EDITORIAL

Making Long-Term Oxygen Therapy Less Burdensome

Darren B. Taichman, Jeffrey M. Drazen

N Engl J Med 2024;391:1050-1051

Long-term oxygen therapy, the first intervention that was shown to improve survival in patients with both severe hypoxemia and chronic obstructive pulmonary disease (COPD), had an effect size so large that data from fewer than 300 patients were all that was needed to establish its efficacy. In the Nocturnal Oxygen Therapy Trial (NOTT), performed in North America, 203 patients with COPD and severe hypoxemia were randomly assigned to receive continuous oxygen supplementation (24 hours per day) or nocturnal oxygen therapy for 12 hours per day.¹ In another trial, which was conducted by the U.K. Medical Research Council (MRC), 15 hours per day of oxygen therapy was compared with no supplemental oxygen in 87 such patients.² In both trials, mortality was lower with long-term oxygen therapy (at 1 year in the NOTT trial and at 5 years in the trial by the MRC). These two small trials, performed more than 40 years ago, are the basis on which multiple professional societies and medical policy makers around the world recommend the use of long-term oxygen therapy for at least 15 hours per day in patients with severe resting hypoxemia.^3-6 In the United States alone, long-term oxygen therapy is prescribed to more than 1 million patients.³

Despite these data, it remains difficult to convince patients to use oxygen therapy. First, patients with chronic lung disease fear that their use of supplemental oxygen will make them look like a “sick person.” Second, the equipment used to deliver supplemental oxygen is heavy and cumbersome, and the oxygen tubing poses a risk of falling, which is a particular burden for frail patients. Third, smaller portable oxygen systems can cost thousands of dollars and may not be covered by insurance. Fourth, the capacity of the device to sustain the needed flow rate of oxygen may be insufficient for a patient to be able to spend meaningful time away from home, thereby leaving the patient fearful of running out of oxygen supply. Fifth, many patients do not feel better while using supplemental oxygen, and as a consequence, long-term oxygen therapy contributes to substantial social isolation and depression, to the extent that many patients choose to endure hypoxemia rather than use oxygen therapy as recommended.⁷

But there is more. When a patient agrees to start long-term oxygen therapy, another troubling question arises: if it improves survival, is therapy used for 15 hours per day enough or would 24 hours per day be better? The two treatment durations have not been directly compared. Consequently, guidelines recommend therapy to be used for at least 15 hours per day or 18 hour per day (the median duration of use attained in the continuous-oxygen group of the NOTT trial) and further note that therapy used for 24 hours per day may have additional benefits. This uncertainty makes weighing the fear of losing a potential survival benefit against the additional moment-to-moment burden of continuous supplemental oxygen use even more onerous.

Ekström and colleagues⁸ now report in the Journal the results of the Registry-Based Treatment Duration and Mortality in Long-Term Oxygen Therapy (REDOX) trial — results that help to provide an answer to the question regarding how much treatment is needed to obtain the survival benefit. After the previously planned sample size was reduced from 2126 to 230, the investigators randomly assigned 241 patients with severe hypoxemia at rest or slightly less severe hypoxemia and either heart failure or polycythemia, most of whom had COPD, to receive long-term oxygen therapy for 24 or 15 hours per day. Adherence to the assigned duration of therapy was excellent, with a median duration of use of 15 hours per day among patients assigned to the 15-hour group and 24 hours per day among those assigned to the 24-hour group, and no patients were lost to follow-up. The result for the primary outcome, a composite of hospitalization or death from any cause within 1 year, was not superior with oxygen therapy used for 24 hours per day than with therapy used for 15 hours per day (mean rate, 124.7 and 124.5 primary-outcome events per 100 person-years, respectively). Mortality was 31.6% in the 24-hour group and 27.4% in the 15-hour group, and hospitalization occurred in 57.3% of the patients in both treatment groups. Although data were less complete, there were no apparent differences in patient-reported measures of breathlessness, fatigue, physical activity, cognitive status, or well-being.

So, these are the best data we have, and perhaps will ever have, to answer this important question: does it do so adequately? Although a larger trial may show a difference in mortality between 15 hours and 24 hours per day of oxygen therapy, the current results should reassure patients and clinicians that such a difference would probably be quite small. Added to the lack of an apparent difference in patient-reported functional outcomes, the results provide peace of mind that we can lessen the burden of long-term oxygen therapy — at least somewhat.

However, even with 15 hours per day of therapy, many burdens remain for patients receiving long-term oxygen supplementation. Among these patients, nearly half cite mobility limitations due to their oxygen equipment as the most important challenge to improving their quality of life, with nearly a third needing help from another person to carry it.⁹ In the United States, current payment policies of the Centers for Medicare and Medicaid Services prevent many patients from obtaining more portable and durable systems that might alleviate these impediments. Bipartisan legislation before the U.S. Congress aims to address these barriers so that the oxygen-delivery system provided to a patient is determined according to medical necessity and not by financial considerations.¹⁰

Long-term oxygen therapy would ideally provide a ticket to freedom for patients with severe hypoxemia at rest, rather than a ball and chain that is added to their physical and emotional burdens caused by underlying disease. For the foreseeable future, however, patients appear to be stuck with a ball and chain. But these new data suggest that the ability to reduce the daily hours of oxygen supplementation without fear of long-term harm makes it possible for a patient to think about attending a concert or family gathering without the oxygen apparatus. Shorter treatment durations, together with efforts to improve access to more portable oxygen delivery systems that meet individual needs, should help lighten the load for a patient with hypoxemic lung disease.