Long-term oxygen treatment (LTOT) is the best proven means available for prolonging life in chronic obstructive pulmonary disease (COPD) patients with severe resting hypoxemia. However, there remain many deficits in knowledge regarding the mechanisms of LTOT action, optimal indications for its prescription, and its effects on patient outcomes other than survival. In fact, clinical decision making and insurance coverage policies today are primarily based on only two, relatively small trials performed in the 1970's. Little has been done in the past 20 years to refine or extend the results of early clinical trials, and there is remarkably little current research in this area. These deficiencies in knowledge and in current research activity are especially striking in comparison to the central role of LTOT in the management of COPD and its associated costs -- exceeding $2 billion per year in total Medicare reimbursements for O2.
Recognizing that additional research may be needed to inform clinical decision making and insurance coverage policies, the National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts entitled "Long-term Oxygen Treatment in COPD". Two other components of the Department of Health and Human Services cooperated with the NHLBI in planning this meeting: the Centers for Medicare and Medicaid Services (CMS) and the Agency for Healthcare Research and Quality (AHRQ). The Working Group was charged with evaluating the current state of knowledge regarding LTOT, identifying research questions of clinical importance, and discussing technical issues that might influence the feasibility and design of LTOT trials.
The group identified several general areas in which further research is needed. These include efficacy of LTOT in patients with moderate resting hypoxemia, efficacy of LTOT in patients who are normoxic when awake and at rest but who desaturate during physical activity or sleep, optimal timing and dosage of oxygen supplementation, mechanisms of action, clinical and biochemical predictors of responsiveness to LTOT, and methods for enhancing adherence to LTOT.
The Working Group also recommended performance of four randomized, controlled clinical trials. The first is a single-blinded efficacy trial to test the hypothesis that clinical outcomes are better in those who receive oxygen supplementation during ambulation in comparison to those who do not receive O2. This study will include as subjects COPD patients who are not severely hypoxemic when awake at rest but who show oxyhemoglobin desaturation during physical activity. Oxygen will be provided via a light-weight, portable supply.
The second study is a double-blinded, efficacy trial in COPD patients who initially qualify for LTOT on the basis of a single determination of PaO2, but for whom a repeat arterial blood gas analysis does not support prescription of LTOT. The hypothesis to be tested is that clinical outcomes do not differ between groups of subjects randomized to receive LTOT or air.
The third recommended study is a double-blinded, efficacy trial in COPD patients who are not severely hypoxic when awake at rest but who show oxyhemoglobin desaturation during sleep that is not due to obstructive sleep apnea. The hypothesis to be tested is that clinical outcomes are better in those who receive O2 supplementation during sleep than in those who receive air in a similar manner.
The final recommended study is a non-blinded, effectiveness trial to test the hypothesis that clinical outcomes are better in subjects whose O2 prescriptions (flow rates) are based on periodic clinical testing at rest, during physical activity, and when asleep in comparison to those whose O2 prescriptions are based on testing that is performed only when the subjects are awake and at rest. The study population will consist of COPD patients who qualify for LTOT by standard criteria.
The meeting was held on May 10-11, 2004 in Bethesda, Maryland, USA
Working Group Members
Chair: William Bailey, M.D., University of Alabama