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      Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations

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          Abstract

          Background

          COPD exacerbations have negative impact on patients’ survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival.

          Methods

          This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation.

          Results

          Included were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13–41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively ( p <  0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6–3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08–3.1, p <  0.05).

          Conclusions

          Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.

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          Most cited references21

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          GPOWER: A general power analysis program

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            Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study

            Background Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people. The relevance of frailty to chronic respiratory disease and its management is unknown. Objectives To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation. Methods 816 outpatients with COPD (mean (SD) age 70 (10) years, FEV1% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015. Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation. Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex. Results 209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail. Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01). Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission. However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001). After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty. Conclusions Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion. However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term.
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              Sarcopenia and frailty in chronic respiratory disease.

              Sarcopenia and frailty are geriatric syndromes characterized by multisystem decline, which are related to and reflected by markers of skeletal muscle dysfunction. In older people, sarcopenia and frailty have been used for risk stratification, to predict adverse outcomes and to prompt intervention aimed at preventing decline in those at greatest risk. In this review, we examine sarcopenia and frailty in the context of chronic respiratory disease, providing an overview of the common assessments tools and studies to date in the field. We contrast assessments of sarcopenia, which consider muscle mass and function, with assessments of frailty, which often additionally consider social, cognitive and psychological domains. Frailty is emerging as an important syndrome in respiratory disease, being strongly associated with poor outcome. We also unpick the relationship between sarcopenia, frailty and skeletal muscle dysfunction in chronic respiratory disease and reveal these as interlinked but distinct clinical phenotypes. Suggested areas for future work include the application of sarcopenia and frailty models to restrictive diseases and population-based samples, prospective prognostic assessments of sarcopenia and frailty in relation to common multidimensional indices, plus the investigation of exercise, nutritional and pharmacological strategies to prevent or treat sarcopenia and frailty in chronic respiratory disease.
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                Author and article information

                Contributors
                Gad.segal@sheba.health.gov.il
                Journal
                BMC Pulm Med
                BMC Pulm Med
                BMC Pulmonary Medicine
                BioMed Central (London )
                1471-2466
                11 May 2020
                11 May 2020
                2020
                : 20
                : 133
                Affiliations
                [1 ]GRID grid.413795.d, ISNI 0000 0001 2107 2845, Internal medicine T, Chaim Sheba Medical Center, ; Tel-Hashomer, 2nd Sheba road, Ramat Gan, Israel
                [2 ]GRID grid.12136.37, ISNI 0000 0004 1937 0546, Sackler faculty of medicine, , Tel-Aviv University, ; Tel-Aviv, Israel
                [3 ]Department of Internal Medicine “A”, Yoseftal Hospital, Eilat, Israel
                [4 ]GRID grid.413731.3, ISNI 0000 0000 9950 8111, Department of Internal Medicine “B”, , Rambam Health Care Campus, ; Haifa, Israel
                [5 ]GRID grid.6451.6, ISNI 0000000121102151, Rappaport’s Faculty of Medicine, , The Technion Institute, ; Haifa, Israel
                [6 ]GRID grid.413731.3, ISNI 0000 0000 9950 8111, Division of Pulmonary Medicine, , Rambam Health Care Campus, ; Haifa, Israel
                Author information
                http://orcid.org/0000-0002-3851-3245
                Article
                1169
                10.1186/s12890-020-1169-z
                7216624
                32393221
                643ce6f9-e5e0-45f4-ad6e-8e2d3e5c7a21
                © The Author(s). 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

                History
                : 12 November 2019
                : 28 April 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Respiratory medicine
                alt,copd,exacerbation,frailty,sarcopenia,survival
                Respiratory medicine
                alt, copd, exacerbation, frailty, sarcopenia, survival

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