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