WASHINGTON — Mucus Plugs obstructing the airways of patients with chronic obstructive pulmonary disease (COPD) were associated with higher all-cause mortality compared with no mucus plugs, according to an observational retrospective analysis.

Over a median 9.5-year follow-up, mortality rates were 34.0%, 46.7%, and 54.1% in patients who had mucus plugs in zero, one to two, and three or more lung segments, respectively, on chest CT, reported Alejandro A. Diaz, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital in Boston, during the American Thoracic Society annual meeting.

The presence of mucus plugs in one to two versus zero and three or more versus zero lung segments was associated with an adjusted hazard ratio of death of 1.15 (95% CI 1.02-1.29) and 1.24 (95% CI 1.10-1.41), respectively, they noted in their study, which was also published in JAMA.

These findings suggest the possibility that airway mucus plugs might be a modifiable target for improving mortality in patients with COPD, Diaz said, noting that while the observational study could not show causality, the findings support further investigation of airway mucus plugs to determine if they are a relevant imaging biomarker.

A 2007 study found that occlusion of the small airways by inflammatory exudates containing mucus was linked to early mortality in patients with severe emphysema treated by lung volume reduction surgery.

“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,” Diaz and team wrote.

Seen in anywhere from 25-67% of COPD patients’ CT scans, mucus plugs that completely block the airways are linked with “airflow obstruction, lower oxygen saturation, and reduced exercise capacity,” according to background info in their study.

George T. O’Connor, MD, of Boston Medical Center, who co-chaired the session in which the data were presented, said if research shows a causal relationship between airway mucus plugs on CT and COPD mortality, treatments addressing these obstructions may improve survival.

“This is the kind of study that will not influence practice now, but it opens the door to investigation of something that could,” he said.

However, Donald Mahler, MD, a pulmonologist at Valley Regional Hospital in Claremont, New Hampshire, who was not involved with the study, expressed skepticism about a causal association between airway mucus plug presence and early death.

“With any statistical association, you have to investigate cause and effect, but I just don’t see the mechanism for mucus plugs being causally linked to a change in mortality,” Mahler told MedPage Today.

This study used data on participants ages 45 to 80 enrolled in the Genetic Epidemiology of COPD (COPDGene) cohort across 21 U.S. centers from November 2007 to April 2011. The analysis included 4,363 participants who smoked at least 10 pack-years of cigarettes. Median age was 63, 44% were women, and only non-Hispanic Black and white people were included.

Of the participants, 59.3% had mucus plugs in 0 lung segments, 21.8% had mucus plugs in one to two lung segments, and 18.9% had mucus plugs in three or more lung segments.

Over follow-up, 40.6% of participants died.

Models were adjusted for age, sex, race and ethnicity, body mass index (BMI), pack-years smoked, current smoking status, forced expiratory volume in the first second of expiration (FEV₁), and CT measures of emphysema and airway disease.

An additional adjustment for coronary artery disease showed similar results (score 1-2 vs 0: aHR 1.16, 95% CI 1.03-1.30; score ≥3 vs 0: aHR 1.26, 95% CI 1.11-1.43).

“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 (i.e., current smoking status, age, sex, race and ethnicity),” Diaz and colleagues wrote.

The observed association also persisted after adjustment for the diagnosis of chronic bronchitis, which is characterized by mucus hypersecretion and is an established risk factor for early death.

The researchers noted that the study’s observational design was a limitation, along with a lack of diversity in the COPDGene cohort.

In addition, mucus that did not completely occlude airway lumen was not assessed, which “might have underestimated the burden of mucus plugs,” they wrote.