Relationships between basement membrane zone thickness and airway physiology, epithelial gene expression, and innate immune cell infiltration in asthma

Rationale Thickening of the basement membrane zone (BMZ) has often been identified in airway biopsies of individuals with asthma, but the relationship of BMZ thickness with airway dysfunction and inflammation is incompletely understood. Objectives Characterize the relationship between BMZ thickness and airway physiology, immune cell infiltration, and airway gene expression. Methods We used design-based stereology to measure BMZ thickness in endobronchial biopsy samples obtained from 10 healthy control subjects and 31 individuals with asthma not receiving asthma-directed anti-inflammatory therapies (only using as needed albuterol for the study period). BMZ thickness was correlated with measures of airway physiology, sputum inflammatory markers, airway wall immunopathology, and gene expression from airway epithelial brushings. Results Individuals with asthma had a significantly thicker BMZ relative to healthy controls. BMZ thickness was negatively correlated with age and positively correlated with higher baseline lung function (FVC), mast cell (MC) infiltration of the airway epithelial compartment, and expression of type 2 (T2) inflammatory genes in the airway. Thickening of the BMZ was not significantly associated with the bronchodilator response, direct airway hyperresponsiveness (AHR) to methacholine, indirect AHR in the form of exercise-induced bronchoconstriction, T1 or T3 inflammation, or airway eosinophilia. Conclusions MC infiltration of the airway epithelial compartment and T2 inflammation are significantly associated with a thickened BMZ in asthma.