Nasal transcriptomics characterize T-helper (T)2-low asthma endotypes in a study of Puerto Rican and Dominican adults living in the U.S.

IMPORTANCE: CD4+ T helper (T) 1, T2 and T17 cells have helped identify asthma endotypes in predominantly non-Hispanic White adults. Identifying asthma endotypes in diverse subgroups should help develop personalized medicine in asthma. OBJECTIVE: To characterize asthma endotypes and their association with selected variables and asthma severity/control in adults. DESIGN SETTING AND PARTICIPANTS: Cross-sectional and longitudinal analyses of nasal samples from the SOL-Asthma study of Puerto Rican and Dominican adults with (cases, n=313) and without (controls, n=371) asthma in the Bronx (NY) and Chicago (IL), with replication of selected findings in 376 adults of African ancestry in CAAPA. MAIN OUTCOMES AND MEASURES: Our primary outcome was asthma endotypes identified through nasal expression of "signature genes" for 3 T2, 5 T1, and 5 T17 pathways. Multinomial logistic regression was used for the analysis of asthma endotypes (with controls as the reference outcome category) at a baseline visit, as well as for the analysis of severe asthma exacerbations (SAEs) at baseline and during a 1-year follow-up. We attempted to replicate the identified profiles in CAAPA. RESULTS: In SOL-Asthma, cases were more likely to be female, Puerto Rican, and current/former smokers, and to have physician-diagnosed COPD than controls. Five transcriptomic profiles were identified in cases: T2 HIGH (n=16 [5.1%]), T1 HIGH (n=71 [22.7%]), T17 HIGH (n=96 [30.7%]), T1 HIGH /T17 HIGH (n=53 [16.9%]), and T2 LOW /T1 LOW /T17 LOW (n=77 [24.6%]). In a multivariable analysis, Puerto Ricans were more likely to have a T17 HIGH profile than Dominicans (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.08-5.74) and female sex was associated with T1 HIGH (OR=3.44, 95% CI=1.33-8.88), T1 HIGH /T17 HIGH and T2 LOW /T1 LOW /T17 LOW profiles, while COPD was associated with profiles other than T2 HIGH or T1 HIGH The Ti HIGH profile was associated with >1 SAE in the year prior to baseline and during the one-year follow-up (OR=4.31, 95% CI=1.26-14.77). Each profile had unique differentially expressed genes (DEGs), with substantial replication of the profile distribution and DEGs in CAAPA. CONCLUSIONS AND RELEVANCE: Nasal transcriptomics identified profiles corresponding to five asthma endotypes in a cohort of Puerto Rican and Dominican adults. Puerto Rican background, female sex, and physician-diagnosed COPD were associated with non-T2 HIGH (T2 LOW ) asthma endotypes, and T1 HIGH asthma was strongly associated with SAEs. KEY POINTS: Question: Can nasal transcriptomics identify asthma endotypes and associated variables and outcomes in high-risk adults?Findings: Five transcriptomic profiles were identified in Puerto Rican and Dominican adults: T helper (T)2 HIGH , T1 HIGH , T17 HIGH , T1 HIGH /T17 HIGH , and T2 LOW /T1 LOW /T17 LOW . Puerto Ricans were more likely to have a T17 HIGH profile than Dominicans and female sex was associated with T1 HIGH , T1 HIGH /T17 HIGH and T2 LOW /T1 LOW /T17 LOW profiles, while COPD was associated with profiles other than T2 HIGH or T1 HIGH . The T1 HIGH profile was strongly associated with severe asthma exacerbations. Meaning: Women and Puerto Ricans were more likely to have T2 LOW asthma endotypes, for which there is no specific treatment.