Airway smooth muscle remodelling in mild and moderate equine asthma.

Abstract

BACKGROUND: Airway smooth muscle remodelling in severe equine asthma includes both thickening of airway smooth muscle, resulting from hyperplasia and hypertrophy, and changes in contractility. However, airway smooth muscle changes have not been studied in milder forms of the disease. OBJECTIVES: To investigate bronchial smooth muscle remodelling in horses with mild and moderate asthma (MEA). STUDY DESIGN: Retrospective case-control study. METHODS: The endobronchial biopsies from 18 horses with MEA referred to the Equine Hospital of the Université de Montréal and from seven healthy age-matched control horses were studied. The diagnosis was based on clinical signs and bronchoalveolar lavage fluid cytology. Airway smooth muscle cell proliferation was measured by quantifying the expression of the proliferating cell nuclear antigen (PCNA) using immunohistochemistry and histomorphometry. The expression of the (+)insert smooth muscle myosin heavy chain (SMMHC) isoform, an hypercontractile protein, was assessed by RT-qPCR. RESULTS: Expression of the (+)insert SMMHC isoform in airway smooth muscle was approximately 1.5 times greater in horses with MEA compared with controls (P = .02, mean difference 0.01). Although there were no differences between groups in the proliferation of airway smooth muscle cells (P = .4) or myocyte density (P = .3, mean difference -0.6), the percentage of proliferating myocytes was correlated to pulmonary neutrophilia in horses with neutrophilic inflammation (P = .01, r = .80) and to the expression of the (+)insert SMMHC isoform in asthmatic horses (P = .03, r = .66). MAIN LIMITATIONS: Small cohorts of horses were studied, and conclusions are limited to the central airways. CONCLUSIONS: These results confirm the presence of bronchial smooth muscle remodelling in mild forms of equine asthma and pave the way for the development of biomarkers to measure asthma progression and response to therapy.