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      A Simplified Score to Quantify Comorbidity in COPD

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          Abstract

          Importance

          Comorbidities are common in COPD, but quantifying their burden is difficult. Currently there is a COPD-specific comorbidity index to predict mortality and another to predict general quality of life. We sought to develop and validate a COPD-specific comorbidity score that reflects comorbidity burden on patient-centered outcomes.

          Materials and Methods

          Using the COPDGene study (GOLD II-IV COPD), we developed comorbidity scores to describe patient-centered outcomes employing three techniques: 1) simple count, 2) weighted score, and 3) weighted score based upon statistical selection procedure. We tested associations, area under the Curve (AUC) and calibration statistics to validate scores internally with outcomes of respiratory disease-specific quality of life (St. George's Respiratory Questionnaire, SGRQ), six minute walk distance (6MWD), modified Medical Research Council (mMRC) dyspnea score and exacerbation risk, ultimately choosing one score for external validation in SPIROMICS.

          Results

          Associations between comorbidities and all outcomes were comparable across the three scores. All scores added predictive ability to models including age, gender, race, current smoking status, pack-years smoked and FEV 1 (p<0.001 for all comparisons). Area under the curve (AUC) was similar between all three scores across outcomes: SGRQ (range 0·7624–0·7676), MMRC (0·7590–0·7644), 6MWD (0·7531–0·7560) and exacerbation risk (0·6831–0·6919). Because of similar performance, the comorbidity count was used for external validation. In the SPIROMICS cohort, the comorbidity count performed well to predict SGRQ (AUC 0·7891), MMRC (AUC 0·7611), 6MWD (AUC 0·7086), and exacerbation risk (AUC 0·7341).

          Conclusions

          Quantifying comorbidity provides a more thorough understanding of the risk for patient-centered outcomes in COPD. A comorbidity count performs well to quantify comorbidity in a diverse population with COPD.

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          Most cited references18

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          Design of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS).

          Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multicentre observational study of chronic obstructive pulmonary disease (COPD) designed to guide future development of therapies for COPD by providing robust criteria for subclassifying COPD participants into groups most likely to benefit from a given therapy during a clinical trial, and identifying biomarkers/phenotypes that can be used as intermediate outcomes to reliably predict clinical benefit during therapeutic trials. The goal is to enrol 3200 participants in four strata. Participants undergo a baseline visit and three annual follow-up examinations, with quarterly telephone calls. Adjudication of exacerbations and mortality will be undertaken.
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            Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001.

            COPD is one of the leading causes of mortality and morbidity in the United States, yet little is known about the prevalence of comorbid conditions and mortality in hospitalized patients with COPD. From the National Hospital Discharge Survey, 1979 to 2001, we evaluated whether or not COPD in adults > or = 25 years old is associated with increased prevalence and in-hospital mortality of several comorbidities. During 1979 to 2001, there were an estimated total of 47,404,700 hospital discharges (8.5% of all hospitalizations in adults > 25 years old) of patients with COPD; 37,540,374 discharges (79.2%) were made with COPD as a secondary diagnosis, and 9,864,278 discharges (20.8%) were made with COPD as the primary diagnosis. The prevalence and in-hospital mortality for pneumonia, congestive heart failure, ischemic heart disease, thoracic malignancies, and respiratory failure were larger in hospital discharges with any mention of COPD. In a nationally representative sample of hospitalizations, any mention of COPD in the discharge diagnosis is associated with higher hospitalization prevalence and in-hospital mortality from other comorbidities. These results highlight the fact that the burden of disease associated with COPD is likely underestimated.
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              Neuropsychologic findings in hypoxemic chronic obstructive pulmonary disease.

              As part of a six-center clinical trial of the effectiveness of continuous v nocturnal oxygen in the management of hypoxemic chronic obstructive pulmonary disease (COPD), we performed detailed neuropsychologic assessments of these patients prior to their beginning treatment. The 203 patients (age, 65 years; Pao2, 51 mm Hg; forced expiratory volume in 1 s, 0.74 L) performed significantly worse than controls on virtually all neuropsychologic tests. Moderate to severe test impairment suggestive of cerebral dysfunction was found in 42% of the patients, as compared with 14% of controls. Higher cognitive functions (abstracting ability, complex perceptual-motor integration) were most severely affected, although half the patients also showed decrements in motor speed, strength, and coordination. Low-order significant inverse correlations were found between neuropsychologic impairment and Pao2, resting arterial oxygen saturation and hemoglobin levels and maximum work. It is concluded that cerebral disturbance is common in hypoxemic COPD and may be related in part to decreased availability of oxygen to the brain.
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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
                16 December 2014
                : 9
                : 12
                : e114438
                Affiliations
                [1 ]Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
                [2 ]Epidemiology, Biostatistics & Prevention Institute, University of Zurich, Zurich, Switzerland
                [3 ]Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, United States of America
                [4 ]Department of Medicine, National Jewish Health, Denver, Colorado, United States of America
                [5 ]Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, Texas, United States of America
                [6 ]Pulmonary and Critical Care Medicine, Morehouse School of Medicine, Atlanta, Georgia, United States of America
                [7 ]Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America
                [8 ]Pulmonary and Critical Care, National Jewish Health, Denver, Colorado, United States of America
                [9 ]Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, California, United States of America
                [10 ]Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
                [11 ]Department of Medicine, Department of Epidemiology, Columbia University Medical Center, New York City, New York, United States of America
                [12 ]Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska, United States of America
                [13 ]Pulmonary and Critical Care Medicine, New York Presbyterian-Weill Cornell Medical College, New York City, New York, United States of America
                Instituto de Higiene e Medicina Tropical, Portugal
                Author notes

                Competing Interests: RGB reports receiving funding from the National Institutes of Health and United States-Environmental Protection Agency, with an in-kind donation from Cenestra Health and royalties from UpToDate. In the past 3 years, MKH has participated in advisory boards for Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Genentech, Novartis, Forest, Regeneron and Medimmune; participated on speaker's bureaus for Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Novartis, Grifols therapeutics, and the National Association for Continuing Education, and WebMD; has consulted for Novartis, Evidera and United Biosource Corporation; and has received royalties from UpToDate and ePocrates. She has also participated in research sponsored by GlaxoSmithKline with funds paid to her institution. In the past three years, EKS received honoraria and consulting fees from Merck and grant support from GlaxoSmithKline. In the past three years, MBD had participated in advisory boards for Lupin Pharmaceuticals and Boehringer Ingelheim. In the last three years, BJM has participated in medical advisory boards for Aerocrine, AstraZeneca, Boehringer Ingelheim, Breathe, Coviden, GlaxoSmithKline, Forest, Ikaria, Merck, Novartis, Pfizer, Respironics, Theravance; has received grant funds provided to and controlled by National Jewish Health from AstraZeneca, Boehringer Ingelheim, Forest, NABI, National Heart, Lung, and Blood Institute, Sunovian; consulted for Forest; and participated in CME activities with Consensus Medical, Cleveland Clinic, Integrity, Carden Jennings, Mt Sinai, Cedars Sinai, WebMD, Foundation for Improving Patient Outcomes; and royalties from Up-To-Date. The remaining authors have no relevant financial disclosures. The above stated interests do not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: NP NNH RAW MAP MBD MKH. Analyzed the data: NNH NP RAW MBD. Contributed reagents/materials/analysis tools: NP MAP MBD MKH NAH EKS JC RAW NNH. Wrote the paper: NP MAP MBD MKH EAR NAH CM MF SPB BM JR DD RGB SIR FM EKS JC RAW NNH.

                Article
                PONE-D-14-27336
                10.1371/journal.pone.0114438
                4267736
                25514500
                bdfcc880-ae77-4f5a-b69e-44da5b2d7fed
                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
                : 18 June 2014
                : 7 November 2014
                Page count
                Pages: 14
                Funding
                NP is a postdoctoral research fellow supported by the institutional training grant at Johns Hopkins University, funded the National Heart, Lung, and Blood Institute (NHLBI) [T32HL007534]. She obtained further support for this specific project through the Chest Foundation (Respiratory Health Association of Metropolitan Chicago Women's Lung Health Award). The COPDGene® Study is funded by 2R01HL089897 (PI: James Crapo) and 2R01HL089856 (PI: Edwin Silverman). This work is also supported by the COPD Foundation. AstraZeneca Pharmaceuticals LP, Novartis Pharmaceuticals Corporation, Pfizer, Siemens and Sunovion Inc are ongoing supporters of the project through the COPDGene® Industry Advisory Board. The SPIROMICS study is funded by the NHLBI of the National Institutes of Health, contract and grant numbers: HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN2682009000019C, and HHSN268200900020C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Health Care
                Quality of Life
                Pulmonology
                Chronic Obstructive Pulmonary Disease
                Custom metadata
                The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. All the data sets in this study are available as indicated below. The COPDGene data upon which these findings are based are available through the dbGaP study page for COPDGene: http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000179.v3.p2. There is a link from this page (Authorized Access Section) to dbGaP's controlled access system that allows someone to request the data. The accession number for this data is phs000179.v3.p2. The SPIROMICS study can provide datasets upon submission and approval of the Data Access Request Form as per the study policy. Available data and forms can be found at the following link: http://www.cscc.unc.edu/spir/public/docfilter.php?study=spir&filter_type=public. A list of available datapoints is posted on the study website under the heading “No Committee Association.” For this study, we utilized data from the following forms: Anthropometry Form, Baseline Exacerbation Questionnaire, Baseline Medical History Form, Demographic Form, Modified Medical Research Council Dyspnea Scale, Respiratory Disease and Smoke Exposure Questionnaire, Spirometry Data Form, and Six Minute Walk Test Form. Requested data only was assembled into an appropriate dataset by the central Data Coordinating Center and provided to the investigators of this study. For requests, investigators should submit the Data Access and Request Form found under the Heading “Data Sharing Subcommittee” and forward to spiromics@ 123456unc.edu such that an appropriate dataset can be assembled by the data coordinating center, in the same way as was provided to the authors of this study.

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