Work

Mucus plugs and exacerbations in tobacco-exposed people with normal and impaired spirometry

Year: 2026

Type: article

Abstract: To the editor, Individuals with normal spirometry and preserved ratio and impaired spirometry (PRISm) frequently experience worsening of their respiratory symptoms requiring treatment,1 episodes termed exacerbations. In persons with chronic obstructive pulmonary disease (COPD), airway-occluding mucus plugs (MPs) may be a source of infection and inflammation, triggering exacerbations.2-5 However, whether MPs are associated with exacerbations in tobacco-exposed individuals without COPD remains to be explored. Therefore, we aimed to assess the relationship between MPs and exacerbations in persons with normal spirometry and PRISm. We scored MPs on computed tomography (CT) from persons exposed to tobacco (smoking history of ≥10 pack-years) without COPD from the multicenter COPDGene Study. Of the 10 305 enrolled participants, 5831 were excluded, including nonsmoker controls (n = 107), those with COPD (n = 4483), and those with missing data on spirometry (n = 66), MPs (n = 566), and exacerbation over time (n = 609). The remaining 4474 participants had normal spirometry—defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ≥0.70 and FEV1 ≥80% predicted—and PRISm—defined as FEV1/FVC ≥0.70 and FEV1 <80% predicted. Trained readers determined the scores by counting the number of lung segments with MPs, ranging from 0 to 18.6 For this analysis, the scores were categorized into 0, 1–3, and ≥4.2,3,7 At enrollment, participants were exacerbation-free for at least 4 weeks and asked to report the frequency of exacerbations in the prior year. Prospective moderate exacerbations were defined as new onset or increased cough, phlegm, and dyspnea requiring prescription of antibiotics or systemic steroids, ascertained every 6 months through the COPDGene follow-up program using telephone and web-based interfaces.1 Severe exacerbations were defined as those resulting in hospitalization or an emergency room visit.1 To account for the overdispersion of exacerbations during follow-up, we used a multivariable zero-inflated Poisson regression model to test the association between mucus plug (1–3 vs 0 and ≥4 vs 0) and moderate-to-severe exacerbations (hereafter, exacerbations) over time.2 A priori–selected covariates included age, sex, self-reported race, body mass index, current smoking status, pack-years smoked, physician-diagnosed asthma, self-reported history of ≥1 exacerbation in the year before enrollment, postbronchodilator FEV1 (L), center, and CT measures of emphysema (defined as the percentage of lung attenuation areas <−950 Hounsfield units) and airway wall thickness (square root of wall area for a standardized 10-mm-perimeter airway).2,3 Model estimates for exacerbations are reported as incidence rate ratios. All analyses were performed using SAS 9.4 software. Table 1 shows participants’ characteristics. Among 3500 participants with normal spirometry, 663 (18.9%) had an MP score of 1–3 and 66 (1.9%) had a score of ≥4; among the 974 PRISm participants, 224 (23%) had 1–3 lung segments with MPs and 37 (3.8%) had ≥4 (normal spirometry vs PRISm comparison, P <.0001). The crude exacerbation rates per 100 person-years were 14 (95% CI, 14–15) for participants with normal spirometry and 28 (95% CI, 27–29) for those with PRISm (P <.0001). Next, we conducted analyses separately in each spirometry group to evaluate the association between MPs and exacerbation rates.

Source: Annals of the American Thoracic Society

DOI: 10.1093/annalsats/aaoaf001