In patients with severe chronic obstructive pulmonary disease (COPD) who are receiving long-term oxygen therapy (LTOT), automated titration of oxygen clinically and significantly improves endurance walking time without any worsening of partial pressure of carbon dioxide, according to the results of a small, randomized, double-blind, crossover study ( Identifier: NCT01575327) published in Thorax.1

The investigators compared the use of automatically titrated oxygen flows (FreeO2) with that of constant oxygen flow on exercise capacity, oxygen saturation, and risk for hyperoxia-associated hypercapnia in patients with severe COPD and baseline hypercapnia who were receiving LTOT. The primary study outcome was endurance time (along with the corresponding walking distance) during the endurance shuttle walking test conducted at 85% estimated peak oxygen consumption (ie, the maximum rate of oxygen consumption as measured during incremental exercise).2 Secondary outcomes included time spent within prespecified pulsed oxygen saturation targets, capillary blood gases (pH, PcCO2), heart rate, dyspnea, and leg fatigue.

A total of 12 patients 65±10 years of age with Global Initiative for Chronic Obstructive Lung Disease 3 COPD (n=4) or Global Initiative for Chronic Obstructive Lung Disease 4 COPD (n=8) who were receiving LTOT and had resting hypercapnia were included in the analysis. All participants performed exercise with either FreeO2 or constant oxygen flow.

Patients with severe COPD improved significantly both in endurance time and walking distance with the use of FreeO2 vs constant oxygen flow (+127±236 m; P= .02 and +138 ±269 m; P =.03, respectively). This functional improvement was linked to significantly greater oxygen flow rates during exercise (FreeO2: 5.4±2.7 L/min vs constant oxygen flow: 3.1±1.2 L/min; P =.01), which led to improved oxygen saturation. In fact, the lowest oxygen saturation was 83.6%±7.0% with constant oxygen flow compared with 89.5%±3.9% with FreeO2 (P <.001).

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Despite higher oxygen flow rates with FreeO2 vs constant oxygen flow, however, PcCO2 was similar in both conditions across resting, walking test, and recovery, implying that hypercapnia did not worsen using higher oxygen flows in these participants (P =.71).

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The investigators concluded that caution should be used before generalizing the current results to a broader population of patients. Additional studies are warranted to determine which pulsed oxygen saturation upper limit represents the best trade-off value between optimized oxygenation and minimized risk for carbon dioxide retention. A further consideration in future trials should be that a heavier and larger oxygen source may be required to permit higher oxygen flows during exercise.


  1. Vivodtzev I, L’Her E, Vottero G, et al. Automated O2 titration improves exercise capacity in patients with hypercapnic chronic obstructive pulmonary disease: a randomised controlled cross-over trial [published online August 30, 2018]. Thorax. doi:10.1136/thoraxjnl-2018-211967
  2. Revill SM, Morgan MD, Singh SJ, Williams J, Hardman AE. The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax. 1999;54(3):213-222.