News release

From: University of Technology Sydney (UTS)

A new study has confirmed that male and female lungs are “wired differently” at the molecular level, providing further evidence supporting sex-inclusive respiratory disease research and treatment.

Led by researchers from the University of Technology Sydney (UTS) and Woolcock Institute of Medical Research, the project used a preclinical model to focus on the effect of a single genetic variable – the X or Y chromosome determining biological sex.

Published in the Federation of American Societies for Experimental Biology (FASEB) journal, the research team says it is the first study to demonstrate that sex modulates gene networks controlling bronchial responsiveness under normal physiological conditions.

“Biological sex fundamentally shapes how the lungs function, even under healthy, non-diseased conditions,” said study lead author, UTS and Woolcock Institute Research Fellow Dr Razia Zakarya.

“Male lungs are intrinsically more reactive to inhaled triggers than female lungs, which helps explain why the sexes experience respiratory disease differently.

“This is due to differences in coordinated activity within discrete gene networks in the lung, rather than a single gene or hormone.”

Dr Zakarya said the study had shown that sex differences in lung function exist at a deep molecular level, long before disease develops.

“Essentially the sexes utilise different genetic toolboxes when exposed to environmental factors,” she said.

“Importantly, we show that early-life environmental exposures can alter these molecular networks in a sex-dependent way potentially influencing later vulnerability to disease.

“Respiratory diseases like asthma and chronic obstructive pulmonary disease affect millions, yet men and women experience them differently.

“This study shows that those differences don’t start with disease, they are built into lung biology from early life.

“Understanding this helps explain why people respond differently to environmental exposures and treatments, and why precision medicine must consider sex from the outset.

“The findings thus highlight why sex must be factored into biomedical and environmental health research, not just in clinical trials but from the earliest stages of discovery.

“Policies that encourage sex-inclusive research are essential for developing more accurate risk assessment, prevention strategies and treatments for respiratory disease.

“Ignoring sex differences risks overlooking key biology that shapes health outcomes.”

Dr Zakarya said that while the preclinical model used in the study provided developmental and immunological relevance, further studies validating the results in patients would be essential to contextualise findings within the broader landscape of sex-specific respiratory health.