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      Survival after pulmonary rehabilitation in patients with COPD: impact of functional exercise capacity and its changes

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          Abstract

          The impact of rehabilitation-induced changes in 6-minute walk distance (6MWD) on the survival of patients with chronic obstructive pulmonary disease (COPD) has not been fully elucidated. This study sought to determine the association of baseline 6MWD and its changes after pulmonary rehabilitation (PR) with 5-year survival in patients with COPD. Patients who were referred to a 12-week outpatient PR program were followed up for 5 years postcompletion, and survival status was verified. Survival was analyzed according to four groups based upon initial 6MWD (6MWDi) and its changes (Δ6MWD) after PR (Group 1: 6MWDi ≥350 m and Δ6MWD ≥30 m; Group 2: 6MWDi ≥350 m and Δ6MWD <30 m; Group 3: 6MWDi <350 m and Δ6MWD ≥30 m; and Group 4: 6MWDi <350 m and Δ6MWD <30 m) via Kaplan–Meier analysis and log rank test. Cox regression was performed to identify possible confounders of mortality estimates. In total, 423 patients (with mean ± standard deviation of forced expiratory volume in the first second [FEV 1] 43±16% predicted, age 65±8 years, and 6WMDi 381±134 m) underwent PR between 1999 and 2010. Survival rates decreased progressively from Group 1 to Group 4 (Group 1, 81%; Group 2, 69%; Group 3, 47%; Group 4, 27%; log rank test, P<0.05). 6MWDi ≥350 m (hazard ratio [HR] 0.39 [95% confidence interval {CI} 0.30–0.50]) and Δ6MWD ≥30 m (HR 0.66 [95% CI 0.51–0.85]) were strongly and independently associated with survival. Compared with Group 1, mortality risks progressively increased in Group 2 (HR 1.36 [95% CI 0.92–2.00]; not significant), Group 3 (HR 1.90 [95% CI 1.28–2.84]; P=0.001), and Group 4 (HR 3.28 [95% CI 2.02–5.33]; P<0.0001). Both poor 6MWD and lack of improvement >30 m after PR are associated with worse 5-year survival in patients with COPD.

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          Most cited references 16

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          The natural history of chronic airflow obstruction.

          A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).
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            Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing.

            The six-minute walk test is a submaximal exercise test that can be performed even by a patient with heart failure not tolerating maximal exercise testing. To elucidate the clinical significance and prognostic value of the six-minute walk test in patients with primary pulmonary hypertension (PPH), we sought (1) to assess the relation between distance walked during the six-minute walk test and exercise capacity determined by maximal cardiopulmonary exercise testing, and (2) to investigate the prognostic value of the six-minute walk test in comparison with other noninvasive parameters. The six-minute walk test was performed in 43 patients with PPH, together with echocardiography, right heart catheterization, and measurement of plasma epinephrine and norepinephrine. Symptom-limited cardiopulmonary exercise testing was performed in a subsample of patients (n = 27). Distance walked in 6 min was significantly shorter in patients with PPH than in age- and sex-matched healthy subjects (297 +/- 188 versus 655 +/- 91 m, p < 0. 001). The distance significantly decreased in proportion to the severity of New York Heart Association functional class. The distance walked correlated modestly with baseline cardiac output (r = 0.48, p < 0.05) and total pulmonary resistance (r = -0.49, p < 0. 05), but not significantly with mean pulmonary arterial pressure. In contrast, the distance walked correlated strongly with peak V O(2) (r = 0.70, p < 0.001), oxygen pulse (r = 0.57, p < 0.01), and V E-VCO(2) slope (r = -0.66, p < 0.001) determined by cardiopulmonary exercise testing. During a mean follow-up period of 21 +/- 16 mo, 12 patients died of cardiopulmonary causes. Among noninvasive parameters including clinical, echocardiographic, and neurohumoral parameters, only the distance walked in 6 min was independently related to mortality in PPH by multivariate analysis. Patients walking < 332 m had a significantly lower survival rate than those walking farther, assessed by Kaplan-Meier survival curves (log-rank test, p < 0.01). These results suggest that the six-minute walk test, a submaximal exercise test, reflects exercise capacity determined by maximal cardiopulmonary exercise testing in patients with PPH, and it is the distance walked in 6 min that has a strong, independent association with mortality.
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              Predictors of mortality in patients with emphysema and severe airflow obstruction.

              Limited data exist describing risk factors for mortality in patients having predominantly emphysema. A total of 609 patients with severe emphysema (ages 40-83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p=0.001), oxygen utilization (p=0.04), lower total lung capacity % predicted (p=0.05), higher residual volume % predicted (p=0.04), lower maximal cardiopulmonary exercise testing workload (p=0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p=0.005), and lower upper-to-lower-lung perfusion ratio (p=0.007), and modified BODE (p=0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p=0.005), but not in multivariate analysis (p=0.21). Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2016
                26 October 2016
                : 11
                : 2671-2679
                Affiliations
                [1 ]KU Leuven, Department of Rehabilitation Sciences, Leuven, Belgium
                [2 ]University Hospital Leuven, Respiratory Division and Rehabilitation, Leuven, Belgium
                [3 ]Monash University, Department of Physiotherapy, Melbourne, VIC, Australia
                [4 ]Institute for Breathing and Sleep, Melbourne, VIC, Australia
                [5 ]Monash Health, Monash Lung and Sleep, Melbourne, VIC, Australia
                [6 ]Hasselt University, Rehabilitation Research Centre, Biomedical Research Institute, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium
                Author notes
                Correspondence: Thierry Troosters, University Hospital Leuven, Respiratory Division and Rehabilitation, UZ Gasthuisberg, Onderwijs en Navorsing 1, Labo Pneumologie, Herestraat 49, Bus 706, B-3000, Leuven, Belgium, Tel +32 16 33 07 98, Fax +32 16 33 08 05, Email thierry.troosters@ 123456kuleuven.be
                Article
                copd-11-2671
                10.2147/COPD.S113450
                5087703
                © 2016 Camillo et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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