Alejandro A. Diaz

Background: Bronchiectasis is increasingly recognized on chest CT among tobacco-exposed individuals, yet its longitudinal changes and prognostic significance are poorly understood. We tested whether progression of CT-based bronchial dilation over time is associated with higher mortality among tobacco-exposed individuals. Methods: We conducted a longitudinal analysis of the prospective COPDGene Study. Participants were aged 45-80 years and had a smoking history of at least 10 pack-years. They were enrolled at 21 centers across the United States between November 2007 and April 2011 and were followed up through July 2023 The percentage of airways with an airway-to-artery diameter ratio (AAR)>1 was quantified on CT using a validated artificial intelligence–based tool. A higher percentage of AAR>1 indicates a greater extent of bronchial dilation. Progression of bronchial dilation was defined as an increase in percentage of AAR>1 from baseline to 5-yr follow-up CT scan. Multivariable proportional hazard models were used to assess the association between bronchial dilation and all-cause mortality. Findings: Among 4,282 participants with baseline and 5-yr imaging data, 3,508 (81.9%) demonstrated CT-based bronchial dilation progression. During a median follow-up of 10.7 years (IQR 5.4-13.0), 836 (19.5%) deaths occurred. Mortality rates were higher in participants with progression than in those without (20.8% vs 13.7%). Bronchial dilation progression was associated with increased all-cause mortality after adjustment (adjusted hazard ratio 1.48, 95% CI 1.18-1.87). Interpretation: In tobacco-exposed individuals, progression of CT-based bronchial dilation was prevalent and was associated with increased all-cause mortality.

Objective: To investigate associations between rheumatoid arthritis (RA), chronic lung diseases, and acute respiratory exacerbations.Methods: Using the multicenter prospective COPDGene cohort of current and former people who smoke, RA cases were identified using self-report and disease-modifying antirheumatic drug use. Interstitial lung abnormalities (ILA), bronchiectasis (BR), chronic obstructive pulmonary disease (COPD), and mucus plugging (MP) were identified via high-resolution computed tomography scans and spirometry and prevalences were compared among participants with and without RA. Risk of acute respiratory exacerbation over 10 years of follow-up was compared for those with and without RA and stratified by lung abnormality using multivariable Cox regression, accounting for competing mortality risk.Results: We analyzed 76 RA cases (mean age 64.0 years, 67.1% female) and 8,175 non-RA comparators (mean age 59.4 years, 46.2% female). RA cases vs non-RA comparators had higher prevalences of ILA (17.3% vs 7.1%, p=0.0002) and BR (35.5% vs 24.6%, p=0.027), but prevalences of COPD (46.1% vs 43.7%, p=0.69) and MP (36.8% vs 29.6%, p=0.17) were similar. RA was associated with higher risk of acute respiratory exacerbation than non-RA (adjusted HR 1.68, 95%CI 1.25 to 2.26), and those with RA and COPD had the highest risk (adjusted HR 3.57, 95%CI 2.15 to 5.94) compared to non-RA without COPD.Conclusion: In this large prospective study, people who smoke with RA were more likely to have ILA and BR than those without RA, but had similar prevalences of COPD and MP. Participants with RA, particularly those with COPD, had higher risk of acute respiratory exacerbation.

Airway-occluding mucus plugs (MPs)—as identified on CT scans—are frequent in patients with chronic obstructive pulmonary disease (COPD). Prior studies have shown that body mass index (BMI) tends to be lower among individuals with MPs. To further investigate this relationship, we assessed whether BMI is associated with MPs in two large, multicentre cohorts of tobacco-exposed participants with and without COPD. In multivariable models, lower BMI was associated with an increased prevalence of MPs in COPD and non-COPD groups. Future studies are warranted to elucidate the mechanisms underlying this association.

Mucus plugs have been previously recognized as an important pathological feature in asthma and COPD, but their clinical role in these diseases has not been explored in-depth until recently. Mucus plug formation is driven by mucus hyperconcentration, changes in mucus viscoelastic properties, impaired clearance, and mucociliary collapse. Scoring systems, such as the bronchopulmonary segment mucus plug score, have been used to associate greater mucus plug burden with poor clinical outcomes. Additional scoring methods obtained through quantitative image processing are currently under development. Mucus plug burden has been associated with greater exacerbations and spirometric decline in both asthma and COPD, as well as greater mortality in COPD. Recently, mucus plug burden has been used as an endpoint in clinical trials to evaluate the effectiveness of biologic therapies in asthma; multiple biologic therapies demonstrated decreases in mucus plug burden and associated improvements in spirometry with treatment. Together, this data suggests mucus plugs may be a treatable trait in asthma and COPD. Mucus plug burden has current clinical, phenotypic, and predictive utility and shows promise as a future biomarker. Increased incorporation into clinical trials, expanded evidence of treatment effect, and standardization of methodology and imaging protocols will be needed. CT-detection of mucus plug burden is ready for greater incorporation into both research outcomes and clinical care.

Author Index for BRN Reviews, official journal of Barcelona Respiratory Network.

Background: Change in 6-min walk distance (6MWD) over time serves as a measure of change in functional exercise performance. We analysed a large cohort of current or former tobacco smokers over a 5-year period to identify correlates of 6MWD decline. Methods: A total of 4734 participants with normal spirometry or spirometric evidence of chronic obstructive pulmonary disease (COPD) who completed a 5-year follow-up in the COPDGene study were included. Baseline and 5-year assessments included 6MWD, spirometry, St. George’s Respiratory Questionnaire (SGRQ), gender, race and CT measures of emphysema, gas trapping and airway wall thickness. 6MWD decline correlates relative to baseline and 5-year changes were examined using univariate and multivariate linear regression. Results: At baseline, 2573 had normal spirometry; 487 were classified as GOLD1, 1044 as GOLD2, 514 as GOLD3 and 116 as GOLD4. Average 5-year decline in 6MWD was 35.6±101.7 (SD) metres (p2 =12.1% and 9.1%, respectively). 5 year change in variables assessed (including FEV ₁ and SGRQ) explained only small fractions of 6MWD decline variance (each R ² ≤5%). Conclusion: 6MWD declined significantly, but with high variability; spirometry, CT, health status, demographic and anthropometric measures accounted for only small portions of this variance. Our findings suggest that a meaningful decline in 6MWD observed over 5 years in COPD patients is in large part related to factors other than decline in pulmonary structure or function.

Extract Our conceptualisation of COPD continues to evolve. An increasingly outlined component of this is a progressive pulmonary vasculopathy, ranging from early endothelial dysfunction in smokers to overt pulmonary hypertension, a comorbidity that portends a grim prognosis [1–4]. Shareable abstract Vessel counting based biomarkers on chest computed tomography outperform traditional volume-based biomarkers in predicting COPD progression and lung function decline. This study provides further evidence on the value of vascular imaging biomarkers. https://bit.ly/3NBYPYX