Researchers from the University of Pittsburgh School of Public Health, in collaboration with the Severe Asthma Research Program, announced on June 24 that they have identified biological pathways showing how air-pollution exposure interacts with a person's genes to exacerbate asthma. The findings were published in eBioMedicine and could eventually lead to new approaches for asthma treatment and targeted public health interventions.
The study analyzed data from nearly 1,000 adults with asthma across the United States who had enrolled in the Severe Asthma Research Program. The researchers combined whole genome sequencing, air pollution exposure data, and gene-expression profiling. They focused on about 450 genes involved in oxidative stress—a process where reactive molecules can damage cells and tissues.
"Those stresses on cells can translate into serious physiologic effects, like worsening lung function or asthma exacerbations," said Sally Wenzel, M.D., corresponding author of the study, chair of Pitt Public Health's Department of Environmental and Occupational Health, and director of Pitt's Asthma and Environmental Lung Health Institute at UPMC. Wenzel co-led the study with Shuangjia Xue.
The team specifically examined how these genes interacted with fine particulate matter known as PM2.5—microscopic particles less than 2.5 microns in diameter that are considered one of the most harmful components of air pollution due to their ability to penetrate deep into lungs. "In these individuals who were living with asthma, the higher their exposure to this particulate matter, the lower their lung function overall," said Wenzel.
This research was notable for using human airway samples collected through bronchial brushings from about 200 participants to analyze gene transcription—how DNA is converted into RNA, which then directs protein production within cells. According to Wenzel, "Genes lay out who we could be, but the RNA, and the proteins they transcribe, are what make us who we are." The data revealed changes in gene activity following pollution exposure.
The study found that patients carrying variants in seven oxidative stress–related genes responded differently to PM2.5 exposure; some variants enhanced protection while others worsened damage caused by pollution. Individuals with less common variants in two specific genes (OXSR1 and PXDN) had worse lung function due to weaker protective RNA responses; those with a variant in another gene (TPO) also showed worse lung function but had stronger RNA responses instead.
Wenzel suggested future directions: "You could imagine a simple test for a panel of genes that could be used to flag someone as highly susceptible to the effects of pollution." The research team plans further investigation into these pathways and will test whether targeted interventions—including behavioral changes or antioxidant therapies—can reduce harm from pollution among high-risk individuals.
