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      Lower mortality after early supervised pulmonary rehabilitation following COPD-exacerbations: a systematic review and meta-analysis

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          Abstract

          Background

          Pulmonary rehabilitation (PR), delivered as a supervised multidisciplinary program including exercise training, is one of the cornerstones in the chronic obstructive pulmonary disease (COPD) management. We performed a systematic review and meta-analysis to assess the effect on mortality of a supervised early PR program, initiated during or within 4 weeks after hospitalization with an acute exacerbation of COPD compared with usual post-exacerbation care or no PR program. Secondary outcomes were days in hospital, COPD related readmissions, health-related quality of life (HRQoL), exercise capacity (walking distance), activities of daily living (ADL), fall risk and drop-out rate.

          Methods

          We identified randomized trials through a systematic search using MEDLINE, EMBASE and Cocharne Library and other sources through October 2017. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using the Cochrane Risk of Bias tool.

          Results

          We included 13 randomized trials (801 participants). Our meta-analyses showed a clinically relevant reduction in mortality after early PR (4 trials, 319 patients; RR = 0.58 (95% CI: [0.35 to 0.98])) and at the longest follow-up (3 trials, 127 patients; RR = 0.55 (95% CI: [0.12 to 2.57])). Early PR reduced number of days in hospital by 4.27 days (1 trial, 180 patients; 95% CI: [− 6.85 to − 1.69]) and hospital readmissions (6 trials, 319 patients; RR = 0.47 (95% CI: [0.29 to 0.75])). Moreover, early PR improved HRQoL and walking distance, and did not affect drop-out rate. Several of the trials had unclear risk of bias in regard to the randomization and blinding, for some outcome there was also a lack of power.

          Conclusion

          Moderate quality of evidence showed reductions in mortality, number of days in hospital and number of readmissions after early PR in patients hospitalized with a COPD exacerbation. Long-term effects on mortality were not statistically significant, but improvements in HRQoL and exercise capacity appeared to be maintained for at least 12 months. Therefore, we recommend early supervised PR to patients with COPD-related exacerbations. PR should be initiated during hospital admission or within 4 weeks after hospital discharge.

          Electronic supplementary material

          The online version of this article (10.1186/s12890-018-0718-1) contains supplementary material, which is available to authorized users.

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          Most cited references22

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          Pulmonary rehabilitation for chronic obstructive pulmonary disease.

          Widespread application of pulmonary rehabilitation (also known as respiratory rehabilitation) in chronic obstructive pulmonary disease (COPD) should be preceded by demonstrable improvements in function (health-related quality of life, functional and maximal exercise capacity) attributable to the programmes. This review updates the review reported in 2006.
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            Interpreting thresholds for a clinically significant change in health status in asthma and COPD.

            Health status (or Health-Related Quality of Life) measurement is an established method for assessing the overall efficacy of treatments for asthma and chronic obstructive pulmonary disease (COPD). Such measurements can indicate the potential clinical significance of a treatment's effect. This paper is concerned with methods of estimating the threshold of clinical significance for three widely used health status questionnaires for asthma and COPD: the Asthma Quality of Life Questionnaire, Chronic Respiratory Questionnaire and St George's Respiratory Questionnaire. It discusses the methodology used to obtain such estimates and shows that the estimates appear to be fairly reliable; ie. for a given questionnaire, similar estimates may be obtained in different studies. These empirically derived thresholds are all mean estimates with confidence intervals around them. The presence of these confidence intervals affects the way in which the thresholds may be used to draw inferences concerning the clinical relevance of clinical trial results. A new system of judging the magnitude of clinically significant results is proposed. Finally, an attempt is made to translate these thresholds into scenarios that illustrate what a clinically significant change with treatment may mean to an individual patient.
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              Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease.

              There is a need to identify clinically meaningful predictors of mortality following hospitalized COPD exacerbation. The aim of this study was to systematically review the literature to identify clinically important factors that predict mortality after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD). Eligible studies considered adults admitted to hospital with COPD exacerbation. Two authors independently abstracted data. Odds ratios were then calculated by comparing the prevalence of each predictor in survivors versus nonsurvivors. For continuous variables, mean differences were pooled by the inverse of their variance, using a random effects model. There were 37 studies included (189,772 study subjects) with risk of death ranging from 3.6% for studies considering short-term mortality, 31.0% for long-term mortality (up to 2 yr after hospitalization), and 29.0% for studies that considered solely intensive care unit (ICU)-admitted study subjects. Twelve prognostic factors (age, male sex, low body mass index, cardiac failure, chronic renal failure, confusion, long-term oxygen therapy, lower limb edema, Global Initiative for Chronic Lung Disease criteria stage 4, cor pulmonale, acidemia, and elevated plasma troponin level) were significantly associated with increased short-term mortality. Nine prognostic factors (age, low body mass index, cardiac failure, diabetes mellitus, ischemic heart disease, malignancy, FEV1, long-term oxygen therapy, and PaO2 on admission) were significantly associated with long-term mortality. Three factors (age, low Glasgow Coma Scale score, and pH) were significantly associated with increased risk of mortality in ICU-admitted study subjects. Different factors correlate with mortality from COPD exacerbation in the short term, long term, and after ICU admission. These parameters may be useful to develop tools for prediction of outcome in clinical practice.
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                Author and article information

                Contributors
                +45 35 45 76 26 , camilla.koch.ryrsoe@regionh.dk , http://www.inflammation-metabolism.dk , http://aktivsundhed.dk
                nina.skavlan.godtfredsen@regionh.dk
                linette.marie.kofod@regionh.dk
                marie.lavesen.karlsson@regionh.dk
                lam@odense.dk
                randisvarstad@gmail.com
                ifarver@psy.au.dk
                heec@sst.dk
                brit@sst.dk
                peter.lange@sund.ku.dk
                ulrik_winning@hotmail.com
                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                1471-2466
                15 September 2018
                15 September 2018
                2018
                : 18
                : 154
                Affiliations
                [1 ]ISNI 0000 0001 0674 042X, GRID grid.5254.6, The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, , University of Copenhagen, ; Blegdamsvej 9, DK-2100 Copenhagen, Denmark
                [2 ]Danish Health Authority, Copenhagen, Denmark
                [3 ]ISNI 0000 0004 0646 7373, GRID grid.4973.9, Department of Respiratory Medicine, , Copenhagen University Hospital, ; Hvidovre, Denmark
                [4 ]ISNI 0000 0001 0674 042X, GRID grid.5254.6, Department of Clinical Medicine, , University of Copenhagen, ; Copenhagen, Denmark
                [5 ]ISNI 0000 0004 0646 7373, GRID grid.4973.9, Department of Physiotherapy, , Copenhagen University Hospital, ; Hvidovre, Denmark
                [6 ]ISNI 0000 0004 0646 7373, GRID grid.4973.9, Department of Pulmonary and Infectious Diseases, , Copenhagen University Hospital, ; Nordsjælland, Hillerød, Denmark
                [7 ]ISNI 0000 0004 0446 5147, GRID grid.466973.9, The Department of the Elderly and Disabled, Odense Municipality, ; Odense, Denmark
                [8 ]ISNI 0000 0004 0646 7349, GRID grid.27530.33, Department of Gastroenterology, Center for Nutrition and Bowel Disease, , Aalborg University Hospital, ; Aalborg, Denmark
                [9 ]ISNI 0000 0004 0512 597X, GRID grid.154185.c, Unit for Psychooncology and Health Psychology, , Aarhus University Hospital and Aarhus University, ; Aarhus, Denmark
                [10 ]ISNI 0000 0001 0674 042X, GRID grid.5254.6, Department of Public Health, Section of Social Medicine, , University of Copenhagen, ; Copenhagen, Denmark
                [11 ]ISNI 0000 0004 0646 7402, GRID grid.411646.0, Medical Department O, Respiratory Section, , Herlev and Gentofte Hospital, ; Herlev, Denmark
                Author information
                http://orcid.org/0000-0002-8059-7331
                Article
                718
                10.1186/s12890-018-0718-1
                6139159
                30219047
                bee05abd-760c-42a8-95ae-1f7d45149ad8
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 12 June 2018
                : 4 September 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100007324, Sundhedsstyrelsen;
                Funded by: Centre of Inflammation and Metabolism and Centre for Physical Activity Research
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Respiratory medicine
                chronic obstructive pulmonary disease,supervised early pulmonary rehabilitation,exacerbation of copd,hospital readmissions,mortality,systematic review

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