Patients with stable chronic obstructive pulmonary disease (COPD) and resting or exercise-induced moderate desaturation do not appear to benefit from long-term supplemental oxygen, a randomized trial shows.

"[W]e found that long-term supplemental oxygen did not provide any benefit with respect to the time to death or first hospitalization or any sustained benefit with respect to any other measured outcome," write study chair William C. Bailey, MD, from the University of Alabama, Birmingham, and colleagues on behalf of the Long-Term Oxygen Treatment Trial Research Group. They report their findings in an article published in the October 27 issue of New England Journal of Medicine.

The investigators originally designed the trial to study the effect of long-term supplemental oxygen on time to death in patients with COPD and moderate resting desaturation (Spo 2 , 89% - 93%); however, they revised their study after 7 months as a result of slow recruitment. The amended trial expanded the inclusion criteria, allowing patients with moderate exercise-induced desaturation (during the 6-minute walk test, Spo 2 , ≥80% for ≥5 minutes and <90% for ≥10 seconds), and added the outcome of time to first hospitalization for any cause as a composite primary outcome.

The investigators randomly assigned 738 patients to receive supplemental oxygen (n = 368) or no supplemental oxygen (n = 370). Patients in the supplemental oxygen group received 24-hour oxygen if their resting Spo 2 was 89% to 93% (n = 220) and oxygen only during sleep and exercise if they only experienced desaturation during exercise (n = 148). Oxygen was given at 2 L/minute. The researchers followed the patients for from 1 to 6 years.

Time to death or first hospitalization did not differ significantly between the supplemental oxygen group and the no supplemental oxygen group in the time to death or first hospitalization (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.79 - 1.12; P = .52). The rates of all hospitalizations (rate ratio [RR], 1.01; 95% CI, 0.91 - 1.13), COPD exacerbations (RR, 1.08; 95% CI, 0.98 - 1.19), and COPD-related hospitalizations (RR, 0.99; 95% CI, 0.83 - 1.17) also did not differ significantly between the two groups.

Time to death or first hospitalization was longer in patients in the supplemental oxygen group who experienced a COPD exacerbation 1 to 3 months before enrollment (HR, 0.58; 95% CI, 0.39 - 0.88; P = .007 for interaction), were 71 years of age or older at enrollment (HR, 0.75; 95% CI, 0.57 - 0.99; P = .03 for interaction), or reported a lower quality of life (Quality of Well-Being Scale score, <0.55) at enrollment (HR, 0.77; 95% CI, 0.60 - 0.99; P = .03 for interaction). However, none of these interactions was significant after adjustment for multiple, prespecified comparisons.

There were no consistent differences between the study groups in the change from baseline in measures of quality of life, anxiety, or depression or in lung function, distance walked in 6 minutes, or other measures of functional status.

"This landmark study is the largest to date with regard to long-term oxygen therapy," Magnus Ekström, MD, PhD, from the Department of Clinical Sciences, Division of Respiratory Medicine and Allergology, Lund University, and the Department of Medicine, Blekinge Hospital, Karlskrona, Sweden, writes in an accompanying editorial. "The validity of the findings is supported by the consistent lack of effect across outcomes, which was not modified by type of oxygen prescription, desaturation profile, oxygen use, sex, smoking status, and lung function," he adds.

"I believe that on the basis of all available current data, long-term oxygen therapy should be prescribed to prolong survival among patients with COPD who have chronic (>3 weeks) severe resting hypoxemia (Pao 2 of ≤55 mm Hg or Sao

Dr Bailey has disclosed no relevant financial relationships. Several coauthors reported various financial relationships with Novartis, Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Astellas Pharma, ICON Medical Imaging, Breathe Technologies, Ventec Life Systems, Bayer, Centocor, Gilead Sciences, Takeda Pharmaceuticals (formerly Nycomed), Afferent Pharmaceuticals, Forest Laboratories, Janssen, Pearl Therapeutics, Ikaria, Bellerophon Therapeutics (formerly Ikaria), Kadmon, Pfizer, Veracyte, Roche, Sunovion Pharmaceuticals, Theravance Biopharma, Concert Pharmaceuticals, Biogen (formerly Stromedix), AcademicCME, MedEd Consulting, Continuing Education, Potomac Center for Medical Education, CME Incite, Annenberg Center for Health Sciences at Eisenhower, Integritas Communications, inThought Research, Miller Medical Communications, Paradigm Medical Communications, PeerVoice, HayMarket Communications, Prime Healthcare, WebMD, PeerView Academic Network, Axon Communications, Johnson & Johnson, Clarion Communications, Adept Field Solutions, Proterixbio (formerly Bioscale), Unity Biotechnology, Lucid Communique Medical Education, Baxalta, CSL Behring, Grifols, Arrowhead Pharmaceuticals, Bristol-Myers Squibb, ContraFect, Mylan, Pulmonx, Spiration, Teva Pharmaceutical Industries, Verona Pharma, and Vertex Pharmaceuticals. The remaining authors and Dr Ekström have disclosed no relevant financial relationships.

N Engl J Med. 2016;375:1617-1627, 1683-1684. Article full text, Editorial full text

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