New study investigates the role of mucus plugs in COPD

Chronic obstructive pulmonary disease (COPD) affects approximately 29 million people in the U.S. and is the fourth leading cause of death. Mucus plugging (mucus that accumulates in the lungs and reduces airflow) and chronic bronchitis are both related to dysfunctional airway mucus, which is common in people with COPD. Sometimes mucus plugging and chronic bronchitis co-occur, but it is quite common to have one or the other but not both conditions. Given the limited availability of disease-modifying treatments for COPD, understanding the underlying biology of mucus pathology is critical to identifying new therapeutic targets.

In a new study, researchers at Boston University Chobanian & Avedisian School of Medicine have found that mucus plugs in the lungs alter the pattern of gene activity in a way that is similar to chronic bronchitis, suggesting that there may be similar underlying causes to both conditions. It is believed these researchers are the first group to study gene activity differences associated with mucus plugging.

“Mucus plugs are quite common in people with COPD and they are associated with diminished quality of life and increased mortality. By identifying how the presence of mucus plugs impacts the biology of the lung we hope to be able to better treat them, or prevent them from forming in the first place,” says corresponding author Marc Lenburg, PhD, professor of medicine at the school.

The researchers studied participants in the Detection of Early Lung Cancer Among Military Personnel (DECAMP) 2 study who were mostly older U.S. military veterans at high risk for lung cancer due to a history of heavy smoking, many of whom had COPD. Computed tomography was performed on them to determine who had mucus plugs and for those that had them, how extensive they were. From that group, a pulmonologist collected cells from their airways and sequenced the RNA from those cells to determine the level of gene activity. The researchers then compared the gene activity from each individual with the extent of mucus plugging to find genes that had increased (or decreased) activity in individuals with more extensive mucus plugging. Once they had this mucus plugging “gene signature” they compared it with gene signatures from other diseases.

According to the researchers, having a better understanding of how mucus plugging impacts the lung and its relationship to chronic bronchitis may give new clues about how mucus dysfunction develops, which could be helpful for developing new therapies to better treat mucus dysfunction. “By uncovering the molecular pathways that drive mucus plugging and chronic bronchitis, we aim to identify biological targets for earlier diagnosis and intervention. Ultimately, we hope these insights will translate into therapies that restore airway health, reduce respiratory symptoms, and improve the quality of life for people living with these chronic lung diseases,” says coauthor Ehab Billatos, MD, an assistant professor of medicine at the school.

These findings appear online in the American Journal of Respiratory and Critical Care Medicine.

Reference: Whitney N. Souery, Ehab Billatos, Rim Elalami, Raúl San José Estépar, Michael H. Cho, Alejandro A Diaz , Marc E. Lenburg, New study investigates the role of mucus plugs in COPD, Boston University School of Medicine, Journal: American Journal of Respiratory and Critical Care Medicine, DOI 10.1164/rccm.202501-0262OC