Obesity linked to poor response to inhaled steroids in children with asthma 

By Selina Wellbelove

15 Sep 2021

Children with asthma who are overweight or obese may be less likely to respond to treatment with inhaled steroids potentially increasing their risk of asthma attack, according to findings of an observational study presented at ERS 2021.

The research, led by Dr Cristina Longo at Amsterdam University Medical Centre is the first to consider genetic variants linked to body mass index (BMI) in determining whether a poor response to inhaled corticosteroids (ICS) was likely caused by excess weight or other factors.

The study looked at data on 1,511 children with asthma, aged between two and 16 years, from five international studies (ALSPAC in England, PAGES in Scotland, PACMAN in The Netherlands, HPR in the US, CLARA in Germany). All children were using ICS, and a poor response was defined as one or more asthma attacks requiring urgent medical care and/or a course of oral corticosteroids.

The researchers developed a ‘risk score’ for children’s BMI z-scores (a measure of relative weight adjusted for age and sex) incorporating information on the child’s age and sex, asthma diagnosis, asthma characteristics, BMI, allergies, exposure to harmful environmental triggers like smoking, and genetic variants linked to BMI status.

The findings showed a clear relationship between ICS response and weight. “Although poor ICS response ranged from 20% to 80% between the five international studies, we consistently show that the proportion of children with poor ICS response more than doubled for each one unit increase in the BMI z-score,” Dr Longo said.

ICS guideline rethink

Inhaled steroids are currently recommended in treatment guidelines for children with asthma who have a higher-than-normal BMI, but according to the study authors their data suggests that this might need to change.

“Our findings imply that overweight children could be taking ICS without any benefit”, said Dr Longo. “Our research group felt that the one-size fits-all approach to treating children with asthma with inhaled steroids as their first-line treatment, particularly those with excess weight, warrants revision.”

She called for prioritisation of research to identify potential alternative treatments to ICS, as 30% of children with asthma are also obese. “With the childhood obesity epidemic rising, we expect this percentage to increase, meaning this problem of poor control will be seen more frequently in routine clinical practice.”

Professor Andrew Bush, a Consultant Paediatric Chest Physician at Royal Brompton Harefield NHS Foundation Trust, agreed that the current approach needs revising. “Inhaled steroids are great for treating those with eosinophilic airway disease, but not those without, and some/many obese asthmatics fall into the latter category,” he told the limbic.

Obesity and asthma involved a complex set of interactions, he said and was highly relevant to societies with high rares of childhood obesity.

“Key issues include over-diagnosis of asthma in the obese and evidence that asthma in the obese may be different; for example, obese children may have dysanaptic airway growth and the airways may be the target of systemic inflammation, given that obesity is pro-inflammatory,” he noted.

Dr Longo has also investigated whether genetic variants known to be linked to poor ICS response were more commonly found in obese children with asthma than those of normal weight.

“We found that a particular variant in the NEGR1 gene was significantly more common in obese versus non-obese children,” shje said.

“This variant has been implicated in dysfunction of a hormone called leptin that regulates feelings of hunger. This could suggest that leptin dysfunction could be a potential culprit for poor ICS response in children with obesity-related asthma,” she said.

Professor Chris Brightling, Chair of the ERS Science Council and Professor of Respiratory Medicine at the University of Leicester, UK, said the findings highlight that “policymakers, healthcare providers and families need to do much more to tackle the growing obesity epidemic in young people.”

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