Portal de Periódicos da CAPES

Life Expectancy in Severe COPD

1994; Elsevier BV; Volume: 105; Issue: 2 Linguagem: Inglês

10.1378/chest.105.2.335

1931-3543

Christopher B. Cooper,

Pulmonary Hypertension Research and Treatments

Life expectancy in patients with severe COPD is strongly correlated with the severity of airflow obstruction.1Boushy SF Thompson HK North LB Beale AR Snow TR Prognosis in chronic obstructive pulmonary disease.Am Rev Respir Dis. 1973; 108: 1373-1383PubMed Google Scholar, 2Traver GA Cline MG Burrows B Predictors of mortality in chronic obstructive pulmonary disease: a 15-year follow-up study.Am Rev Respir Dis. 1979; 119: 895-902PubMed Google Scholar, 3Postma DS Burema J Gimeno F May JF Smit JM Steenhuis EJ Prognosis in severe chronic obstructive pulmonary disease.Am Rev Respir Dis. 1979; 119: 357-367PubMed Google Scholar Some studies have also indicated an association between the degree of secondary pulmonary hypertension and survival.4Bishop JM Hypoxia and pulmonary hypertension in chronic bronchitis.Prog Respir Res. 1975; 9: 10-16Crossref Google Scholar, 5Weitzenblum E Hirth C Ducolone A Mirhom R Rasaholinjanahary J Ehrhart M Prognostic value of pulmonary artery pressure in chronic obstructive pulmonary disease.Thorax. 1981; 36: 752-758Crossref PubMed Scopus (71) Google Scholar Long-term oxygen therapy (LTOT) ameliorates the pulmonary hypertension resulting from chronic hypoxemia and also improves survival, at least in patients with COPD.6Nocturnal Oxygen Therapy Trial GroupContinuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2071) Google Scholar, 7Report of the Medical Research Council Working PartyLong-term oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema.Lancet. 1981; 1: 681-686PubMed Google Scholar, 8Cooper CB Waterhouse J Howard P Twelve-year clinical study of patients with hypoxic cor pulmonale given long-term domiciliary oxygen therapy.Thorax. 1987; 42: 105-110Crossref PubMed Scopus (136) Google Scholar Some investigators have found that the fall in pulmonary artery pressure is predictive of improved survival.9Timms RM Khaja FU Williams GW NOTT GroupHemodynamic response to oxygen therapy in chronic obstructive pulmonary disease.Ann Intern Med. 1985; 102: 29-36Crossref PubMed Scopus (238) Google Scholar, 10Ashutosh K Mead G Dunsky M Early effects of oxygen administration and prognosis in chronic obstructive pulmonary disease and cor pulmonale.Am Rev Respir Dis. 1983; 127: 399-404Crossref PubMed Scopus (87) Google Scholar An analysis of the combined data from the NIH and MRC studies has led to the development of international prescribing criteria for the prescription of LTOT. Most countries which have adopted such criteria require an arterial oxygen tension below 55 mm Hg, breathing air in chronic stable state, and stipulate that oxygen should be administered for at least 15 h each day. While LTOT is usually prescribed with the conviction that patients will survive longer due to an amelioration of pulmonary hypertension, our understanding of the pathophysiology and exact cause of death in patients with severe COPD is far from complete. What can be expected is a relentless deterioration in airway function with a decline in FEV1 despite LTOT.11Cooper CB Howard P An analysis of sequential physiologic changes in hypoxic cor pulmonale during long-term oxygen therapy.Chest. 1991; 100: 76-80Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Also, the histologic abnormalities which disrupt the pulmonary arterioles in the presence of chronic hypoxemia have been reported to continue right up to the time of death in patients who have LTOT.12Wilkinson M Langhorne CA Heath D Barer GR Howard P A pathophysiological study of 10 cases of hypoxic cor pulmonale.Q J Med. 1988; 249: 65-85Google Scholar Other investigators have reported that LTOT reverses the pulmonary hemodynamic disturbances in COPD.13Weitzenblum E Sautegeau A Ehrhart M Mammoser M Pelletier A Long-term oxygen therapy can reverse the progression of pulmonary hypertension in patients with chronic obstructive pulmonary disease.Am Rev Respir Dis. 1985; 131: 493-498Crossref PubMed Scopus (337) Google Scholar Yet those studies which associate a fall in pulmonary artery pressure (Ppa) with improved survival have, without exception, demonstrated very modest reductions in Ppa (generally about 2 to 5 mm Hg). Perhaps such changes are not directly responsible for improved survival. This issue of Chest includes an analysis by Dubois et al (see page 469) of survival in 270 patients with severe COPD who received LTOT according to the prescribing criteria of the Belgian Social Security regulations. The survival proportions for these patients were slightly worse than other reported groups (43 percent alive after 3 years), probably because they had more severe disease and patients without COPD were rigorously excluded. Complex statistical methods were used to seek associations between various physiologic parameters and survival. The strongest associations were with reduced transfer coefficient (TLCO/Va), severity of airflow obstruction, and poor response to oxygen administration in terms of the rise in PaO2. Studies of this nature only expose associations between various parameters and do not allow us to draw any conclusions regarding the cause of death in severe COPD or the means of improved survival with LTOT. However, this report is interesting in that chronic hypercapnia appeared to be associated with better survival. Campbell14Campbell EJM A method of controlled oxygen administration which reduces the risk of carbon-dioxide retention.Lancet. 1960; 2: 12-14Abstract PubMed Scopus (57) Google Scholar was the first to suggest that permissive hypercapnia might be a physiologic adaptation which allows a greater CO2 output for a given level of minute ventilation. In other words, for a given CO2 output, the ventilatory requirement is less if the arterial PaCO2 is allowed to rise and the work of breathing would be correspondingly reduced. A distinction is necessary between “permissive hypercapnia,” as seen in the blue and bloated type of COPD patient, and “progressive hypercapnia” due to terminal respiratory failure. Permissive hypercapnia might, indeed, be a physiologic adaptation which leads to better life expectancy, whereas progressive hypercapnia can be expected in the final stages of severe COPD with or without LTOT. We need to explore alternative explanations for the beneficial effect of LTOT and consider the precise reason for death in patients with severe COPD. Patients most commonly die of terminal respiratory failure due to overwhelming problems with ventilatory mechanics and gas exchange. Predictably, this clinical course will be accompanied by worsening hypoxemia and hypercapnia. Alternatively, some might die of dysrhythmias or myocardial infarction secondary to hypoxemia. Clinical experience suggests that patients do not die from the hemodynamic disturbances which arise in the pulmonary circulation. Why, then, is LTOT effective? One possible answer emerges when we re-examine the NIH and MRC data. Survival in the NIH group supposedly having continuous oxygen therapy was noticeably better than for the MRC group having oxygen for 15 h per day. This might not be remarkable but for the fact that these NIH patients were not fully compliant, and in practice, received oxygen for only about 18 h per day. The difference between these groups might lie not so much in the duration of oxygen therapy taken each day (a difference of only about 3 h), but more in the means of oxygen administration. The NIH patients were provided with apparatus for ambulatory oxygen therapy, whereas the MRC patients had fixed installations and were effectively confined to their homes. Part of the benefit of LTOT might therefore derive from patients’ increased ability to physically exercise and offset the vicious cycle of disability which is almost inevitable in patients with chronic respiratory disease. What can we conclude about life expectancy in patients with severe COPD, appropriate treatment measures, and the effects of LTOT? Certainly physicians are obliged to recognize the overriding importance of the airways obstruction and recommend vigorous bronchodilator therapy.15Ferguson GT Cherniack RM Management of chronic obstructive pulmonary disease.N Engl J Med. 1993; 328: 1017-1022Crossref PubMed Scopus (258) Google Scholar Interestingly, the survival prospects of patients in the multicenter clinical trial of intermittent positive pressure breathing were equivalent to patients supposedly having continuous oxygen therapy.16Anthonisen NR Wright EC Hodgkin JE IPPB Trial GroupPrognosis in chronic obstructive pulmonary disease.Am Rev Respir Dis. 1986; 133: 14-20Crossref PubMed Scopus (492) Google Scholar This would suggest that intensive bronchodilator therapy is equally as important as LTOT. The importance of maintaining physical activity has probably been underestimated, and LTOT might be beneficial, particularly in facilitating exercise. Finally, should we reconsider manipulations of respiratory drive in the management of COPD bearing in mind that permissive hypercapnia might be a physiologic adaptation contributing to better life expectancy? The traditional approach has been to stimulate respiratory drive with drugs such as methylxanthines. An alternative strategy worth exploring is the suppression of respiratory drive to allow a mild degree of hypercapnia and thus reduce ventilatory requirement. Oxygen is the only drug which can do this without fear of worsening hypoxemia. Perhaps this is another mechanism by which it improves survival in patients with COPD.