Certain dietary fats found to trigger hard-to-treat asthma in children

Researchers at Children's Hospital of Philadelphia (CHOP) found that certain lipids, or fats, in obesity-causing foods also cause asthma-like lung inflammation. The findings suggest that in addition to modifying dietary choices, certain existing drugs could be repurposed to help treat this type of asthma. The findings were published online today by the journal Science Translational Medicine.

The study was prompted by researchers noticing an association between childhood obesity and neutrophilic asthma, a non-allergic type of asthma triggered by microbial and bacterial proteins. Neutrophilic asthma is more difficult to treat than allergic asthma and more likely to be severe enough to send patients to the hospital, but researchers did not understand the underlying causes of this type of asthma.

To study this in more detail, researchers focused on lung macrophages, which are specialized white blood cells that coordinate immune function during inflammation. While metabolic stress can alter macrophage function, the effects of specific dietary components were unclear. In this study, the researchers found that certain dietary fats, including those used in processed foods, shape macrophage activation in the lungs during inflammatory responses.

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. What we found in both preclinical work and studies in children was that diets containing certain saturated long chain fatty acids can cause neutrophilic asthma independent from obesity."

David A. Hill, MD, PhD, senior study author, attending physician, Division of Allergy and Immunology, Children's Hospital of Philadelphia

The researchers first explored a high fat diet in a preclinical animal model, where they found that lung macrophages accumulated a saturated long chain fatty acid called stearic acid, which is often found in animal fat and processed foods. Notably, dietary stearic acid worsened airway inflammation without causing obesity. Conversely, oleic acid, a monounsaturated long chain fatty acid, suppressed inflammatory activity. The researchers also found that blocking the inflammatory cytokine IL-1β or inhibiting the protein IRE1⍺ – both of which are found in increased levels in neutrophilic asthma – protected against stearic acid-driven lung inflammation. The study confirmed some of these preclinical findings in a group of obese children with 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 co-author Lisa Young, MD, Chief of the Division of Pulmonary and Sleep Medicine at Children's Hospital of Philadelphia. "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."

This study was supported by National Institutes of Health grants K08 DK116668, R01 HL162715, 5T32 DK007314-43, K24HL143281, an American College of Allergy, Asthma, and Immunology Junior Faculty Grant, the Children's Hospital of Philadelphia Research Institute, and the University of Pennsylvania Michael Brown Graduate Research Fellowship.