Researchers from the Yale University Center for Asthma and Airway Disease have uncovered how biological sex influences asthma symptoms and severity through differences in gene expression, offering new insights into personalized treatment approaches.
Their study, “Sex-Biased Gene Expression Underlies Immune Dysfunction in Asthma,” was conducted in partnership with the university’s Center for Pulmonary Precision Medicine and recently published in the American Journal of Respiratory Cell and Molecular Biology.
The study analyzed gene expression data from more than 3,600 adults with and without asthma. Researchers identified 61 genes that are differentially expressed between males and females in circulating immune cells — genes that are closely tied to immune responses in the lungs.
According to Shannon Kay, MD, an assistant professor of critical care medicine at the center and first author of the study, asthma affects males and females differently throughout life. Pre-pubescent boys are more likely to develop asthma, while post-pubescent girls experience more severe symptoms and reduced type 2 inflammation. The study’s findings suggest that these differences are rooted in sex-biased gene expression, which changes with age and hormonal fluctuations.
“Asthma is incredibly heterogeneous,” Dr. Kay said. “What really stood out to me in clinical training was how differently it affected males and females.”
The research team conducted a meta-analysis of public gene expression databases and validated their findings in a local Yale cohort of 132 patients. They found that sex-biased genes were linked to clinical traits such as lung function and symptom severity. These genes are involved in key immune pathways, including those related to eosinophils, lymphocytes and type 2 inflammation.
“By defining the biological determinants of asthma, we can move beyond conventional classifications to provide a more precise view of this complex syndrome,” said Jose Gomez, MD, the study’s senior author and associate professor of medicine at the center.
Researchers said the study highlights the potential for sex-specific asthma therapies, especially as newer treatments like biologics target immune system components.
“Right now, we don’t typically consider sex when choosing asthma treatment plans,” Dr. Kay said. “But these insights can start the conversation and ideally bring us closer to personalized asthma care.”
The research team encourages clinicians to remember that asthma doesn’t look the same for everyone, and understanding the role of sex and hormones is key to better care. Researchers said they plan to explore hormonal influences more directly and investigate how asthma interacts with conditions like obesity.
