A mucus plug-COPD Mortality Study Could Save Lives

According to a retrospective examination of patient data from the COPDGene project, targeting mucus plug may help avoid fatalities from chronic obstructive pulmonary disease, the fourth highest cause of mortality in the United States.

Many patients with chronic obstructive pulmonary disease (COPD) suffer from mucus plugs, a deposit of mucus in the lungs that can impair quality of life and lung function. A new study sponsored by Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, discovered that mucus plugs were similarly linked to higher mortality. The findings, which were published in JAMA and presented concurrently at the American Thoracic Society 2023 International Conference, may help doctors minimize the death toll from COPD, one of the most common and dangerous respiratory diseases.

“As a chronic disease, COPD can’t be cured, but our findings suggest that using therapies to break up these mucus plugs could help improve outcomes for COPD patients, which is the next best thing,” said corresponding author Alejandro A. Diaz, MD MPH, an associate scientist in the Division of Pulmonary and Critical Care Medicine at the Brigham. “Mucus is something that we already know a lot about from a basic science standpoint, and there are also a lot of mucus-targeting therapies that either already exist or are in development for other diseases, so it’s an extremely promising target.”

COPD is the fourth biggest cause of death in the United States, affecting 15.9 million individuals. It is most commonly caused by cigarette smoking or long-term exposure to air pollution. The advancement of COPD can be delayed by avoiding exposure to certain contaminants, but the condition cannot be cured. For many years, the standard therapy approach for COPD has remained basically unchanged.

For the last four decades we’ve had only two targets for COPD therapies –either promoting bronchial dilation, which means making the airways themselves wider, or reducing bronchial inflammation,” said Diaz. “This is telling us that there may be more we can do about this disease than we realized before.”

The current study was a retrospective observational analysis of data from the Genetic Epidemiology of COPD (COPDGene) study, a large-scale clinical investigation aimed at exploring the underlying genetic risk factors for COPD. The study comprised over 10,000 patients recruited between 2007 and 2011, with COPD at various stages ranging from mild to severe.

The researchers examined data from almost 4,000 of these individuals for this new observational study. The researchers evaluated chest CT scans from the patients’ first visits to the clinic to determine which patients had mucus plug. The researchers discovered mucus plugs in individuals who did not feel unwell by performing CT scans on all patients, regardless of their self-reported symptoms.

“Creating mucus is a normal part of the body’s immune response, but usually we cough it up as we’re getting better,” said Diaz. “COPD causes the body to produce too much mucus and makes it harder to clear out, so you end up with these mucus plugs that aren’t strongly correlated with any specific symptoms and can go undetected.”

The researchers discovered that the mortality rate for COPD patients with no visible mucus plug was 34% over the course of the trial. The death rate increased to 46.7 percent in individuals with mucus blockages in up to two lung segments. The death rate for patients with plugs in three or more lung segments was 54.1 percent.

“The data show a compelling association between the accumulation of these mucus plugs and overall mortality, but we don’t know anything about what’s driving it yet,” adds Diaz.

Because mucus is a proven therapeutic target for other diseases, the researchers intend to test existing mucus-targeting medicines in COPD patients to see if treating the mucus plugs improves patient outcomes.

Meanwhile, the research shows that there are factors influencing COPD mortality that we currently know little about, and that not all of these factors will manifest as symptoms for the patient.

“The fact that these mucus plugs were associated with mortality across different disease phases tells us that there are aspects of COPD progression that can be picked up by a CT scan even if they’re not felt by the patient,” said Diaz. “It’s not so simple as to say every person with COPD needs to run out and get a CT scan tomorrow, but it’s something for clinicians to consider when they’re working with their patients.”

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