New Research from the Celedón Lab for Pediatric Asthma Research Links Persistent Secondhand Smoke Exposure to Specific Asthma Subtypes in Puerto Rican Youth

A research team from the Celedón Lab for Pediatric Asthma Research in the Division of Pediatric Pulmonary Medicine at UPMC Children's Hospital of Pittsburgh published new findings on the relationship between secondhand smoke exposure and molecular subtypes or endotypes of asthma in Puerto Rican children and adolescents. The study was published in Annals of Allergy, Asthma & Immunology in March 2026.

Yueh-Ying Han, PhD, was the study's lead author. Juan C. Celedón, MD, DrPH, ATSF, chief, Division of Pediatric Pulmonary Medicine at UPMC Children's, was the senior author. Also contributing to the study from the Celedón Lab were Kimberly Pereira, MD; Franziska J. Rosser, MD, MPH; Kristina Gaietto, MD, MPH; and Wei Chen, PhD. Molin Yue, PhD, of the Department of Biostatistics and Health Data Science at the University of Pittsburgh Graduate School of Public Health, also contributed to the study.

“Our study findings support an association between persistent exposure to second-hand smoke and a subtype of asthma called “T2-low”, for which there are no specific treatments,” Dr. Han says. “In children with this type of asthma, we also show that persistent exposure to second-hand smoke was linked to worse lung function. Our study further supports the screening for tobacco smoke exposure in children with asthma and providing evidence-based smoking cessation counseling and resources to relatives of exposed children.”

About the Study

Secondhand smoke is known to make asthma worse, but it is not clear whether it contributes to a specific kind of asthma. Asthma has at least three molecular subtypes. TH2-high is the allergic form and responds to current biologic drugs. TH17-high and TH2-low/TH17-low involve different immune pathways and at present have no targeted therapeutic options for individuals with asthma.

Identifying these subtypes has traditionally required analysis of tissue from the lower airways, which is challenging to obtain. Dr. Han and colleagues instead sampled cells from the nasal epithelium, which serve as a proxy for cells in the lower airway and measured the expression of eight signature genes to assign each child to an asthma subtype.

The study followed 337 Puerto Rican youths from childhood through adolescence, with a first visit between ages 6 and 14 years and a second between ages 9 and 20 years. Caretakers reported on smoke exposure during pregnancy, in the first two years of life, and at school age. Children were sorted into four groups: never exposed, early life only, school age only, and persistent.

Children with persistent exposure had 2.2 times higher odds of TH17-high asthma and 2.6 times higher odds of TH2-low/TH17-low asthma than children who were never exposed. The risk of TH2 asthma was not significantly different. Children with TH2-low/TH17-low asthma and persistent exposure also had worse lung function, with percent predicted FEV1 and FEV1/FVC measures 6.6% to 13.7% lower than their unexposed peers.

When examining underlying biology, they found that the gene activity patterns in these children pointed to mitochondrial dysfunction and oxidative stress, two cellular processes that have been tied to long-term smoke-related lung damage in other studies.

Translating the Findings

The children most affected by these findings are the ones for whom current asthma care has the least to offer. Biologic therapies target the allergic pathway, leaving children with TH17-high or TH2-low/TH17-low asthma without precision options. Identifying secondhand smoke as a likely driver of these subtypes points to a population that should be a priority for smoke reduction efforts and to processes (altered lung development and structure, mitochondrial damage and oxidative stress) that could be targets for new therapies. This would be of particular importance for Puerto Rican youths, who have both a high asthma burden and high household smoke exposure.

Reference

Han YY, Yue M, Pereira K, Rosser FJ, Gaietto K, Chen W, Celedón JC. Persistent exposure to second-hand smoke and asthma endotypes in a study of Puerto Rican youth. Ann Allergy Asthma Immunol. 2026 Mar 22; Online ahead of print. Note: Paper is open access.