Eating more high-fat (HF) foods was associated with asthma-like lung inflammation, based on new data from a mouse model followed by testing on human lung tissue.

Previous research has shown an association between a HF diet and airway inflammation among individuals with asthma, wrote Sam J. McCright, PhD, a medical student at the University of Pennsylvania, Philadelphia, and colleagues. The innate immune cells known as resident tissue macrophages and monocytes are generally involved in maintaining healthy tissue and defending against pathogens, but inflammatory stimuli, such as the effects of a HF diet, may cause them to contribute to obesity-associated asthma (OAA) in particular, the researchers said.

“Obesity-associated asthma is a distinct and difficult-to-treat endotype characterized by mixed granulocytic inflammation and relative steroid resistance,” said corresponding author David A. Hill, MD, of the University of Pennsylvania, in an interview. “While systemic metabolic dysfunction is known to alter innate immunity, the contribution of specific dietary lipids has been unclear,” he said.

In a study published in Science Translational Medicine, the researchers randomized mice to a HF or normal chow (NC) diet for 12 weeks and then analyzed cells isolated from their lungs. Previous research has shown immune activation in adipose tissue and the liver associated with metabolic stress, such as a HF diet. Similarly, the mice in the HF group showed worse airway inflammation than mice in the NC group.

In particular, the HF diet was associated with an increase in long-chain fatty acids, notably stearic acid, which contributed to lung inflammation.

The researchers then observed a similar inflammation in lung tissue taken from human patients with OAA, which further suggested that long-chain fatty acids may promote this type of asthma through diet.

“Our study directly interrogated the role of dietary saturated vs unsaturated fatty acids in shaping resident lung macrophage and monocyte function, with a particular focus on NLRP3 inflammasome activation and IL-1β [interleukin 1-beta] signaling,” Hill told Medscape Medical News. Establishing this mechanistic link provides a framework for understanding how diet composition modulates pulmonary inflammation and asthma severity independent of obesity, he added.

“Two observations were particularly striking,” said Hill. “First, dietary stearic acid was sufficient to exacerbate neutrophilic lung inflammation and impair lung function in the absence of overt weight gain, which highlights a direct immunomodulatory effect of saturated fat,” he said. “Second, oleic acid had the opposite effect of attenuating inflammasome activation and airway inflammation, which suggests that the balance of dietary fatty acids can bidirectionally shape lung immunity,” he noted. “These findings extend prior work on metabolic regulation of myeloid cells and emphasize the specificity of nutrient-immune interactions in the lung,” Hill said.

Takeaways and Clinical Implications

“For clinicians, the key message is that diet quality may influence the pathobiology of OAA, beyond BMI or adiposity alone,” Hill told Medscape Medical News. Although the findings are too preliminary to support dietary prescriptions for asthma management, they support ongoing attention to healthy diet patterns, such as limiting saturated fats and encouraging unsaturated fats, he said.

Importantly, the current study reinforces OAA as mechanistically distinct from classic eosinophilic, type 2-driven asthma, which has implications for treatment choice and trial design, and highlights IL-1-beta as a potential therapeutic target in OAA, Hill added. “Clinical evaluation of IL-1β blockade or upstream regulators may yield novel therapeutic strategies,” he said.

“Translational studies are now required to determine whether dietary modification alters airway inflammation or asthma outcomes in humans,” said Hill. “Specifically, controlled feeding trials assessing fatty acid composition, coupled with biomarker profiling of IL-1β and myeloid cell activation, will be critical,” he said. Studies to define which patient subgroups, such as those with obesity, neutrophil-predominant asthma, or elevated inflammasome signatures, benefit most from dietary modifications, he said. “Ultimately, integrating dietary, metabolic, and immunologic interventions could shift the paradigm for managing this high-risk asthma type,” Hill said.

Future Applications and Human Research

Studying OAA and its inflammation drivers is important because obesity-induced metabolic dysfunction may change lung immune cell populations, potentially worsening asthma, and the role of dietary components vs obesity itself in this process remains unclear, said Arianne K. Baldomero, MD, a pulmonologist and assistant professor of medicine at the University of Minnesota, Minneapolis, in an interview.

“Understanding these mechanisms can help identify new targets for treatment and improve management for affected individuals,” said Baldomero, who was not involved in the study.

The current study suggests that recognizing the impact of diets, particularly HF diet, on lung inflammation could lead to clinical recommendations promoting dietary changes to help reduce lung inflammation and potentially prevent worsening of airway diseases in at-risk patients, Baldomero told Medscape Medical News.

“Future research directions include studying live human lung resident tissue macrophages and monocytes to test the effects of dietary components on obesity-associated asthma directly,” she said. Randomized clinical trials on human participants are also needed to evaluate potential effects on health outcomes among patients with asthma, she added.

The study was supported by National Institutes of Health. Hill received additional support from the American College of Allergy, Asthma, and Immunology Junior Faculty Grant and the Children’s Hospital of Philadelphia Research Institute. Baldomero had no financial conflicts to disclose.