, with 114 patients who had asthma and 77 controls.
The asthma group included 42% with obesity, 21% with overweight, 34% with healthy weight and 3% with underweight. Asthma was categorized as severe persistent (13%), moderate persistent (21%), mild persistent (27%) or intermittent (35%).
The researchers also analyzed 926 metabolites with less than 50% missing values.
Plasma concentrations of androgenic steroids, fatty acids and sphingomyelins were statistically significantly elevated whereas levels of glycerophospholipids and metabolites related to tyrosine metabolism were lower among the patients with asthma and overweight or obesity, compared with those with asthma and healthy weight or underweight.
Also, Permaul said that inner-city children with obesity and asthma experience substantially more metabolic alterations affecting a variety of pathways compared with those with obesity alone.
“An interesting finding in the obese child with asthma was the involvement of pathways related to oxidative stress and inflammation,” she said. “Alterations in the metabolites of vitamin A, glutathione and sphingolipid metabolism are significantly associated with obesity-related asthma in children.”
Further, during an analysis of the interaction between asthma and BMI, children with persistent asthma and increasing BMI had higher nicotinate and nicotinamide plasma metabolite levels compared with controls with no asthma, the researchers said, but these differences were not statistically significant.
Considering these findings, the researchers noted that genes and environmental factors including diet and exposures may impact disease development and severity and that these results are informative of the mechanisms associated with obesity-related asthma in children.
“Our hope is to better understand how these metabolic disturbances contribute to the challenges we face as clinicians in treating patients with this obesity-related asthma phenotype,” Permaul said. “It is likely that environmental exposures including diet as well as pollutant and allergen exposures are affecting these pathways.”
To better understand these connections and inform care, she continued, further work is needed.
“We plan on further analyzing these specific pathways in the hopes of revealing underlying mechanisms and to help develop precision therapeutics targeting this specific obesity-related phenotype as current asthma treatments are not enough,” Permaul said. “There are likely a number of endotypes underlying this obesity-related phenotype that still need to be teased out.”