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      Chronotropic incompetence can limit exercise tolerance in COPD patients with lung hyperinflation

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          Metabolic-chronotropic relationship is the only concept that assesses the entire chronotropic function during exercise, as it takes into account individual fitness. To better understand interrelationships between chronotropic incompetence (CI), dynamic hyperinflation (DH) and exercise limitation among Global initiative for chronic Obstructive Lung Disease (GOLD) stages of chronic obstructive pulmonary disease (COPD) disease severity, we evaluated cardiopulmonary responses to symptom-limited cycle exercise in stable patients.

          Patients and methods

          We prospectively studied 47 COPD patients classified by GOLD stage severity. Pulmonary function tests and cardiopulmonary responses to symptom-limited incremental exercise were studied. CI was defined by regression line between percent heart rate (HR) reserve and percent oxygen uptake ( V’O 2) reserve, ie, chronotropic-metabolic index (CMI). DH was defined from the knot resulting from the nonlinear regressions of inspiratory capacity changes from rest to peak (dynamic inspiratory capacity (IC dyn)) with percentage of maximal HR and CMI.


          Aerobic capacity (median interquartile ranges) peak V’O 2, 24.3 (23.6; 25.2), 18.5 (15.5; 21.8), 17.5 (15.4; 19.1) mL·kg −1·min −1 and CMI worsened according to GOLD severity. The optimal knot of IC dyn was equal to −0.34 L. The multivariate logistic regression showed a strong relationship between CI (outcome) and DH (odds ratio [confidence interval 95]) 25 (3.5; 191.6).


          COPD patients with DH have a poor cardiovascular response to exercise, which may be attributed to CI.

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          Most cited references 35

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          Chronotropic incompetence: causes, consequences, and management.

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            The COPD assessment test: a systematic review.

            The COPD assessment test (CAT) is a self-administered questionnaire that measures health-related quality of life. We aimed to systematically evaluate the literature for reliability, validity, responsiveness and minimum clinically important difference (MCID) of the CAT. Multiple databases were searched for studies analysing the psychometric properties of the CAT in adults with chronic obstructive pulmonary disease. Two reviewers independently screened, selected and extracted data, and assessed methodological quality of relevant studies using the COSMIN checklist. From 792 records identified, 36 studies were included. The number of participants ranged from 45 to 6469, mean age from 56 to 73 years, and mean forced expiratory volume in 1 s from 39% to 98% predicted. Internal consistency (reliability) was 0.85-0.98, and test-retest reliability was 0.80-0.96. Convergent and longitudinal validity using Pearson's correlation coefficient were: SGRQ-C 0.69-0.82 and 0.63, CCQ 0.68-0.78 and 0.60, and mMRC 0.29-0.61 and 0.20, respectively. Scores differed with GOLD stages, exacerbation and mMRC grades. Mean scores decreased with pulmonary rehabilitation (2.2-3 units) and increased at exacerbation onset (4.7 units). Only one study with adequate methodology reported an MCID of 2 units and 3.3-3.8 units using the anchor-based approach and distribution-based approach, respectively. Most studies had fair methodological quality. We conclude that the studies support the reliability and validity of the CAT and that the tool is responsive to interventions, although the MCID remains debatable.
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              Oxygen uptake efficiency slope: an index of exercise performance and cardiopulmonary reserve requiring only submaximal exercise.

              We sought to evaluate, in adults, the efficacy of the Oxygen Uptake Efficiency Slope (OUES), an index of cardiopulmonary functional reserve that can be based upon a submaximal exercise effort. Maximal oxygen uptake (VO2,max), the most reliable measure of exercise capacity, is seldom attained in standard exercise testing. The OUES, which relates oxygen uptake to total ventilation during exercise, was proposed by Baba and coworkers (7) in a study of pediatric cardiac patients. They felt this submaximal index of cardiopulmonary reserve might be more practical than VO2max and more appropriate than the commonly used peak oxygen consumption (VO2 peak). Treadmill exercise tests with simultaneous respiratory gas measurement were performed in 998 older subjects free of clinically recognized cardiovascular disease and 12 male patients with congestive heart failure. During incremental exercise, oxygen uptake was plotted against the logarithm of total ventilation, and the OUES was determined. The OUES, when calculated only from the first 75% of the exercise test, differed by 1.9% from the OUES calculated from 100% of exercise time in subjects with a peak respiratory exchange rate > or =1.10. On serial tests the OUES was less variable than exercise duration or VO2 peak. It correlated strongly with VO2max, with forced expiratory volume in 1 s and negatively with a history of current smoking. The OUES declined linearly with age in both women and men. A small sample of patients with congestive heart failure had OUES values much lower than those of older subjects without cardiovascular disease. The OUES is an objective, reproducible measure of cardiopulmonary reserve that does not require a maximal exercise effort. It integrates cardiovascular, musculoskeletal and respiratory function into a single index that is largely influenced by pulmonary dead space ventilation and exercise-induced lactic acidosis.

                Author and article information

                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
                17 October 2016
                : 11
                : 2553-2561
                [1 ]Université Lille, CHU Lille, EA 4483, IMPact de l’Environnement Chimique sur la Santé humaine, Lille, France
                [2 ]Département de Cardiologie – CHU Fort de France, Martinique – Faculté de Médecine – Université des Antilles, France
                [3 ]Pôle d’Anesthésie Réanimation ADRU, CHU Nîmes, Nîmes, France
                [4 ]Université Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France
                [5 ]Université Lille, Inserm, CHU Lille, Lille Inflammation Research International Center, Lille, France
                Author notes
                Correspondence: Sébastien Hulo, Université de Lille – IMPECS – IMPact de l’Environnement Chimique sur la Santé Humaine (EA 4483), Faculté de Médecine de Lille – Pôle Recherche – 2 ème Étage Aile EST 1, Place Verdun 59045 Lille Cedex, France, Tel +33 320 627 761, Fax +33 320 627 784, Email sebastien.hulo@
                © 2016 Hulo et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( 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.

                Original Research

                Respiratory medicine

                exercise, copd, chronotropic incompetence, hyperinflation


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