The study prompts a closer look at how asthma is managed in such settings, when treatment appears to fail, what’s actually happening in the child’s body, and at what point doctors consider changing course.
Published Aug 05, 2025 | 6:33 PM ⚊ Updated Aug 05, 2025 | 6:33 PM
Asthma. (Representative image/ iStock)
Synopsis: A U.S. study reveals that children with asthma may suffer flare-ups despite biologic treatment like mepolizumab due to non-T2 inflammation. In India, persistent asthma is common amid poor air quality, viral infections, and indoor triggers. Experts stress personalised care, better diagnostics, and policy-level action to address environmental factors and improve access to advanced, cost-effective treatments.
A recent US study published in JAMA Paediatrics by Altman MC, Janczyk T, Murphy RC, et al., has offered new insights into why some children with asthma continue to have severe flare-ups even when they’re on advanced biologic treatments.
The researchers followed urban children with eosinophilic asthma who were part of a clinical trial testing mepolizumab, a drug that targets type 2 (T2) inflammation.
While the medication did reduce T2 activity, many of the children still experienced exacerbations triggered by other immune responses, particularly those linked to airway cells, macrophages, and mucus-related pathways. The findings suggest that asthma flare-ups in children may involve multiple inflammatory mechanisms, not just the ones most treatments currently target.
Though the study was conducted in the U.S., its relevance extends beyond borders, especially to countries like India, where paediatric asthma remains a daily struggle for many families. In cities where pollution, cramped housing, and delayed care are common, it’s not unusual to see children experience repeated attacks despite sticking to their medication.
The study prompts a closer look at how asthma is managed in such settings, when treatment appears to fail, what’s actually happening in the child’s body, and at what point doctors consider changing course.
This U.S.-based study was a secondary analysis of the MUPPITS-2 clinical trial, which enrolled children with eosinophilic asthma who were prone to frequent exacerbations. Participants, from nine low-income urban centres, were given either mepolizumab or a placebo once every four weeks over the course of a year. The aim was to understand why some children still experienced flare-ups despite being on targeted biologic treatment.
To investigate, researchers analysed nasal samples collected during episodes of acute respiratory illness. They found that in children receiving mepolizumab, there was a notable decrease in type 2 (T2) inflammation markers, specifically those linked to eosinophils.
However, this reduction was accompanied by increased expression of other inflammatory pathways involving the airway lining, mucus production, and macrophage activation. The study noted, “during illness events resulting in asthma exacerbations, these non-T2 pathways were significantly more active compared to those in the placebo group.”
While both treatment and placebo groups showed signs of mucus hypersecretion and stress responses during flare-ups, the underlying immune activity differed. In the mepolizumab group, epithelial inflammation was seen even without a respiratory virus, whereas macrophage-related pathways were more prominent during virus-linked exacerbations.
The researchers observed that “macrophage pathways contributed specifically to viral exacerbations,” pointing to how distinct triggers activate different arms of the immune system.
The findings point to a complex picture: reducing T2 inflammation alone may not prevent all asthma flare-ups. The study concluded that “multiple distinct inflammatory axes can independently contribute to asthma exacerbations,” highlighting the need for broader, more personalised treatment strategies, especially in children with persistent symptoms despite standard biologic therapies.
Managing asthma in children can be especially challenging in Indian settings, where both environmental and treatment-related factors often differ from those seen in the West.
“In India, despite strict adherence to medications and controlling known triggers, a significant proportion of children continue to have uncontrolled asthma,” said Dr Sameer Bansal, Senior Consultant Pulmonologist at Vaayu Chest and Sleep Specialists and Apollo Hospital, Bangalore.
Speaking with South First, he noted that this is seen in both adults and children, particularly with the rise in viral infections and deteriorating air quality. “These are the people who become candidates for biologic therapies,” he added, especially when high levels of airway inflammation are confirmed through blood tests or diagnostics such as Fractional Exhaled Nitric Oxide (FENO), a non-invasive test used to measure the level of inflammation in the airways.
Environmental exposures in India present a very different profile compared to Western countries. “Unlike the western world, we have multiple triggers ranging from the poor air quality outside to loads of in-house triggers such as mosquito repellents, incense sticks, routine dusting, fungus due to dampness on the walls and cockroaches,” he said.
Viral infections further increase airway sensitivity, especially among predisposed children. Dr Bansal emphasised that treatment always begins with identifying and addressing these triggers, alongside ensuring consistent and correct use of medication.
Access to advanced treatments like mepolizumab continues to be limited in India due to cost. Still, in some cases, they become necessary. “The cost of repeated exacerbations leading to hospitalisations alone is a lot. And if biologics can reduce this burden, the cost is justified,” he said.
For children who don’t respond to standard inhaled corticosteroids, Dr Bansal underscored the need to re-evaluate every aspect, from trigger exposure and medication compliance to comorbidities like gastritis and vitamin D deficiency. Immunotherapy may be considered in some cases, although outcomes can vary.
Precision diagnostics, such as the nasal RNA sequencing used in the U.S. study, hold potential but face major barriers in India. “Precision, targeted medicine therapy are the buzzwords in the current era,” he said.
While such tools are available, their high cost puts them out of reach for many patients, especially from lower-income backgrounds. “The need of the hour is affordable point-of-care testing which is reliable, accurate and cost-effective,” he said, calling for government support to bring down costs and widen access.
In recent years, hospitals have reported a notable rise in persistent cough cases and viral infections among children, with estimates suggesting a 30 to 40 percent increase. This trend has also driven up the number of children needing biologic therapy. Dr Bansal added, “It is high time we take decisions at policy level to take care of modifiable factors such as pollution, vaccinations and awareness.”
(Edited by Sumavarsha)
