Nocturnal oxygen therapy for patients with COPD and isolated nocturnal oxygen desaturation does not improve survival or delay disease progression, according to findings published Sept. 17 in The New England Journal of Medicine. The new report adds to evidence that the widely implemented and costly practice may be unnecessary.
Patients with COPD who do not qualify for long-term oxygen therapy (LTOT) are commonly prescribed nocturnal oxygen in the belief that it can delay disease progression, possibly by decreasing alveolar hypoventilation and ventilation-perfusion mismatch.
But investigations so far and the new study from the International Nocturnal Oxygen (INOX) Trial have not borne this out.
“There is no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with nocturnal hypoxemia in COPD. Consequently, there is no reason for physicians to screen for nocturnal hypoxemia in COPD,” study leader Yves Lacasse, MD, told Medscape Medical News.
Lacasse is from the Institut Universitaire de Cardiologie et de Pneumologie de Québec–Université Laval, Quebec, Canada.
The idea that the therapy helps is firmly entrenched.
In the early 1980s, two trials indicated that patients who had COPD and severe chronic daytime hypoxemia benefit from LTOT (15-18 hours a day or longer).
A decade later, two landmark trials (the Nocturnal Oxygen Therapy Trial and the British Medical Research Council Trial) added to evidence that LTOT may prolong life for patients with COPD and severe daytime hypoxemia.
“The good news from both trials was that oxygen saves lives. From this moment, oxygen therapy became a standard of care, and confirmatory trials would be considered unethical,” Lacasse explained.
“Oxygen therapy gained widespread acceptance by official organizations for treatment of most chronic cardiorespiratory conditions complicated by severe hypoxemia, even if proof of efficacy is lacking. New indications emerged, such as isolated nocturnal oxygen desaturation. Even in COPD, inappropriate prescriptions of home oxygen therapy are not unusual. Oxygen is everywhere,” Lacasse continued.
A meta-analysis from 2005 identified two trials that evaluated home oxygen therapy specifically for isolated nocturnal desaturation. Both found no survival benefit from nocturnal oxygen.
The study by Lacasse and colleagues assessed effects on mortality or worsening of disease (progression to LTOT) with 3-4 years of nocturnal oxygen supplementation.
Participants, whose oxygen saturation was less than 90% for at least 30% of the recording time on nocturnal oximetry, received oxygen or ambient air from a sham device as a placebo for at least 4 hours per session. The goal of treatment was nocturnal oxygen saturation exceeding 90% for at least 90% of the recorded time.
The trial protocol excluded patients with severe, apnea, lung cancer, left , interstitial lung disease, or .
The study was initially powered in 2010 to include 600 participants, with half to receive placebo. The study assumed mortality of 20% among control patients over 3 years; 20% of patients progressed to LTOT.
When recruiting lagged, the data safety monitoring board and steering committee extended follow-up to 4 years. In 2014, they requested an interim analysis, and recruitment ceased. Overall, 243 patients participated.
Lacasse cited several reasons for the difficulty with recruitment as well as retention: unwillingness to take the risk of receiving placebo instead of a readily available treatment, fading interest over time, and frailty that affects compliance.
Patients in the study came from 28 community or university-affiliated hospitals in Canada, Portugal, Spain, and France. At the 3-year mark, 39% of patients (48 of 123) who were assigned to nocturnal oxygen therapy and 42% (50 of 119) of those taking placebo had met criteria for LTOT or had died (difference, −3.0 percentage points; P = .64). The groups did not differ appreciably in rates of exacerbation and hospitalization.
The researchers could not analyze subgroups because the patients were very similar with regard to the severity of nocturnal oxygen desaturation, Lacasse said.
Economics enters into the picture – home oxygen therapy is second only to hospitalization as the most expensive healthcare expenditure associated with clinical care for COPD in developed countries. “The math is simple. There is enormous potential for saving money if the results of our clinical trial are applied appropriately,” said Lacasse.
William Bailey, MD, professor emeritus of pulmonary, allergy, and critical care medicine at the University of Alabama at Birmingham, agrees that the practice is overused.
“There is a built-in bias in the medical community. Most believe that anyone with lung disease benefits from oxygen. Even some of our investigators had a hard time believing the results. The study was well designed, carefully carried out, and I feel confident that the results are reliable,” he said.
Shawn P. E. Nishi, MD, director of bronchoscopy and advanced pulmonary procedures, division of pulmonary and critical care medicine, the University of Texas Medical Branch, Galveston, Texas, mentioned the study’s main limitation, which the authors readily acknowledge.
“Unfortunately, the trial had difficulty recruiting subjects, with less than half of expected enrollment achieved, and was underpowered to make any conclusions. Other studies have examined nocturnal oxygen use and have not shown a mortality benefit,” Nishi explained.
She added that the study did not evaluate use of LTOT for improving outcomes other than mortality, including quality of life, cardiovascular morbidity,, cognitive function, exercise capacity, and frequency of COPD exacerbations or hospitalization.
Other limitations of the study include suboptimal adherence to the therapy and interpretation of the clinical significance on the basis of a survey of Canadian pulmonologists.
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