Mucus Plugs in Medium- to Large-Sized Airways Increases Risk of Death in COPD Patients

In patients with chronic obstructive pulmonary disease (COPD), presence of mucus plugs in airways was linked to a significantly increased risk of all-cause mortality, according to the results of a new study.

Presented at the American Thoracic Society (ATS) 2023 International Conference, results of the study, which included data from more than 4300 patients with COPD, suggests mucus plugs obstructing medium- to large-sized airways were associated with an increased risk of all-cause mortality in comparison to those without evidence of mucus plugging on chest computed tomography (CT) scans.

“This study provides new insights into the association of mucus plugging and mortality by evaluating mucus plugging causing complete occlusion of medium- to large-sized airways based on CT imaging and by including individuals with a full spectrum of COPD severity,” wrote investigators. “The association between mucus plugs and all-cause mortality was sustained after adjustment for BMI, pack-years of smoking, FEV1, cardiovascular comorbidity, asthma, CT measures of emphysema and airway wall thickness, and other potential confounders.”

A group of disease characterized by the respiratory issues, COPD represents a significant, but often overlooked, threat to public health. With US Centers for Disease Control and Prevention data suggesting COPD had an age-adjusted each rate of 105.6 per 100,000 adults aged 45 years or older in the US in 2019 and an age-adjusted prevalence of 5.6% among US adults aged 18 years or older in 2020.² Citing a prior study indicating small-sized airway obstruction with mucus plugs was associated with premature death in advanced-stage COPD³, investigators sought to further expand the contemporary knowledge base by examining the association between all-cause mortality and mucus plugs in medium- to large-sized airways.

With this in mind, a team of investigators led by Alejandro Diaz, MD, MPH, assistant professor of medicine in the Division of Pulmonary and Critical Care Medicine at Harvard Medical School, designed the current study as an analysis of data obtained from the Genetic epidemiology of COPD (COPDGene) study. A multicenter, observational study launched with the intent of identifying genetic factors associated with COPD, the COPDGene study enrolled a cohort of 10,198 non-Hispanic Black and non-Hispanic White participants who were aged 45-80 years and smoked 10 pack-years or more of cigarettes.

Of the more than 10,000 included in the study, 4483 were diagnosed with COPD. After exclusion of those with poor-quality or missing CT scans, investigators identified a cohort of 4363 individuals for inclusion in the current study. This cohort had a median age of 63 (IQR, 57-70) years, 44% were women, and a median follow-up of 9.5 years.¹

Among this cohort, 59.3% (n=2585) had a mucus plug score of 0, 21.8% (n=953) had a score of 1-2, and 18.9% (n=825) had a score of 3 more or more in baseline chest CT scans. Investigators pointed out the median number of lung segments with mucus plugs was 2, with a range of 1-17, among the 1778 individuals with mucus plugging. Compared to their counterparts without mucus plugs, those with mucus plugs in 3 or more lung segments were older, more likely to be female, and more likely to be non-Hispanic White.¹

The primary outcome of interest for the current study was all-cause mortality. Investigators pointed out all-cause mortality was assessed with proportional hazard regression analysis, with adjustment for numerous factors, including age, sex, race and ethnicity, BMI, pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration, and CT measures of emphysema and airway disease. For the purpose of analysis, medium- to large-sized airways were defined as airways approximately 2- to 10-mm lumen diameter and further categorized as affecting 0, 1-2, or 3 or more lung segments.¹

During the follow-up period, 40.6% (n=1769) of participants died. Upon analysis, results indicated the observed mortality rates were 34.0% (95% confidence interval [CI], 32.2-35.8), 46.7% (95% CI, 43.5-49.9), and 54.1% (95% CI, 50.7-57.4) among those who had mucus plugs in 0, 1-2, and 3 or more lung segments, respectively. When assessing risk, results suggested presence of mucus plugs in 1-2 lung segments was associated with a 15% increase in risk of all-cause mortality relative to those without mucus plugs (adjusted hazard ratio [aHR], 1.15 [95% CI, 1.02-1.29]; P = .02). Presence of mucus plugs in 3 or more lung segment was associated with a 24% increase in risk of all-cause mortality relative to their counterparts without mucus plugs(aHR, 1.24 [05% CI, 1.10-1.41]; P < .001).¹

“A potential implication of detecting occluding mucus plugs on CT scans is that they might provide a target for treatment. Therapies to improve lung function, slow disease progression, and decrease mortality are unmet needs for patients with COPD,” investigators wrote.¹

References:

1. Diaz AA, Orejas JL, Grumley S, et al. Airway-Occluding Mucus Plugs and Mortality in Patients With Chronic Obstructive Pulmonary Disease. Journal of the American Medical Association. Published online May 21, 2023. doi: 10.1001/jama.2023.2065
2. National trends - chronic obstructive pulmonary disease (COPD). Centers for Disease Control and Prevention. July 20, 2022. Accessed May 21, 2023. https://www.cdc.gov/copd/data-and-statistics/national-trends.html.
3. Hogg JC, Chu FS, Tan WC, et al. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology. Am J Respir Crit Care Med. 2007;176(5): 454-459. doi:10.1164/rccm.200612-1772OC