Long-term Oxygen Treatment in COPD
Working Group Executive Summary
May 10-11, 2004
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
Members
- Nicholas Anthonisen, M.D., Ph.D., University of Manitoba
- Richard Casaburi, Ph.D., M.D., University of California Los Angeles
- Dennis Doherty, M.D., University of Kentucky Chandler Medical Center
- Charles Emery, Ph.D., The Ohio State University
- Leslie Hoffman, R.N., Ph.D., University of Pittsburgh School of Nursing
- William MacNee, M.D., University of Edinburgh Medical School, United
Kingdom
- Sadis Matalon, Ph.D., University of Alabama
- Dennis Niewoehner, M.D., Veterans Affairs Medical Center, Minneapolis,
Minnesota
- George O'Connor, M.D., Boston University School of Medicine
- Thomas Petty, M.D., University of Colorado Health Sciences Center
- Barbara Phillips, M.D., University of Kentucky
- Steven Piantadosi, M.D., Ph.D., Johns Hopkins Center for Clinical
Trials
- Andrew Ries, M.D., University of California San Diego
- Haya Rubin, M.D., Ph.D., Johns Hopkins School of Medicine
- J. Sanford Schwarz, M.D., University of Pennsylvania
- Frank Sciurba, M.D., University of Pittsburgh Medical Center
- Byron Thomashaw, M.D., Columbia-Presbyterian Medical Center
- Rubin Tuder, M.D., The Johns Hopkins Medical Institutions
- Peter Wagner, M.D., University of California San Diego
- Robert Wise, M.D., Johns Hopkins Asthma and Allergy Center
NHLBI Staff
- Thomas Croxton, M.D., Ph.D., Division of Lung Diseases
October 2004
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