Abstract: Background – Altered innervation structure and function contributes to airway hyperresponsiveness in humans with asthma. However, the morphology of equine airway innervation and its contribution to airflow limitation in equine asthma remains largely unknown.
Hypothesis/Objectives – To characterize peribronchial innervation in horses with asthma. We hypothesized that peribronchial innervation increases in horses with asthma compared to controls.
Animals – Formalin-fixed lung samples from eight horses with severe asthma (five in exacerbation, three in remission) and eight controls. Lung function had been recorded prior to sample collection.
Methods – Blinded case-control study. Immunohistochemistry was performed using rabbit anti-s100 antibody as a marker for myelinating and non-myelinating Schwann cells. Using histomorphometry, the number and the area of nerves in the peribronchial region and associated to airway smooth muscle were recorded and corrected for airway size.
Results – Both the number and the area of peripheral nerves were increased in the peribronchial region of horses with asthma (median (range): 1.87x10-5 nerves/um2 (6.25x10-6-6.29x10-5) and 1.03x10-3 nerve area/um2 (5.40x10-4-2.38x10-3)) compared to controls (5.17x10-6 nerves/um2 (2.37x10-6-1.94x10-5) and 4.14x10-4 nerve area/um2 (1.08x10-4-1.61x10-3)) (Mann-Whitney, p< 0.01). The number of nerves within or surrounding airway smooth muscle was significantly increased in horses with asthma (4.47x10-6 nerves/uum2 (2.10x10-6-2.73x10-5)) compared to controls (2.26x10-6 nerves/um2 (4.60x10-7-1.07x10-5)) (Mann-Whitney, p< 0.05). Airway innervation in horses in exacerbation was not correlated with resistance or elastance (Spearman’s correlation: r< 0.35, p>0.50).
Conclusions and clinical importance – Equine asthma is associated with increased airway innervation, which may contribute to airway smooth muscle remodeling and asthma severity.
