Dietary fats linked to neutrophilic asthma through lung inflammation pathways | Image Credit: © Orawan – stock.adobe.com.
Researchers at Children’s Hospital of Philadelphia (CHOP) report that dietary fats found in common processed and animal-based foods can trigger asthma-like inflammation in the lungs. The findings, published in Science Translational Medicine, suggest that dietary modifications and repurposing of existing drugs may provide new strategies for managing a difficult-to-treat asthma subtype.1,2
The study focused on neutrophilic asthma, a nonallergic subtype characterized by immune cell–driven airway inflammation. This form of asthma is often severe, less responsive to conventional therapies, and more likely to result in hospitalizations compared with allergic asthma. Although previous evidence has linked obesity with neutrophilic asthma, the underlying mechanisms have remained unclear.
“Prior to this study, many suspected that childhood obesity was causing this form of asthma. However, we were observing neutrophilic asthma in children who weren’t obese, which is why we suspected there might be another mechanism,” said senior study author David A. Hill, MD, PhD, an attending physician with the Division of Allergy and Immunology at CHOP.
Mechanisms of dietary fat–driven inflammation
The research team investigated how specific dietary lipids influence the activity of lung macrophages, immune cells that coordinate inflammatory responses. Using a preclinical model, they showed that a high-fat diet increased levels of saturated long-chain fatty acids within lung macrophages. In particular, stearic acid, a fatty acid abundant in animal fat and processed foods, accumulated in these cells and amplified airway inflammation without contributing to obesity.
In contrast, oleic acid, a monounsaturated fatty acid, reduced inflammatory activity. These divergent effects highlight the role of lipid type rather than overall fat intake in shaping immune responses.
At the molecular level, the investigators found that dietary stearic acid promoted activation of the NLRP3 inflammasome, leading to elevated secretion of the cytokine IL-1β. Both IL-1β blockade and pharmacologic inhibition of the stress-response protein inositol-requiring enzyme 1α (IRE1α) attenuated inflammation in the model.
Evidence in children with asthma
To evaluate clinical relevance, the researchers examined samples from children with obesity and asthma. They identified macrophage populations with molecular features similar to those observed in the preclinical studies, reinforcing the link between dietary fatty acids and neutrophilic asthma.
“Asthma is one of the most common chronic diseases in children, and different treatments may be needed depending on the subtype of asthma,” said study coauthor Lisa Young, MD, chief of the Division of Pulmonary and Sleep Medicine at CHOP. “While there are many risk factors and triggers that are associated with asthma, this study provides evidence about how specific dietary components are linked to a particularly difficult-to-treat form of asthma. These findings are encouraging because they provide new treatment strategies and suggest that targeted dietary modifications may help prevent this asthma type.”
Implications for management
The findings suggest that neutrophilic asthma can be driven by dietary lipids independent of obesity, offering an explanation for cases observed in children with normal weight. By clarifying the role of saturated fats in lung immune activation, the study provides a biological basis for dietary interventions as well as potential pharmacologic approaches targeting IL-1β or IRE1α pathways.
These results contribute to a growing understanding of how nutrition intersects with immune-mediated disease. The authors emphasize that although lifestyle factors remain important in asthma management, targeted therapy directed at inflammation pathways may improve outcomes for children with this subtype.
References
- Children’s Hospital of Philadelphia researchers link dietary fats to more severe form of asthma. News release. Children’s Hospital of Philadelphia. August 27, 2025. Accessed August 28, 2025. https://www.eurekalert.org/news-releases/1095986
- McCright SJ, Harding O, Chini J, et al. Dietary saturated fatty acids promote lung myeloid cell inflammasome activation and IL-1β-mediated inflammation in mice and humans. Sci Transl Med. 2025;17(813):eadp5653. doi:10.1126/scitranslmed.adp5653