News — Numerous COPD patients face mucus blockages, causing lung function and quality of life issues. Brigham and Women’s Hospital researchers, part of Mass General Brigham healthcare system, conducted a study linking mucus plugs to higher mortality. Published in JAMA and presented at the American Thoracic Society 2023 Conference, these findings offer potential for doctors to lower the death rate of COPD, a prevalent and lethal respiratory illness.
"Our results indicate that while COPD cannot be cured due to its chronic nature, employing treatments to disintegrate these mucus plugs may enhance outcomes for patients, which is the subsequent optimal approach," stated Dr. Alejandro A. Diaz, MD MPH, the corresponding author and an associate scientist in the Division of Pulmonary and Critical Care Medicine at the Brigham. "Mucus is an extensively studied element in basic science, and there are numerous therapies targeting mucus either currently available or being developed for other ailments, making it an exceptionally encouraging target."
In the United States, COPD impacts approximately 15.9 million individuals and ranks as the fourth principal cause of mortality. The primary triggers for COPD are prolonged exposure to air pollutants or smoking cigarettes. While ceasing exposure to these pollutants can decelerate the advancement of COPD, a cure for the disease remains elusive. Moreover, the conventional therapeutic methodology for COPD has remained largely unaltered over the years.
"Over the past forty years, our COPD treatment strategies have primarily focused on two objectives: expanding bronchial passages to facilitate airflow or mitigating bronchial inflammation," explained Diaz. "However, these findings suggest that there may be untapped potential to address this disease beyond our previous understanding."
The present investigation conducted a retrospective observational analysis utilizing data from the COPDGene study, a comprehensive clinical study focused on unraveling the genetic predisposition to COPD. This large-scale study encompassed over 10,000 participants recruited between 2007 and 2011, encompassing individuals at varying stages of COPD severity, ranging from mild to severe.
In this recent observational study, the researchers examined data from a subset of over 4,000 patients from the original participant pool. To identify the presence of mucus plugs, the researchers conducted a thorough analysis of chest CT scans obtained during the patients' initial clinic visits. By performing CT scans on all patients, irrespective of their self-reported symptoms, the researchers were able to identify mucus plugs even in individuals who did not perceive themselves as unwell.
"Coughing up mucus is a natural part of the body's immune defense mechanism, typically observed during the recovery process," explained Diaz. "However, in COPD, excessive mucus production occurs, impeding effective clearance and resulting in the formation of mucus plugs. Interestingly, these plugs do not exhibit strong correlations with specific symptoms, which can lead to their unnoticed presence."
Throughout the duration of the study, the research team discovered noteworthy mortality rates among COPD patients. Those without detectable mucus plugs exhibited a mortality rate of 34 percent. However, for patients with mucus plugs observed in up to two lung segments, the mortality rate escalated to 46.7 percent. The most substantial increase was observed in patients with plugs present in three or more lung segments, with a mortality rate of 54.1 percent. These findings highlight a significant association between mucus plugs and increased mortality in COPD patients.
Diaz further added, "The data reveal a compelling link between the presence of mucus plugs and overall mortality, but the underlying factors driving this association remain unknown at this point. Further investigation is necessary to elucidate the mechanisms involved."
Given that mucus is a recognized target in the treatment of various diseases, the researchers have outlined their future plans to explore the efficacy of existing mucus-targeting therapies in individuals with COPD. The objective is to assess whether addressing mucus plugs directly could potentially yield favorable outcomes for COPD patients. By conducting such tests, the researchers aim to uncover new possibilities for improving patient well-being and overall prognosis.
The current research findings emphasize the existence of factors influencing COPD mortality that are not yet fully understood. This highlights the limited knowledge regarding these factors and suggests that not all of them may manifest as recognizable symptoms in patients. The study underscores the need for further investigation and a comprehensive understanding of the underlying complexities involved in COPD progression and its impact on patient outcomes.
Diaz pointed out, "The association between mucus plugs and mortality in various stages of COPD implies that CT scans can identify certain aspects of disease progression that may not be perceived by the patient. While it may not be necessary for every COPD patient to undergo a CT scan immediately, clinicians should take this into consideration when evaluating and treating their patients." The study's findings provide valuable insights for healthcare professionals, encouraging them to consider the potential benefits of incorporating CT scans into the management of COPD patients.
Disclosures: Alejandro A Diaz reports speaker fees from Boehringer Ingelheim and a pending USPT patent. Victor Kim reports personal fees from Gala Therapeutics, ABIM Critical Care Testwriting Committee, AstraZeneca, and Boehringer Ingelheim. Meilan K. Han has received personal fees from Boehringer Ingelheim, AstraZeneca and research support from Novartis and Sunovio. George R. Washko reports grants and other support from Boehringer Ingelheim, Quantitative Imaging Solutions, PulmonX, Janssen Pharmaceuticals, Vertex, and CSLE Berhing, and his spouse is an employee of Biogen. Raúl San José Estépar reports personal fees from Chiesi, Leuko Labs, Lung Biotechnology, Boehringer Ingelheim and is a founder and equity holder of Quantitative Image Solutions.
Funding: The COPDGene project was supported by Award Number U01 HL089897 and Award Number U01HL089856 from the National Heart, Lung, and Blood Institute. The COPD Foundation also supports the COPDGene® project through contributions to an Industry Advisory Board comprised of AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, and Sunovion. Dr. Diaz is supported by funding from the US National Heart, Lung, and Blood Institute (R01-HL133137, R01-HL149861, R01-HL164824) and the Brigham and Women’s Hospital Minority Faculty Career Development Award.
Paper cited: Diaz, AA et al. “Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease” JAMA DOI: 10.1001/jama.2023.2065
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