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

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.

To characterize asthma endotypes and their association with selected variables and asthma severity/control in adults.

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.

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.

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.

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.

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.