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      Emphysema Predicts Hospitalisation and Incident Airflow Obstruction among Older Smokers: A Prospective Cohort Study

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          Abstract

          Background

          Emphysema on CT is common in older smokers. We hypothesised that emphysema on CT predicts acute episodes of care for chronic lower respiratory disease among older smokers.

          Materials and Methods

          Participants in a lung cancer screening study age ≥60 years were recruited into a prospective cohort study in 2001–02. Two radiologists independently visually assessed the severity of emphysema as absent, mild, moderate or severe. Percent emphysema was defined as the proportion of voxels ≤ −910 Hounsfield Units. Participants completed a median of 5 visits over a median of 6 years of follow-up. The primary outcome was hospitalization, emergency room or urgent office visit for chronic lower respiratory disease. Spirometry was performed following ATS/ERS guidelines. Airflow obstruction was defined as FEV1/FVC ratio <0.70 and FEV1<80% predicted.

          Results

          Of 521 participants, 4% had moderate or severe emphysema, which was associated with acute episodes of care (rate ratio 1.89; 95% CI: 1.01–3.52) adjusting for age, sex and race/ethnicity, as was percent emphysema, with similar associations for hospitalisation. Emphysema on visual assessment also predicted incident airflow obstruction (HR 5.14; 95% CI 2.19–21.1).

          Conclusion

          Visually assessed emphysema and percent emphysema on CT predicted acute episodes of care for chronic lower respiratory disease, with the former predicting incident airflow obstruction among older smokers.

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          Most cited references20

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.

            W MacNee, , B Celli (2004)
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              The National Lung Screening Trial: overview and study design.

              The National Lung Screening Trial (NLST) is a randomized multicenter study comparing low-dose helical computed tomography (CT) with chest radiography in the screening of older current and former heavy smokers for early detection of lung cancer, which is the leading cause of cancer-related death in the United States. Five-year survival rates approach 70% with surgical resection of stage IA disease; however, more than 75% of individuals have incurable locally advanced or metastatic disease, the latter having a 5-year survival of less than 5%. It is plausible that treatment should be more effective and the likelihood of death decreased if asymptomatic lung cancer is detected through screening early enough in its preclinical phase. For these reasons, there is intense interest and intuitive appeal in lung cancer screening with low-dose CT. The use of survival as the determinant of screening effectiveness is, however, confounded by the well-described biases of lead time, length, and overdiagnosis. Despite previous attempts, no test has been shown to reduce lung cancer mortality, an endpoint that circumvents screening biases and provides a definitive measure of benefit when assessed in a randomized controlled trial that enables comparison of mortality rates between screened individuals and a control group that does not undergo the screening intervention of interest. The NLST is such a trial. The rationale for and design of the NLST are presented. © RSNA, 2010
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                3 April 2014
                : 9
                : 4
                : e93221
                Affiliations
                [1 ]Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom
                [2 ]Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
                [3 ]Department of Radiology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America
                [4 ]Department of Radiology, Mount Sinai Medical Center, New York, New York, United States of America
                [5 ]Department of Biomedical Engineering, University of Pennsylvania, Philadelphia, United States of America
                [6 ]School of Electrical and Computer Engineering, College of Engineering, Cornell University, Ithaca, New York, United States of America
                [7 ]Department of Radiology, New York University Langone Medical Center, New York, New York, United States of America
                [8 ]Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America
                Central Michigan University School of Medicine, United States of America
                Author notes

                Competing Interests: The authors have the following interests: DY, AR, and CH are named inventors on the following patents and patent applications relating to the evaluation of diseases of the chest including measurement of nodules: 7274810 (System and method for three-dimensional image rendering and analysis), 7499578 (System, method and apparatus for small pulmonary nodule computer aided diagnosis from computed tomography scans), 7693729 (System and method for conducting a clinical trial study),7751607 (System, method and apparatus for small pulmonary nodule computer aided diagnosis from computed tomography scans), 8045770 (System and method for three-dimensional image rendering and analysis), 8050481 (Method and apparatus for small pulmonary nodule computer aided diagnosis from computed tomography scans), 8165385 (System and method for three-dimensional image rendering and analysis), 8577129 (System and method for three-dimensional image rendering and analysis). Some of these, which are owned by Cornell Research Foundation (CRF) are nonexclusively licensed to General Electric. As an inventor of these patents, DY, AR, and CH are entitled to a share of any compensation which CRF may receive from its commercialization of these patents. As of April 2009, CH has signed away any financial benefit including royalties and any other proceeds related to the patents or patent applications. SV is currently employed by GSK but exclusively performed the work while an employee of Columbia University. This study was partly funded by Empire Blue Cross and Blue Shield. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: DM JA RGB. Performed the experiments: DM JA CH BK AL AR SM GP MS JS DY RGB. Analyzed the data: DM FA RGB. Wrote the paper: DM. Made critical revisions of the manuscript for important intellectual content: FA JA CH BK AL AR SM GP MS JS DY RGB.

                Article
                PONE-D-13-06976
                10.1371/journal.pone.0093221
                3974731
                24699215
                2f08f91a-9bf1-419c-9cc9-55c12749180f
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 February 2013
                : 4 March 2014
                Page count
                Pages: 8
                Funding
                Collection of spirometric and percent emphysema measures, longitudinal components from the third visit onwards, and analysis and interpretation of the data were supported via grants R01-HL075476, R01-HL077612, R01-HL093081, RR024156, and ES09089 from the National Institutes of Health. The baseline and second visits were funded by the City of New York Department of Health and Mental Hygiene; the Starr Foundation; Empire Blue Cross and Blue Shield; the New York Community Trust; New York State Office of Science, Technology, and Academic Research; the Rogers Family Fund; Weill Medical College of Cornell University; Cornell University; and AMDeC Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Population Biology
                Psychology
                Addiction
                Drug Addiction
                Recreational Drug Addiction
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Tomography
                Computed Axial Tomography
                Epidemiology
                Oncology
                Cancer Detection and Diagnosis
                Cancer Screening
                Public and Occupational Health
                Health Screening
                Pulmonology
                Asthma
                Chronic Obstructive Pulmonary Disease
                Radiology and Imaging

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