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Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in Chronic Obstructive Pulmonary
Emily Wan1,2,3, Andrew Yen4, Rim Elalami5
1Channing Division of Network Medicine.
Abstract:
Rationale: Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively. Objective: To examine associations between mucus plugs on chest computed tomography (CT) and future moderate-to-severe AEs in two independent cohorts with spirometrically-confirmed COPD. Methods: Mucus plugs were visually identified on baseline chest computed tomography scans from smokers with Global Initiative for Chronic Obstructive Lung Disease grade 2-4 COPD enrolled in two multicenter cohort studies: ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and COPDGene (Genetic Epidemiology of COPD). Associations between ordinal mucus plug score categories (0, 1-2, and ≥3) and prospectively ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate to severe) and/or emergency room visit or hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Measurements and Main Results: Among 3,250 participants in COPDGene (mean age ± SD, 63.7 ± 8.4 yr; FEV1, 50.6 ± 17.8% predicted; 45.1% female) and 1,716 participants in ECLIPSE (age, 63.3 ± 7.1 yr; FEV1, 48.3 ± 15.8% predicted; 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio [aRR], 1.07 [95% CI, 1.05-1.09] and 1.15 [1.1-1.2] in COPDGene; aRR, 1.06 [95% CI, 1.02-1.09] and 1.12 [1.04-1.2] in ECLIPSE, respectively) for prospective moderate to severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR, 1.05 [95% CI, 1.01-1.08] and 1.09 [1.02-1.18] in COPDGene; aRR, 1.17 [95% CI, 1.07-1.27] and 1.37 [1.15-1.62] in ECLIPSE, respectively). Conclusions: Computed tomography-detected mucus plugs are associated with an increased risk for future COPD AEs.
Insights
Mucus plugs visible on CT scans predict future acute exacerbations (AEs) in chronic obstructive pulmonary disease (COPD). Identifying these plugs can help assess a COPD patient
Area of Science:
- Pulmonary Medicine
- Radiology
- Respiratory Research
Background:
- Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) significantly increase morbidity and mortality.
- The role of mucus plugs in predicting future COPD AEs requires further investigation.
Purpose of the Study:
- To investigate the association between mucus plugs identified on baseline chest CT scans and the risk of future AEs in COPD patients.
- To determine if the extent of mucus plugging correlates with the frequency or severity of AEs.
Main Methods:
- Chest CT scans from 3,250 COPDGene and 1,716 ECLIPSE participants (GOLD grades 2-4) were analyzed for mucus plugs.
- Participants were categorized by mucus plug score (0, 1-2, ≥3) and followed for prospectively ascertained moderate-to-severe AEs.
- Multivariable-adjusted zero-inflated Poisson regression was used to assess the association between mucus plugs and AEs.
Main Results:
- Mucus plugs were present in 44.4% (COPDGene) and 46.0% (ECLIPSE) of participants.
- The presence of 1-2 or ≥3 mucus plugs was associated with a statistically significant increased risk of moderate-to-severe AEs in both cohorts.
- Increased mucus plugging also correlated with a higher risk of severe AEs requiring hospitalization or ER visits.
Conclusions:
- CT-identified mucus plugs are a significant risk factor for future COPD AEs.
- This finding suggests mucus plugs may serve as a useful imaging biomarker for predicting exacerbation risk in COPD patients.
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