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Visual Emphysema at Chest CT in GOLD Stage 0 Cigarette Smokers Predicts Disease Progression: Results from the COPDGene Study.

ABSTRACT: Background The clinical significance of visually evident emphysema on CT images in individuals without spirometric evidence of chronic obstructive pulmonary disease (COPD) by current diagnostic criteria is, to the knowledge of the authors, unknown. Purpose To evaluate whether participants with visually evident emphysema at CT were more likely to have progressive disease and increased mortality at 5 years compared with those without visual emphysema. Materials and Methods This secondary analysis of the prospective Genetic Epidemiology of COPD study evaluated current or former smokers enrolled between 2008 and 2011 who did not meet current criteria for COPD (defined as Global Initiative for Obstructive Lung Disease stage 0). Statistical analysis was performed by using linear mixed models to estimate mean physiologic, imaging, and clinical outcomes for those with and without visual emphysema. Hazard ratios for mortality were calculated by using Cox regression models with emphysema as the main predictor. Results Of the 4095 participants, 48.3% (1979 participants; 1096 men and 883 women; mean age, 57 years ± 8 [standard deviation]) had trace or greater visual emphysema at CT and 51.7% (2116 participants; 1068 men and 1048 women; mean age, 56 years ± 8) had no emphysema at CT. At 5 years, participants with visual emphysema at CT demonstrated progressive airflow obstruction with lower values of ratio of forced expiratory volume in 1 second (FEV₁)-to-functional vital capacity (FVC) ratio (-1.7 vs -0.7) and greater progression in quantitative emphysema measured by 15th percentile lung density (-3.3 vs -0.3 HU), adjusted lung density (-3.1 vs -0.2 g/L), and percentage of lung voxels with CT attenuation less than -950 HU (0.17 vs -0.20) than participants without emphysema (P < .001 for each). The rate of quantitative emphysema progression increased with greater grades of emphysema severity within the emphysema group. Conclusion The presence of visual emphysema at CT in current and former Global Initiative for Obstructive Lung Disease stage 0 smokers predicted structural and physiologic disease progression. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.

SUBMITTER: Oh AS

PROVIDER: S-EPMC7457948 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background The correlation between visual emphysema patterns and subsequent progression of disease may provide a way to enrich a study population for treatment trials of emphysema. Purpose To evaluate the potential relationship between emphysema visual subtypes and progression of emphysema and gas trapping. Materials and Methods Current and former smokers with and without chronic obstructive pulmonary disease (COPD) enrolled in the prospective Genetic Epidemiology of COPD (COPDGene) study (ClinicalTrials.gov identifier: NCT02445183) between 2008 and 2011 had their Fleischner Society visual CT scores assessed at baseline, quantitative inspiratory, and expiratory CT and at 5 years. They also underwent pulmonary function testing at baseline CT and at 5 years. The dependent variables were inspiratory lung density at 15th percentile (adjusted for lung volume) as a measure of emphysema and percentage of lung volume with attenuation less than -856 HU at expiratory CT as a measure of air trapping. Statistical analysis used a linear mixed model, adjusted for age, height, sex, race, smoking status, and scanner make. Results A total of 4166 participants (mean age, 60 years ± 9 [standard deviation]; 2091 [50%] men) were evaluated. In participants with COPD (1655 participants, 40%), those with visual presence of mild, moderate, and confluent emphysema at baseline CT showed a mean decline in lung density of 4.6 g/L ± 1.1 (P < .001), 6.7 g/L ± 1.1 (P < .001), and 6.4 g/L ± 1.2 (P < .001), respectively, compared with 2.4 g/L ± 1.3 (P < .001) for those with trace emphysema. For participants without COPD, those with visual presence of mild and moderate emphysema at baseline CT showed a mean decline in lung density of 3.6 g/L ± 1.0 (P < .001) and 3.1 g/L ± 1.6 (P < .001), respectively, compared with 1.8 g/L ± 1.0 (P < .001) for those with trace emphysema. Conclusion The pattern of parenchymal emphysema at baseline CT was an independent predictor of subsequent progression of emphysema in participants who are current or former cigarette smokers with and without chronic obstructive pulmonary disease. © RSNA, 2020 Online supplemental material is available for this article.

Project description:Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality.

Project description:Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (clinicaltrials.gov, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; clinicaltrials.gov, NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results A total of 5143 participants (2613 men [51%]; mean age, 60 years ± 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years ± 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years ± 0.6 in COPDGene and 3.0 years ± 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16; P = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13; P = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31; P < .001) for the same increase in the rate of change in lung density perc15. Conclusion In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee and Park in this issue.

Project description:Background Visual assessment remains the standard for evaluating emphysema at CT; however, it is time consuming, is subjective, requires training, and is affected by variability that may limit sensitivity to longitudinal change. Purpose To evaluate the clinical and imaging significance of increasing emphysema severity as graded by a deep learning algorithm on sequential CT scans in cigarette smokers. Materials and Methods A secondary analysis of the prospective Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene) study participants was performed and included baseline and 5-year follow-up CT scans from 2007 to 2017. Emphysema was classified automatically according to the Fleischner emphysema grading system at baseline and 5-year follow-up using a deep learning model. Baseline and change in clinical and imaging parameters at 5-year follow-up were compared in participants whose emphysema progressed versus those who did not. Kaplan-Meier analysis and multivariable Cox regression were used to assess the relationship between emphysema score progression and mortality. Results A total of 5056 participants (mean age, 60 years ± 9 [SD]; 2566 men) were evaluated. At 5-year follow-up, 1293 of the 5056 participants (26%) had emphysema progression according to the Fleischner grading system. This group demonstrated progressive airflow obstruction (forced expiratory volume in 1 second [percent predicted]: -3.4 vs -1.8), a greater decline in 6-minute walk distance (-177 m vs -124 m), and greater progression in quantitative emphysema extent (adjusted lung density: -1.4 g/L vs 0.5 g/L; percentage of lung voxels with CT attenuation less than -950 HU: 0.6 vs 0.2) than those with nonprogressive emphysema (P < .001 for each). Multivariable Cox regression analysis showed a higher mortality rate in the group with emphysema progression, with an estimated hazard ratio of 1.5 (95% CI: 1.2, 1.8; P < .001). Conclusion An increase in Fleischner emphysema grade on sequential CT scans using an automated deep learning algorithm was associated with increased functional impairment and increased risk of mortality. ClinicalTrials.gov registration no. NCT00608764 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.

Project description:Background Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. Purpose To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. Materials and Methods SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. Results Of 737 participants, 387 (median age, 64 years [interquartile range, 58-71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV1, and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively; P ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD (n = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema; P ≤ .001 for both). Conclusion In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021.

Project description:RATIONALE:A significant proportion of smokers have lung function impairment characterized by a reduced FEV(1) with a preserved FEV(1)/FVC ratio. These smokers are a poorly characterized group due to their systematic exclusion from chronic obstructive pulmonary disease (COPD) studies. OBJECTIVES:To characterize the clinical, functional, and radiographic features of Global Initiative for Chronic Obstructive Lung Disease (GOLD)-Unclassified (FEV(1)/FVC ≥ 0.7 and FEV(1) < 80% predicted) and lower limits of normal (LLN)-unclassified (FEV(1)/FVC ≥ LLN and FEV(1) < LLN) subjects compared to smokers with normal lung function and subjects with COPD. METHODS:Data from the first 2,500 subjects enrolled in the COPDGene study were analyzed. All subjects had 10 or more pack-years of smoking and were between the ages of 45 and 80 years. Multivariate regression models were constructed to determine the clinical and radiological variables associated with GOLD-Unclassified (GOLD-U) and LLN-Unclassified status. Separate multivariate regressions were performed in the subgroups of subjects with complete radiologic measurement variables available. MEASUREMENTS AND MAIN RESULTS:GOLD-U smokers account for 9% of smokers in COPDGene and have increased body mass index (BMI), a disproportionately reduced total lung capacity, and a higher proportion of nonwhite subjects and subjects with diabetes. GOLD-U subjects exhibit increased airway wall thickness compared to smoking control subjects and decreased gas trapping and bronchodilator responsiveness compared to subjects with COPD. When LLN criteria were used to define the "unclassified" group, African American subjects were no longer overrepresented. Both GOLD-U and LLN-Unclassified subjects demonstrated a wide range of lung function impairment, BMI, and percentage of total lung emphysema. CONCLUSIONS:Subjects with reduced FEV(1) and a preserved FEV(1)/FVC ratio are a heterogeneous group with significant symptoms and functional limitation who likely have a variety of underlying etiologies beyond increased BMI. Clinical trial registered with www.clinicaltrials.gov (NCT000608764).

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Visual Emphysema at Chest CT in GOLD Stage 0 Cigarette Smokers Predicts Disease Progression: Results from the COPDGene Study.

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