A retrospective analysis of data of patients with chronic obstructive pulmonary disease (COPD) suggests that mucus plugs could contribute to patient mortality, offering a possible treatment target.
Participants with chronic obstructive pulmonary disease (COPD) who had mucus plugs that blocked medium to large airways had higher all-cause mortality compared with patients without mucus plugging on chest CT scans, according to a study published in JAMA. 1 N N-Diallyl-2 2-Dichloro-Acetamid
Airway mucus plugs are prevalent in patients with COPD, but the association between airway mucus plugging and mortality in patients with COPD was not known.
“Chronic obstructive pulmonary disease (COPD) affects 15.9 million people in the United States and is the fourth leading cause of death. Mucus dysfunction, a central pathology in patients with COPD, is characterized by excess mucus production, hypersecretion, and reduced clearance, leading to accumulation in the airways as plugs,” said the researchers.
First, researchers tried to determine if airway mucus plugs recognized on CT scans were associated with increased all-cause mortality.
Next, prospective data of patients with a COPD diagnosis in the Genetic Epidemiology of COPD cohort were collected in an observational retrospective analysis. Participants were non-Hispanic Black or White individuals, aged 45 to 80 years, who smoked at minimum 10 pack-years. Participants were enrolled at 21 centers throughout the United States between November 2007 and April 2011, and were followed up through August 31, 2022.
Mucus plugs that completely blocked airways on chest CT scans, found in medium- to large-sized airways (approximately 2-10-mm lumen diameter), were categorized as affecting 0, 1 to 2, or 3 or more lung segments.
Then, researchers identified the primary outcome as all-cause mortality, evaluated with proportional hazard regression analysis. Model adjustments were made for age, sex, race and ethnicity, body mass index, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease.
Of the 4483 participants with COPD, 4363 were included in the primary analysis (median age, 63 years [IQR, 57-70 years]; 44% were women). A total of 2585 (59.3%), 953 (21.8%), and 825 (18.9%) participants had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively.
Throughout a median 9.5-year follow-up, 1769 participants (40.6%) died. The mortality rates were 34.0% (95% CI, 32.2%-35.8%), 46.7% (95% CI, 43.5%-49.9%), and 54.1% (95% CI, 50.7%-57.4%) in participants who had mucus plugs in 0, 1 to 2, and 3 or more lung segments, respectively.
The existence of mucus plugs in 1 to 2 vs 0 and 3 or more vs 0 lung segments was associated with an adjusted HR of death of 1.15 (95% CI, 1.02-1.29) and 1.24 (95% CI, 1.10-1.41), respectively.
Corresponding author Alejandro A. Diaz, MD, MPH, an associate scientist in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital said in a press release, “As a chronic disease, COPD can’t be cured, but our findings suggest that using therapies to break up these mucus plugs could help improve outcomes for COPD patients, which is the next best thing.”2
Mucus plugs blocking multiple bronchi might increase pneumonia risk and COPD exacerbation risk.
“Additionally, the presence of mucus plugs is associated with ventilation/perfusion mismatch, which may lead to respiratory failure, a common cause of death in COPD,” continued the researchers.
The study results and those of prior studies might be hypothesis-generating to test clinical interventions targeting mucus plugs in COPD that might provide a treatment target for health care providers. Preliminary asthma studies suggest that biologics treatment decreases mucus plugs on CT and that the reduction of mucus plugs was associated with improved lung function.
One limitation of this study was that it was observational, so conclusions cannot be drawn that mucous plugging causes death. Secondly, the COPDGene cohort only enrolled non-Hispanic Black and non-Hispanic White participants, so findings might not be applicable to other racial and ethnic groups that weren’t included.
“The fact that these mucus plugs were associated with mortality across different disease phases tells us that there are aspects of COPD progression that can be picked up by a CT scan even if they’re not felt by the patient,” concluded Diaz in the release.
1. Diaz AA, Orejas JL, Grumley S, et al. Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease. JAMA. Published online May 21, 2023. doi: 10.1001/jama.2023.2065
2. Study linking mucus plugs and COPD mortality could help save lives. Eurekalert! May 21, 2023. Accessed June 5, 2023. https://www.eurekalert.org/news-releases/989777
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