Researchers from Northwestern University’s Feinberg School of Medicine are reporting findings that could change the way COPD is viewed.
Their study, Hypercapnia Promotes Maladaptive Airway and Vascular Remodeling in Mice, was published in the Journal of Clinical Investigation. In it, the researchers looked at how elevated levels of carbon dioxide in the blood could actively reshape lung structures and worsen disease outcomes in those with COPD.
Specifically, the researchers hypothesized that chronic hypercapnia (elevated CO2 levels) induces lung remodeling by altering resident mesenchymal cell phenotype and those changes, while potentially reversable, contribute to COPD pathology.
To test their theory, they used mice and human lung tissue that were exposed to high CO2 levels with normal oxygen and pH conditions. The lungs showed significant signs of structural changes such as thickening of airway muscles, increased extracellular matrix deposition and vascular remodeling.
First author of the study Masahiko Shigemura, PhD, told Northwestern Medicine’s News Center that the study’s findings suggest that elevated CO2 may not just be a result of the disease, but they could also be a key contributor to the progression of COPD.
“Carbon dioxide has traditionally been viewed as simply a waste product of breathing,” said Dr. Shigemura, research assistant professor of surgery in the division of thoracic surgery at Feinberg School of Medicine. “Because of this, elevated CO2 in the blood — what we call hypercapnia — has often been tolerated in patients with lung disease, as part of a strategy known as permissive hypercapnia. Our group and Northwestern have been challenging that view.”
The researchers also found that the lung changes were partly reversible. They wrote: “Fourteen days of recovery in room air markedly reduced smooth muscle thickening and ECM deposition.”
Dr. Shigemura also told the News Center that the study could have implications for environmentally related health issues.
“Although atmospheric CO2 levels are far lower than those found in the human body, they are steadily climbing. Human activity is the main driver, but natural events such as volcanic eruptions and wildfires can also cause local spikes,” he said. “This rising CO2 doesn’t just fuel climate change — it may also carry long-term risks for human health. Our work highlights that elevated CO2 may be an underappreciated risk factor — one that affects not only patients with lung disease, but potentially people living in different environments.”
