Eosinophils, Airway Hyperresponsiveness, and Type 2 Inflammation in Asthma

Intraepithelial eosinophils are specific to asthma and are associated with endogenous airway hyperresponsiveness (AHR) and type-2 (T2) inflammation, thereby interacting with intraepithelial mast cells to regulate airway inflammation, according to a cross-sectional study published in the European Respiratory Journal.

Eosinophils have been found to be involved in the pathogenesis of asthma and have been associated with T2 inflammation based on correlations with immunostaining for eosinophils in the airway tissue, induced sputum, and peripheral blood. However, no studies have used quantitative morphometry to precisely measure the density of eosinophils within the different compartments of the airway wall.

In the current study, researchers sought to quantify these eosinophils and associate the findings with clinical features of asthma and markers of airway inflammation. They used design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space in individuals with asthma, relating these findings to AHR and features of airway inflammation. The study analysis used endobronchial biopsy samples from a repository collected at the University of Washington in Seattle for the purpose of examining differences between mild to moderate asthma in those with and without exercise-induced bronchoconstriction [EIB].  The current study included 30 samples from individuals with asthma (18 with EIB and 12 without) and from 10 healthy controls.

The investigators found that intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type of AHR that is most specific for asthma. However, both intraepithelial and subepithelial eosinophils were associated with T2 inflammation, with the strongest association between interleukin 5 (IL-5) expression and intraepithelial eosinophils. The researchers also found that eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. Interleukin-33 (IL-33) and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils, and CysLT leukotriene C₄ (LTC4) along with IL-33 increased IL-13 expression in mast cells and altered their protease profile.

“These findings provide evidence that eosinophils and mast cells interact within the airway epithelial compartment in a cytokine milieu that includes IL-33, IL-5, and CysLTs and may cooperate to regulate features of T2 inflammation and AHR,” concluded the authors.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Al-Shaikhly T, Murphy RC, Parker A, et al. Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma. Eur Respir J. Published online January 13, 2022. doi:10.1183/13993003.01865-2021