Presence of occluding mucus plugs in medium- to large-sized airways on chest CT scans in patients with chronic obstructive pulmonary disease (COPD is associated with an increased risk of all-cause mortality compared to those who do not have mucus plugging, according to a new study of over 4,000 patients published online May 21, 2023 in JAMA.¹

A retrospective analysis of data of patients with COPD was conducted to examine the association of mucus plugs in the airways with all-cause mortality. For this, data was procured from the multicenter Genetic Epidemiology of COPD (COPDGene) study. The study participants, aged 45 to 80 years, comprised both current and former smokers. Mucus plugs that completely occluded the medium- to large-sized airways were identified on chest CT scans and categorized as affecting 0, 1 to 2, or 3 or more lung segments. All-cause mortality was the primary outcome of the study. Out of the 10,198 patients enrolled in the COPDgene study, 4483 were found to have COPD. Of these, 4363 participants with a median age of 63 years were included in the present study. Majority of the study group was male. The median follow up period was 9.5 years.

The mucus plug score was 0 in 2585 (59.3%) subjects; the score ranged from 1 to 2 in 953 (21.8%) and ≥3 in 825 (18.9%) participants. During the follow-up period, a total of 1769 (40.6%) deaths occurred. the mortality rate among participants with no detectable mucus plugs was 34.0%; among those with mucus plugs in 1-2 lung segments, the mortality rate increased to 46.7%, while in those with mucus plugs in ≥3 lung segments, the mortality was 54.1%. The risk of all-cause mortality increased 15% among those with mucus plugs in 1 to 2 lung segments compared to patients without any mucus plugs with adjusted hazard ratio (aHR) of 1.15. The risk increased by 24% among patients in whom the mucus plugs were present in ≥3 lung segments compared to patients without any mucus plugs with aHR of 1.24.

Patients with mucus plugs in ≥3 lung segments tended to be older, female and non-Hispanic White compared to those who did not have any mucus plugs. They had “a greater pack-year history of smoking, more chronic bronchitis, more current asthma, worse BODE index, lower FEV1, greater airway wall thickness and higher percentage of emphysema on CT scans”. They also suffered greater number of exacerbations annually than those without mucus plugs (median 0.3 vs 0.1, respectively).

This study demonstrates an association between presence of mucus plugs in the airways of patients with COPD and increased all-cause mortality vs those who did not have mucus plugs. This association persisted even after adjusting for variables such as age, sex, race/ethnicity, BMI, pack-years of smoking, current smoking status, FEV1, cardiovascular comorbidity, asthma, CT measures of emphysema and airway wall thickness. The mortality was maximum among those who had mucus plugs in 3 or more segments of the lungs or in 1 to 2 lung segments and were in the highest GOLD 4 stage, while patients in GOLD 1 stage and no mucus plugs or mucus plugs in 1 to 2 lung segments had the least mortality risk. Targeting mucus plugs therefore may potentially save lives in this patient group.

Reference

1. Diaz AA, et al. Airway-occluding mucus plugs and mortality in patients with chronic obstructive pulmonary disease. JAMA. 2023 May 21. doi: 10.1001/jama.2023.2065.