Association of Long-term Air Pollution and Allergen Exposure with Endotype Shift in Chronic Rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is classified into Type 2 and non-Type 2 inflammation based on mucosal cytokine level. Over 20 years, the Type 2/non-Type 2 ratio has increased, potentially influenced by air pollution and aeroallergens.

Objective: This study investigates the association between long-term exposure to air pollutants and aeroallergens and the endotype shift in CRSwNP.

Methods: We enrolled 2,358 CRSwNP patients from Guangzhou and 416 from Ghent. Endotypes were defined using a diagnostic model or IL-5 levels in nasal polyps. Pollutant exposure was estimated based on residential ZIP code. Generalized additive models with restricted cubic splines and generalized linear mixed models were used to assess the effects of PM2.5, PM10, NO2, SO2, O3, and aeroallergen exposure on Type 2 CRSwNP risk compared to non-Type 2.

Results: Higher air pollutant exposure was linked to a lower Type 2/non-Type 2 ratio. In Guangzhou, every 1 μg/m³ increase in 3-year cumulative PM2.5 exposure was associated with an OR of 0.97 (95% CI: 0.96-0.98, P < 0.001) for Type 2 CRSwNP. In Ghent, the Relative Risk (RR) was 0.78 (95% CI: 0.65-0.94, P = 0.009) for the same exposure increase. Elevated total IgE and Dermatophagoides pteronyssinus sensitization increase Type 2 risk over non-Type 2 CRSwNP in Guangzhou, while allergic rhinitis, elevated total IgE, pollen sensitization, and multi-allergens sensitization increased Type 2 CRSwNP risk in Ghent.

Conclusion: Decreasing long-term air pollution exposure and increasing allergen sensitization is associated with higher Type 2/non-T 2 CRSwNP ratio, highlighting the role of environmental factors in endotype shifting.