Distinct molecular profiles underpin mild to moderate equine asthma cytological profiles

This project used a state-of-the-art, multi-omics approach to improve our understanding of the aetiopathogenesis of a highly prevalent, performance-limiting disorder of racehorses; mild to moderate equine asthma (MMEA). This advanced knowledge is a prerequisite to improving prophylactic, management and therapeutic options for this condition. Although a number of risk factors for MMEA have been identified, incomplete understanding of the precise aetiopathogenesis of this syndrome means that options for intervention are currently limited. This study aimed to apply a multi-omic approach, reveal key inflammatory pathways involved in inflammatory cell recruitment to the lower airways and highlight pathways specific to different MMEA inflammatory cell profiles (MMEA endotypes). Thus, we compared BALF cell gene and protein expression data from horses with normal bronchoalveolar lavage fluid (BALF) cytology (n = 8) with those isolated from horses with neutrophilic (n = 4), mastocytic (n = 8), mixed neutrophilic/mastocytic (n=4) and mixed eosinophilic/mastocytic (n=3) inflammation. Analyses on transcriptomic and proteomic data derived from BALF cells from horses with neutrophilic cytology showed enrichment in classical inflammatory pathways, while horses with mastocytic cytology showed enrichment in pathways involved in hypersensitivity reactions related to non-classical inflammation that could mimic a Th2 immune response. The mixed eosinophilic/mastocytic group also presented with a non-classical inflammatory profile while, the mixed neutrophilic/mastocytic group revealed profiles consistent with both neutrophilic inflammation and hypersensitivity. Our adopted multi-omics approach (both gene and protein expression) has enabled a more holistic assessment of the immunological status of the lower airways associated with the different cytological profiles of equine asthma. Overall design: Bronchoalveolar lavage fluid cell gene and protein expression data from horses with normal bronchoalveolar lavage fluid cytology (n = 8) with those isolated from horses with neutrophilic (n = 4), mastocytic (n = 8), mixed neutrophilic/mastocytic (n=4) and mixed eosinophilic/mastocytic (n=3) inflammation was analysed using RNAseq and proteomic analysis, respectively.