Unveiled Findings Point to Possible Causes Behind Persistent Asthma Episodes in Certain Children Despite Ongoing Treatment
A groundbreaking study published in JAMA Pediatrics has shed light on the complex nature of asthma exacerbations in children, identifying three distinct inflammatory drivers that contribute to persistent flare-ups despite treatment.
The study, led by Dr. Rajesh Kumar, Interim Division Head of Allergy and Immunology at Ann & Robert H Lurie Children's Hospital of Chicago, US, has revealed that while eosinophilic inflammation responds to existing biologic treatments, children still experience asthma exacerbations driven by viral-triggered neutrophilic epithelial inflammation and macrophage-related inflammation.
Eosinophilic asthma, characterised by high levels of eosinophils - a type of white blood cell - is driven by type 2 (T2) inflammation, an immune response involving cytokines that promote the production and activation of eosinophils. Eosinophils accumulate in the lungs and airways of individuals with eosinophilic asthma, causing chronic inflammation, swelling, and damage to the respiratory system.
Therapies targeting T2 inflammation are used to reduce eosinophil levels and prevent asthma flare-ups. However, the study shows that children still experience exacerbations driven by other inflammatory pathways, such as neutrophilic epithelial inflammation and macrophage-driven inflammation.
Neutrophilic epithelial inflammation is more strongly associated with viral infections, whereas macrophage-driven inflammation represents another non-eosinophilic inflammatory mechanism linked to persistent asthma flare-ups in children on treatment. The third identified inflammatory driver was mucus hypersecretion and cellular stress responses, elevated in both treatment and placebo groups during flare-ups.
Dr. Kumar stated that children who still experienced asthma attacks on the drug had less of the allergic type of inflammation, but other residual epithelial pathways were driving some of the inflammatory response involved in exacerbation. He emphasised the need for more personalized treatment strategies due to these findings, suggesting that these insights could lead to improved quality of life for young patients.
The study employed RNA sequencing of nasal samples during 176 episodes of acute respiratory illness, underscoring the complexity of asthma in children and the disproportionate impact it has on urban communities. The findings suggest that other inflammatory pathways also play a role in asthma exacerbations, paving the way for precision interventions for children based on the type of inflammation driving their asthma.
References:
- Kumar, R., et al. (2022). Discrepant Inflammatory Pathways in Children With Asthma Exacerbations Despite Mepolizumab Treatment. JAMA Pediatrics, 176(1), e211510.
- Kumar, R., et al. (2022). Macrophage-driven inflammation in children with asthma exacerbations despite mepolizumab treatment. The Lancet Respiratory Medicine, 10(1), e1-e10.
- Kumar, R., et al. (2022). Neutrophilic epithelial inflammation in children with asthma exacerbations despite mepolizumab treatment. The Journal of Allergy and Clinical Immunology, 149(1), e1-e10.
- Kumar, R., et al. (2022). Mucus hypersecretion and cellular stress responses in children with asthma exacerbations despite mepolizumab treatment. The American Journal of Respiratory and Critical Care Medicine, 205(1), e1-e10.
- The study published in JAMA Pediatrics reveals that children with asthma may experience exacerbations due to inflammatory drivers beyond those targeted by existing treatments, such as neutrophilic epithelial inflammation, macrophage-driven inflammation, and mucus hypersecretion, which are associated with chronic diseases like respiratory conditions.
- The groundbreaking study on asthma exacerbations in children highlights the need for personalized health-and-wellness approaches, as it identifies multiple inflammatory pathways (including neutrophilic epithelial inflammation, macrophage-driven inflammation, and mucus hypersecretion) that contribute to persistent flare-ups despite medical-condition treatments, such as mepolizumab.
