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n engl j med 348;26 www.nejm.org june 26, 2003 The new england journal of medicine 2679 editorials Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease Richard S. Irwin, M.D., and J. Mark Madison, M.D. Chronic obstructive pulmonary disease (COPD) is a common disease that affects up to 24 million people in the United States and leads to substantial disability and death. 1 Patients with COPD have about three acute exacerbations of their disease per year, 2 many of which result in unscheduled visits to a physician or emergency department and to hospitalization. Although it is currently the fourth leading cause of death in the United States 1 and the sixth world- wide, 3 COPD is predicted to be the third leading cause of death and fifth leading cause of disability in the world by 2020. 3 Although there is no universally accepted definition of COPD 4 or an acute exacerbation of COPD, 5 because experts have promulgated criteria that vary in some respects, most current definitions contain the same key elements. 4 The definition of the Glob- al Initiative for Chronic Obstructive Lung Disease 6 has gained widespread acceptance: “COPD is a disease state characterized by airflow limitation that is not fully reversible. The airflow obstruction is usu- ally both progressive and associated with an abnor- mal inflammatory response of the lungs to noxious particles or gases.” This definition specifies that poorly reversible airflow limitation due to other obstructive airway diseases (e.g., bronchiectasis, cyst- ic fibrosis, or asthma) is not included unless these diseases coexist with COPD. 4,6 An acute respiratory deterioration in a patient with COPD can be due to many conditions, such as pneumonia, congestive heart failure, pneumotho- rax, and venous thromboembolism, but they are not generally considered acute exacerbations of COPD itself. Many have defined an acute exacerbation of COPD as a subjective increase, from base line, in some combination of dyspnea, sputum purulence, and sputum volume owing to acute tracheobronchitis, 5,7 which has an infectious cause approximately 80 percent of the time and occurs in a patient with established COPD. An important element of this definition is that causes of respiratory deterioration other than acute tracheobronchitis are excluded. 5 It is not clear why this definition has not been universally accepted, because it is the one that has been used most consistently in rigorous double-blind, randomized, placebo-controlled trials assessing therapies for an acute deterioration in respiratory status in patients with COPD. 8-11 Recent randomized, double-blind, placebo-controlled trials or meta-analyses of such trials have fi- nally provided clinicians with high-quality evidence that patients with an acute exacerbation of COPD can benefit from multiple therapies, 12 including systemic corticosteroids. 10,12 For patients with at least moderate COPD at base line (as defined by a forced expiratory volume in one second [FEV 1 ] of less than 0.8 liter or a ratio of FEV 1 to forced vital ca- pacity of less than 50 percent), short-term systemic corticosteroids, in combination with other effective therapies, 12 have provided relatively small but clinically significant improvements in the duration of hospitalization, lung function, and the incidence of treatment failure; the results have been observed in specific groups of inpatients (those with hypercapnia and those without hypercapnia who are breath- ing spontaneously) and outpatients. 10 The results of the study by Aaron et al. 11 in this issue of the Journal lend further support to the short- term use of systemic corticosteroids for acute exacerbations of COPD and fill a gap in information re- garding the role of systemic corticosteroids after discharge from the emergency department. As com- pared with placebo, a 40-mg dose of oral prednisone once daily for 10 days, given in combination with Copyright © 2003 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org on November 29, 2004 . This article is being provided free of charge for use in Viet Nam. The new england journal of medicine 2680 n engl j med 348;26 www.nejm.org june 26, 2003 oral antibiotics and inhaled bronchodilators, de- creased the rate of clinical relapse (defined as an unscheduled visit to a physician, a return to the emergency department, or worsening dyspnea) within the next 30 days (relapse rate, 27 percent, vs. 43 percent in the placebo group; P=0.05) and, after 10 days of therapy, improved FEV 1 (mean increase from base line, 34 percent vs. 15 percent; P=0.007) and dyspnea (P=0.04). Although we know which patients with an exacerbation of COPD are likely to benefit from systemic corticosteroids and in which settings, the optimal dose and need for tapering, route of administration, and length of treatment are uncertain. The most recent data 10,11 support the use of a short course of no more than 10 to 15 days. Improved clinical outcomes have been achieved with dosages ranging from 30 mg of oral prednisolone daily or 40 mg of oral prednisone daily in outpatient and emergency department settings to 125 mg of intravenous meth- ylprednisolone every six hours for three days, fol- lowed by 60 mg of oral prednisone daily for four days and then by a gradual tapering of the dose to zero on day 15, in hospitalized patients. 10 Oral corticosteroids are often prescribed for patients with stable COPD to prevent acute exacerbations and improve lung function and reduce symp- toms. However, the benefits of this strategy have been studied in patients with stable COPD of at least moderate severity and have been found to be mar- ginal at best. In a meta-analysis of 10 trials, patients with stable COPD who were receiving oral corticosteroids had a clinically meaningful improvement in FEV 1 only 10 percent more often than did similar patients who were receiving placebo. 13 Moreover, in a double-blind, randomized, placebo-controlled trial involving 38 patients, the discontinuation of long-term treatment with oral prednisone did not lead to a significant increase in exacerbations of COPD over a six-month period. 14 In summary, evidence from rigorously designed trials has helped to clarify the role of systemic corticosteroids in treating and preventing acute exacerbations of COPD. First, systemic corticosteroids have an established role in the treatment of specific groups of patients who have acute exacerbations of COPD. Even though it is still not clear how their beneficial effects are achieved, 15 short courses of systemic corticosteroids in patients with at least moderately severe COPD, in combination with other effective therapies, can significantly improve clinical outcomes in outpatient and inpatient settings and after discharge from the emergency department. On the other hand, the role of systemic corticosteroids in treating acute exacerbations of COPD in patients who are receiving mechanical ventilation has yet to be rigorously studied. Second, although systemic corticosteroids are often prescribed for patients with stable COPD to prevent acute exacerbations, the evidence does not support the routine use of this practice. Although it is not the focus of this editorial, the fact that the role of inhaled, as opposed to systemic, corticosteroids in preventing acute exacerbations of COPD continues to be intensely in- vestigated is important. 16-18 We encourage readers to monitor this literature closely. Although the benefits of short-term therapy with systemic corticosteroids during acute exacerbations of COPD are real and important, they are of moderate magnitude and are not the answer to controlling or reversing the epidemic of COPD. In addition, because patients with COPD are at increased risk for drug-related side effects, it is important to inform them of the potential side effects (as well as benefits) of corticosteroids, to monitor patients for side effects, and to intervene to minimize such effects whenever possible. 19 From the Division of Pulmonary, Allergy, and Critical Care Medi- cine, University of Massachusetts Medical School, Worcester. 1. Mannino DM, Homa DM, Akinbami LJ, Ford ES, Redd SC. Chronic obstructive pulmonary disease surveillance — United States, 1971–2000. MMWR CDC Surveill Summ 2002;51:(SS-6):1-16. 2. Seemungal TAR, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-22. 3. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lan- cet 1997;349:1498-504. 4. Snider GL. Nosology for our day: its application to chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2003;167: 678-83. 5. Madison JM, Irwin RS. Chronic obstructive pulmonary disease. Lancet 1998;352:467-73. 6. Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initia- tive for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001;163:1256-76. 7. Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis. Chest 2000;117:Suppl 2:380S-385S. 8. Saint S, Bent S, Vittinghoff E, Grady D. Antibiotics in chronic obstructive pulmonary disease exacerbations: a meta-analysis. JAMA 1995;273:957-60. 9. McCrory DC, Brown C, Gelfand SE, Bach PB. Management of acute exacerbations of COPD: a summary and appraisal of published evidence. Chest 2001;119:1190-209. 10. Singh JM, Palda VA, Stanbrook MB, Chapman KR. Corticoster- oid therapy for patients with acute exacerbation of chronic obstructive pulmonary disease: a systematic review. Arch Intern Med 2002; 162:2527-36. 11. Aaron SD, Vandemheen KL, Hebert P, et al. Outpatient oral Copyright © 2003 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org on November 29, 2004 . This article is being provided free of charge for use in Viet Nam. n engl j med 348;26 www.nejm.org june 26, 2003 editorials 2681 prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 2003;348:2618-25. 12. Snow V, Lascher S, Mottur-Pilson C. The evidence base for management of acute exacerbations of COPD: clinical practice guide- line. Chest 2001;119:1185-9. 13. Callahan CM, Dittus RS, Katz BP. Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease: a meta- analysis. Ann Intern Med 1991;114:216-23. 14. Rice KL, Rubins JB, Lebahn F, et al. Withdrawal of chronic systemic corticosteroids in patients with COPD: a randomized trial. Am J Respir Crit Care Med 2000;162:174-8. 15. Brightling CE, Monteiro W, Ward R, et al. Sputum eosinophilia and short-term response to prednisone in chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2000;356:1480-5. 16. Alsaeedi A, Sin DD, McAlister FA. The effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review of randomized placebo-controlled trials. Am J Med 2002; 113:59-65. 17. Van der Valk P, Monninkoff E, van der Palen J, Zielhuis G, van Herwaarden C. Effect of discontinuation of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: the COPE study. Am J Respir Crit Care Med 2002;166:1358-63. 18. Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 2003;361:449-56. 19. McEvoy CE, Niewoehner DE. Adverse effects of corticosteroid therapy for COPD: a critical review. Chest 1997;111:732-43. Copyright © 2003 Massachusetts Medical Society. Improving the Quality of Care — Can We Practice What We Preach? Earl P. Steinberg, M.D., M.P.P. It has been 30 years since Wennberg and Gittelsohn published their landmark article demonstrating substantial variation among different geographic areas in the provision of medical services. 1 Since then, investigators have found variation in the de- livery of virtually every aspect of health care that has been examined. From the perspective of the quality of care, the variation that is the greatest cause for concern is that between actual practice and evidence-based “best practice.” Over the past 30 years, progress has been made in several areas that are vital to quality improvement. Practice guidelines have become more rigorously evidence-based and are now packaged in ways that make it easier to put them into practice. Tremen- dous progress has been made in the development of valid, reliable, and practical measures of the quality of care 2 that are now applied in managed care 3 and fee-for-service settings. 4 There are many indications of an increased focus on quality, and we have made great progress in our understanding of factors that contribute to substandard quality 2 and of interven- tions that do (and those that do not) improve the quality of care. 2,5,6 In this issue of the Journal, McGlynn and col- leagues 7 report the results of a large national study of the content of care provided to adults between 1996 and 1998. Although the “headline” finding of the study is that adults received 55 percent of rec- ommended care according to 439 process-of-care measures, the most enlightening findings are those in the measure-specific results. The biggest limitation of the study derives from the likelihood that documentation was poor in the charts that were used to determine what care patients had received. Because of this limitation, along with the focus on compliance with multiple recommendations for the management of a given clinical condition rather than on how well the condition was controlled, it would not be appropriate to interpret the findings of this study as showing that a typical adult in the United States has a 50–50 chance of receiving ade- quate care of a particular clinical condition. None- theless, the study adds detailed information to a substantial body of research that shows that the quality of the care delivered in the United States is considerably lower than it should be. 8 What will it take to do better? Four actions are likely to have the greatest effect. First, quality of care should be measured and reported routinely at both the national and provider-specific (e.g., hos- pital and physician) levels. In September 2003, the Agency for Healthcare Research and Quality will publish the first annual National Healthcare Qual- ity Report, which will include 150 measures. A sep- arate effort is needed, however, to report on the quality of care delivered by individual facilities and physicians. Such an effort would benefit from the involvement of professional societies in measure- ment and quality-improvement activities. 9 Both types of activities are consistent with the missions of professional societies. Examples of such leader- ship, as well as the benefits of it, can be observed in the Dialysis Outcomes Quality Initiative of the Na- tional Kidney Foundation, 10 the End-Stage Renal Disease (ESRD) Clinical Performance Measures Project, 11 and the Guidelines Applied in Practice Initiative of the American College of Cardiology. 12 Copyright © 2003 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org on November 29, 2004 . This article is being provided free of charge for use in Viet Nam. . exacerbations of COPD are real and important, they are of moderate magnitude and are not the answer to controlling or reversing the epidemic of COPD. In addition, because patients with COPD are at. 3 COPD is predicted to be the third leading cause of death and fifth leading cause of disability in the world by 2020. 3 Although there is no universally accepted definition of COPD . or asthma) is not included unless these diseases coexist with COPD. 4,6 An acute respiratory deterioration in a patient with COPD can be due to many conditions, such as pneumonia, congestive