In people with COPD, the presence of persistent mucus plugs is associated with faster decline in forced expiratory volume in one second (FEV1) compared with similar COPD patients with mucus plugs that come and go. Experts say the observational finding suggests that mucus plugs should be investigated further as a therapeutic target that could slow lung function decline and disease progression.
“We were surprised to find that mucus plugs are a highly dynamic phenomenon, with notable proportions of participants showing either persistence or resolution over time,” said Sofia Mettler, MD, MPH, Clinical and Research Fellow in Medicine at Brigham and Women’s Hospital. Dr. Mettler is lead author on “Longitudinal changes in airway mucus plugs and FEV1 in COPD,” a research letter recently published in the New England Journal of Medicine.1
“This finding raises the possibility that this may be an intervenable pathology, although further research is needed,” Dr. Mettler said.
Researchers assessed 2,118 participants in the Genetic Epidemiology of COPD (COPDGene) study who had a smoking history of at least 10 pack-years and diagnosed COPD. Mucus plugs were assessed by CT scans at baseline and at a five-year follow-up visit. At five years, plug status was persistently negative in just under half of participants (44.1%); 16.1% had resolved plugs, 19.7% had newly formed plugs, and 20.1% were persistently positive.1
The mean FEV1 decline in the persistently negative group, used as reference, was 37.2 ml per year. It was 39.3 ml per year in the resolved group, 54.9 ml per year in the newly formed group, and 60.4 ml per year in the persistent group. Compared with the persistently negative group, the FEV1 decline was clinically meaningful in both the persistent group at 23.2 ml per year (95% CI, 15.0-31.4) and the newly formed group at 17.7 ml per year (95% CI, 11.3-24.1). When assessed by smoking status, the steepest decline in lung function was seen in participants in the persistent group who resumed smoking, and the smallest decline was in participants in the resolved group who quit smoking.1
Another unexpected finding, Dr. Mettler said, is that individuals with persistent radiographic mucus plugging experienced the fastest decline in FEV1 even though they had the lowest FEV1 at baseline. Earlier COPD research has shown an inverse link between baseline disease severity and FEV1 decline. She said patients with grade 4 COPD—according to the Global Initiative for Chronic Obstructive Lung Disease—tend to have the slowest fall in FEV1, possibly becausethey have less potential to worsen. Dr. Mettler also said that they found disease progression was most pronounced in patients who either resumed or continued tobacco smoking, although the link between persistent mucus plugs and faster FEV1 decline was seen regardless of smoking status.
“Our findings suggest that mucus plugs are a distinct phenotype of COPD, one that is closely associated with lung function and its trajectory over time,” she explained. “We are increasingly seeing clinical CT scan reports note the presence of airway mucus plugs, and this may become standard practice. Patients with accelerated lung function decline may be screened and monitored for the presence, persistence, and worsening of mucus plugs to explain their disease progression. Looking ahead, it gives us hope that mucus plugs may serve as a distinct therapeutic target in obstructive airway disease and warrant further investigation.”
Dr. Mettler added that studies are currently underway to assess the effects of biologic agents on mucus plug burden, as well as nonbiologic approaches such as mucolytics and mechanical devices. Future trials might include mucus plug phenotype as an inclusion criterion and evaluate the effect of plug type or plug removal, or both, on COPD progression, she said.
References
1. SK Mettler. Longitudinal changes in airway mucus plugs and FEV1 in COPD. N Engl J Med. 2025 May 15;392(19):1973-1975. doi:10.1056/NEJMc2502456
