Wang, Wei

Abstract Introduction / Rationale Mucus plugs (MPs) on chest computed tomography (CT) are associated with increased respiratory symptoms, worse lung function, and elevated mortality and acute exacerbations among individuals with GOLD2-4 COPD. Whether mucus plug distribution in the upper versus lower lobes differentially impacts future acute exacerbations (AEs) has been incompletely explored. Methods Data from current and former tobacco users, ages 40-80, with ≥10 pack-years, at the enrollment visit in COPDGene were analyzed. MPs were visually-assessed on chest CTs using a sequential reading system; the MP score was calculated as the number of bronchopulmonary segments with plugs (range 0-18). Among subjects with MPs, the percent of lower lobe MPs (%LLMPs) was calculated as the number of bronchopulmonary segments in the right and left lower lobes divided by the total number of bronchopulmonary segments (range 0-100%). Moderate-to-severe AEs were assessed prospectively biannually for up to 15.5 years. Zero-inflated Poisson regression, adjusting for age, sex, BMI, race, smoking status, pack-years, FEV1% predicted, history of AEs (year prior to enrollment), and clinical center assessed the relationship between %LLMPs, total MPs, and prospective AEs; duration of follow-up was included as the offset. Subgroup analyses by lung function category (GOLD0, GOLD 1-4 COPD, and Preserved Ratio Impaired Spirometry, PRISm) were also performed using the same model. Results Among 10,198 tobacco-exposed individuals, 9,406 subjects (mean age 59.7±9.0, 53.4% male, 68% non-Hispanic white) had chest CT scans scored for MPs. The overall prevalence of MP>0 was 30.4%, with an average MP score of 0.78±1.88 and average %LLMP of 48%±39%. The prevalence of MPs varied by lung function category (20.1% GOLD0, 26.2% PRISm, 40.8% COPD) as did the mean MP score (0.28±0.93 GOLD0, 0.49±1.38 PRISm, 1.30±2.42 COPD) (Figure 1). The %LLMP also varied by lung function category (33%±39% GOLD0, 38%±37% PRISm, 57%±37% COPD). Among subjects with MPs>0 (n=2,857), higher %LLMP was associated with a significantly increased risk for future AEs (adjusted rate ratio (aRR) [95%CI]= 1.11[1.05-1.17]; Figure 1). Subgroup analyses by lung function category supported a significant association between increased %LLMP and future AEs in GOLD0 (aRR 1.45 [1.25-1.69]), but not in the COPD or PRISm subgroups (Figure 1). Conclusions A higher proportion of lower lobe mucus plugs is significantly associated with increased risk for future AEs among tobacco-exposed persons. Despite having the lowest burden of MPs, the highest risk for prospective AEs with increasing %LLMP was observed in the subgroup with normal spirometry (GOLD0).

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. Objectives 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.