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Persistent Mucus Plugs Associated With Faster Lung Decline in COPD
New research follows a previous landmark study that linked mucus plugs to increased mortality in people with COPD even without hallmark symptoms.
New research has found that persistent mucus plugs in the lungs are associated with a faster decline in forced expiratory volume in 1 second (FEV1) in people with chronic obstructive pulmonary disease (COPD).1
“Mucus plugs can come and go; in some people they resolve, and in others they seem to stick around,” lead investigator Sofia Mettler, MD, MSc, a clinical fellow in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital (BWH), said in a statement.2 “If the mucus plugs resolve, the patients have a slower lung function decline than those who have a persisting block.”
Mettler and colleagues assessed participants in the Genetic Epidemiology of COPD (COPDGene) study with COPD who had a smoking history of at least 10 pack-years. They surveyed mucus plugs with computed tomography (CT) at baseline and at a 5-year follow-up visit (phase 2) and examined associations between mucus-plug change and FEV1 decrease with multivariable regression models.
The research involved 4363 participants, 2118 of which had a CT scan and spirometry data available at the 5-year follow-up. After 5 years, evaluable participants were grouped into 4 categories according to mucus-plug change: persistently negative (n = 934; 44.1%), resolved (n = 341; 16.1%), newly formed (n = 417; 19.7%), and persistently positive (n = 436; 21.01%).1
The investigators found that the persistently- negative group had a mean FEV1 decrease of 37.2mL per year, the resolved group had a mean decrease of 39.3 mL per year, the newly-formed group had a mean decrease of 54.9 mL per year, and the persistently-positive group had a mean decrease of 60.4 mL per year. These differences were clinically meaningful when comparing the persistently-positive group (difference, 23.2 mL/year [95% CI, 15.0-31.4]) and the newly-formed group (17.7 mL/year [95% CI, 11.3-24.1]) with the persistently negative group. The difference in FEV1 decrease in the resolved group compared to the persistently-negative group was not substantial (difference, 2.2 mL/year [95% CI, –5.3 to 9.6]).1
Mettler and colleagues also found that when an interaction term between the category of mucus-plug change and smoking status was included, participants in the persistently-positive group who resumed smoking had the steepest decrease in FEV1 and among participants in the resolved group who quit smoking had the least decrease.
“Because it is an observational study, we cannot conclude a causal relationship,” Mettler added.2 “So the next logical step is to conduct a clinical trial to see if mucus plugs are really what’s responsible for the change in lung function decline.”
The investigators noted limitations of the study, including cohort attrition during follow-up and a study population that included only White and Black participants and those with heavy tobacco use. They encouraged further research into mucus accumulation in COPD to better understand its effects and potential interventions.1
The research is a follow-up to a previous paper that senior investigator Alejandro Diaz, MD, MPH, of the BWH Division of Pulmonary and Critical Care Medicine, and colleagues published that demonstrated that mucus plugs were linked to increased mortality in patients with COPD, even for those who were not experiencing the hallmark symptoms like cough and phlegm production.3
