Mucus plugs blocking airways linked to increased mortality risk in adults with COPD
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Key takeaways:
- More adults with COPD and mucus plugs died vs. adults with COPD and no mucus plugs.
- A heightened mortality risk in these patients remained after adjusting for multiple variables.
WASHINGTON — All-cause mortality rates in patients with COPD rose when they had mucus plugs blocking medium- to large-sized airways, according to a study presented at the American Thoracic Society International Conference.
This study was published in JAMA at the same time as the ATS 2023 presentation.
“In smokers with COPD, mucus plugs are frequent and associated with all-cause of death,” Alejandro A. Diaz, MD, MPH, assistant professor at Brigham and Women’s Hospital, said during the presentation. “The findings support airway mucus plugs as a clinically relevant imaging biomarker requiring further investigation and may be a potentially modifiable target.”
In an observational retrospective analysis, Diaz and colleagues analyzed 4,363 adults with COPD (median age, 63 years; 44% women) who smoked a minimum of 10 pack-years from the COPDGene study to see if there was a relationship between mucus plugs on chest CT scans and higher all-cause mortality.
Using what they saw on CT scans, researchers grouped patients according to how many lung segments were affected by mucus plugs blocking medium- to large-sized airways that ranged from 2 mm to 10 mm lumen diameter: zero (n = 2,585; 59.3%), one to two (n = 953; 21.8%) or three or more (n = 825; 18.9%).
Researchers then used proportional hazard regression analysis that accounted for age, sex, race and ethnicity, BMI, pack-years smoked, current smoking status, FEV1 and measures of emphysema and airway disease found on CT to evaluate mortality.
Of the total cohort, 1,769 patients (40.6%) died over a median of 9.5 years, and those with mucus plugs in at least three lung segments had the highest mortality rate at 54.1% (95% CI, 50.7%-57.4%), followed by those with mucus plugs in one to two lung segments (46.7%; 95% CI, 43.5%-49.9%) and those with no mucus plugging on CT scans (34%; 95% CI, 32.2%-35.8%).
Compared with patients who had no mucus plugs, those with mucus plugs in three or more segments had a greater mortality risk (adjusted HR = 1.24; 95% CI, 1.1-1.41). Patients with mucus plugs affecting one to two lung segments also had an increased mortality risk than those without mucus plugs (aHR = 1.15; 95% CI, 1.02-1.29).
Researchers further adjusted for coronary artery disease and chronic bronchitis and found comparable results to those of the initial analysis, with a higher risk for mortality in patients with mucus plugs in three or more segments (aHR = 1.25; 95% CI, 1.1-1.42) and in one to two lung segments (aHR = 1.15; 95% CI, 1.02-1.3) compared with patients with no mucus plugs.
This relationship continued following the adjustment for the history of current asthma in addition to all previously mentioned variables. In this model, researchers saw the same hazard ratios as the ones previously observed.
Notably, the risk for death in patients with COPD and mucus plugs slightly weakened with the additional adjustment for the number of exacerbations per year observed in the study’s follow-up when compared with those without mucus plugs (one to two lung segments, aHR = 1.1; 95% CI, 0.96-1.25; three or more lung segments, aHR = 1.2; 95% CI, 1.05-1.38).
In one final adjustment, researchers included BODE mortality index and took out FEV1 and BMI. In this model, patients with mucus plugging in at least three lung segments (aHR = 1.21; 95% CI, 1.06-1.37) and patients with mucus plugging in one to two segments (aHR = 1.14; 95% CI, 1.01-1.29) continued to have a higher risk for all-cause mortality compared with those without mucus plugging.
Some limitations of this study included the patient population of the COPDGene cohort, use of the lung segment-based score and unavailable potential confounders, such as mucus-related inflammatory sputum biomarkers, Diaz said.
“We used COPDGene that only has two races, so it may not be applicable in other groups of people, and the lung segment-based score we used is likely to underestimate the real burden of this process in the lung,” he said.
When commenting on why JAMA published this study, George T. O'Connor, MD, chair of the session, said the publication, in addition to focusing on studies that influence clinical management and health policy, is interested in studies that provide an understanding of something that could affect clinical management later down the line.
“[JAMA] is also interested in novel insights that may lead to changes in clinical management as they advance the science and are further investigated,” O’Connor said during the session.