Title: How (Why) Does Oxygen Work in Advanced COPD?
Abstract: Long-term oxygen therapy (LTOT) is established as the standard of care for selected patients with advanced chronic stable hypoxemia.1Petty TL Home oxygen: a revolution in the care of advanced COPD.Med Clin North Am. 1990; 74: 715-729Crossref PubMed Scopus (20) Google Scholar A large body of scientific evidence, including two well-defined and well-conducted controlled clinical trials,2Nocturnal Oxygen Therapy Trial Group Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2096) Google Scholar3The Medical Research Council Working Party Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: report of The Medical Research Council Working Party.Lancet. 1981; 1: 681-686PubMed Google Scholar shows that oxygen has a survival benefit. In the Nocturnal Oxygen Therapy Trial (NOTT),2Nocturnal Oxygen Therapy Trial Group Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2096) Google Scholar survival was better in patients who received ambulatory oxygen therapy compared with those assigned to receive oxygen from a stationary source. However, the mean duration of the oxygen therapy was greater for ambulatory oxygen (17.7 vs 11.8 h per day, respectively) than in those assigned to nocturnal and stationary oxygen.2Nocturnal Oxygen Therapy Trial Group Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2096) Google Scholar Thus, the difference in survival could be due to the duration of oxygen therapy, the method (ie, ambulation), or both. It is interesting that in the British Medical Research Council study, the survival benefit did not appear for 500 days.3The Medical Research Council Working Party Long-term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: report of The Medical Research Council Working Party.Lancet. 1981; 1: 681-686PubMed Google Scholar In the NOTT study,2Nocturnal Oxygen Therapy Trial Group Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2096) Google Scholar statistical survival differences compared to continuous oxygen therapy compared to nocturnal oxygen therapy did not become statistically significant until after 3 years. Why the delay? O'Donohue4O'Donohue WJ Effect of oxygen therapy on increasing arterial oxygen tension in hypoxemic patients with chronic stable chronic obstructive pulmonary disease while breathing ambient air.Chest. 1991; 100: 968-972Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar has argued in favor of the “restorative” effect of oxygen. A short explanation of the thesis of the late Walter O'Donohue is that oxygen somehow restores ventilation perfusion matching in the lung, resulting in normoxemia in patients who previously had chronic stable hypoxemia. These patients did not experience a measured improvement in lung mechanical function during the follow-up. This is a quite different matter than when LTOT is prescribed following exacerbations of COPD. Many of these individuals have an improvement in lung function and may not be candidates for LTOT on full recovery. I have long argued for another NOTT study to compare outcomes in terms of survival, number of exacerbations, quality of life, and the economics of continuous oxygen therapy, using a modern ambulatory system carried by the patient weighing less than 5 lbs compared with stationary oxygen therapy. New technologies now allow this. If a survival benefit can be traced to ambulatory oxygen, the question will be how and why. Answers must be sought at the molecular cellular level. Does continuous oxygen therapy counter the adverse effects of “hypoxia genes.”5Maxwell PH Wiesener MS Chang GW et al.The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis.Nature. 1999; 399: 271-275Crossref PubMed Scopus (4084) Google Scholar Does ambulatory oxygen improve energy production at the tissue level better than when stationary oxygen therapy is used?6Petty TL Bliss PL Ambulatory oxygen therapy, exercise, and survival with advanced chronic obstructive pulmonary disease: the Nocturnal Oxygen Therapy Trial revisited.Respir Care. 2000; 45: 204-213PubMed Google Scholar The length and quality of life has improved for COPD patients over the past 30 years. Part of this improvement can be assigned to better pharmacologic therapy and part to the widespread use of LTOT. COPD patients can now live into their 70s and 80s. Today, some 1 million people with COPD and related disorders receive oxygen therapy, and approximately 70% of them are assigned to a stationary system, a largely arbitrary decision made through a lack of knowledge of the available technologies by prescribing physicians or for economic considerations of suppliers. We badly need the answers to how and why oxygen works in patients with chronic stable hypoxemia in the present era. Prospective controlled clinical trials conducted with a sufficient number of patients to achieve a clear-cut outcome should be an extremely high priority for funding agencies.