Clinical and Biological Features of a Thickened Basement Membrane Zone in Asthma

Rationale: A subset of patients with asthma have airway pathology characterized by a thickened subepithelial basement membrane zone (“BMZ-thick asthma”). Objectives: To characterize the clinical features of BMZ-thick asthma and to determine if BMZ thickness accompanies specific patterns of inflammation in the airway epithelium. Methods: Design-based stereology was used to quantify BMZ thickness in endobronchial biopsy tissue sections from 109 patients with asthma and 41 healthy control subjects from SARP (Severe Asthma Research Program)–3, whose participants had undergone spirometry and gene expression profiling in airway epithelial brushings. Measurements and Main Results: The upper 90th-percentile value for BMZ thickness in the healthy cohort was 2.9 μM, and 35% of the asthma cohort had values above this upper limit. Compared with patients with BMZ-thin asthma, patients with BMZ-thick asthma were younger and had higher blood eosinophil numbers and serum immunoglobulin E concentrations that were specific to animal proteins. Mean prebronchodilator FEV₁ was significantly lower in patients with BMZ-thick asthma than in those with BMZ-thin asthma, but postbronchodilator FEV₁ was not. Upregulation of genes signifying IL-13 activation and the presence of mast cells were evident in epithelial brushings in patients with BMZ-thick asthma, but gene signatures for activation by IFN-g or IL-17 were not. Conclusions: A thickened BMZ marks a subset of younger patients with asthma characterized by higher immunoglobulin E concentrations to animal aeroallergens and by increased bronchomotor tone occurring in the context of airway epithelial cells activated by IL-13 and infiltrated by mast cells.