Airway hyperresponsiveness is dissociated from airway wall structural remodeling

Background

Nonasthmatic eosinophilic bronchitis (EB) has emerged as a useful tool to study the structural and inflammatory mechanisms of airway hyperresponsiveness (AHR) in asthma. We have previously shown that vascular remodeling and reticular basement membrane (RBM) thickening are present in EB. However, it is not known whether other features of structural remodeling including increased airway smooth muscle (ASM) mass, matrix deposition, and glandular hyperplasia are also present in EB.

Objectives

We sought to determine whether structural remodeling occurs in EB and is associated with AHR and airflow limitation.

Methods

Forty-two patients with asthma, 21 patients with EB, and 19 healthy volunteers were recruited. ASM area, RBM thickness, collagen 3 deposition, glandular area, mast cells, and granulocytes were assessed in bronchial biopsy samples.

Results

Nonasthmatic eosinophilic bronchitis and asthma were associated with a significant increase in ASM mass and RBM thickness compared with healthy subjects. In contrast, we did not observe any significant differences in collagen 3 deposition in the lamina propria and ASM or the % area of glands in the lamina propria. Univariate analysis demonstrated that mast cell numbers in the ASM were the only feature of remodeling associated with AHR (β = –0.51; P = .004). Stepwise linear regression revealed that a combination of mast cell numbers in the ASM (β = –0.43) and disease duration (β = –0.25; model-adjusted R² = 0.26; P = .027) best modeled AHR.

Conclusion

Mast cell localization to the ASM bundle, but not structural remodeling of the airway wall, is associated with AHR in asthma.

Key words: Asthma, nonasthmatic eosinophilic bronchitis, airway hyperresponsiveness, mast cell, remodeling

Abbreviations used: AHR, Airway hyperresponsiveness, ASM, Airway smooth muscle, EB, Nonasthmatic eosinophilic bronchitis, GINA, Global Initiative for Asthma, RBM, Reticular basement membrane, UK, United Kingdom