Severe asthma in horses is associated with increased airway innervation.

Abstract

BACKGROUND: Altered innervation structure and function contribute to airway hyperresponsiveness in human asthma, yet the role of innervation in airflow limitation in asthma in horses remains unknown. HYPOTHESIS: To characterize peribronchial innervation in horses with asthma. We hypothesized that airway innervation increases in horses with asthma compared with controls. ANIMALS: Formalin-fixed lung samples from 8 horses with severe asthma and 8 healthy horses from the Equine Respiratory Tissue Biobank. Ante-mortem lung function was recorded. METHODS: Blinded case-control study. Immunohistochemistry was performed using rabbit anti-s100 antibody as a neuronal marker for myelinating and non-myelinating Schwann cells. The number and cumulative area of nerves in the peribronchial region and associated with airway smooth muscle were recorded using histomorphometry and corrected for airway size. RESULTS: Both the number (median [IQR]: 1.87 × 10nerves/μm[1.28 × 10]) and the cumulative nerve area (CNA; 1.03 × 10CNA/μm[1.57 × 10]) were higher in the peribronchial region of horses with asthma compared with controls (5.17 × 10nerves/μm[3.76 × 10], 4.14 × 10CNA/μm[2.54 × 10], Mann-Whitney, P = .01). The number of nerves within or lining airway smooth muscle was significantly higher in horses with asthma (4.47 × 10nerves/μm[5.75 × 10]) compared with controls (2.26 × 10nerves/μm[1.16 × 10], Mann-Whitney, P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Asthma in horses is associated with greater airway innervation, possibly contributing to airway smooth muscle remodeling and exacerbating severity of the disease.