Nasal transcriptomics characterize T-helper (T)2-low asthma endotypes in a study of Puerto Rican and Dominican adults living in the U.S.
- 1UMPC Children's Hospital of Pittsburgh, University of Pittsburgh
Abstract
IMPORTANCECD4+ 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.
OBJECTIVETo characterize asthma endotypes and their association with selected variables and asthma severity/control in adults.
DESIGN, SETTING, AND PARTICIPANTSCross-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 MEASURESOur 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.
RESULTSIn 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: T2HIGH (n=16 [5.1%]), T1HIGH (n=71 [22.7%]), T17HIGH (n=96 [30.7%]), T1HIGH/T17HIGH (n=53 [16.9%]), and T2LOW/T1LOW/T17LOW(n=77 [24.6%]). In a multivariable analysis, Puerto Ricans were more likely to have a T17HIGH profile than Dominicans (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.08-5.74) and female sex was associated with T1HIGH (OR=3.44, 95% CI=1.33-8.88), T1HIGH/T17HIGHand T2LOW/T1LOW/T17LOW profiles, while COPD was associated with profiles other than T2HIGH or T1HIGH The TiHIGH 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 RELEVANCENasal 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-T2HIGH (T2LOW) asthma endotypes, and T1HIGH asthma was strongly associated with SAEs.
KEY POINTSO_ST_ABSQuestionC_ST_ABSCan nasal transcriptomics identify asthma endotypes and associated variables and outcomes in high-risk adults?
FindingsFive transcriptomic profiles were identified in Puerto Rican and Dominican adults: T helper (T)2HIGH, T1HIGH, T17HIGH, T1HIGH/T17HIGH, and T2LOW/T1LOW/T17LOW. Puerto Ricans were more likely to have a T17HIGH profile than Dominicans and female sex was associated with T1HIGH, T1HIGH/T17HIGH and T2LOW/T1LOW/T17LOW profiles, while COPD was associated with profiles other than T2HIGH or T1HIGH. The T1HIGH profile was strongly associated with severe asthma exacerbations.
MeaningWomen and Puerto Ricans were more likely to have T2LOW asthma endotypes, for which there is no specific treatment.
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BibTeX
@misc{yang2026nasal,
title = {{Nasal transcriptomics characterize T-helper (T)2-low asthma endotypes in a study of Puerto Rican and Dominican adults living in the U.S.}},
author = {S. Yang and Y.-Y. Han and S. Farid Azar and A. Pirzada and F. J. Rosser and G. Hudes and R. Kaplan and W. Chen and C. R. Isasi and R. A. Mathias and J. C. Celedon},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.14.26363037},
url = {https://www.medrxiv.org/content/10.64898/2026.09.14.26363037v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Nasal transcriptomics characterize T-helper (T)2-low asthma endotypes in a study of Puerto Rican and Dominican adults living in the U.S.
AU - S. Yang
AU - Y.-Y. Han
AU - S. Farid Azar
AU - A. Pirzada
AU - F. J. Rosser
AU - G. Hudes
AU - R. Kaplan
AU - W. Chen
AU - C. R. Isasi
AU - R. A. Mathias
AU - J. C. Celedon
PY - 2026
DA - 2026/09/14
PB - medRxiv
DO - 10.64898/2026.09.14.26363037
UR - https://www.medrxiv.org/content/10.64898/2026.09.14.26363037v1
AB - IMPORTANCECD4+ 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. OBJECTIVETo characterize asthma endotypes and their association with selected variables and asthma severity/control in adults. DESIGN, SETTING, AND PARTICIPANTSCross-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 MEASURESOur 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. RESULTSIn 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: T2HIGH (n=16 [5.1%]), T1HIGH (n=71 [22.7%]), T17HIGH (n=96 [30.7%]), T1HIGH/T17HIGH (n=53 [16.9%]), and T2LOW/T1LOW/T17LOW(n=77 [24.6%]). In a multivariable analysis, Puerto Ricans were more likely to have a T17HIGH profile than Dominicans (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.08-5.74) and female sex was associated with T1HIGH (OR=3.44, 95% CI=1.33-8.88), T1HIGH/T17HIGHand T2LOW/T1LOW/T17LOW profiles, while COPD was associated with profiles other than T2HIGH or T1HIGH The TiHIGH 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 RELEVANCENasal 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-T2HIGH (T2LOW) asthma endotypes, and T1HIGH asthma was strongly associated with SAEs. KEY POINTSO_ST_ABSQuestionC_ST_ABSCan nasal transcriptomics identify asthma endotypes and associated variables and outcomes in high-risk adults? FindingsFive transcriptomic profiles were identified in Puerto Rican and Dominican adults: T helper (T)2HIGH, T1HIGH, T17HIGH, T1HIGH/T17HIGH, and T2LOW/T1LOW/T17LOW. Puerto Ricans were more likely to have a T17HIGH profile than Dominicans and female sex was associated with T1HIGH, T1HIGH/T17HIGH and T2LOW/T1LOW/T17LOW profiles, while COPD was associated with profiles other than T2HIGH or T1HIGH. The T1HIGH profile was strongly associated with severe asthma exacerbations. MeaningWomen and Puerto Ricans were more likely to have T2LOW asthma endotypes, for which there is no specific treatment.
ER -