Enhancement of Exercise Performance in COPD Patients by Hyperoxia: A Call for Research

doi:10.1378/chest.122.5.1830

Chest

Volume 122, Issue 5, November 2002, Pages 1830-1836

https://doi.org/10.1378/chest.122.5.1830 Get rights and content

This essay summarizes 16 reports, published since 1956, that describe the effects of hyperoxia on exercise endurance in persons with COPD who have severe airflow obstruction (ie, FEV₁ < 1.0 L or < 39% of predicted) and mild hypoxemia at rest (ie, Pao₂ > 62 mm Hg or arterial oxygen saturation [Sao₂] measured by pulse oximetry of > 91%). The term hyperoxia is used because, in a proportion of study participants, oxygen administration increased exercise endurance in a dose-dependent fashion, up to a fraction of inspired oxygen of 0.5 or a flow of 100% O₂ of 6 L/min. The process appears to be dependent on an increase in Pao₂ rather than on the restoration of Sao₂ to normal levels. The results of pulmonary function tests were not predictive of response. Increased exercise performance was associated with a decrease in dyspnea, respiratory frequency, and minute ventilation. The slowing of respiratory frequency and the decrease in pulmonary air trapping likely accounted for the decrease in dyspnea. Slowing of the respiratory rate, which occurred at the expense of the retention of CO₂, is most likely due to a hyperoxia-induced decrease in chemoreceptor ventilatory drive from the aortic and carotid bodies. Research is called for to determine the following: (1) the prevalence of COPD patients who have severe airflow limitation accompanied by mild hypoxemia; (2) the proportion of these patients who show improvements in exercise performance during a test of hyperoxic exercise; and (3) whether enhanced exercise performance during a brief test translates into a meaningful increase in the ability to perform the activities of daily living.

Section snippets

Summary of Literature

In 1956, Cotes and Gilson⁴ reported that portable oxygen therapy, given in a blinded fashion, usefully increased exercise performance in most of 29 patients with severe respiratory insufficiency. Twenty-eight of the 29 patients in the study had been coal miners, 18 had pneumoconiosis, and all had chronic bronchitis and emphysema. In 22 of 29 patients, walking distance on a treadmill was at least doubled when they were breathing oxygen. Studies of maximally effective oxygen concentration

Clinical Trial of Hyperoxic Exercise

There has been only one double-blind, randomized, crossover trial assessing the effects of supplemental oxygen therapy during exercise on quality of life. McDonald and colleagues²⁰ measured the effects of therapy with supplemental air and oxygen, at 4 L/min, on exercise performance during a step test and a 6-min walk test that were performed before and after two 6-week periods at home while breathing compressed air or oxygen during exercise. Spo₂ and Borg dyspnea score were measured during

The Physiology of Hyperoxic Exercise in Chronic Airflow Obstruction

Airflow obstruction is the hallmark of COPD. Resting hyperinflation of the lungs, as indicated by increases in functional residual capacity and total lung capacity, is frequent in patients with severe COPD. Tidal breathing occurs over a less advantageous portion of the length-tension curve of the diaphragm. Work done by accessory muscles of respiration is increased.¹³ During exercise, the ventilatory muscles are unable to do the work necessary to adequately increase tidal volume. Tachypnea and

Suggested Action Plan

It is estimated that in the United States there are currently about 16 million persons with COPD. There were 107,000 deaths due to COPD in 1998, and, extrapolating from the 1998 data, in the current year there will be about 115,000 deaths due to COPD.²⁶ Assuming that on the average, persons have severe COPD for 10 years before they die, it follows that of the 16 million persons with severe COPD currently alive in the United States, at least 1.2 million (7.5%) have severe disease. A conservative

The Research Questions

1.
What is the prevalence of COPD patients, who are not receiving LTOT and who have severe airflow limitation (ie, FEV₁, < 1.0 L or 35% of predicted values) and mild hypoxemia (ie, resting Spo₂, ≥ 90%)?
2.
What proportion of severely obstructed, mildly hypoxemic COPD patients will improve their exercise endurance in a brief test?
3.
Is improved performance during a brief hyperoxic exercise test translated into a meaningful increase in the activities of daily living?

It is apparent that, apart from a full

The Next Step

It is beyond the scope of this essay to spell out the precise procedures for answering these questions. However, I have some suggestions for consideration by experts in the rehabilitation of persons with COPD.

Hyperoxia Endurance Test

Since pulmonary function tests do not predict who will benefit from oxygen treatment, an exercise endurance hyperoxia test should be developed that will indicate which patients might benefit from supplemental oxygen therapy during exercise. Almost 10 years ago, Leach et al¹⁷ pointed out that training runs were needed for both an endurance walk and a 6-min walk, but that fewer runs were needed for the endurance walk. More importantly, these authors showed that the endurance walk was more

Hyperoxic Exercise Performance

If preliminary studies warrant, a randomized, clinical, interventional trial should be organized to determine whether exercise hyperoxia has a therapeutic role in the segment of the population of COPD patients with high-grade airflow obstruction but limited hypoxemia. The end points of the study should be enhanced exercise performance, decreased dyspnea during exercise, enhanced performance of activities of daily living, and increased well-being.

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Effect of oxygen on exercise ability in chronic respiratory insufficiency: use of portable apparatus
Lancet
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AA Woodcock et al.
Oxygen relieves breathlessness in “pink puffers.”
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DA Stein et al.
Mechanisms of oxygen effects on exercise in patients with chronic obstructive pulmonary disease
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Relationship between improvement in exercise performance with supplemental oxygen and hypoxic ventilatory drive in patients with chronic airflow obstruction
Chest
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Effect of hyperoxia on gas exchange and lactate kinetics following exercise onset in non-hypoxemic COPD patients
Chest
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Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease
Ann Intern Med
(1980)
Medical Research Council Working Party
Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema
Lancet
(1981)
Health Care Financing Administration
Coverage issues manual, durable medical equipment, 60–4, home use of oxygen
JE Cotes et al.
Effects of breathing oxygen upon cardiac output, heart rate, ventilation, systemic and pulmonary blood pressure in patients with chronic lung disease
Clin Sci
(1963)
AC Raimondi et al.
Exercise tolerance breathing a low density gas mixture, 35 per cent oxygen and air in patients with chronic obstructive bronchitis
Clin Sci
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MN Vyas et al.

Response to exercise in patients with chronic airway obstruction: II. Effects of breathing 40 per cent oxygen

Am Rev Respir Dis

(1971)

BL Bradley et al.

Oxygen-assisted. exercise in chronic obstructive lung disease: the effect on exercise capacity and arterial blood gas tensions

Am Rev Respir Dis

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G Scano et al.

Effect of oxygen on breathing during exercise in patients with chronic obstructive lung disease

Eur J Respir Dis

(1982)

Cited by (47)

The effect of heated humidified nasal high flow oxygen supply on exercise tolerance in patients with interstitial lung disease: A pilot study
2021, Respiratory Medicine
Citation Excerpt :
A minimal expiratory positive pressure between 1.5 and 5.3 cmH2O was assured using adapted nasal cannulas. FiO2 was fixed at 0.5 based on previous studies in COPD [30,31] and ILD [28] patients during exercise. Subjects exercised on a computer-controlled electronically-braked cycle ergometer (Medisoft ergometer, Leeds, United Kingdom).
Patients with interstitial lung disease (ILD) experience early symptoms of dyspnoea and leg fatigue during exercise together with severe and rapid oxygen desaturation. Heated and humidified nasal high flow oxygen (NHF) has been proven to enhance exercise endurance and physiological parameters in COPD patients. This study aims to evaluate the effect of NHF on exercise tolerance in ILD patients.
Twenty-five patients (10 female) with severe ILD performed three constant-load (70% maximal workload) cycling tests to exhaustion under different breathing conditions: room air, oxygen supplementation (4 L min⁻¹ O₂) and NHF (inspiratory O₂ fraction 0.5, 30–50 L min⁻¹, heated 34 °C and humidified).
Endurance time was significantly longer with NHF (618 ± 297 s) compared to O₂ (369 ± 217 s, p < 0.001) and room air (171 ± 76 s, p < 0.001). Kinetics of oxygen desaturation, chronotropic response, dyspnoea and leg fatigue sensations were delayed with NHF. At exhaustion with NHF, compared to the two other conditions, oxygen desaturation was less severe while heart rate, dyspnoea and leg fatigue were similar.
NHF significantly improved endurance time, physiological parameters and sensations during exercise in severe ILD patients. NHF may be useful to improve functional capacities and facilitate pulmonary rehabilitation in ILD.
Oxygen supplementation increases the total work and muscle damage markers but reduces the inflammatory response in COPD patients
2020, Respiratory Physiology and Neurobiology
Citation Excerpt :
Consistent with this, an increase in total work during exercise with O2-Suppl compared to that without O2-Suppl was observed in 100 % of the patients in the present study. Previous studies have shown that O2-Suppl is more efficient in patients with EID (Oliveira et al., 2012; Snider, 2002), however, this improvement in physical function can also occur in patients without EID (Oliveira et al., 2012; Richardson et al., 1999; Spielmanns et al., 2015). O2-Suppl with 40 % FIO2 has been shown to promote an increase in peak load (Watts) of 7.4 % and 21.1 % in non-desaturated and desaturated patients with COPD, respectively (Oliveira et al., 2012).
Oxygen supplementation (O₂-Suppl) is recommended for pulmonary rehabilitation with higher exercise intensities. However, high-intensity exercise tends toward muscle damage and a greater inflammatory response. We aimed to investigate the effect of O₂-Suppl during exercise test (EET) on CRP level and muscle damage (CPK, LDH, lactate) in non-hypoxemic COPD patients.
Eleven non-depleted patients with COPD (FEV₁ 65.5 ± 4.3 %) performed two EET (room-air or O₂-Suppl-100 %), through a blind, randomized, and placebo-controlled crossover design. CPK, LDH and CRP were measured before, immediately after and 24 h after EET.
Exercise time was higher with O₂-Suppl (49.9 ± 37.3 %; p = 0.001) and increases in CPK and LDH were observed compared to basal values in the O₂-Suppl (28.4UI/L and 28.3 UI/L). The O₂-Suppl protocol resulted in a lower increase in CRP (92.1 ± 112.4 % vs. 400.1 ± 384.9 %; p = 0.003).
O₂-Suppl increases exercise-tolerance, resulting in increased muscle injury markers in COPD. However, oxygen supplementation attenuates the inflammatory response, even upon increased physical exercise.
Effective bronchoscopic lung volume reduction accelerates exercise oxygen uptake kinetics in emphysema
2016, Chest
Citation Excerpt :
Novel treatment strategies aimed to increase peripheral O2 delivery (eg, supplemental oxygen or oral antioxidants),48,49 and/or decrease O2 needs (eg, nitrate supplementation)50 may prove to be of additional benefit with training to prevent or delay the onset of limb muscle fatigue.
The impact of bronchoscopic lung volume reduction (BLVR) on physiologic responses to exercise in patients with advanced emphysema remains incompletely understood. We hypothesized that effective BLVR (e-BLVR), defined as a reduction in residual volume > 350 mL, would improve cardiovascular responses to exercise and accelerate oxygen uptake ( $\dot{V}$ o₂) kinetics.
Thirty-one patients (FEV₁, 36% ± 9% predicted; residual volume, 219% ± 57% predicted) underwent a constant intensity exercise test at 70% peak work rate to the limit of tolerance before and after treatment bronchoscopy (n = 24) or sham bronchoscopy (n = 7). Physiologic responses in patients who had e-BLVR (n = 16) were compared with control subjects (ineffective BLVR or sham bronchoscopy; n = 15).
e-BLVR reduced residual volume (−1.1 ± 0.5 L, P = .001), improved lung diffusing capacity by 12% ± 13% (P = .001), and increased exercise tolerance by 181 ± 214 s (P = .004). $\dot{V}$ o₂ kinetics were accelerated in the e-BLVR group but remained unchanged in control subjects (Δ mean response time, −20% ± 29% vs 1% ± 25%, P = .04). Acceleration of $\dot{V}$ o₂ kinetics was associated with reductions in heart rate and oxygen pulse response half-times by 8% (84 ± 14 to 76 ± 15 s, P = .04) and 20% (49 ± 16 to 34 ± 16 s, P = .01), respectively. There were also increases in heart rate and oxygen pulse amplitudes during the cardiodynamic phase post e-BLVR. Faster $\dot{V}$ o₂ kinetics in the e-BLVR group were significantly correlated with reductions in residual volume (r = 0.66, P = .005) and improvements in inspiratory reserve volume (r = 0.56, P = .024) and exercise tolerance (r = 0.63, P = .008).
Lung deflation induced by e-BLVR accelerated exercise $\dot{V}$ o₂ kinetics in patients with emphysema. This beneficial effect appears to be related mechanistically to an enhanced cardiovascular response to exercise, which may contribute to improved functional capacity.
Exercise oxygen flow titration methods in COPD patients with respiratory failure
2012, Respiratory Medicine
Citation Excerpt :
High oxygen flows are able to reduce minute ventilation and the respiratory rate for a given workload, improve ventilatory muscle function during exercise by postponing the onset of respiratory muscle fatigue and improving the capacity of the diaphragm to sustain work, increase oxygen delivery and its utilization by muscles during exercise, decrease dyspnea and improve endurance by directly reducing chemoreceptor activity.3 Furthermore, it has been confirmed that hyperoxia reduces dynamic hyperinflation,29 which is the main limiting factor of daily physical activity in COPD patients.13 An attractive alternative to oxygen-flow titration procedures might consist of the integration of sensors in the portable oxygen devices that would measure oxyhemoglobin saturation in real time and adjust the oxygen flow until reaching over 90% saturation levels at every moment and for each activity.
We compare the adequacy of several titration procedures of oxygen flow in maintaining SpO₂ > 90% during the activities of daily life in patients with very severe COPD.
Thirty-one very severe COPD patients undergoing oxygen-therapy were recruited. Three titration methods were randomly performed: (1) 6-min walking tests; (2) cycle-ergometer constant work-rate tests at a load equivalent to 12 ml/min/kg of oxygen uptake; (3) one single constant work-rate test at 40 W 12-h pulse-oximeter monitoring was performed on four consecutive days with the following oxygen flow during exercise: 1 l·min⁻¹ above the resting prescription (NOTT guidelines) and those established by the titration procedures.
The time spent SpO₂ < 90% was higher for the titration based on NOTT and walking tests than for the oxygen flow established by the constant work-rate tests at 12 ml O₂/min/kg (22.1 ± 18.7, 20.8 ± 19.5 and 6.7 ± 12.7%, respectively). As for the oxygen uptake-based titration, the simplified procedure (a single exercise test at 40 w) generates longer times spent SpO₂ < 90% and SpO₂ < 85%, although it maintains a SpO₂ > 90% for more 90% of the time.
In COPD patients, exercise oxygen flow titrations by NOTT guidelines or walking tests do not allow a suitable oxygenation during the activities of daily life. Two more adequate alternative methods, based on constant work-rate tests, are proposed.
A randomised trial of domiciliary, ambulatory oxygen in patients with COPD and dyspnoea but without resting hypoxaemia
2011, Thorax
Citation Excerpt :
Hyperoxia is believed to reduce dyspnoea during exercise by reducing ventilatory demand and delaying the onset of dynamic hyperinflation. Previous studies suggest that this may occur in a dose-dependent fashion, up to a fraction of inspired oxygen of 0.5 or a flow of 6 l/min of 100% oxygen.4 We chose a flow rate of 6 l/min in order to maximise this effect and because the lower flow rates used in previous studies may have provided inadequate relief from exercise-induced desaturation.8–10
Patients with chronic obstructive pulmonary disease (COPD) who are not severely hypoxaemic at rest may experience significant breathlessness on exertion, and ambulatory oxygen is often prescribed in this circumstance despite a lack of conclusive evidence for benefit. This study aimed to determine whether such patients benefit from domiciliary ambulatory oxygen and, if so, which factors may be associated with benefit.
This was a 12 week, parallel, double-blinded, randomised, placebo-controlled trial of cylinder air versus cylinder oxygen, provided at 6 l/min intranasally, for use during any activity provoking breathlessness. Patients underwent baseline measurements of arterial blood gases and lung function. Outcome measures assessed dyspnoea, health-related quality of life, mood disturbance, functional status and cylinder utilisation. Data were analysed on an intention-to-treat basis, p≤0.05.
143 subjects (44 female), mean±SD age 71.8±9.8 years, forced expiratory volume in 1 s (FEV₁) 1.16±0.51 lites, Pao₂ 9.5± 1.1 kPa (71.4±8.5 mm Hg) were randomised, including 50 patients with exertional desaturation to ≤88%. No significant differences in any outcome were found between groups receiving air or oxygen. Statistically significant but clinically small improvements in dyspnoea and depression were observed in the whole study group over the 12 weeks of the study.
In breathless patients with COPD who do not have severe resting hypoxaemia, domiciliary ambulatory oxygen confers no benefits in terms of dyspnoea, quality of life or function. Exertional desaturation is not predictive of outcome. Intranasal gas (either air or oxygen) may provide a placebo benefit.
ACTRN12605000457640.
Exertional desaturation in idiopathic pulmonary fibrosis: The role of oxygen supplementation in modifying cerebral-skeletal muscle oxygenation and systemic hemodynamics
2021, Respiration

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Chest

Opinions/HypothesesEnhancement of Exercise Performance in COPD Patients by Hyperoxia: A Call for Research

Section snippets

Summary of Literature

Clinical Trial of Hyperoxic Exercise

The Physiology of Hyperoxic Exercise in Chronic Airflow Obstruction

Suggested Action Plan

The Research Questions

The Next Step

Hyperoxia Endurance Test

Hyperoxic Exercise Performance

Lancet

Lancet

Chest

Chest

Chest

Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease

Ann Intern Med

Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema

Lancet

Coverage issues manual, durable medical equipment, 60–4, home use of oxygen

Effects of breathing oxygen upon cardiac output, heart rate, ventilation, systemic and pulmonary blood pressure in patients with chronic lung disease

Clin Sci

Exercise tolerance breathing a low density gas mixture, 35 per cent oxygen and air in patients with chronic obstructive bronchitis

Clin Sci

Response to exercise in patients with chronic airway obstruction: II. Effects of breathing 40 per cent oxygen

Am Rev Respir Dis

Oxygen-assisted. exercise in chronic obstructive lung disease: the effect on exercise capacity and arterial blood gas tensions

Am Rev Respir Dis

Effect of oxygen on breathing during exercise in patients with chronic obstructive lung disease

Eur J Respir Dis

Opinions/Hypotheses
Enhancement of Exercise Performance in COPD Patients by Hyperoxia: A Call for Research