Distinct molecular profiles underpin mild to moderate equine asthma cytological profiles

A state-of-the-art multi-omics approach was applied to improve our understanding of the aeti-opathogenesis of a highly prevalent, performance-limiting disorder of racehorses; mild to moderate equine asthma (MMEA). This is a prerequisite to improving prophylactic, management and ther-apeutic options for this condition. Although a number of risk factors have been identified, options for intervention are limited. This study applied a multi-omic approach to reveal key inflammatory pathways involved in inflammatory cell recruitment to the lower airways and highlight distinct MMEA inflammatory profiles. We compared bronchoalveolar lavage fluid (BALF) cell gene and protein expression data from horses with non-inflammatory BALF cytology with those isolated from horses with neutrophilic, mastocytic, mixed neutrophilic/mastocytic and eosinophilic/mastocytic inflammation. Analyses on transcriptomic/proteomic data derived from BALF from horses with neutrophilic cytology showed enrichment in classical inflammatory pathways, while horses with mastocytic showed enrichment in pathways involved in hypersensitivity reactions related to non-classical inflammation potentially mimicking a Th2-immune response. The mixed eosino-philic/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 provided a holistic assessment of the immu-nological status of the lower airways associated with the different cytological profiles of equine asthma.