Study Finds Clearing Mucus Plugs May Slow COPD Progression

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A five-year study found that people with chronic obstructive pulmonary disease (COPD) who had persistent or newly developed mucus plugs — sticky blockages in the lungs — experienced a faster decline in lung function, especially if they kept smoking.

The current study builds on previous research conducted by senior investigator Alejandro Diaz, M.D., of the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital, in which the team discovered a link between mucus plus and increased mortality in patients with COPD, even when patients were not experiencing usual symptoms such as cough and phlegm production.

Given these results, investigators wanted to understand whether mucus plugs contribute to how fast COPD gets worse over time.

The team focused on how these plugs affect lung function, especially a measurement called forced expiratory volume in 1 second (FEV₁), which shows how much air a person can forcefully exhale in one second. A decline in FEV₁ means a person’s lungs are getting weaker.

“Mucus plugs can come and go; in some people they resolve, and in others they seem to stick around,” said lead investigator Sofia Mettler, M.D., a clinical fellow in the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital. “If the mucus plugs resolve, the patients have a slower lung function decline than those who have a persisting block.”

What did they do?

The study followed 2,118 people with COPD and a history of smoking for five years. They took CT scans at the beginning and again five years later to look for mucus plugs in the lungs.

Participants were grouped based on changes in their mucus plug status over time:

• Persistently negative: No plugs at either time point
• Resolved: Had plugs at the start but not after 5 years
• Newly formed: No plugs at the start but developed them later
• Persistently positive: Had plugs both at the start and 5 years later

What did they find?

People with persistent or new mucus plugs had a faster drop in lung function compared with people who never had plugs.

• Persistently positive: Lost 60.4 milliliters per year of lung function
• Newly formed: Lost 54.9 milliliters per year
• Persistently negative: Lost 37.2 milliliters per year (this was the best case)

People whose mucus plugs resolved over time didn’t see a meaningful difference compared with those who never had plugs — suggesting clearing plugs may help slow disease progression.

The worst outcomes were seen in people who kept smoking and also had persistent plugs. The best outcomes were in those who quit smoking and saw their plugs resolve.

Why does this matter?

This study, published in the New England Journal of Medicine (NEJM), shows that mucus plugs — especially those that stick around or form over time — may be a key reason why COPD worsens. It also reinforces how quitting smoking and possibly clearing mucus plugs could help protect lung function.

“Because it is an observational study, we cannot conclude a causal relationship,” Mettler noted. “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.”

Additionally, Mettler and her team also want to understand the factors that determine the resolution of mucus plugs in some patients and to identify possible interventions that can help delay progression and improve patients’ lives.