Airborne toxin exposure drives unique biological pattern of chronic rhinosinusitis

Researchers at the University of California San Diego and the Veterans Affairs San Diego Healthcare System have identified a distinct biological pattern of chronic rhinosinusitis (CRS), a chronic respiratory illness frequently associated with exposure to airborne toxins, such as wildfire smoke and military burn pits. The research team, led by first author and UC San Diego Assistant Professor of Medicine Xinyu "Steve" Wang, MD, PhD, found that veterans with CRS who were exposed to burn pits and other toxins show a marked increase in sinus mast cells - immune cells involved in inflammation and allergic responses. The results highlight mast cells as a potential therapeutic target for toxin-related CRS, a subtype for which no FDA‑approved treatments currently exist.

Despite numerous outstanding questions, the underlying biological drivers of the more persistent forms of CRS have remained unclear until now.

Key findings from the new study include:

• Sinus samples from toxin-exposed (military burn pit and other deployment toxins) veterans showed more than a two‑fold increase in mast cells compared to CRS patients without exposure history, despite similar levels of other types of immune cells, such as eosinophils and neutrophils.
• Veterans who were deployed longer had a greater number of mast cells compared to veterans with shorter deployments.
• Analysis of veteran tissue revealed increased activation of mast cell–related genes, including TPSAB1, HDC, and ITGB7, as well as enrichment of metabolic pathways involved in processing and eliminating foreign substances.
• In a mouse model, exposure to combustion-related compounds amplified allergen-driven inflammation and led to sustained mast cell accumulation in the sinuses, even after exposures ended.

Male mice exhibited a more pronounced mast cell response to combined allergen and toxin exposure than female mice.

While the findings indicate that airborne toxin exposure may drive a previously unrecognized form of CRS, additional research is needed in larger patient cohorts to clarify the links between toxin exposure, sex differences, allergic status, sleep-related conditions and long-term clinical outcomes.

The study was published in the Journal of Clinical Investigation and funded, in part, by the National Institutes of Health and Veterans Affairs.

Source:

University of California - San Diego

Journal reference:

Wang, X., et al. (2026). Sinus mast cell accumulation and persistence suggest a unique endotype in toxin exposure-associated chronic rhinosinusitis. Journal of Clinical Investigation. DOI: 10.1172/JCI201075. https://www.jci.org/articles/view/201075