- Email: [email protected]
Supplemental Oxygen During High-Intensity Exercise Training in Nonhypoxemic Chronic Obstructive Pulmonary Disease
Accepted Manuscript Supplemental oxygen during high intensity exercise training in nonhypoxemic COPD Daniel Neunhäuserer, MD, PhD, Eva Steidle-Kloc, SD, Gertraud Weiss, MSc, Bernhard Kaiser, MSc, David Niederseer, MD, PhD, Sylvia Hartl, MD, Marcus Tschentscher, SD, Andreas Egger, MSc, Martin Schönfelder, SD, Bernd Lamprecht, MD, Prof. Michael Studnicka, MD, Prof. Josef Niebauer, MD, PhD, MBA PII:
S0002-9343(16)30691-X
DOI:
10.1016/j.amjmed.2016.06.023
Reference:
AJM 13591
To appear in:
The American Journal of Medicine
Received Date: 26 May 2016 Revised Date:
2 June 2016
Accepted Date: 3 June 2016
Please cite this article as: Neunhäuserer D, Steidle-Kloc E, Weiss G, Kaiser B, Niederseer D, Hartl S, Tschentscher M, Egger A, Schönfelder M, Lamprecht B, Studnicka M, Niebauer J, Supplemental oxygen during high intensity exercise training in nonhypoxemic COPD, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.06.023. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Supplemental oxygen during high intensity exercise training in nonhypoxemic COPD
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Daniel Neunhäuserer MD, PhDa,b,d, Eva Steidle-Kloc SDa,b, Gertraud Weiss MScc, Bernhard Kaiser MScc, David Niederseer MD, PhDa,b,g, Sylvia Hartl MDf, Marcus Tschentscher SDa,b, Andreas Egger MSca,b, Martin Schönfelder SDa,b, Bernd Lamprecht MDc,e, Prof. Michael
University Institute of Sports Medicine, Prevention and Rehabilitation, Paracelsus
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a
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Studnicka MDc, Prof. Josef Niebauer MD, PhD, MBAa,b
Medical University of Salzburg, Lindhofstraße 20, 5020 Salzburg, Austria. b
Research Institute for Molecular Sports Medicine and Rehabilitation, Paracelsus
c
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Medical University of Salzburg, Lindhofstraße 20, 5020 Salzburg, Austria. University Clinic of Pneumology, Paracelsus Medical University of Salzburg, Müllner Hauptstraße 48, 5020 Salzburg, Austria. Sport and Exercise Medicine Division, Department of Medicine, University of
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d
e
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Padova, Via Giustiniani 2, 35128 Padova, Italy. Department of Pulmonary Medicine, Faculty of Medicine, Kepler-University-Hospital, Johannes-Kepler-University, Krankenhausstraße 9, 4021 Linz, Austria.
f
First
Internal
Department
of Pulmonary Medicine,
Otto-Wagner Hospital,
Baumgartner Höhe 1, 1140 Vienna, Austria. g
Division of Cardiology, University Heart Centre, University Hospital Zurich, Rämistraße 100, 8091 Zurich, Switzerland. 1
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Email address of each author: Daniel
Neunhäuserer
Gertraud
Weiss
Eva
([email protected]),
Steidle-Kloc
Bernhard
Kaiser
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([email protected]),
([email protected]),
([email protected]), David Niederseer ([email protected]), Sylvia Hartl ([email protected]), Marcus Tschentscher ([email protected]), Andreas Egger ([email protected]), Martin Schönfelder ([email protected]), Bernd
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Lamprecht ([email protected]), Michael Studnicka ([email protected]), Josef
Corresponding author: Prof. Josef Niebauer, MD, PhD, MBA
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Niebauer ([email protected]).
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Institute of Sports Medicine, Prevention and Rehabilitation, Paracelsus Medical University Lindhofstraße 20, Salzburg 5020, Austria
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Email: [email protected]
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Tel.: +43 (0) 5 7255 – 23200
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ACCEPTED MANUSCRIPT Funding source: The SCOPE study was supported by an unconditional and unrestricted grant by Air Liquide. The sponsor was neither involved in design and conduct of the study, nor in the interpretation of the data, preparation, review, or approval of the manuscript; also the
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decision to submit the manuscript for publication was taken without the sponsor.
Conflict of interest: All authors declare hereby to have no conflict of interest for this
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manuscript.
meet the criteria for authorship.
Article type: Clinical research study.
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All authors had full access to all data, participated in the preparation of this manuscript and
training, exercise capacity.
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Keywords: Chronic obstructive pulmonary disease, dyspnea, interval training, strength
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Running head: Supplemental oxygen for exercise training in COPD.
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Abstract Background: Physical exercise training is an evidence-based treatment in chronic obstructive pulmonary disease (COPD), and patients’ peak work rate is associated with reduced COPD
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mortality. We assessed whether supplemental oxygen during exercise training in nonhypoxemic COPD patients might lead to superior training outcomes, including improved peak work rate.
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Methods: This was a randomized, double-blind, controlled, crossover trial. Twenty-nine COPD patients (63.5±5.9 years; forced expiratory volume in 1 s (FEV1) % pred.: 46.4±8.6)
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completed two consecutive 6-week periods of endurance and strength training with progressive intensity, which was performed three times/week with either supplemental oxygen or compressed medical air (flow via nasal cannula: 10 L/min). Each session of electrocardiography (ECG)-controlled interval cycling lasted 31 min and consisted of a warm
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up, seven cycles of one-min intervals at 70–80% of peak work rate alternating with two min of active recovery, and final cool down. Thereafter, patients completed eight strength-training exercises of one set each with 8–15 repetitions to failure. Change in peak work rate was the
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primary study endpoint.
Results: The increase in peak work rate was more than twice as high when patients exercised
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with supplemental oxygen as compared with medical air (0.16±0.02 vs. 0.07±0.02 W/kg; p<0.001), which was consistent with all other secondary study endpoints related to exercise capacity. The impact of oxygen on peak work rate was 39.1% of the overall training effect, whereas it had no influence on strength gain (p>0.1 for all exercises). Conclusions: We report that supplemental oxygen in nonhypoxemic COPD doubled the effect of endurance training, but had no effect on strength gain.
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Introduction Physical exercise training is recommended in all international chronic obstructive pulmonary disease (COPD) guidelines.1–9 What remains unresolved, however, is whether nonhypoxemic
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COPD patients should exercise with supplemental oxygen.8,10 Several studies have applied oxygen during exercise training in patients with11–17 and without exertional hypoxemia,18–21 with conflicting results in both cases. Indeed, a significant increase in peak work rate because of supplemental oxygen has not yet been shown. Strength training is also recommended for
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COPD patients,22 and may coincide with increased local but also systemic oxygen demand,
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particularly during upper body strength training when auxiliary respiratory muscles are involved. Thus, supplemental oxygen could also positively influence strength training. The Salzburg COPD Exercise and Oxygen (SCOPE) study was performed to test whether exercise training with supplemental oxygen might lead to higher training intensity when
rate and muscle strength.
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Methods
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compared with medical air, and would therefore result in greater improvements in peak work
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This is a prospective, randomized, controlled, double-blind, crossover trial in patients with stable nonhypoxemic COPD. The ethics committee of Salzburg approved this study, which was registered on clinicaltrials.gov (NCT01150383). All participating patients provided written informed consent.
The study design is shown in figure 1. A block-randomization was carried out at training begin to ensure allocation of a similar number of patients to group O2-Air and group Air-O2.
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ACCEPTED MANUSCRIPT Gas supply was blinded through locked away gas cylinders and a distributing system that connected to identical junctions for nasal cannulas. During endurance and strength training, as well as during additional gas-specific exercise testing, 10 L/min of oxygen (inspired oxygen-fraction ≈60%) or medical air was
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administered. For warm-up and cool down, gas supply was reduced to 4 L/min.
Eligibility criteria
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Patients with stable COPD aged ≥30 years, forced expiratory volume in 1 s (FEV1) between
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30-60% predicted and resting arterial oxygen partial pressure (PaO2) >55 mmHg and carbon dioxide partial pressure (PaCO2) <45 mmHg were included, independently of peak exercise PaO2. Patients with co-morbidities known to impair physical exercise training, myocardial infarction within the previous six months, left ventricular ejection fraction <40%, creatinine
participation.
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Exercise training
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>2 mg/dL, hemoglobin <10 g/dL, or expected non-compliance were not eligible for
Patients performed supervised, electrocardiography (ECG)-monitored endurance and strength
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training three times a week. Peripheral oxygen saturation was not measured during exercise training to avoid unblinding. Each endurance training session lasted 31 min and consisted of interval cycling. Seven one-min high-intensity intervals at 70–80% of gas-specific peak work rate were each separated by two min of active recovery. These intermittent recovery periods as well as the five min warm-up and cool down were performed at about 50% of peak work rate. The exercise intensity was adapted according to calculated training heart rates (HRrest+(HRmax–HRrest)x(0.7–0.8)).23 Workload was progressively increased whenever a patient’s heart rate decreased. 6
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Eight high-intensity strength training exercises were performed on weight lifting machines: latissimus pull-down, shoulder press, back extension, abdominal crunch, butterfly, butterfly reverse, leg extension and leg flexion. Patients performed one set with 8–15 repetitions to
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failure. Whenever more than 15 repetitions were realized, weight was increased.
Exercise testing
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Exercise capacity was assessed by incremental cardiopulmonary exercise testing without gas
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supply. Testing started at 20 watts and increased by 10 watts/min in men and 5 watts/min in women until exhaustion (Borg rating of perceived exertion (RPE): 18-20). Additional exercise testing was performed with the respective gas at training begin and crossover, implemented only for accurate gas-specific exercise prescription. Tests were performed at least 48h apart.
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All presented data were obtained from normoxic cardiopulmonary exercise tests.
Muscle strength was assessed by a standardized ten-repetition maximum strength test (10-
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RM) without gas supply, for each of the eight exercises. The 10-RM refers to the weight with
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which the patient can perform no more than ten repetitions.
Study endpoints
Peak work rate is dependent upon a patient’s aerobic and anaerobic exercise capacity and may best reflect the performed exercise training. Furthermore, maximal work capacity is negatively correlated with COPD mortality.2,7 Thus, peak work rate was chosen as the primary study endpoint. Secondary endpoints related to exercise capacity included peak oxygen uptake (VO2peak), maximal heart rate and blood lactate sampled from the ear lobe.
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ACCEPTED MANUSCRIPT Further secondary endpoints were the 10-RM and pulmonary function, which was determined by spirometry, body plethysmography and diffusion capacity measurements. Predicted values were calculated as recommended by the ERS.24 The Hospital Anxiety and Depression Scale
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(HADS) was also assessed.25
Statistical analysis
The analysis method for crossover trials was performed as previously described by Hills and
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Armitage, whereas carryover effects between study periods were analyzed as described by
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Schumacher and Schulgen.26,27 Unpaired t-tests were used for comparisons between study arms, and paired t-tests within study arms.
Results
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Patient characteristics are shown in table 1 and the study flow is presented in figure 2. During the 12 weeks of exercise training patients improved progressively their exercise capacity and tolerance. However, the improvement of peak work rate (W/kg: 14.5 vs. 6.4%,
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p<0.001) and VO2peak (8.1 vs. 3.5%, p=0.067) was more than twice as high if patients trained with oxygen as compared with medical air. Although the other secondary study
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endpoints related to exercise capacity, i.e. maximal heart rate and blood lactate, consistently showed training-related changes with supplemental oxygen, statistical significance was not reached (p=0.143, p=0.120, respectively; table 2, figure 3). When group O2-Air and group Air-O2 were compared after the first study period, i.e. before crossover, it was observed that endurance training with supplemental oxygen led to a superior increase in peak work rate than medical air (0.19±0.09 vs. 0.11±0.10 W/kg, respectively, p=0.024). Furthermore, group Air-O2 increased peak work rate during both periods of endurance training (both p<0.001), whereas group O2-Air improved during the first 8
ACCEPTED MANUSCRIPT intervention period only (p<0.001). Similar training responses were found for peak work rate and VO2peak (figure 4). Moreover, significant carryover effects between study periods were excluded for all variables related to exercise capacity (table 2). Fifty-one percent of the patients (n=15) desaturated during incremental exercise testing (blood
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oxygen saturation (SpO2)<95%, decrease>5%).28 These patients experienced a greater oxygen effect on peak work rate (0.13±0.12 W/kg; 57.0% of the overall training effect) as compared with non-desaturating patients (0.05±0.17 W/kg; 21.8% of the overall training effect).
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Moreover, supplemental oxygen accounted for 56.1% (1.24±3.27 mL/min/kg) of the training
desaturating patients.
Secondary study endpoints
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gain in VO2peak in desaturating patients, but for only 18.7% (0.43±2.66 mL/min/kg) in non-
Muscle strength progressively improved during the study course, however, strength gain was
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similar whether patients trained with supplemental oxygen or medical air. Furthermore, pulmonary function was neither affected by the exercise training intervention
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nor by supplemental oxygen.
Overall, during 12 weeks of exercise training, patients improved anxiety (−17.5%, p=0.022)
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and there was a trend toward improved depression (−14.3%, p=0.069). When both were analyzed according to the gas supplied, oxygen had no effect on depression but showed a statistical trend toward decreased anxiety (p=0.084; table 2, figure 3).
Discussion Physical exercise training is an important pillar of evidence-based treatment in COPD.3,4,6,8,9 However, patients are often limited by dyspnea, which could possibly overcome by supplying
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ACCEPTED MANUSCRIPT oxygen during training. Indeed, there is an ongoing debate on whether exercise training should be performed with or without supplemental oxygen.10,3,29 This is the first study testing supplemental oxygen against medical air during both endurance and strength training. SCOPE differs also from preceding studies by high oxygen flow rate, gas-specific exercise
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prescription and progressively-adapted, ECG-monitored high-intensity interval training.
Endurance training
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Endurance training was performed as high-intensity interval training because such training
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has previously been shown to be at least as effective as continuous endurance training, but with the advantage of lower perception of dyspnea.30 Moreover, patients thereby trained aerobic and anaerobic exercise capacities, which both influence the main study outcome of peak work rate.
As a result, peak work rate increased overall by 20.9%. Also, there was a significant decrease
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in patients’ heart rate reserve at peak exercise, which was found to be increased at baseline because of ventilatory limitations. Endurance training induced improved aerobic and
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anaerobic metabolism of the skeletal musculature. Therefore, higher maximal heart rates could be reached and heart rate reserve was decreased, i.e. rather normalized. In fact, a 41%
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increase in blood lactate at exhaustion demonstrates improved tolerance to the ventilatory burden. These training effects occurred despite unchanged pulmonary function.
Supplemental oxygen
In COPD, a greater ventilatory demand, dynamic hyperinflation and the associated increase in the work of breathing might lead to an earlier onset of dyspnea, respiratory muscle fatigue and physical exhaustion.5 Providing higher inspiratory oxygen concentrations might indirectly help overcome limitations of airway obstruction. Moreover, we hypothesized that patients 10
ACCEPTED MANUSCRIPT would thus be able to perform exercise training for longer durations and at higher intensities, and consequently benefit from effects on the cardiopulmonary system as well as from reconditioning of peripheral muscles. This has previously motivated studies of exercise training with supplemental oxygen in COPD, but with conflicting results.8 Most studies were
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unable to detect superior effects of training with supplemental oxygen.11–15,18,19,31 Indeed, the latest guidelines provide little support for oxygen supplementation during exercise training in nonhypoxemic COPD.3,8–10 However, in this study we report that the improvement of
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patients’ peak work rate and VO2peak during exercise training with supplemental oxygen was more than twice that of medical air. Moreover, the additional impact of oxygen was
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responsible for 39.1% and 39.7% of the overall training effect on peak work rate and VO2peak, respectively. Although one preceding study showed a positive effect of supplemental oxygen on endurance time at a submaximal constant work rate, this is the first study to demonstrate an increase in peak work rate.20 This variable is of particular interest
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because it is well known that the level of physical activity and maximal work capacity are significantly associated with COPD mortality.2,7
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During endurance training, supplemental oxygen led to a statistically greater increase in exercise capacity than medical air, regardless of whether endurance training was performed
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with supplemental oxygen from baseline or after crossover (figure 4). Moreover, supplemental oxygen was shown to be useful at training begin to more rapidly improve patients’ exercise capacity, but in particular facilitated effective training stimuli during the second period of exercise training (figure 4). Cardiovascular adaptations and peripheral muscle reconditioning could occur due to greater tolerance to higher training intensities. These findings support the consideration of oxygen as a clinically important supplement during endurance training even in patients who do not otherwise require home oxygen
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ACCEPTED MANUSCRIPT supplementation. This recommendation may be particularly true for long-term training interventions, when exercise intensities must increase to further provoke training adaptations.
One important difference between this study and previous trials is the higher oxygen flow rate
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during training (10 L/min vs. 2–5 L/min), which was well tolerated by the patients.11,12,15,18,20,31 Oxygen delivery in preceding studies was considered low in the concentration or flow rate.10 Even though our oxygen supplementation appears high, given the
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average static and dynamic lung volumes of these patients, even more oxygen might be needed to fully compensate airflow limitation. Furthermore, a dose–response relationship for
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endurance exercise was shown for an inspired oxygen fraction of up to at least 50% (≈8 L/min) and Nonoyama et al. recommended providing higher oxygen concentrations to improve exercise training outcomes.10,32 However, high inspiratory concentrations of oxygen could reduce carotid body activation, leading to depression of the ventilatory drive and
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hypercapnia, especially in patients with severe hypoxemia.33 Nonetheless, Helgerud et al. demonstrated the feasibility of an even higher oxygen concentration administered during an exercise training intervention.16 Moreover, Wadell et al. did not find significant carbon
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dioxide retention during submaximal walking tests, despite the applied oxygen flow of 5 L/min.15 Ventilatory pattern is an integrated output that is influenced by changes in sensory
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inputs and behavioral demands.33 Mechanoreceptors in the lung and chest walls, adrenergic incitement, behavioral factors such as discomfort during physical activity and the ventilatory response to exercise increase the work of breathing.33,34 Thus, the risk of relevant oxygeninduced hypercapnia during exercise training was considered low for our study population.
The SCOPE study performed gas-specific exercise testing and prescription, i.e. gas supply during additional testing and subsequent training was identical. This specificity resulted in
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ACCEPTED MANUSCRIPT superior exercise performance during testing with oxygen supplementation and thus in an exercise prescription of higher intensity during training. Because supplemental oxygen can increase exercise performance, training prescriptions based only on tests with room air would have led to inadequately low intensities for exercise training with supplemental
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oxygen.11,12,14–16,18,20,31,32,35
Additionally, progressive adaptation of training load was crucial for the improvement of the
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peak work rate. Whereas some studies performed exercise training without changing workload18 and others adjusted intensity in response to the patient’s dyspnea and fatigue,11,20
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the SCOPE protocol called for progressive adaptation of workload whenever an improvement in a patient’s heart rate, which was continuously monitored throughout each training session, would permit it. This resulted in objective training control and consistently increased training intensities. However, patients’ rating of perceived exertion was monitored throughout each
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training session to fine tune exercise intensity.
Patients’ peak exercise arterial oxygen saturation was not considered of central importance for
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the study design because preceding studies on oxygen supplementation during exercise training were discordant for both desaturating11–17 and non-desaturating18–21 patients. Whereas
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oxygen supply is highly recommended for exercise training in hypoxemic and severely desaturating patients,6,9,20 our data support the use of supplemental oxygen for exercise training in desaturating and non-desaturating patients, even though the oxygen effect was more pronounced in COPD with mild exertional hypoxemia. Supplemental oxygen has already been shown to improve exercise tolerance, even in non-desaturating patients.20,21,32,36 Indeed, the oxygen effect was negatively correlated with airflow restriction, but not with exercise hypoxemia.35 Therefore, supplemental oxygen seems not only to act by increasing
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ACCEPTED MANUSCRIPT arterial oxygen content and improving muscle oxygenation, but also through inhibition of carotid body stimulation, reduced respiratory drive and pulmonary vasodilatation.35,37 This effect might increase cardiac output and muscle oxygen delivery, but decrease ventilation as
for oxygen supplementation during training.
Strength training
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well as dynamic hyperinflation.32,35–37 Exercise-induced hypoxemia is thus not a prerequisite
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High-intensity strength training led to a progressive improvement in 10-RM. Interestingly, regardless of whether strength training was performed with oxygen supplementation or
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medical air, muscle strength increased by a similar extent. Moreover, strength exercises were probably too short to induce a relevant demand on the cardiopulmonary system. Respiratory and auxiliary respiratory muscles might not have been sufficiently stressed during single-set, high-intensity, upper body strength training to induce significant worsening of dyspnea.
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Indeed, it is muscular exhaustion and not dyspnea that limits strength exercise performance.
HADS
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Thus, supplemental oxygen does not confer additional benefit in strength.
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Our data confirm in part that exercise training improves aspects of quality of life in COPD. Pulmonary rehabilitation has been shown to reduce anxiety and depression, in particular if patients scored highest on HADS.38 Considering that patients of this study reported little anxiety and depression at baseline, improvements of -17.5% and -14.3%, respectively, are noteworthy. Although supplemental oxygen did not significantly improve depression, it appears to positively influence patients’ anxiety. This effect on anxiety might be owed to less dyspnea during activities of daily living and exercise training. Indeed, short-term ambulatory oxygen 14
ACCEPTED MANUSCRIPT during physical activities and training has previously been shown to significantly improve health-related quality of life and general health, respectively.17,20
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Limitations Although study withdrawal was not associated with study group, a 34% dropout rate complicated statistical analyses for secondary endpoints. Furthermore, we provided a
designed for statistically valid subgroup analyses.
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descriptive evaluation of desaturating and non-desaturating patients because SCOPE was not
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In addition, this exercise training study was performed without washout period at crossover to analyze dynamics of the oxygen effect during study course. However, no significant carryover effects were found for the main study outcomes of exercise capacity. Finally, endurance and strength training were differently influenced by supplemental oxygen,
Conclusions
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which could have compromised treatment effects within the same muscle fibers.
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SCOPE is the first double-blind randomized controlled trial demonstrating that supplemental oxygen doubles the training effect in terms of peak work rate, the study’s primary endpoint
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and a predictor associated with COPD mortality.7 Data showed that endurance but not strength training was more effective with supplemental oxygen. Oxygen seems to have also a beneficial effect on anxiety. High oxygen flow rate, gas-specific exercise prescription and progressive, ECG-monitored high-intensity interval training were key elements of this intervention. The study findings could be used in future rehabilitation strategies in COPD by promoting innovative ways to improve outcomes. Indeed, supplemental oxygen during outpatient exercise training, or in a home-based setting, might be used to more rapidly improve patients’ 15
ACCEPTED MANUSCRIPT exercise capacity and therefore might emerge as an important tool to increase patient compliance and long-term adherence to training programs.
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Acknowledgments This study was supported by an unconditional and unrestricted grant by Air Liquide.
1.
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Schumacher M, Schulgen G. Methodik Klinischer Studien: Methodische Grundlagen Der Planung, Durchführung Und Auswertung. 3rd ed. Springer; 2008.
28.
Guazzi M, Adams V, Conraads V, et al. EACPR/AHA Scientific Statement. Clinical
patient
populations.
Circulation
doi:10.1161/CIR.0b013e31826fb946.
2012;126(18):2261-74.
Lee AL, Holland AE. Time to adapt exercise training regimens in pulmonary
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recommendations for cardiopulmonary exercise testing data assessment in specific
doi:10.2147/COPD.S54925.
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rehabilitation – a review of the literature. Int. J. COPD 2014;9:1275-1288.
Vogiatzis I, Nanas S, Roussos C. Interval training as an alternative modality to continuous exercise in patients with COPD. Eur Respir J 2002;20(1):12-19.
31.
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doi:10.1183/09031936.02.01152001.
Fichter J, Fleckenstein J, Stahl C SG. Effect of oxygen (FI02: 0.35) on the aerobic
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capacity in patients with COPD. Pneumologie 1999;53(3):121-6.
Somfay a., Porszasz J, Lee SM, Casaburi R. Dose-response effect of oxygen on
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hyperinflation and exercise endurance in nonhypoxaemic COPD patients. Eur. Respir. J. 2001;18(1):77-84. doi:10.1183/09031936.01.00082201.
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Jacono FJ. Control of ventilation in COPD and lung injury. Respir. Physiol. Neurobiol. 2013;189(2):371-6. doi:10.1016/j.resp.2013.07.010.
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Mitchell GS, Babb TG. Layers of exercise hyperpnea: modulation and plasticity. Respir. Physiol. Neurobiol. 2006;151(2-3):251-66. doi:10.1016/j.resp.2006.02.003.
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Fujimoto K, Matsuzawa Y, Yamaguchi S, Koizumi T, Kubo K. Benefits of Oxygen on Exercise Performance and Pulmonary Hemodynamics in Patients With COPD With Mild Hypoxemia *. Chest 2002;122:457-463.
O’Donnell DE, BAIN DJ, Webb KA. Factors contributing to relief of exertional
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breathlessness during hyperoxia in chronic airflow limitation. Am J Respir Crit Care Med 1997;155(2):530-535.
Somfay A, Porszasz J, Lee S, Casaburi R. Effect of hyperoxia on gas exchange and
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37.
2002;121(2):393-400.
Harrison SL, Greening NJ, Williams JE a, Morgan MDL, Steiner MC, Singh SJ. Have we underestimated the efficacy of pulmonary rehabilitation in improving mood?
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Respir. Med. 2012;106(6):838-44. doi:10.1016/j.rmed.2011.12.003.
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lactate kinetics following exercise onset in nonhypoxemic COPD patients. Chest
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Tables Table 1 Patient characteristics
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Table 1.a: At rest Table 1.b: At peak exercise
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Patients’ baseline characteristics at rest (table 1.a) and at peak exercise (table 1.b) measured at training begin. Group O2-Air and group Air-O2 did not differ significantly with regard to
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exercise capacity, i.e. peak work rate, VO2peak, heart rate max, and blood lactate concentration at exhaustion. Data are presented as mean ± standard deviation (SD). BMI: Body mass index, BP: Blood pressure, FEV1: Forced expiratory volume in 1 s, FVC: Forced vital capacity, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume,
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ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV: Alveolar volume, PaO2: Arterial oxygen partial pressure, PaCO2: Arterial carbon dioxide partial pressure, SaO2: Oxygen saturation, VO2peak: Peak oxygen
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consumption, O2 pulse: Oxygen pulse (VO2peak/heart rate), VCO2: Carbon dioxide output, VE: Minute ventilation, petCO2: Partial pressure of end-tidal carbon dioxide, peCO2: Mixed-
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expired CO2 pressure, RER: Respiratory exchange ratio, BF: Breathing frequency, Breathing reserve: is based on a calculated MVV from resting FEV1 × 38, RPE: Rating of perceived exertion scale (6-20).
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ACCEPTED MANUSCRIPT Table 2 Exercise capacity, muscle strength, pulmonary function and patient’s anxiety and depression observed during the study
Table 2 shows the effect of exercise training and supplemental oxygen on main parameters of
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the SCOPE study. For each variable, the relative effect of supplemental oxygen in relation to the overall training effect was analyzed. Parameters that showed a significant carryover effect between study periods are indicated by an asterisk (*).
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SE: Standard Error, Wpeak: Peak work rate, EREC: Expected relative exercise capacity (%Wpeak of standard values of the Austrian society of cardiology considering age, sex and
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body surface), VO2peak: Peak oxygen consumption, HR: Heart rate, 10-RM: ten-repetition maximum strength test, Lat: Latissimus, FVC: Forced vital capacity, FEV1: Forced expiratory volume in 1 s, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume, ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV:
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Alveolar volume, HADS: Hospital Anxiety and Depression Scale.
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Figures figure 1
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The SCOPE study design
A timeline (weeks) is shown at the bottom of the figure. All patients underwent a training-free run-in period lasting 6 weeks to optimize pharmacological treatment according to
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international guidelines. Forty-four patients were randomized at training begin to group O2Air or group Air-O2 and performed two 6-week periods of exercise training; patients started
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the training program with supplemental oxygen followed by medical air or vice-versa. Study investigations were performed at run-in begin, training begin, crossover, and training end.
Flow diagram
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figure 2
Fifty of 137 contacted patients met eligibility criteria and entered the run-in phase. Although
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during the training periods 15 patients dropped out, no differences in dropout rates were
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observed between groups. Furthermore, only two patients opted out during the training period, at a very early stage of the intervention. Other withdrawals were because of comorbidities and exacerbations during the cold winter months.
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The oxygen effect was defined as the difference between results achieved during exercise training with supplemental oxygen as compared with medical air. Statistical significance is indicated by an asterisk (*), whereas trends (0.1>p>0.05) are flagged by a plus sign (+).
Watt/kg (peak work rate), VO2peak: peak oxygen consumption, HRmax: maximal heart rate,
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Lactate (at exhaustion), Lat pull down: Latissimus pull down (10-RM), Leg extension (10-
Depression (HADS).
figure 4
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Training response in both study arms
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RM), FEV1: Forced expiratory volume in 1 s, FVC: Forced vital capacity, Anxiety (HADS),
Patients’ peak work rate (Wpeak) and peak oxygen consumption (VO2peak) during the run-in
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period, as well as the first- and second exercise-training period. Group Air-O2 is depicted by a
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chain dotted line (---) and group O2-Air by a dotted line (···).
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Tables Table 1 Patient characteristics
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Sex, female/male Age, y
63.5 (± 5.9)
BMI, kg/m2
27.3 (± 5.4) 119.0 (± 14.2)
Diastolic BP, mm Hg
74.5 (± 9.3)
FEV1/FVC, %
59.7 (± 11.3)
FEV1, % pred.
46.4 (± 8.6)
VC inspired, % pred.
80.2 (± 15.6)
TLC, % pred.
121.3 (± 16.7)
RV/TLC, % pred.
134.1 (± 18.3)
ITGV, % pred.
143.8 (± 24.8)
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DLCOc, % pred. DLCOc/AV, % pred.
65.3 (± 15.1) 69.2 (± 8.6)
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PaO2, mmHg PaCO2, mmHg
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Systolic BP, mm Hg
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Mean (± SD)
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Table 1.a: At rest
38.0 (± 3.2) 16.7 (± 1.5)
SaO2, %
94.4 (± 2.2)
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Hemoglobin, g/ld.
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128.1 (± 17.8)
Work rate, W
85.7 (± 31.2)
VO2peak, L/min/kg
18.4 (± 3.8)
Systolic BP, mmHg
170.2 (± 34.1)
Diastolic BP, mmHg
77.1 (± 13.2)
O2 pulse, mL/beat/kg
11.4 (± 2.9)
VCO2, L/min
1.4 (± 0.4) 53.0 (± 11.4)
VE/VO2 slope
37.8 (± 8.9)
VE/VCO2 slope
34.7 (± 7.4)
petCO2, mmHg
32.3 (± 4.6)
RER
1.0 (± 0.1)
BF, breaths/min
33 (± 5.4)
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VE, L/min
2.0 (± 15.3)
BORG, RPE (6-20)
18.9 (± 1.1)
Lactate, mmol/L
3.8 (± 1.1)
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Breathing Reserve, %
SaO2, %
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Heart rate, bpm
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Mean (± SD)
90.2 (± 7.7)
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Patients’ baseline characteristics at rest (table 1.a) and at peak exercise (table 1.b) measured at training begin. Group O2-Air and group Air-O2 did not differ significantly with regard to
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exercise capacity, i.e. peak work rate, VO2peak, heart rate max, and blood lactate concentration at exhaustion. Data are presented as mean ± standard deviation (SD). BMI: Body mass index, BP: Blood pressure, FEV1: Forced expiratory volume in 1 s, FVC: Forced vital capacity, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume, ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV: Alveolar volume, PaO2: Arterial oxygen partial pressure, PaCO2: Arterial carbon dioxide partial pressure, SaO2: Oxygen saturation, VO2peak: Peak oxygen consumption, O2 pulse: Oxygen pulse (VO2peak/heart rate), VCO2: Carbon dioxide output, 2
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exertion scale (6-20).
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Table 2 Exercise capacity, muscle strength, pulmonary function and patient’s anxiety and depression observed during the study Training End
Training
effect
effect
Exercise
Exercise
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Begin
Training
Oxygen
Oxygen
effect
effect
Oxygen effect / Training
Training with
Training with
oxygen
medical air
Delta (± SE)
Delta (± SE)
[%]
p-value
[%]
effect
Mean (± SE)
Mean (± SE)
Mean (± SE)
[%]
p-value
Wpeak/kg, W/kg
1.11 (± 0.07)
1.10 (± 0.07)
1.33 (± 0.07)
20.91
< 0.001
0.16 (± 0.02)
0.07 (± 0.02)
8.18
0.001
39.13
Wpeak, W
85.83 (± 5.56)
85.72 (± 5.84)
104.17 (± 6.50)
21.52
< 0.001
12.72 (± 1.39)
5.72 (± 1.34)
8.17
0.001
37.94
EREC, %
60.52 (± 2.89)
58.86 (± 2.97)
72.47 (± 3.28)
V02peak, mL/min/kg
19.04 (± 0.65)
18.43 (± 0.70)
20.57 (± 0.71)
HR max, bpm
126.28 (± 3.45)
128.10 (± 3.29)
137.55 (± 3.39)
Lactate, mmol/L
3.80 (± 0.19)
3.77 (± 0.24)
5.32 (± 0.37)
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Run-In Begin
Training
Lat pull down *
40.55 (± 2.04)
40.52 (± 2.15)
60.45 (± 2.77)
Shoulder press *
38.38 (± 2.16)
40.17 (± 2.25)
Back extension
42.24 (± 2.87)
Abdominal crunch
23.12
< 0.001
9.31 (± 1.05)
4.29 (± 1.05)
8.53
0.003
36.88
11.61
< 0.001
1.50 (± 0.30)
0.65 (± 0.34)
4.61
0.067
39.72
7.38
< 0.001
6.07 (± 1.60)
3.38 (± 1.64)
2.10
0.143
28.47
41.11
< 0.001
1.02 (± 0.28)
0.53 (± 0.21)
13.00
0.120
31.61
49.19
9.83 (± 0.89)
10.10 (± 1.29)
-0.69
0.428
-1.40
61.62 (± 2.52)
53.40
< 0.001
11.17 (± 1.08)
10.28 (± 1.59)
2.24
0.347
4.20
46.31 (± 2.62)
66.93 (± 2.47)
44.53
< 0.001
9.59 (± 1.33)
11.03 (± 1.74)
-3.13
0.298
-7.03
20.83 (± 1.68)
22.24 (± 1.66)
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< 0.001
38.76 (± 2.05)
74.28
< 0.001
8.14 (± 1.24)
8.38 (± 1.27)
-1.08
0.456
-1.45
Butterfly *
21.66 (± 2.36)
23.45 (± 2.21)
43.57 (± 3.35)
85.80
< 0.001
9.25 (± 1.06)
10.39 (± 1.69)
-4.86
0.300
-5.67
Butterfly reverse *
16.10 (± 1.81)
16.62 (± 1.60)
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Exercise capacity
31.37 (± 2.17)
88.75
< 0.001
7.11 (± 0.82)
7.37 (± 1.09)
-1.56
0.424
-1.76
Leg extension
28.21 (± 1.99)
29.03 (± 1.97)
47.69 (± 2.17)
64.28
< 0.001
9.14 (± 0.86)
9.52 (± 1.56)
-1.31
0.428
-2.04
Leg flexion *
24.52 (± 1.78)
26.10 (± 1.77)
40.93 (± 2.25)
56.82
< 0.001
7.45 (± 0.66)
7.38 (± 1.06)
0.27
0.481
0.47
FVC, [%pred.]
75.20 (± 2.29)
78.65 (± 1.90)
79.60 (± 2.27)
1.21
0.286
-0.78 (± 1.56)
1.73 (± 1.37)
-3.19
0.154
n.a.
FEV1, [%pred.]
44.44 (± 1.41)
46.41 (± 1.63)
47.56 (± 2.13)
2.48
0.212
1.05 (± 1.18)
0.10 (± 1.24)
2.05
0.316
n.a.
FEV1/FVC, %
59.81 (± 1.60)
59.68 (± 2.06)
60.24 (± 1.87)
0.94
0.312
2.09 (± 1.38)
-1.53 (± 1.13)
6.05
0.075
n.a.
Pulmonary function
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10-RM [kg]
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77.83 (± 2.18)
80.22 (± 2.87)
81.54 (± 2.83)
1.65
0.258
2.49 (± 2.95)
-1.18 (± 2.36)
4.57
0.233
n.a.
TLC, [%pred.]
122.56 (± 2.44)
121.29 (± 3.05)
123.49 (± 3.72)
1.81
0.212
2.19 (± 3.23)
0.01 (± 4.06)
1.80
0.375
n.a.
RV, [%pred.]
164.97 (± 4.66)
156.21 (± 6.30)
159.31 (± 7.39)
1.98
0.311
-2.98 (± 6.07)
6.08 (± 7.01)
-5.80
0.232
n.a.
RV/TLC, [%pred.]
140.64 (± 2.68)
134.09 (± 3.38)
134.62 (± 3.39)
0.40
0.433
-1.67 (± 3.45)
2.21 (± 3.48)
-2.89
0.275
n.a.
ITGV, [%pred.]
147.97 (± 4.46)
143.84 (± 4.63)
143.25 (± 5.74)
-0.41
0.448
DLCOc, [%pred.]
50.91 (± 2.33)
51.08 (± 2.29)
52.63 (± 2.76)
3.03
0.160
DLCOc/AV, [%pred.]
65.45 (± 2.70)
65.32 (± 2.83)
64.01 (± 2.96)
-2.01
0.199
Anxiety *
6.41 (± 0.96)
5.72 (± 0.70)
4.72 (± 0.73)
-17.48
0.022
Depression *
4.55 (± 0.63)
4.76 (± 0.67)
4.08 (± 0.61)
-14.29
0.069
-1.09 (± 7.02)
1.11
0.446
n.a.
-0.57 (± 1.27)
2.11 (± 1.37)
-5.25
0.112
n.a.
-1.03 (± 1.34)
-0.28 (± 1.29)
-1.16
0.363
n.a.
-1.00 (± 0.45)
0.00 (± 0.39)
-17.48
0.084
100.00
-0.48 (± 0.48)
-0.20 (± 0.31)
-5.88
0.341
41.18
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0.50 (± 4.67)
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HADS [0-21]
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VC inspired, [%pred.] *
Table 2 shows the effect of exercise training and supplemental oxygen on main parameters of the SCOPE study. For each variable, the relative
study periods are indicated by an asterisk (*).
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effect of supplemental oxygen in relation to the overall training effect was analyzed. Parameters that showed a significant carryover effect between
SE: Standard Error, Wpeak: Peak work rate, EREC: Expected relative exercise capacity (%Wpeak of standard values of the Austrian society of
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cardiology considering age, sex and body surface), VO2peak: Peak oxygen consumption, HR: Heart rate, 10-RM: ten-repetition maximum strength
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test, Lat: Latissimus, FVC: Forced vital capacity, FEV1: Forced expiratory volume in 1 s, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume, ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV: Alveolar volume, HADS: Hospital Anxiety and Depression Scale.
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Supplemental oxygen during high intensity exercise training in nonhypoxemic COPD
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Highlights:
Endurance training with supplemental oxygen doubles the effect on peak work rate
•
Strength gain was similar whether patients trained with supplemental oxygen or air
•
Supplemental oxygen during exercise training seems to also improve patients’ anxiety
•
Consider interval training with high O2-flow and gas-specific exercise prescription
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S0002-9343(16)30691-X
DOI:
10.1016/j.amjmed.2016.06.023
Reference:
AJM 13591
To appear in:
The American Journal of Medicine
Received Date: 26 May 2016 Revised Date:
2 June 2016
Accepted Date: 3 June 2016
Please cite this article as: Neunhäuserer D, Steidle-Kloc E, Weiss G, Kaiser B, Niederseer D, Hartl S, Tschentscher M, Egger A, Schönfelder M, Lamprecht B, Studnicka M, Niebauer J, Supplemental oxygen during high intensity exercise training in nonhypoxemic COPD, The American Journal of Medicine (2016), doi: 10.1016/j.amjmed.2016.06.023. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Supplemental oxygen during high intensity exercise training in nonhypoxemic COPD
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Daniel Neunhäuserer MD, PhDa,b,d, Eva Steidle-Kloc SDa,b, Gertraud Weiss MScc, Bernhard Kaiser MScc, David Niederseer MD, PhDa,b,g, Sylvia Hartl MDf, Marcus Tschentscher SDa,b, Andreas Egger MSca,b, Martin Schönfelder SDa,b, Bernd Lamprecht MDc,e, Prof. Michael
University Institute of Sports Medicine, Prevention and Rehabilitation, Paracelsus
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a
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Studnicka MDc, Prof. Josef Niebauer MD, PhD, MBAa,b
Medical University of Salzburg, Lindhofstraße 20, 5020 Salzburg, Austria. b
Research Institute for Molecular Sports Medicine and Rehabilitation, Paracelsus
c
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Medical University of Salzburg, Lindhofstraße 20, 5020 Salzburg, Austria. University Clinic of Pneumology, Paracelsus Medical University of Salzburg, Müllner Hauptstraße 48, 5020 Salzburg, Austria. Sport and Exercise Medicine Division, Department of Medicine, University of
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d
e
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Padova, Via Giustiniani 2, 35128 Padova, Italy. Department of Pulmonary Medicine, Faculty of Medicine, Kepler-University-Hospital, Johannes-Kepler-University, Krankenhausstraße 9, 4021 Linz, Austria.
f
First
Internal
Department
of Pulmonary Medicine,
Otto-Wagner Hospital,
Baumgartner Höhe 1, 1140 Vienna, Austria. g
Division of Cardiology, University Heart Centre, University Hospital Zurich, Rämistraße 100, 8091 Zurich, Switzerland. 1
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Email address of each author: Daniel
Neunhäuserer
Gertraud
Weiss
Eva
([email protected]),
Steidle-Kloc
Bernhard
Kaiser
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([email protected]),
([email protected]),
([email protected]), David Niederseer ([email protected]), Sylvia Hartl ([email protected]), Marcus Tschentscher ([email protected]), Andreas Egger ([email protected]), Martin Schönfelder ([email protected]), Bernd
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Lamprecht ([email protected]), Michael Studnicka ([email protected]), Josef
Corresponding author: Prof. Josef Niebauer, MD, PhD, MBA
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Niebauer ([email protected]).
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Institute of Sports Medicine, Prevention and Rehabilitation, Paracelsus Medical University Lindhofstraße 20, Salzburg 5020, Austria
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Email: [email protected]
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Tel.: +43 (0) 5 7255 – 23200
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ACCEPTED MANUSCRIPT Funding source: The SCOPE study was supported by an unconditional and unrestricted grant by Air Liquide. The sponsor was neither involved in design and conduct of the study, nor in the interpretation of the data, preparation, review, or approval of the manuscript; also the
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decision to submit the manuscript for publication was taken without the sponsor.
Conflict of interest: All authors declare hereby to have no conflict of interest for this
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manuscript.
meet the criteria for authorship.
Article type: Clinical research study.
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All authors had full access to all data, participated in the preparation of this manuscript and
training, exercise capacity.
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Keywords: Chronic obstructive pulmonary disease, dyspnea, interval training, strength
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Running head: Supplemental oxygen for exercise training in COPD.
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Abstract Background: Physical exercise training is an evidence-based treatment in chronic obstructive pulmonary disease (COPD), and patients’ peak work rate is associated with reduced COPD
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mortality. We assessed whether supplemental oxygen during exercise training in nonhypoxemic COPD patients might lead to superior training outcomes, including improved peak work rate.
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Methods: This was a randomized, double-blind, controlled, crossover trial. Twenty-nine COPD patients (63.5±5.9 years; forced expiratory volume in 1 s (FEV1) % pred.: 46.4±8.6)
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completed two consecutive 6-week periods of endurance and strength training with progressive intensity, which was performed three times/week with either supplemental oxygen or compressed medical air (flow via nasal cannula: 10 L/min). Each session of electrocardiography (ECG)-controlled interval cycling lasted 31 min and consisted of a warm
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up, seven cycles of one-min intervals at 70–80% of peak work rate alternating with two min of active recovery, and final cool down. Thereafter, patients completed eight strength-training exercises of one set each with 8–15 repetitions to failure. Change in peak work rate was the
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primary study endpoint.
Results: The increase in peak work rate was more than twice as high when patients exercised
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with supplemental oxygen as compared with medical air (0.16±0.02 vs. 0.07±0.02 W/kg; p<0.001), which was consistent with all other secondary study endpoints related to exercise capacity. The impact of oxygen on peak work rate was 39.1% of the overall training effect, whereas it had no influence on strength gain (p>0.1 for all exercises). Conclusions: We report that supplemental oxygen in nonhypoxemic COPD doubled the effect of endurance training, but had no effect on strength gain.
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Introduction Physical exercise training is recommended in all international chronic obstructive pulmonary disease (COPD) guidelines.1–9 What remains unresolved, however, is whether nonhypoxemic
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COPD patients should exercise with supplemental oxygen.8,10 Several studies have applied oxygen during exercise training in patients with11–17 and without exertional hypoxemia,18–21 with conflicting results in both cases. Indeed, a significant increase in peak work rate because of supplemental oxygen has not yet been shown. Strength training is also recommended for
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COPD patients,22 and may coincide with increased local but also systemic oxygen demand,
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particularly during upper body strength training when auxiliary respiratory muscles are involved. Thus, supplemental oxygen could also positively influence strength training. The Salzburg COPD Exercise and Oxygen (SCOPE) study was performed to test whether exercise training with supplemental oxygen might lead to higher training intensity when
rate and muscle strength.
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Methods
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compared with medical air, and would therefore result in greater improvements in peak work
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This is a prospective, randomized, controlled, double-blind, crossover trial in patients with stable nonhypoxemic COPD. The ethics committee of Salzburg approved this study, which was registered on clinicaltrials.gov (NCT01150383). All participating patients provided written informed consent.
The study design is shown in figure 1. A block-randomization was carried out at training begin to ensure allocation of a similar number of patients to group O2-Air and group Air-O2.
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administered. For warm-up and cool down, gas supply was reduced to 4 L/min.
Eligibility criteria
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Patients with stable COPD aged ≥30 years, forced expiratory volume in 1 s (FEV1) between
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30-60% predicted and resting arterial oxygen partial pressure (PaO2) >55 mmHg and carbon dioxide partial pressure (PaCO2) <45 mmHg were included, independently of peak exercise PaO2. Patients with co-morbidities known to impair physical exercise training, myocardial infarction within the previous six months, left ventricular ejection fraction <40%, creatinine
participation.
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Exercise training
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>2 mg/dL, hemoglobin <10 g/dL, or expected non-compliance were not eligible for
Patients performed supervised, electrocardiography (ECG)-monitored endurance and strength
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training three times a week. Peripheral oxygen saturation was not measured during exercise training to avoid unblinding. Each endurance training session lasted 31 min and consisted of interval cycling. Seven one-min high-intensity intervals at 70–80% of gas-specific peak work rate were each separated by two min of active recovery. These intermittent recovery periods as well as the five min warm-up and cool down were performed at about 50% of peak work rate. The exercise intensity was adapted according to calculated training heart rates (HRrest+(HRmax–HRrest)x(0.7–0.8)).23 Workload was progressively increased whenever a patient’s heart rate decreased. 6
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Eight high-intensity strength training exercises were performed on weight lifting machines: latissimus pull-down, shoulder press, back extension, abdominal crunch, butterfly, butterfly reverse, leg extension and leg flexion. Patients performed one set with 8–15 repetitions to
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failure. Whenever more than 15 repetitions were realized, weight was increased.
Exercise testing
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Exercise capacity was assessed by incremental cardiopulmonary exercise testing without gas
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supply. Testing started at 20 watts and increased by 10 watts/min in men and 5 watts/min in women until exhaustion (Borg rating of perceived exertion (RPE): 18-20). Additional exercise testing was performed with the respective gas at training begin and crossover, implemented only for accurate gas-specific exercise prescription. Tests were performed at least 48h apart.
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All presented data were obtained from normoxic cardiopulmonary exercise tests.
Muscle strength was assessed by a standardized ten-repetition maximum strength test (10-
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RM) without gas supply, for each of the eight exercises. The 10-RM refers to the weight with
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which the patient can perform no more than ten repetitions.
Study endpoints
Peak work rate is dependent upon a patient’s aerobic and anaerobic exercise capacity and may best reflect the performed exercise training. Furthermore, maximal work capacity is negatively correlated with COPD mortality.2,7 Thus, peak work rate was chosen as the primary study endpoint. Secondary endpoints related to exercise capacity included peak oxygen uptake (VO2peak), maximal heart rate and blood lactate sampled from the ear lobe.
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ACCEPTED MANUSCRIPT Further secondary endpoints were the 10-RM and pulmonary function, which was determined by spirometry, body plethysmography and diffusion capacity measurements. Predicted values were calculated as recommended by the ERS.24 The Hospital Anxiety and Depression Scale
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(HADS) was also assessed.25
Statistical analysis
The analysis method for crossover trials was performed as previously described by Hills and
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Armitage, whereas carryover effects between study periods were analyzed as described by
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Schumacher and Schulgen.26,27 Unpaired t-tests were used for comparisons between study arms, and paired t-tests within study arms.
Results
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Patient characteristics are shown in table 1 and the study flow is presented in figure 2. During the 12 weeks of exercise training patients improved progressively their exercise capacity and tolerance. However, the improvement of peak work rate (W/kg: 14.5 vs. 6.4%,
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p<0.001) and VO2peak (8.1 vs. 3.5%, p=0.067) was more than twice as high if patients trained with oxygen as compared with medical air. Although the other secondary study
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endpoints related to exercise capacity, i.e. maximal heart rate and blood lactate, consistently showed training-related changes with supplemental oxygen, statistical significance was not reached (p=0.143, p=0.120, respectively; table 2, figure 3). When group O2-Air and group Air-O2 were compared after the first study period, i.e. before crossover, it was observed that endurance training with supplemental oxygen led to a superior increase in peak work rate than medical air (0.19±0.09 vs. 0.11±0.10 W/kg, respectively, p=0.024). Furthermore, group Air-O2 increased peak work rate during both periods of endurance training (both p<0.001), whereas group O2-Air improved during the first 8
ACCEPTED MANUSCRIPT intervention period only (p<0.001). Similar training responses were found for peak work rate and VO2peak (figure 4). Moreover, significant carryover effects between study periods were excluded for all variables related to exercise capacity (table 2). Fifty-one percent of the patients (n=15) desaturated during incremental exercise testing (blood
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oxygen saturation (SpO2)<95%, decrease>5%).28 These patients experienced a greater oxygen effect on peak work rate (0.13±0.12 W/kg; 57.0% of the overall training effect) as compared with non-desaturating patients (0.05±0.17 W/kg; 21.8% of the overall training effect).
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Moreover, supplemental oxygen accounted for 56.1% (1.24±3.27 mL/min/kg) of the training
desaturating patients.
Secondary study endpoints
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gain in VO2peak in desaturating patients, but for only 18.7% (0.43±2.66 mL/min/kg) in non-
Muscle strength progressively improved during the study course, however, strength gain was
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similar whether patients trained with supplemental oxygen or medical air. Furthermore, pulmonary function was neither affected by the exercise training intervention
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nor by supplemental oxygen.
Overall, during 12 weeks of exercise training, patients improved anxiety (−17.5%, p=0.022)
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and there was a trend toward improved depression (−14.3%, p=0.069). When both were analyzed according to the gas supplied, oxygen had no effect on depression but showed a statistical trend toward decreased anxiety (p=0.084; table 2, figure 3).
Discussion Physical exercise training is an important pillar of evidence-based treatment in COPD.3,4,6,8,9 However, patients are often limited by dyspnea, which could possibly overcome by supplying
9
ACCEPTED MANUSCRIPT oxygen during training. Indeed, there is an ongoing debate on whether exercise training should be performed with or without supplemental oxygen.10,3,29 This is the first study testing supplemental oxygen against medical air during both endurance and strength training. SCOPE differs also from preceding studies by high oxygen flow rate, gas-specific exercise
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prescription and progressively-adapted, ECG-monitored high-intensity interval training.
Endurance training
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Endurance training was performed as high-intensity interval training because such training
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has previously been shown to be at least as effective as continuous endurance training, but with the advantage of lower perception of dyspnea.30 Moreover, patients thereby trained aerobic and anaerobic exercise capacities, which both influence the main study outcome of peak work rate.
As a result, peak work rate increased overall by 20.9%. Also, there was a significant decrease
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in patients’ heart rate reserve at peak exercise, which was found to be increased at baseline because of ventilatory limitations. Endurance training induced improved aerobic and
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anaerobic metabolism of the skeletal musculature. Therefore, higher maximal heart rates could be reached and heart rate reserve was decreased, i.e. rather normalized. In fact, a 41%
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increase in blood lactate at exhaustion demonstrates improved tolerance to the ventilatory burden. These training effects occurred despite unchanged pulmonary function.
Supplemental oxygen
In COPD, a greater ventilatory demand, dynamic hyperinflation and the associated increase in the work of breathing might lead to an earlier onset of dyspnea, respiratory muscle fatigue and physical exhaustion.5 Providing higher inspiratory oxygen concentrations might indirectly help overcome limitations of airway obstruction. Moreover, we hypothesized that patients 10
ACCEPTED MANUSCRIPT would thus be able to perform exercise training for longer durations and at higher intensities, and consequently benefit from effects on the cardiopulmonary system as well as from reconditioning of peripheral muscles. This has previously motivated studies of exercise training with supplemental oxygen in COPD, but with conflicting results.8 Most studies were
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unable to detect superior effects of training with supplemental oxygen.11–15,18,19,31 Indeed, the latest guidelines provide little support for oxygen supplementation during exercise training in nonhypoxemic COPD.3,8–10 However, in this study we report that the improvement of
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patients’ peak work rate and VO2peak during exercise training with supplemental oxygen was more than twice that of medical air. Moreover, the additional impact of oxygen was
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responsible for 39.1% and 39.7% of the overall training effect on peak work rate and VO2peak, respectively. Although one preceding study showed a positive effect of supplemental oxygen on endurance time at a submaximal constant work rate, this is the first study to demonstrate an increase in peak work rate.20 This variable is of particular interest
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because it is well known that the level of physical activity and maximal work capacity are significantly associated with COPD mortality.2,7
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During endurance training, supplemental oxygen led to a statistically greater increase in exercise capacity than medical air, regardless of whether endurance training was performed
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with supplemental oxygen from baseline or after crossover (figure 4). Moreover, supplemental oxygen was shown to be useful at training begin to more rapidly improve patients’ exercise capacity, but in particular facilitated effective training stimuli during the second period of exercise training (figure 4). Cardiovascular adaptations and peripheral muscle reconditioning could occur due to greater tolerance to higher training intensities. These findings support the consideration of oxygen as a clinically important supplement during endurance training even in patients who do not otherwise require home oxygen
11
ACCEPTED MANUSCRIPT supplementation. This recommendation may be particularly true for long-term training interventions, when exercise intensities must increase to further provoke training adaptations.
One important difference between this study and previous trials is the higher oxygen flow rate
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during training (10 L/min vs. 2–5 L/min), which was well tolerated by the patients.11,12,15,18,20,31 Oxygen delivery in preceding studies was considered low in the concentration or flow rate.10 Even though our oxygen supplementation appears high, given the
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average static and dynamic lung volumes of these patients, even more oxygen might be needed to fully compensate airflow limitation. Furthermore, a dose–response relationship for
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endurance exercise was shown for an inspired oxygen fraction of up to at least 50% (≈8 L/min) and Nonoyama et al. recommended providing higher oxygen concentrations to improve exercise training outcomes.10,32 However, high inspiratory concentrations of oxygen could reduce carotid body activation, leading to depression of the ventilatory drive and
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hypercapnia, especially in patients with severe hypoxemia.33 Nonetheless, Helgerud et al. demonstrated the feasibility of an even higher oxygen concentration administered during an exercise training intervention.16 Moreover, Wadell et al. did not find significant carbon
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dioxide retention during submaximal walking tests, despite the applied oxygen flow of 5 L/min.15 Ventilatory pattern is an integrated output that is influenced by changes in sensory
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inputs and behavioral demands.33 Mechanoreceptors in the lung and chest walls, adrenergic incitement, behavioral factors such as discomfort during physical activity and the ventilatory response to exercise increase the work of breathing.33,34 Thus, the risk of relevant oxygeninduced hypercapnia during exercise training was considered low for our study population.
The SCOPE study performed gas-specific exercise testing and prescription, i.e. gas supply during additional testing and subsequent training was identical. This specificity resulted in
12
ACCEPTED MANUSCRIPT superior exercise performance during testing with oxygen supplementation and thus in an exercise prescription of higher intensity during training. Because supplemental oxygen can increase exercise performance, training prescriptions based only on tests with room air would have led to inadequately low intensities for exercise training with supplemental
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oxygen.11,12,14–16,18,20,31,32,35
Additionally, progressive adaptation of training load was crucial for the improvement of the
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peak work rate. Whereas some studies performed exercise training without changing workload18 and others adjusted intensity in response to the patient’s dyspnea and fatigue,11,20
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the SCOPE protocol called for progressive adaptation of workload whenever an improvement in a patient’s heart rate, which was continuously monitored throughout each training session, would permit it. This resulted in objective training control and consistently increased training intensities. However, patients’ rating of perceived exertion was monitored throughout each
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training session to fine tune exercise intensity.
Patients’ peak exercise arterial oxygen saturation was not considered of central importance for
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the study design because preceding studies on oxygen supplementation during exercise training were discordant for both desaturating11–17 and non-desaturating18–21 patients. Whereas
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oxygen supply is highly recommended for exercise training in hypoxemic and severely desaturating patients,6,9,20 our data support the use of supplemental oxygen for exercise training in desaturating and non-desaturating patients, even though the oxygen effect was more pronounced in COPD with mild exertional hypoxemia. Supplemental oxygen has already been shown to improve exercise tolerance, even in non-desaturating patients.20,21,32,36 Indeed, the oxygen effect was negatively correlated with airflow restriction, but not with exercise hypoxemia.35 Therefore, supplemental oxygen seems not only to act by increasing
13
ACCEPTED MANUSCRIPT arterial oxygen content and improving muscle oxygenation, but also through inhibition of carotid body stimulation, reduced respiratory drive and pulmonary vasodilatation.35,37 This effect might increase cardiac output and muscle oxygen delivery, but decrease ventilation as
for oxygen supplementation during training.
Strength training
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well as dynamic hyperinflation.32,35–37 Exercise-induced hypoxemia is thus not a prerequisite
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High-intensity strength training led to a progressive improvement in 10-RM. Interestingly, regardless of whether strength training was performed with oxygen supplementation or
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medical air, muscle strength increased by a similar extent. Moreover, strength exercises were probably too short to induce a relevant demand on the cardiopulmonary system. Respiratory and auxiliary respiratory muscles might not have been sufficiently stressed during single-set, high-intensity, upper body strength training to induce significant worsening of dyspnea.
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Indeed, it is muscular exhaustion and not dyspnea that limits strength exercise performance.
HADS
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Thus, supplemental oxygen does not confer additional benefit in strength.
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Our data confirm in part that exercise training improves aspects of quality of life in COPD. Pulmonary rehabilitation has been shown to reduce anxiety and depression, in particular if patients scored highest on HADS.38 Considering that patients of this study reported little anxiety and depression at baseline, improvements of -17.5% and -14.3%, respectively, are noteworthy. Although supplemental oxygen did not significantly improve depression, it appears to positively influence patients’ anxiety. This effect on anxiety might be owed to less dyspnea during activities of daily living and exercise training. Indeed, short-term ambulatory oxygen 14
ACCEPTED MANUSCRIPT during physical activities and training has previously been shown to significantly improve health-related quality of life and general health, respectively.17,20
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Limitations Although study withdrawal was not associated with study group, a 34% dropout rate complicated statistical analyses for secondary endpoints. Furthermore, we provided a
designed for statistically valid subgroup analyses.
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descriptive evaluation of desaturating and non-desaturating patients because SCOPE was not
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In addition, this exercise training study was performed without washout period at crossover to analyze dynamics of the oxygen effect during study course. However, no significant carryover effects were found for the main study outcomes of exercise capacity. Finally, endurance and strength training were differently influenced by supplemental oxygen,
Conclusions
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which could have compromised treatment effects within the same muscle fibers.
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SCOPE is the first double-blind randomized controlled trial demonstrating that supplemental oxygen doubles the training effect in terms of peak work rate, the study’s primary endpoint
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and a predictor associated with COPD mortality.7 Data showed that endurance but not strength training was more effective with supplemental oxygen. Oxygen seems to have also a beneficial effect on anxiety. High oxygen flow rate, gas-specific exercise prescription and progressive, ECG-monitored high-intensity interval training were key elements of this intervention. The study findings could be used in future rehabilitation strategies in COPD by promoting innovative ways to improve outcomes. Indeed, supplemental oxygen during outpatient exercise training, or in a home-based setting, might be used to more rapidly improve patients’ 15
ACCEPTED MANUSCRIPT exercise capacity and therefore might emerge as an important tool to increase patient compliance and long-term adherence to training programs.
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Acknowledgments This study was supported by an unconditional and unrestricted grant by Air Liquide.
1.
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lactate kinetics following exercise onset in nonhypoxemic COPD patients. Chest
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Tables Table 1 Patient characteristics
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Table 1.a: At rest Table 1.b: At peak exercise
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Patients’ baseline characteristics at rest (table 1.a) and at peak exercise (table 1.b) measured at training begin. Group O2-Air and group Air-O2 did not differ significantly with regard to
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exercise capacity, i.e. peak work rate, VO2peak, heart rate max, and blood lactate concentration at exhaustion. Data are presented as mean ± standard deviation (SD). BMI: Body mass index, BP: Blood pressure, FEV1: Forced expiratory volume in 1 s, FVC: Forced vital capacity, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume,
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ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV: Alveolar volume, PaO2: Arterial oxygen partial pressure, PaCO2: Arterial carbon dioxide partial pressure, SaO2: Oxygen saturation, VO2peak: Peak oxygen
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consumption, O2 pulse: Oxygen pulse (VO2peak/heart rate), VCO2: Carbon dioxide output, VE: Minute ventilation, petCO2: Partial pressure of end-tidal carbon dioxide, peCO2: Mixed-
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expired CO2 pressure, RER: Respiratory exchange ratio, BF: Breathing frequency, Breathing reserve: is based on a calculated MVV from resting FEV1 × 38, RPE: Rating of perceived exertion scale (6-20).
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ACCEPTED MANUSCRIPT Table 2 Exercise capacity, muscle strength, pulmonary function and patient’s anxiety and depression observed during the study
Table 2 shows the effect of exercise training and supplemental oxygen on main parameters of
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the SCOPE study. For each variable, the relative effect of supplemental oxygen in relation to the overall training effect was analyzed. Parameters that showed a significant carryover effect between study periods are indicated by an asterisk (*).
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SE: Standard Error, Wpeak: Peak work rate, EREC: Expected relative exercise capacity (%Wpeak of standard values of the Austrian society of cardiology considering age, sex and
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body surface), VO2peak: Peak oxygen consumption, HR: Heart rate, 10-RM: ten-repetition maximum strength test, Lat: Latissimus, FVC: Forced vital capacity, FEV1: Forced expiratory volume in 1 s, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume, ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV:
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Alveolar volume, HADS: Hospital Anxiety and Depression Scale.
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Figures figure 1
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The SCOPE study design
A timeline (weeks) is shown at the bottom of the figure. All patients underwent a training-free run-in period lasting 6 weeks to optimize pharmacological treatment according to
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international guidelines. Forty-four patients were randomized at training begin to group O2Air or group Air-O2 and performed two 6-week periods of exercise training; patients started
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the training program with supplemental oxygen followed by medical air or vice-versa. Study investigations were performed at run-in begin, training begin, crossover, and training end.
Flow diagram
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figure 2
Fifty of 137 contacted patients met eligibility criteria and entered the run-in phase. Although
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during the training periods 15 patients dropped out, no differences in dropout rates were
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observed between groups. Furthermore, only two patients opted out during the training period, at a very early stage of the intervention. Other withdrawals were because of comorbidities and exacerbations during the cold winter months.
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ACCEPTED MANUSCRIPT figure 3 The effect of supplemental oxygen in relation to the overall training effect
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The oxygen effect was defined as the difference between results achieved during exercise training with supplemental oxygen as compared with medical air. Statistical significance is indicated by an asterisk (*), whereas trends (0.1>p>0.05) are flagged by a plus sign (+).
Watt/kg (peak work rate), VO2peak: peak oxygen consumption, HRmax: maximal heart rate,
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Lactate (at exhaustion), Lat pull down: Latissimus pull down (10-RM), Leg extension (10-
Depression (HADS).
figure 4
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Training response in both study arms
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RM), FEV1: Forced expiratory volume in 1 s, FVC: Forced vital capacity, Anxiety (HADS),
Patients’ peak work rate (Wpeak) and peak oxygen consumption (VO2peak) during the run-in
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period, as well as the first- and second exercise-training period. Group Air-O2 is depicted by a
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chain dotted line (---) and group O2-Air by a dotted line (···).
25
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Tables Table 1 Patient characteristics
8/21
Sex, female/male Age, y
63.5 (± 5.9)
BMI, kg/m2
27.3 (± 5.4) 119.0 (± 14.2)
Diastolic BP, mm Hg
74.5 (± 9.3)
FEV1/FVC, %
59.7 (± 11.3)
FEV1, % pred.
46.4 (± 8.6)
VC inspired, % pred.
80.2 (± 15.6)
TLC, % pred.
121.3 (± 16.7)
RV/TLC, % pred.
134.1 (± 18.3)
ITGV, % pred.
143.8 (± 24.8)
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DLCOc, % pred. DLCOc/AV, % pred.
65.3 (± 15.1) 69.2 (± 8.6)
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PaO2, mmHg PaCO2, mmHg
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Systolic BP, mm Hg
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Mean (± SD)
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Table 1.a: At rest
38.0 (± 3.2) 16.7 (± 1.5)
SaO2, %
94.4 (± 2.2)
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Hemoglobin, g/ld.
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ACCEPTED MANUSCRIPT Table 1.b: At peak exercise
128.1 (± 17.8)
Work rate, W
85.7 (± 31.2)
VO2peak, L/min/kg
18.4 (± 3.8)
Systolic BP, mmHg
170.2 (± 34.1)
Diastolic BP, mmHg
77.1 (± 13.2)
O2 pulse, mL/beat/kg
11.4 (± 2.9)
VCO2, L/min
1.4 (± 0.4) 53.0 (± 11.4)
VE/VO2 slope
37.8 (± 8.9)
VE/VCO2 slope
34.7 (± 7.4)
petCO2, mmHg
32.3 (± 4.6)
RER
1.0 (± 0.1)
BF, breaths/min
33 (± 5.4)
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VE, L/min
2.0 (± 15.3)
BORG, RPE (6-20)
18.9 (± 1.1)
Lactate, mmol/L
3.8 (± 1.1)
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Breathing Reserve, %
SaO2, %
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Heart rate, bpm
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Mean (± SD)
90.2 (± 7.7)
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Patients’ baseline characteristics at rest (table 1.a) and at peak exercise (table 1.b) measured at training begin. Group O2-Air and group Air-O2 did not differ significantly with regard to
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exercise capacity, i.e. peak work rate, VO2peak, heart rate max, and blood lactate concentration at exhaustion. Data are presented as mean ± standard deviation (SD). BMI: Body mass index, BP: Blood pressure, FEV1: Forced expiratory volume in 1 s, FVC: Forced vital capacity, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume, ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV: Alveolar volume, PaO2: Arterial oxygen partial pressure, PaCO2: Arterial carbon dioxide partial pressure, SaO2: Oxygen saturation, VO2peak: Peak oxygen consumption, O2 pulse: Oxygen pulse (VO2peak/heart rate), VCO2: Carbon dioxide output, 2
ACCEPTED MANUSCRIPT VE: Minute ventilation, petCO2: Partial pressure of end-tidal carbon dioxide, peCO2: Mixedexpired CO2 pressure, RER: Respiratory exchange ratio, BF: Breathing frequency, Breathing reserve: is based on a calculated MVV from resting FEV1 × 38, RPE: Rating of perceived
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exertion scale (6-20).
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Table 2 Exercise capacity, muscle strength, pulmonary function and patient’s anxiety and depression observed during the study Training End
Training
effect
effect
Exercise
Exercise
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Begin
Training
Oxygen
Oxygen
effect
effect
Oxygen effect / Training
Training with
Training with
oxygen
medical air
Delta (± SE)
Delta (± SE)
[%]
p-value
[%]
effect
Mean (± SE)
Mean (± SE)
Mean (± SE)
[%]
p-value
Wpeak/kg, W/kg
1.11 (± 0.07)
1.10 (± 0.07)
1.33 (± 0.07)
20.91
< 0.001
0.16 (± 0.02)
0.07 (± 0.02)
8.18
0.001
39.13
Wpeak, W
85.83 (± 5.56)
85.72 (± 5.84)
104.17 (± 6.50)
21.52
< 0.001
12.72 (± 1.39)
5.72 (± 1.34)
8.17
0.001
37.94
EREC, %
60.52 (± 2.89)
58.86 (± 2.97)
72.47 (± 3.28)
V02peak, mL/min/kg
19.04 (± 0.65)
18.43 (± 0.70)
20.57 (± 0.71)
HR max, bpm
126.28 (± 3.45)
128.10 (± 3.29)
137.55 (± 3.39)
Lactate, mmol/L
3.80 (± 0.19)
3.77 (± 0.24)
5.32 (± 0.37)
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Training
Lat pull down *
40.55 (± 2.04)
40.52 (± 2.15)
60.45 (± 2.77)
Shoulder press *
38.38 (± 2.16)
40.17 (± 2.25)
Back extension
42.24 (± 2.87)
Abdominal crunch
23.12
< 0.001
9.31 (± 1.05)
4.29 (± 1.05)
8.53
0.003
36.88
11.61
< 0.001
1.50 (± 0.30)
0.65 (± 0.34)
4.61
0.067
39.72
7.38
< 0.001
6.07 (± 1.60)
3.38 (± 1.64)
2.10
0.143
28.47
41.11
< 0.001
1.02 (± 0.28)
0.53 (± 0.21)
13.00
0.120
31.61
49.19
9.83 (± 0.89)
10.10 (± 1.29)
-0.69
0.428
-1.40
61.62 (± 2.52)
53.40
< 0.001
11.17 (± 1.08)
10.28 (± 1.59)
2.24
0.347
4.20
46.31 (± 2.62)
66.93 (± 2.47)
44.53
< 0.001
9.59 (± 1.33)
11.03 (± 1.74)
-3.13
0.298
-7.03
20.83 (± 1.68)
22.24 (± 1.66)
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< 0.001
38.76 (± 2.05)
74.28
< 0.001
8.14 (± 1.24)
8.38 (± 1.27)
-1.08
0.456
-1.45
Butterfly *
21.66 (± 2.36)
23.45 (± 2.21)
43.57 (± 3.35)
85.80
< 0.001
9.25 (± 1.06)
10.39 (± 1.69)
-4.86
0.300
-5.67
Butterfly reverse *
16.10 (± 1.81)
16.62 (± 1.60)
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SC
Exercise capacity
31.37 (± 2.17)
88.75
< 0.001
7.11 (± 0.82)
7.37 (± 1.09)
-1.56
0.424
-1.76
Leg extension
28.21 (± 1.99)
29.03 (± 1.97)
47.69 (± 2.17)
64.28
< 0.001
9.14 (± 0.86)
9.52 (± 1.56)
-1.31
0.428
-2.04
Leg flexion *
24.52 (± 1.78)
26.10 (± 1.77)
40.93 (± 2.25)
56.82
< 0.001
7.45 (± 0.66)
7.38 (± 1.06)
0.27
0.481
0.47
FVC, [%pred.]
75.20 (± 2.29)
78.65 (± 1.90)
79.60 (± 2.27)
1.21
0.286
-0.78 (± 1.56)
1.73 (± 1.37)
-3.19
0.154
n.a.
FEV1, [%pred.]
44.44 (± 1.41)
46.41 (± 1.63)
47.56 (± 2.13)
2.48
0.212
1.05 (± 1.18)
0.10 (± 1.24)
2.05
0.316
n.a.
FEV1/FVC, %
59.81 (± 1.60)
59.68 (± 2.06)
60.24 (± 1.87)
0.94
0.312
2.09 (± 1.38)
-1.53 (± 1.13)
6.05
0.075
n.a.
Pulmonary function
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10-RM [kg]
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77.83 (± 2.18)
80.22 (± 2.87)
81.54 (± 2.83)
1.65
0.258
2.49 (± 2.95)
-1.18 (± 2.36)
4.57
0.233
n.a.
TLC, [%pred.]
122.56 (± 2.44)
121.29 (± 3.05)
123.49 (± 3.72)
1.81
0.212
2.19 (± 3.23)
0.01 (± 4.06)
1.80
0.375
n.a.
RV, [%pred.]
164.97 (± 4.66)
156.21 (± 6.30)
159.31 (± 7.39)
1.98
0.311
-2.98 (± 6.07)
6.08 (± 7.01)
-5.80
0.232
n.a.
RV/TLC, [%pred.]
140.64 (± 2.68)
134.09 (± 3.38)
134.62 (± 3.39)
0.40
0.433
-1.67 (± 3.45)
2.21 (± 3.48)
-2.89
0.275
n.a.
ITGV, [%pred.]
147.97 (± 4.46)
143.84 (± 4.63)
143.25 (± 5.74)
-0.41
0.448
DLCOc, [%pred.]
50.91 (± 2.33)
51.08 (± 2.29)
52.63 (± 2.76)
3.03
0.160
DLCOc/AV, [%pred.]
65.45 (± 2.70)
65.32 (± 2.83)
64.01 (± 2.96)
-2.01
0.199
Anxiety *
6.41 (± 0.96)
5.72 (± 0.70)
4.72 (± 0.73)
-17.48
0.022
Depression *
4.55 (± 0.63)
4.76 (± 0.67)
4.08 (± 0.61)
-14.29
0.069
-1.09 (± 7.02)
1.11
0.446
n.a.
-0.57 (± 1.27)
2.11 (± 1.37)
-5.25
0.112
n.a.
-1.03 (± 1.34)
-0.28 (± 1.29)
-1.16
0.363
n.a.
-1.00 (± 0.45)
0.00 (± 0.39)
-17.48
0.084
100.00
-0.48 (± 0.48)
-0.20 (± 0.31)
-5.88
0.341
41.18
SC
0.50 (± 4.67)
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HADS [0-21]
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VC inspired, [%pred.] *
Table 2 shows the effect of exercise training and supplemental oxygen on main parameters of the SCOPE study. For each variable, the relative
study periods are indicated by an asterisk (*).
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effect of supplemental oxygen in relation to the overall training effect was analyzed. Parameters that showed a significant carryover effect between
SE: Standard Error, Wpeak: Peak work rate, EREC: Expected relative exercise capacity (%Wpeak of standard values of the Austrian society of
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cardiology considering age, sex and body surface), VO2peak: Peak oxygen consumption, HR: Heart rate, 10-RM: ten-repetition maximum strength
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test, Lat: Latissimus, FVC: Forced vital capacity, FEV1: Forced expiratory volume in 1 s, VC: Vital capacity, TLC: Total lung capacity, RV: Residual volume, ITGV: Intrathoracic gas volume, DLCOc: Diffusing capacity of the lung for carbon monoxide, AV: Alveolar volume, HADS: Hospital Anxiety and Depression Scale.
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Supplemental oxygen during high intensity exercise training in nonhypoxemic COPD
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Highlights:
Endurance training with supplemental oxygen doubles the effect on peak work rate
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Strength gain was similar whether patients trained with supplemental oxygen or air
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Supplemental oxygen during exercise training seems to also improve patients’ anxiety
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Consider interval training with high O2-flow and gas-specific exercise prescription
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•