Introduction

Abstract

Chronic obstructive pulmonary disease (COPD) is a major health problem in the United States and worldwide.1National Heart, Lung, and Blood Institute, National Institutes of Health. Chronic obstructive pulmonary disease data fact sheet. Available at: http://www.nhlbi.nih.gov/health/public/lung/other/copd_fact.htm. Accessed June 23, 2006.Google Scholar It is important to note that mortality rates for COPD are rising, while rates for other chronic diseases, such as heart disease, cancer, and stroke, are declining.1National Heart, Lung, and Blood Institute, National Institutes of Health. Chronic obstructive pulmonary disease data fact sheet. Available at: http://www.nhlbi.nih.gov/health/public/lung/other/copd_fact.htm. Accessed June 23, 2006.Google Scholar, 2Jemal A. Ward E. Hao Y. Thun M. Trends in the leading causes of death in the United States, 1970–2002.JAMA. 2005; 294: 1255-1259Crossref PubMed Scopus (821) Google Scholar Because increased incidences of COPD-related mortality and morbidity have a negative impact on public health and the economy,1National Heart, Lung, and Blood Institute, National Institutes of Health. Chronic obstructive pulmonary disease data fact sheet. Available at: http://www.nhlbi.nih.gov/health/public/lung/other/copd_fact.htm. Accessed June 23, 2006.Google Scholar there is an urgent need to control the growing epidemic of COPD. Management of COPD poses a variety of challenges resulting from patients’ misconceptions about their disease and the negative attitude of healthcare professionals regarding the treatment and prognosis of these patients.3Voelkel N.F. Raising awareness of COPD in primary care.Chest. 2000; 117: 372S-375SCrossref PubMed Scopus (40) Google Scholar Despite scientific advances leading to our understanding of the pathophysiology of COPD, clinical evidence based on pivotal trials, and the development of new therapies, much remains to be accomplished in preventing COPD and providing optimal patient care. COPD is a multifaceted problem requiring education in evidence-based medicine, practice management, and patient–provider communications to achieve meaningful improvements in patient care. This supplement to The American Journal of Medicine is based on the proceedings of a CME-accredited regional dinner conference entitled “Creating Optimism in Managing Pulmonary Disease,” which was presented by the Johns Hopkins University School of Medicine, on October 10, 2006, in Brooklyn, New York. The articles in this supplement examine COPD prevalence, diagnosis, clinical evidence, appropriate application of treatment guidelines, and best practices for disease management and patient outcomes. In the first article, we focus on the prevention of COPD and discuss various risk factors, diagnostic challenges, integration of spirometry into diagnosis, and the importance of smoking-cessation efforts. COPD is defined by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) as a disease state that is preventable and treatable.4Celli B.R. MacNee W. Agusti A. et al.ATS/ERS Task Force Committee MembersStandards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.Eur Respir J. 2004; 23: 932-946Crossref PubMed Scopus (3460) Google Scholar The identification of risk factors for COPD is important in developing strategies for its prevention and treatment. According to a US Surgeon General’s report, the leading cause of COPD is cigarette smoking: 80% to 90% of patients diagnosed with COPD have a history of smoking.5National Heart, Lung, and Blood InstituteNational Institutes of HealthChronic Obstructive Lung Disease: Summary of the Health Consequences of Smoking. A Report of the Surgeon General. US Dept of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, Rockville, MD1984Google Scholar The identification of cigarette smoking as a major risk factor has led to the development of smoking-cessation programs. Other risk factors for COPD include genetic components and occupational or environmental exposure.6Pauwels R.A. Buist A.S. Calverley P.M.A. Jenkins C.R. Hurd S.S. GOLD Scientific CommitteeGlobal strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary.Am J Respir Crit Care Med. 2001; 163: 1256-1276Crossref PubMed Scopus (4282) Google Scholar, 7American Thoracic SocietyEuropean Respiratory SocietyAmerican Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency.Am J Respir Crit Care Med. 2003; 168: 818-900Crossref PubMed Scopus (793) Google Scholar, 8Global Initiative for Chronic Obstructive Lung Disease [GOLD]Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: NHLBI/WHO Workshop Report. National Heart, Lung, and Blood Institute, National Institutes of Health, US Dept of Health and Human Services, 2006Google Scholar Educating patients about the avoidance of risk factors and motivating them to stop smoking cigarettes are central components in the management of COPD. It is also important to change the perception of patients and healthcare providers about COPD from one of nihilism to one of optimism that it is a preventable and treatable disease. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines state that smoking cessation is the single most clinically effective and cost-effective intervention to both reduce the risk for developing COPD and limit its progression.8Global Initiative for Chronic Obstructive Lung Disease [GOLD]Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: NHLBI/WHO Workshop Report. National Heart, Lung, and Blood Institute, National Institutes of Health, US Dept of Health and Human Services, 2006Google Scholar Clinical studies have demonstrated that smoking cessation slows the progression of COPD and decreases the associated risk for mortality.8Global Initiative for Chronic Obstructive Lung Disease [GOLD]Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: NHLBI/WHO Workshop Report. National Heart, Lung, and Blood Institute, National Institutes of Health, US Dept of Health and Human Services, 2006Google Scholar, 9Fletcher C. Peto R. The natural history of chronic airflow obstruction.BMJ. 1977; 1 ([review]): 1645-1648Crossref PubMed Scopus (1773) Google Scholar, 10Anthonisen N.R. Connett J.E. Murray R.P. Lung Health Study Research GroupSmoking and lung function of Lung Health Study participants after 11 years.Am J Respir Crit Care Med. 2002; 166: 675-679Crossref PubMed Scopus (561) Google Scholar, 11Anthonisen N.R. Skeans M.A. Wise R.A. Manfreda J. Kanner R.E. Connett J.E. Lung Health Study Research GroupThe effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial.Ann Intern Med. 2005; 142: 233-239Crossref PubMed Scopus (1018) Google Scholar Other treatment options, such as office-based behavioral intervention,12Rennard S.I. Daughton D.M. Smoking cessation.Chest. 2000; 117: 360S-364SCrossref PubMed Scopus (43) Google Scholar “5 As strategy” (ask, advise, assess, assist, and arrange),8 telephone quitlines,13Zhu S.-H. Anderson C.M. Tedeschi G.J. et al.Evidence of real-world effectiveness of a telephone quitline for smokers.N Engl J Med. 2002; 347: 1087-1093Crossref PubMed Scopus (380) Google Scholar and pharmacologic treatments,14Hurt R.D. Sachs D.P.L. Glover E.D. et al.A comparison of sustained-release bupropion and placebo for smoking cessation.N Engl J Med. 1997; 337: 1195-1202Crossref PubMed Scopus (1204) Google Scholar, 15Jorenby D.E. Hays J.T. Rigotti N.A. et al.Varenicline Phase 3 Study GroupEfficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.JAMA. 2006; 296: 56-63Crossref PubMed Scopus (1227) Google Scholar, 16Jorenby D.E. Leischow S.J. Nides M.A. et al.A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.N Engl J Med. 1999; 340: 685-691Crossref PubMed Scopus (1) Google Scholar, 17Tashkin D.P. Kanner R. Bailey W. et al.Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial.Lancet. 2001; 357: 1571-1575Abstract Full Text Full Text PDF PubMed Scopus (354) Google Scholar have also been shown to help smokers—including patients with COPD—quit smoking. COPD most often refers to patients with chronic bronchitis and/or emphysema with airflow obstruction.4Celli B.R. MacNee W. Agusti A. et al.ATS/ERS Task Force Committee MembersStandards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.Eur Respir J. 2004; 23: 932-946Crossref PubMed Scopus (3460) Google Scholar, 18Mannino D.M. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity.Chest. 2002; 121: 121S-126SCrossref PubMed Google Scholar Although a considerable symptomatic overlap exists between COPD and asthma, these 2 conditions are different. Patients with asthma can usually be distinguished because, unlike those with COPD, their airflow obstruction is usually completely reversible with treatment.4Celli B.R. MacNee W. Agusti A. et al.ATS/ERS Task Force Committee MembersStandards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.Eur Respir J. 2004; 23: 932-946Crossref PubMed Scopus (3460) Google Scholar The ATS/ERS and GOLD guidelines state that spirometry is essential for diagnosing COPD.4Celli B.R. MacNee W. Agusti A. et al.ATS/ERS Task Force Committee MembersStandards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.Eur Respir J. 2004; 23: 932-946Crossref PubMed Scopus (3460) Google Scholar, 19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar Spirometry not only helps diagnosis but it can also be useful for monitoring therapy and predicting prognosis over time. However, barriers and misperceptions have prevented its widespread use in office practice.20Petty T.L. Benefits of and barriers to the widespread use of spirometry.Curr Opin Pulm Med. 2005; 11: 115-120PubMed Google Scholar Underdiagnosis of COPD by physicians is also a significant problem. The National Health and Nutrition Examination Survey (NHANES) III study (1988 to 1994) found that 24 million subjects had spirometric evidence of COPD, but only 10.5 million reported physician-diagnosed COPD.21Mannino D.M. Homa D.M. Akinbami L.J. Ford E.S. Redd S.C. Chronic obstructive pulmonary disease surveillance—United States, 1971–2000.MMWR Surveill Summ. 2002; 51: 1-16Google Scholar In our second article, we review both pharmacologic and nonpharmacologic treatment strategies for optimal management of COPD. The GOLD guidelines recommend step-care therapy at each stage of the disease, based on the need for symptom control.19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar For patients with normal spirometry and chronic symptoms, and those with COPD stages I, II, III, and IV, avoidance of risk factors and vaccination against influenza are recommended. For those with few or intermittent symptoms and mild disease (stage I), short-acting inhaled bronchodilators alone can be used as needed to control dyspnea and coughing spasms. For patients with stage II (moderate), stage III (severe), or stage IV (very severe) COPD, in whom symptoms are not adequately controlled with as-needed use of short-acting bronchodilators, the GOLD guidelines recommend adding regular treatment with ≥1 long-acting inhaled bronchodilator. A number of short- and long-acting β2-agonists and short- and long-acting antimuscarinic agents are available for the management of symptoms.19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar Whether a β2-agonist or an antimuscarinic agent is prescribed depends on availability of the drug and the symptom relief and adverse effects experienced by the patient.19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar Several combination products containing a short-acting β2-agonist with a short-acting antimuscarinic agent or a long-acting β2-agonist with an inhaled corticosteroid are available for the relief of symptoms.19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar Combination products may provide greater efficacy and cause fewer side effects than an individual agent used alone.19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar Recently, a preliminary report of a study called Towards a Revolution in COPD Health (TORCH) demonstrated that combination therapy with a long-acting β2-agonist and a corticosteroid improved survival in patients with COPD.22Calverley P.M. Anderson J.A. Celli B. et al.Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease.N Engl J Med. 2007; 356: 775-789Crossref PubMed Scopus (2781) Google Scholar In addition, the study showed improvements in quality of life and lung function, as well as reductions in exacerbations.22Calverley P.M. Anderson J.A. Celli B. et al.Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease.N Engl J Med. 2007; 356: 775-789Crossref PubMed Scopus (2781) Google Scholar TORCH indicates that combination therapy yields better clinical outcomes and may have implications for future treatment strategies. In patients with acute exacerbations of COPD, treatment with antibiotics has been shown to provide significant clinical benefit,23Ram F.S. Rodriguez-Roisin R. Granados-Navarrete A. Garcia-Aymerich J. Barnes N.C. Antibiotics for exacerbations of chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2006; 2 (CD004403)PubMed Google Scholar, 24Martinez F.J. Han M.K. Flaherty K. Curtis J. Role of infection and antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease.Expert Rev Anti Infect Ther. 2006; 4: 101-124Crossref PubMed Scopus (36) Google Scholar as does a short course of oral corticosteroids.25Niewoehner D.E. Erbland M.L. Deupree R.H. et al.Department of Veterans Affairs Cooperative Study GroupEffect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease.N Engl J Med. 1999; 340: 1941-1947Crossref PubMed Scopus (773) Google Scholar, 26Davies L. Angus R.M. Calverley P.M. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial.Lancet. 1999; 354: 456-460Abstract Full Text Full Text PDF PubMed Scopus (495) Google Scholar, 27Aaron S.D. Vandemheen K.L. Hebert P. et al.Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease.N Engl J Med. 2003; 348: 2618-2625Crossref PubMed Scopus (264) Google Scholar Various nonpharmacologic treatments—e.g., pulmonary rehabilitation, oxygen therapy, and lung volume reduction surgery—have also been shown to help some patients with COPD.19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar, 28Griffiths T.L. Burr M.L. Campbell I.A. et al.Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial.Lancet. 2000; 355: 362-368Abstract Full Text Full Text PDF PubMed Scopus (794) Google Scholar, 29Nocturnal Oxygen Therapy Trial GroupContinuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2071) Google Scholar, 30Fishman A. Martinez F. Naunheim K. et al.National Emphysema Treatment Trial Research GroupA randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.N Engl J Med. 2003; 348: 2059-2073Crossref PubMed Scopus (1632) Google Scholar The third article, by Dr. Pamela L. Moore, which focuses on practice management in primary care of COPD, details simple operational changes to facilitate better disease management, patient care, and outcomes. Recognizing that clinical medicine is directly affected by business practices, Dr. Moore highlights strategies and tools for implementing operational improvements for physicians and their staff. These include a model defining the role of the care manager, integrating spirometry, smoking-cessation dialogues, providing written pulmonary action plans, and other strategies. The clinician should find these useful approaches to strengthen practice operations and thus improve patient care. In the final article, Meaghan Nelson and Dr. Heidi Hamilton report findings from an in-office linguistic study examining communication between patients with COPD and physicians. The study reveals that, although several significant gaps exist in current communication, there is an opportunity to improve COPD-related communication in community-based practices. To create engagement surrounding COPD and its treatment, the dialogue should focus more specifically on educating patients about the disease and its management. However, within the confines of a busy practice, successful physician–patient communication must be streamlined, allowing both physicians and patients to accomplish their goals efficiently during each office visit. This article gives community-based physicians a menu of communication techniques to use with patients who have COPD that will foster improved dialogue without increasing time spent with patients. These real-world solutions can help clinicians to more effectively connect with their patients, with the goals of enhancing the interpersonal relationship and improving treatment outcomes. On behalf of the “Creating Optimism in Manging Pulmonary Disease” editorial board, we hope that readers will find this supplement interesting, informative, and beneficial to your COPD practice.1National Heart, Lung, and Blood Institute, National Institutes of Health. Chronic obstructive pulmonary disease data fact sheet. Available at: http://www.nhlbi.nih.gov/health/public/lung/other/copd_fact.htm. Accessed June 23, 2006.Google Scholar, 2Jemal A. Ward E. Hao Y. Thun M. Trends in the leading causes of death in the United States, 1970–2002.JAMA. 2005; 294: 1255-1259Crossref PubMed Scopus (821) Google Scholar, 3Voelkel N.F. Raising awareness of COPD in primary care.Chest. 2000; 117: 372S-375SCrossref PubMed Scopus (40) Google Scholar, 4Celli B.R. MacNee W. Agusti A. et al.ATS/ERS Task Force Committee MembersStandards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper.Eur Respir J. 2004; 23: 932-946Crossref PubMed Scopus (3460) Google Scholar, 5National Heart, Lung, and Blood InstituteNational Institutes of HealthChronic Obstructive Lung Disease: Summary of the Health Consequences of Smoking. A Report of the Surgeon General. US Dept of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, Rockville, MD1984Google Scholar, 6Pauwels R.A. Buist A.S. Calverley P.M.A. Jenkins C.R. Hurd S.S. GOLD Scientific CommitteeGlobal strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary.Am J Respir Crit Care Med. 2001; 163: 1256-1276Crossref PubMed Scopus (4282) Google Scholar, 7American Thoracic SocietyEuropean Respiratory SocietyAmerican Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency.Am J Respir Crit Care Med. 2003; 168: 818-900Crossref PubMed Scopus (793) Google Scholar, 8Global Initiative for Chronic Obstructive Lung Disease [GOLD]Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: NHLBI/WHO Workshop Report. National Heart, Lung, and Blood Institute, National Institutes of Health, US Dept of Health and Human Services, 2006Google Scholar, 9Fletcher C. Peto R. The natural history of chronic airflow obstruction.BMJ. 1977; 1 ([review]): 1645-1648Crossref PubMed Scopus (1773) Google Scholar, 10Anthonisen N.R. Connett J.E. Murray R.P. Lung Health Study Research GroupSmoking and lung function of Lung Health Study participants after 11 years.Am J Respir Crit Care Med. 2002; 166: 675-679Crossref PubMed Scopus (561) Google Scholar, 11Anthonisen N.R. Skeans M.A. Wise R.A. Manfreda J. Kanner R.E. Connett J.E. Lung Health Study Research GroupThe effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial.Ann Intern Med. 2005; 142: 233-239Crossref PubMed Scopus (1018) Google Scholar, 12Rennard S.I. Daughton D.M. Smoking cessation.Chest. 2000; 117: 360S-364SCrossref PubMed Scopus (43) Google Scholar, 13Zhu S.-H. Anderson C.M. Tedeschi G.J. et al.Evidence of real-world effectiveness of a telephone quitline for smokers.N Engl J Med. 2002; 347: 1087-1093Crossref PubMed Scopus (380) Google Scholar, 14Hurt R.D. Sachs D.P.L. Glover E.D. et al.A comparison of sustained-release bupropion and placebo for smoking cessation.N Engl J Med. 1997; 337: 1195-1202Crossref PubMed Scopus (1204) Google Scholar, 15Jorenby D.E. Hays J.T. Rigotti N.A. et al.Varenicline Phase 3 Study GroupEfficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.JAMA. 2006; 296: 56-63Crossref PubMed Scopus (1227) Google Scholar, 16Jorenby D.E. Leischow S.J. Nides M.A. et al.A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.N Engl J Med. 1999; 340: 685-691Crossref PubMed Scopus (1) Google Scholar, 17Tashkin D.P. Kanner R. Bailey W. et al.Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial.Lancet. 2001; 357: 1571-1575Abstract Full Text Full Text PDF PubMed Scopus (354) Google Scholar, 18Mannino D.M. COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity.Chest. 2002; 121: 121S-126SCrossref PubMed Google Scholar, 19Global Initiative for Chronic Obstructive Lung Disease [GOLD]. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, 2006. Available at: http://www.goldcopd.com/Guidelineitem.asp?l1=2&l2=1&intId=989. Accessed April 26, 2007.Google Scholar, 20Petty T.L. Benefits of and barriers to the widespread use of spirometry.Curr Opin Pulm Med. 2005; 11: 115-120PubMed Google Scholar, 21Mannino D.M. Homa D.M. Akinbami L.J. Ford E.S. Redd S.C. Chronic obstructive pulmonary disease surveillance—United States, 1971–2000.MMWR Surveill Summ. 2002; 51: 1-16Google Scholar, 22Calverley P.M. Anderson J.A. Celli B. et al.Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease.N Engl J Med. 2007; 356: 775-789Crossref PubMed Scopus (2781) Google Scholar, 23Ram F.S. Rodriguez-Roisin R. Granados-Navarrete A. Garcia-Aymerich J. Barnes N.C. Antibiotics for exacerbations of chronic obstructive pulmonary disease.Cochrane Database Syst Rev. 2006; 2 (CD004403)PubMed Google Scholar, 24Martinez F.J. Han M.K. Flaherty K. Curtis J. Role of infection and antimicrobial therapy in acute exacerbations of chronic obstructive pulmonary disease.Expert Rev Anti Infect Ther. 2006; 4: 101-124Crossref PubMed Scopus (36) Google Scholar, 25Niewoehner D.E. Erbland M.L. Deupree R.H. et al.Department of Veterans Affairs Cooperative Study GroupEffect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease.N Engl J Med. 1999; 340: 1941-1947Crossref PubMed Scopus (773) Google Scholar, 26Davies L. Angus R.M. Calverley P.M. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial.Lancet. 1999; 354: 456-460Abstract Full Text Full Text PDF PubMed Scopus (495) Google Scholar, 27Aaron S.D. Vandemheen K.L. Hebert P. et al.Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease.N Engl J Med. 2003; 348: 2618-2625Crossref PubMed Scopus (264) Google Scholar, 28Griffiths T.L. Burr M.L. Campbell I.A. et al.Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial.Lancet. 2000; 355: 362-368Abstract Full Text Full Text PDF PubMed Scopus (794) Google Scholar, 29Nocturnal Oxygen Therapy Trial GroupContinuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial.Ann Intern Med. 1980; 93: 391-398Crossref PubMed Scopus (2071) Google Scholar, 30Fishman A. Martinez F. Naunheim K. et al.National Emphysema Treatment Trial Research GroupA randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.N Engl J Med. 2003; 348: 2059-2073Crossref PubMed Scopus (1632) Google Scholar