Decoding the biology of ethnic differences in asthma

Ethnicity seems to be a risk factor for asthma and its exacerbation, but no general consensus has been reached so far. Ethnic diversity and differences have long been overlooked and most studies in these regards are observational, lacking in-depth mechanistic insights. Harnessing comprehensive transcriptomic data at organ system and single cell levels, we comparatively analyzed the signalling landscapes of African American/Black (AA) and other ethnicities. In healthy individuals, most AA PBMC subsets exhibited elevated IL2-STAT5 signals, which is critically implicated in asthma pathogenesis. This extended to various compartments (bronchial and airway epithelium, circulating CD4+ T cells and blood) in asthma, where AA upregulated IL2-STAT5 pathway relative to other ethnicities. Mechanistically, the increased IL2-STAT5 signalling correlated with enhanced T cell migration and recruitment. Together, they might contribute to the greater predisposition towards asthma exacerbation in AA. This first-of-its-kind study sheds some in-depth insights into the biology of ethnic differences in asthma. Our findings, if further validated, will be valuable for future asthma research and clinical practice like therapeutic development and treatment guidance, highlighting the need for ethnicity diversity and inclusions in these areas.