NIHR Signal Long-term oxygen therapy shows no benefit for moderate lung disease

Published on 24 January 2017

Long-term oxygen therapy for 16 hours per day did not lengthen life or the time until hospital admission for people with stable chronic obstructive pulmonary disease (COPD) who experience a moderate drop in blood oxygen levels with exercise or at rest. Nor did it improve their quality of life, lung function or anxiety and depression scores.

Participants in this large US study were randomly assigned to receive either long-term supplemental oxygen or no supplemental oxygen based on a simple pulse oximetry measure of oxygen saturation. Their progress was measured for up to six years.

Oxygen treatment is expensive for the NHS and can be hard for patients to manage. These results add new evidence that might reduce unnecessary long-term oxygen therapy prescriptions for people with moderate COPD. There are differences in the way that a potential fall in blood oxygen levels are measured in the US compared to the pathway advised in the UK, which will need to be considered.

Long-term oxygen therapy shows no benefit for moderate lung disease

Why was this study needed?

COPD causes breathing difficulty that worsens over time. Approximately three million people are thought to have COPD in the UK, but only one million have been diagnosed. COPD costs the NHS over £800 million per year.

Long-term oxygen therapy is not easy to use. A home oxygen concentrator is usually provided but patients need to be able to store and operate the equipment and must not smoke while using oxygen. The concentrator is not portable so oxygen cylinders are needed to get out of the house but these are heavy and have a limited capacity.

The effects of long-term oxygen therapy on frequency of hospital admissions and patients’ quality of life are unclear. Previous evidence is mixed. A Cochrane review from 2005 suggested that long-term oxygen therapy didn’t improve symptoms for people with moderate disease.

This study looks at whether long-term oxygen therapy prolongs health and quality of life in people with stable COPD with moderate blood oxygen level decreases (desaturations) with exercise or low oxygen levels at rest.

What did this study do?

This randomised controlled trial included 738 patients with stable COPD from 14 clinical centres in the US.

COPD patients were eligible to take part in the study if they had a moderate drop in blood oxygen levels breathing air either at rest (133 people) or when they exercised (319 people) or both (286 people). Following assessment, participants were randomly assigned long-term supplemental oxygen (average 16 hours a day), or no additional oxygen.

Participants given oxygen were prescribed two litres per minute when at rest, with tailored doses for exercise, via stationary or portable cylinders to ensure 24 hour oxygen. Those who only had a drop in oxygen levels during exercise were prescribed oxygen only during sleep.

Researchers measured blood oxygen saturation using a pulse oximeter. In the UK, this test is advised as a precursor to a more accurate test using an arterial blood sample including CO2 measurement. This means that the pathway of care cannot be directly compared to that described in NICE guidance where decisions to prescribe oxygen are based on full arterial blood gas measurement.

What did it find?

  • There was no difference between the two groups in the number of people who died, 73/370 on supplemental oxygen compared to 66/368 without (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.64 to 1.25).
  • There was no difference in length of time until they died or were first admitted to hospital.Within the study period of six years, 67% people from the supplemental oxygen group and 68% people with no supplemental oxygen died or were admitted to hospital (HR 0.94, 95%CI 0.79 to 1.12).
  • There was no difference between time to death or hospitalisation within subgroups of patients. These subgroups included patients selected by age, smoking status and lung function. Any differences disappeared after figures had been adjusted to take account of the effect of making multiple comparisons.
  • Those people receiving supplemental oxygen therapy showed no difference in quality of life scores, anxiety and depression scores, or lung function compared with those who didn’t have supplemental oxygen.

What does current guidance say on this issue?

NICE guidance from 2011 recommends long-term oxygen therapy for people with stable COPD who have a moderate to severe drop in blood oxygen at rest or when they are asleep, those with a blood condition or high blood pressure caused by COPD. It recommends that people should breathe supplemental oxygen for at least 15 hours a day and preferably 20 hours a day.

NICE recommends assessing someone for long-term oxygen therapy if they have a blood oxygen saturation level of 92% or less.

What are the implications?

There seems to be little value in people with COPD using long-term oxygen therapy if they don’t have severe desaturation with exercise or are severely low in oxygen at rest. Clinicians using pulse oximetry alone might want to consider referral for further arterial blood gas assessment in cases of doubt, as advised in NICE guidance.

The results from this study may help clinicians to manage patient expectations about long-term oxygen at home. Patients with COPD with moderate desaturation at rest or with exercise can be told there’s no evidence long-term oxygen therapy will help them live longer, stay out of hospital longer, or improve their quality of life.

Targeting long-term oxygen therapy at people with more severe disease who are more likely to benefit would also potentially save money.

Citation and Funding

Long-Term Oxygen Treatment Trial Research Group. A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation. N Engl J Med. 2016;375(17):1617-1627.

This study was funded by the National Heart, Lung and Blood Institute, National Institutes of Health and Department of Health and Human services.

Bibliography

British Thoracic Guideline Development Group. Intermediate care--Hospital-at-Home in chronic obstructive pulmonary disease: British Thoracic Society guideline. Thorax. 2007;62(3):200-10.

Cranston J, Crockett A, Moss J, Alpers J. Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database of Syst Rev. 2005;(4):CD0001744

NHS Choices. Chronic Obstructive Pulmonary disease (COPD). London: Department of Health; 2016.

NICE. Chronic obstructive pulmonary disease. Costing report. Implementing NICE guidance. CG101. London: National Institute for Health and Care Excellence; 2011.

Why was this study needed?

COPD causes breathing difficulty that worsens over time. Approximately three million people are thought to have COPD in the UK, but only one million have been diagnosed. COPD costs the NHS over £800 million per year.

Long-term oxygen therapy is not easy to use. A home oxygen concentrator is usually provided but patients need to be able to store and operate the equipment and must not smoke while using oxygen. The concentrator is not portable so oxygen cylinders are needed to get out of the house but these are heavy and have a limited capacity.

The effects of long-term oxygen therapy on frequency of hospital admissions and patients’ quality of life are unclear. Previous evidence is mixed. A Cochrane review from 2005 suggested that long-term oxygen therapy didn’t improve symptoms for people with moderate disease.

This study looks at whether long-term oxygen therapy prolongs health and quality of life in people with stable COPD with moderate blood oxygen level decreases (desaturations) with exercise or low oxygen levels at rest.

What did this study do?

This randomised controlled trial included 738 patients with stable COPD from 14 clinical centres in the US.

COPD patients were eligible to take part in the study if they had a moderate drop in blood oxygen levels breathing air either at rest (133 people) or when they exercised (319 people) or both (286 people). Following assessment, participants were randomly assigned long-term supplemental oxygen (average 16 hours a day), or no additional oxygen.

Participants given oxygen were prescribed two litres per minute when at rest, with tailored doses for exercise, via stationary or portable cylinders to ensure 24 hour oxygen. Those who only had a drop in oxygen levels during exercise were prescribed oxygen only during sleep.

Researchers measured blood oxygen saturation using a pulse oximeter. In the UK, this test is advised as a precursor to a more accurate test using an arterial blood sample including CO2 measurement. This means that the pathway of care cannot be directly compared to that described in NICE guidance where decisions to prescribe oxygen are based on full arterial blood gas measurement.

What did it find?

  • There was no difference between the two groups in the number of people who died, 73/370 on supplemental oxygen compared to 66/368 without (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.64 to 1.25).
  • There was no difference in length of time until they died or were first admitted to hospital.Within the study period of six years, 67% people from the supplemental oxygen group and 68% people with no supplemental oxygen died or were admitted to hospital (HR 0.94, 95%CI 0.79 to 1.12).
  • There was no difference between time to death or hospitalisation within subgroups of patients. These subgroups included patients selected by age, smoking status and lung function. Any differences disappeared after figures had been adjusted to take account of the effect of making multiple comparisons.
  • Those people receiving supplemental oxygen therapy showed no difference in quality of life scores, anxiety and depression scores, or lung function compared with those who didn’t have supplemental oxygen.

What does current guidance say on this issue?

NICE guidance from 2011 recommends long-term oxygen therapy for people with stable COPD who have a moderate to severe drop in blood oxygen at rest or when they are asleep, those with a blood condition or high blood pressure caused by COPD. It recommends that people should breathe supplemental oxygen for at least 15 hours a day and preferably 20 hours a day.

NICE recommends assessing someone for long-term oxygen therapy if they have a blood oxygen saturation level of 92% or less.

What are the implications?

There seems to be little value in people with COPD using long-term oxygen therapy if they don’t have severe desaturation with exercise or are severely low in oxygen at rest. Clinicians using pulse oximetry alone might want to consider referral for further arterial blood gas assessment in cases of doubt, as advised in NICE guidance.

The results from this study may help clinicians to manage patient expectations about long-term oxygen at home. Patients with COPD with moderate desaturation at rest or with exercise can be told there’s no evidence long-term oxygen therapy will help them live longer, stay out of hospital longer, or improve their quality of life.

Targeting long-term oxygen therapy at people with more severe disease who are more likely to benefit would also potentially save money.

Citation and Funding

Long-Term Oxygen Treatment Trial Research Group. A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation. N Engl J Med. 2016;375(17):1617-1627.

This study was funded by the National Heart, Lung and Blood Institute, National Institutes of Health and Department of Health and Human services.

Bibliography

British Thoracic Guideline Development Group. Intermediate care--Hospital-at-Home in chronic obstructive pulmonary disease: British Thoracic Society guideline. Thorax. 2007;62(3):200-10.

Cranston J, Crockett A, Moss J, Alpers J. Domiciliary oxygen for chronic obstructive pulmonary disease. Cochrane Database of Syst Rev. 2005;(4):CD0001744

NHS Choices. Chronic Obstructive Pulmonary disease (COPD). London: Department of Health; 2016.

NICE. Chronic obstructive pulmonary disease. Costing report. Implementing NICE guidance. CG101. London: National Institute for Health and Care Excellence; 2011.

A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation

Published on 27 October 2016

Group, Long-Term Oxygen Treatment Trial Research

N Engl J Med Volume 375 Issue 17 , 2016

Background Long-term treatment with supplemental oxygen has unknown efficacy in patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation. Methods We originally designed the trial to test whether long-term treatment with supplemental oxygen would result in a longer time to death than no use of supplemental oxygen among patients who had stable COPD with moderate resting desaturation (oxyhemoglobin saturation as measured by pulse oximetry [Spo2], 89 to 93%). After 7 months and the randomization of 34 patients, the trial was redesigned to also include patients who had stable COPD with moderate exercise-induced desaturation (during the 6-minute walk test, Spo2 >/=80% for >/=5 minutes and <90% for >/=10 seconds) and to incorporate the time to the first hospitalization for any cause into the new composite primary outcome. Patients were randomly assigned, in a 1:1 ratio, to receive long-term supplemental oxygen (supplemental-oxygen group) or no long-term supplemental oxygen (no-supplemental-oxygen group). In the supplemental-oxygen group, patients with resting desaturation were prescribed 24-hour oxygen, and those with desaturation only during exercise were prescribed oxygen during exercise and sleep. The trial-group assignment was not masked. Results A total of 738 patients at 42 centers were followed for 1 to 6 years. In a time-to-event analysis, we found no significant difference between the supplemental-oxygen group and the no-supplemental-oxygen group in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval [CI], 0.79 to 1.12; P=0.52), nor in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91 to 1.13), COPD exacerbations (rate ratio, 1.08; 95% CI, 0.98 to 1.19), and COPD-related hospitalizations (rate ratio, 0.99; 95% CI, 0.83 to 1.17). We found no consistent between-group differences in measures of quality of life, lung function, and the distance walked in 6 minutes. Conclusions In patients with stable COPD and resting or exercise-induced moderate desaturation, the prescription of long-term supplemental oxygen did not result in a longer time to death or first hospitalization than no long-term supplemental oxygen, nor did it provide sustained benefit with regard to any of the other measured outcomes. (Funded by the National Heart, Lung, and Blood Institute and the Centers for Medicare and Medicaid Services; LOTT ClinicalTrials.gov number, NCT00692198 .).

There are different ways of measuring blood oxygen levels. The drop in blood oxygen levels for someone with COPD in this study was measured as by a pulse oximeter, an instrument that measures blood oxygen levels through the skin.

This study defined moderate as a resting desaturation (SpO2, 89 to 93%) or moderate exercise-induced desaturation (during the six-minute walk test) reaching levels between SpO2 80% for five minutes and less than 90% for 10 seconds).

A moderate drop in blood oxygen levels is measured in NICE guidance as having a partial pressure of oxygen (PaO2) of between 8.3kPa and 9.3kPa, which is measured using an arterial blood sample. These levels would be equivalent to saturations of about 91 to 93%.

Expert commentary

Long-term oxygen therapy extends life in people with COPD who have severe resting hypoxaemia below 7.3kPa breathing air. This study addressed whether there was also benefit in those with less severe hypoxaemia (oxygen saturation of 89 to 93%) or exercise desaturation.

Bottom line: there wasn’t, as assessed using the primary outcome of all-cause mortality or first hospitalisation, and a range of secondary end points. Oxygen therapy can be burdensome for patients, and is expensive. For the benefit of patients and payers alike, don’t routinely give oxygen to this group but do screen patients with advanced COPD for severe resting hypoxaemia. You might just save a life.

Dr John Hurst, Reader in Respiratory Medicine, UCL Respiratory, University College London

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