The notion that LTOT improves the mortality rate in patients with COPD is derived from studies published in the 1980s, such as the Nocturnal Oxygen Therapy Trial.
9 This study demonstrated that in patients with COPD and chronic, severe hypoxemia, continuous LTOT significantly reduced mortality and improved hematocrit levels and pulmonary vascular resistance when compared with nocturnal oxygen therapy alone.
9 This study was followed by the British Medical Research Council Hypoxemia Trial,
6 which further demonstrated a reduction in mortality in patients with COPD who received LTOT for more than 15 hours per day compared with no oxygen therapy (room air).
6 However, the decrease in mortality rates of patients with mild or moderate hypoxemia who received LTOT has not been routinely demonstrated in subsequent studies.
7,8
Supplemental LTOT became the standard of care for patients with COPD with severe hypoxemia, but its utility in the context of mild to moderate hypoxemia is unclear.
10,11 An end point that may explain the widespread use of LTOT to prevent adverse events is the potential symptomatic benefit of supplemental oxygen in patients with dyspnea. A meta-analysis by Ekström et al
12 aimed to assess how the use of LTOT affects breathlessness and health-related quality of life in patients with COPD and mild to moderate hypoxemia. The results showed that breathlessness could be improved with LTOT, but only when breathlessness was related to exercise and not to daily activities. This study
12 also found that LTOT had no effect on health-related quality of life.
In 2016, a parallel-group, randomized, nonblinded clinical trial across 47 university-affiliated ambulatory medical centers in the United States attempted to assess the benefit of LTOT in patients with COPD with moderate hypoxemia.
13 Seven hundred thirty-eight stable patients with COPD with moderate hypoxemia were randomly assigned to 2 groups: one group received LTOT (n=368) and the other did not (n=370). Among the patients who received LTOT, patients with moderate resting desaturation (Sp
o2 89%-93%; n=220) received 24-hour oxygen (2 L O
2 via nasal cannula), and patients with moderate exercise desaturation (Spo
2 <90% for ≥10 seconds and ≥80% for ≥5 minutes; n=148) received oxygen only during exercise and sleep. After a 6-year follow-up, with a median follow-up of 18.4 months, the time to first hospitalization or to death did not differ between the groups (hazard ratio, 0.95; 95% CI, 0.79-1.12;
P=.52). No difference was found in secondary outcome measures, including quality of life and breathlessness. However, factors regarding the design and methods of this study
13 may have contributed to the nonsignificant outcome.
14,15
One factor is that the study design had to be modified to gain sufficient recruitment of patients, which may have led to a selection bias because sicker patients may have been excluded. Additionally, the study investigators were not blinded, which may have introduced an observer bias in the patients and the clinicians. There were also concerns
15 that patients who were smokers may have been noncompliant with remaining abstinent from smoking or that differences in smoking during times not receiving oxygen may have affected the results of the study. Additionally, the patients in the LTOT group had a lower risk of death than those in the nonsupplemental oxygen group, which would introduce a sampling bias in that both groups’ baseline COPD severity and risk of death would be different. This factor may have affected the outcome, demonstrating a smaller benefit for the supplemental oxygen group. In future studies, it would be helpful to have objective evidence (whether smokers abstain from smoking during the study), perhaps by measuring serum or urinary nicotine levels and also to account for the smoking status of all participants. Moreover, none of the previous studies
6-10,13 mentioned the hazards of smoking while using LTOT, which might be worthwhile in future clinical trials.