Oxygen Not Beneficial to Patients with Stable COPD and Moderate Resting Desaturations
By Jennifer L. Beck, MD
It is well established that patients with chronic obstructive pulmonary disease (COPD) with
“severe” resting hypoxemia as measured by pulse oximetry (Spo2) of less than 89% treated with
long-term supplemental oxygen therapy have reduced mortality. However, a recent study
reports that long-term supplemental oxygen does not provide benefit in terms of survival or
time to first hospitalization in patients with stable COPD with moderate resting desaturations
(Spo2, 89 to 93%) or exercise induced desaturations.
The researchers found that long-term supplemental oxygen therapy is not beneficial in terms of
survival or time to first hospitalization for patients with moderate resting desaturations and
exercise induced desaturations as reported in the October 27, 2016 issue of The New England
Journal of Medicine.5 It has been long accepted that patients with COPD suffering from severe
resting hypoxemia (Spo2 < 89%) live longer when treated with long-term supplemental oxygen
therapy; 1,2 later, further studies 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 the studies were small and therefore underpowered to assess
mortality.3,4
"While oxygen supplementation provides a clear survival benefit to patients with COPD who
experience severe resting oxygen desaturation, there is no survival or time to
hospitalization benefit to patients with mild to moderate resting desaturation or desaturation
only with activity," 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. Dr. Wise added that if a person with mild to moderate
desaturations is already treated with oxygen and has symptomatic benefit then there is no
reason to discontinue it however.
Study design and characteristics
To 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) designed a study to evaluate
prolonged survival in this patient population. However, due to lower than predicted mortality
among patients after 7 months, the trial was redesigned to also include patients with exerciseinduced 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.5
During the 5-year study 738 patients at 42 centers were randomized at a 1:1 ratio into the
oxygen-treatment group versus the 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.5
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 meterreading 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. Therefore,
there was significant similarity between the 2 groups in terms of daily oxygen usage.5
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 nooxygen treatment group in terms of time to death or first hospitalization, both as the composite
primary outcome (hazard ratio = .94; 95% confidence interval [CI], .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, .64 to 1.25; P = .53 and hazard ratio = .92; CI .77 to 1.10; P = .37). Also noted outcomes
that were not affected by oxygen treatment were “time to first COPD exacerbation, the rate of
all hospitalizations, the rate of all COPD exacerbations, or changes in measures of quality of life,
depression, anxiety, or functional status.”5
Once subgroup analysis was complete and adjusted for multiple comparisons, there was no
difference 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).5
Conclusion
Researchers cite a possible explanation for the results of their study pertains to the “nonlinear
effects of oxygen saturation on pulmonary vasoconstriction, mediator release, and ventilitory
drive which occur with an Spo2 of 88% or less and which may be more important in patients
with chronic hypoxemia.”5
One question left unanswered by the study is whether patients with severe nocturnal
desaturations could benefit from long-term nocturnal oxygen supplementation.5
Researchers state that the results of this study corroborates earlier underpowered studies that
long-term supplemental oxygen does not benefit patients with stable COPD with moderate
resting or exercise-associated desaturations relative to mortality or time to first hospitalization.
Additionally, there was no evidence that there was significant benefit in regard to any other
outcome that was measured.
Article Summary: Patients with stable chronic obstructive pulmonary disease (COPD) and
moderate resting desaturations as measured by pulse oximetry (Spo2) of 89% to 93% and
patients with -induced desaturations do not benefit from long-term supplemental oxygen
therapy in terms of decreased mortality or time to first hospitalization despite earlier studies
confirming that patients with severe resting hypoxemia (Spo2 < 89%) treated with oxygen have
significantly reduced mortality.
Take Note:
 Despite solid evidence that long-term supplemental oxygen therapy reduces mortality in
patients with COPD and severe resting hypoxemia (Spo2 < 89%), previous studies
showing no benefit for patients with COPD and mild to moderate desaturations (Spo2
89% to 93%) were underpowered to assess mortality.
 During the 5-year non-blinded study, 738 patients with stable COPD and moderate
resting or exercise-induced desaturations were randomized to an oxygen treatment
group and a no-oxygen group; there was no benefit in terms of mortality or time to first
hospitalization noted for members of the treatment group.
 Other outcomes measured as well as subgroup analysis did not show a significant
difference between the oxygen treatment group and the no-oxygen group.
References:
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chronic obstructive lung disease: a clinical trial. Ann Intern Med 1980;93:391-398.
http://annals.org/aim/article/694234/continuous-nocturnal-oxygen-therapy-hypoxemicchronic-obstructive-lung-disease-clinical
2. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic
hypoxic cor pulmonale complicating chronic bronchitis and emphysema: report of the Medical
Research Council Working Party. Lancet 1981;1:681-686
http://annals.org/aim/article/694234/continuous-nocturnal-oxygen-therapy-hypoxemicchronic-obstructive-lung-disease-clinical
3. Chaouat A, Weitzenblum E, Kessler R, et al. A randomized trial of nocturnal oxygen therapy in
chronic obstructive pulmonary disease patients. Eur Respir J 1999; 14:1002-1008.
http://erj.ersjournals.com/content/14/5/1002.long
4. Górecka D, Gorzelak K, Sliwiński P, Tobiasz M, Zieliński J. Effect of long-term oxygen therapy
on survival in patients with chronic obstructive pulmonary disease with moderate hypoxaemia.
Thorax 1997; 52:674-679.
http://thorax.bmj.com/content/52/8/674.long
5. The 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: 1617-1627.
http://www.nejm.org/doi/full/10.1056/NEJMoa1604344