What do new findings tell us about the role of long-term supplemental oxygen in patients with stable COPD?
Long-term supplemental oxygen provides no benefit in terms of survival or time to first hospitalization in patients with stable chronic obstructive pulmonary disease (COPD) with moderate resting desaturations (pulse oximetry [SpO2], 89 to 93%) or exercise induced desaturations, according to the findings of a new study.
The researchers reported their findings in the October 27, 2016 issue of The New England Journal of Medicine.
Trials conducted in the 1970s suggested that patients with COPD with “severe” resting hypoxemia, as indicated by SpO2 of less than 89% and treated with long-term supplemental oxygen therapy had a survival benefit.
Additional studies have failed to show a survival benefit using both nocturnal oxygen and long-term supplemental oxygen therapy for patients with mild to moderate desaturations (SpO2 89-93%). However these studies were small and therefore underpowered to assess mortality.
The current study sought to assess this issue in a larger group of patients.
Study design and characteristics
To more decisively address the knowledge gap of the effect of long term supplemental oxygen therapy on patients with stable COPD and moderate resting desaturations, researchers conducting the Long-Term Oxygen Treatment Trial (LOTT).
This study evaluated prolonged survival in this patient population. However, due to lower-than-projected mortality among patients after 7 months, the trial was redesigned to also include patients with exercise-induced desaturations and a co-primary outcome of both improved survival and prolonged time to first all cause hospitalization. Patients included in the first study design were included in the second redesigned study.
During the 5-year study, 738 patients at 42 centers were randomized in a 1:1 ratio into an oxygen-treatment group versus a no-oxygen treatment group. Patients with moderate resting desaturations were prescribed supplemental oxygen 24 hours per day while those experiencing only exercise-induced desaturations were prescribed oxygen during sleep and exercise; the study was not blinded. Patients were then followed for between 1 and 6 years with 97% of patients having at least 1 year of follow-up for hospitalization. Most patients used oxygen at a flow of 2 liters per minute.
Adherence to the prescribed regimen in the supplemental oxygen treatment group was measured both by self-report and by comparison to a 100-patient sample in which meter-reading calculations were performed. The 24-hour treatment patient group used their oxygen 15.1 ± 6.2 hours per day versus 11.3 ± 5.0 hours in the sleep-exercise patient group, suggesting some overlap between the 2 groups in terms of daily oxygen usage.
Death and time to first hospitalization as well as other outcomes and subgroups
Researchers noted no significant difference between the trial oxygen therapy group and the no-oxygen treatment group in terms of time to death or first hospitalization, both as the composite primary outcome (hazard ratio = .94; 95% confidence interval [CI], 0.79 to 1.12; P = .52) as well as by the constituent components of death and time to first hospitalization (hazard ratio = 0.90; 95% CI, 0.64 to 1.25; P = .53 and hazard ratio = 0.92; CI 0.77 to 1.10; P = .37).
Outcomes not affected by oxygen treatment included time to first COPD exacerbation, hospitalizations, any COPD exacerbations, and measures of quality of life, depression, anxiety, and functional status.
After adjustment for comparisons, no difference was observed between patients who were treated with oxygen at least 16 hours per day and all other patients in terms of the primary objectives of the study. However, raw data suggested that patients who reported an acute exacerbation of COPD within 3 months prior to enrollment, patients 71 years and older at enrollment, and those who reported a lower quality of life according to the Quality of Well-Being Scale had a longer time to first hospitalization than their cohorts in the no oxygen treatment group (P = .007, P = .03, and P = .03 respectively).
Conclusion
“While oxygen supplementation provides a clear survival benefit to patients with COPD who experience severe resting oxygen desaturation,” lead researcher Robert A. Wise, MD, Professor of Medicine in the Department of Pulmonary and Critical Care at Johns Hopkins University School of Medicine in Baltimore, MD told MedPage Today, “there is no survival or time to hospitalization benefit to patients with mild-to-moderate resting desaturation or desaturation only with activity.”
Dr. Wise added that if a person with mild-to-moderate desaturation is already being treated with oxygen and has symptomatic benefit, then there is no reason to discontinue it.
Dr. Wise and colleagues note that the study results may be due to “nonlinear effects of oxygen saturation on pulmonary vasoconstriction, mediator release, and ventilatory drive, which
occur with an SpO2 of 88% or less and which may be more important in patients with chronic hypoxemia.”
One question left unanswered by the study is whether patients with severe nocturnal desaturations could benefit from long-term nocturnal oxygen supplementation.
Researchers note that the results of this study corroborate earlier underpowered studies which suggest that in patients with stable COPD with moderate resting or exercise-associated desaturations, long-term supplemental oxygen does not provide a benefit with respect to mortality or time to first hospitalization. Additionally, no benefits regarding other outcomes were noted in the current study.