The CHEST guidelines for the prevention of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) were developed through a collaboration between the American College of Chest Physicians (CHEST) and the Canadian Thoracic Society (CTS). They are the first evidence-based guidelines dedicated entirely to the prevention of AECOPD and largely exclude material related to the treatment of symptomatic disease.1
Patients with AECOPD are commonly cared for by hospitalists, so we fill an important role in the longitudinal treatment of this disease. Acute exacerbations and hospitalizations for COPD account for 50% of all COPD-related expenses.2,3 Further, the Agency for Healthcare Research and Quality showed a 20% readmission rate nationally for AECOPD, far higher than the rate for most other diagnoses.4 Consequently, COPD readmission has been added to Medicare’s Hospital Readmissions Reduction Program for fiscal year 2015.5
Hospitalization, when the patient is a captive audience and many of the necessary resources are available, may be a time to initiate preventative strategies.
The guidelines for non-pharmacologic interventions start with vaccination and continue with behavioral modification. They support the use of the 23-valent polysaccharide pneumococcal vaccine and annual influenza vaccination, noting that only influenza vaccination has been shown to decrease AECOPD.
Pulmonary rehabilitation is recommended for patients with a recent (fewer than four weeks) exacerbation. Several recommendations favor combining social work interventions with education, adding that face-to-face verbal education is superior to written educational materials. Interestingly, smoking cessation interventions received a weak recommendation, based upon lack of literature specifically focusing on the prevention of AECOPD. Despite this recommendation, smoking cessation intervention is strongly encouraged by the authors, given evidence of a marked reduction in morbidity, mortality, and healthcare utilization among smokers with COPD who quit.6 Finally, telemonitoring is not considered to be superior to usual care.
The guidelines concerning inhaled therapies fall into three major drug classes, including short- and long-acting inhaled muscarinic antagonists (anticholinergic agents), short- and long-acting inhaled beta-agonists, and inhaled corticosteroids.
Long-acting medications are generally considered more effective in preventing exacerbations than those that are short acting. Long-acting muscarinic antagonists (LAMAs) are highlighted for their efficacy, and combination inhaled long-acting beta-agonists (LABAs) and inhaled corticosteroids are preferred over monotherapy with either agent alone. LAMAs are preferred to inhaled corticosteroids or LABAs when given as monotherapy.
Short-acting agents are rated as inferior at preventing exacerbations compared to their long-acting analogs, but short-acting medications are better than placebo when combined with long-acting agents from other drug classes. Triple drug therapy (inhaled LAMAs, LABAs, and corticosteroids) can be considered based on current evidence.
The final recommendations address the use of oral medications. A potentially practice-changing guideline is the recommendation for long-term use of N-acetylcysteine tablets twice daily for patients who have experienced more than two exacerbations within two years. A more intuitive recommendation in this group is that treating an AECOPD with oral or IV steroids decreases the chance of recurrent exacerbations in the future.
The remaining recommendations include daily macrolide therapy, the phosphodiesterate-4 inhibitor roflumilast for those with chronic bronchitis and a recent exacerbation, and slow-release theophylline for stable disease. These guidelines also point out that statins do not have a role in AECOPD prevention. An expert consensus also recommends carbocysteine for patients who have failed “maximal” therapy.1
Established Guideline Analysis
Prior guidelines that address stable COPD do exist, most notably from Quaseem and colleagues in the 2011 Annals of Internal Medicine (AIM) and the 2015 GOLD guidelines.7,8 The prior guidelines published in AIM offered limited recommendations on the preventative interventions of bronchodilator use, pulmonary rehabilitation, and oxygen use.
The recommendations made in AIM are similar to those in the CHEST guidelines; the lack of breadth in the AIM report reflects new data generated over the last half decade. They include preventing causative exposures (e.g. tobacco, occupational), recommending bronchodilator use (with or without inhaled corticosteroids), possibly using phosphodiesterase-4 inhibitors (PD-4 inhibitors), administering appropriate vaccines, and providing education; however, GOLD does not actually present or rate the evidence associated with those recommendations. GOLD does specifically state that statins have no role in AECOPD prevention, a position that is updated from more recent literature.8,9
The National Guideline Clearinghouse (NGC) also includes some references to prevention of AECOPD but has no sections explicitly dedicated to prevention. Of note, the NGC still endorses statin use and does not appear to have incorporated data from newer studies.8,10
Given the high rate of COPD readmissions and its broad impact on morbidity and healthcare costs, measures to prevent COPD exacerbations cannot remain out of scope of care for inpatient physicians. It is important to initiate pulmonary rehab within four weeks of an exacerbation of COPD to prevent future exacerbations. Systems should be put in place to assure that all patients who qualify are vaccinated for influenza and patients who continue to smoke receive cessation counseling.
Today, hospitalists are comfortable with these non-pharmacologic interventions, as well as medications that include inhaled bronchodilators, nebulized medications, macrolide maintenance therapy, and oral steroids; however, other oral medications, such as phosphodiesterase inhibitors, theophylline, and N-acetylcysteine, may be appropriate for select patients, and hospitalists should become more familiar with their utility.11,12,13,14
Finally, it is important to note that both short- and long-acting inhaled muscarinic antagonists have come to the forefront of pharmacologic interventions for COPD exacerbation prevention.
Dr. Lampman, MD, is a hospitalist, consulting provider, and physician leader of the physician advisor program at Duke Regional Hospital in Durham, N.C. Dr. Lovins is a hospitalist, associate chief medical informatics officer, and assistant professor of medicine at Duke University and Duke Regional Hospital.
- Criner GJ, Bourbeau J, Diekemper RL, et al. Prevention of acute exacerbations of COPD: American College of Chest Physicians and Canadian Thoracic Society Guideline. Chest. 2015;147(4):894-942.
- Miravitlles M, Garcia-Polo C, Domenech A, Villegas G, Conget F, de la Roza C. Clinical outcomes and cost analysis of exacerbations in chronic obstructive pulmonary disease. Lung. 2013;191(5):523-530.
- Miravitlles M, Murio C, Guerrero T, Gisbert R; DAFNE Study Group. Pharmacoeconomic evaluation of acute exacerbations of chronic bronchitis and COPD. Chest. 2002;121(5):1449-1455.
- Elixhauser A, Au DH, Podulka J. Readmissions for Chronic Obstructive Pulmonary Disease, 2008: Statistical Brief #121.In: Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville, Md.: Agency for Health Care Policy and Research: 2006.
- Readmissions Reduction Program. Centers for Medicare and Medicaid Services website. Accessed September 8, 2015.
- Sicras-Mainar A, Rejas-Gutiérrez J, Navarro-Artieda R, Ibáñez-Nolla J. The effect of quitting smoking on costs and healthcare utilization in patients with chronic obstructive pulmonary disease: a comparison of current smokers versus ex-smokers in routine clinical practice. Lung. 2014;192(4):505-518.
- Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011;155(3):179-191.
- Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2015. Global Strategy for the Diagnosis, Management, and Prevention of COPD. Accessed September 8, 2015.
- Criner GJ, Connett JE, Aaron SK, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014;370(23):2201-2210.
- Agency for Healthcare Research and Quality. National Guideline Clearinghouse. COPD – chronic obstructive pulmonary disease. In: Pulmonary (acute & chronic). Accessed September 8, 2015.
- Cazzola M, Matera MG. N-acetylcysteine in COPD may be beneficial, but for whom? Lancet Respir Med. 2014;2(3):166-167.
- Turner RD Bothamley. N-acetylcysteine for COPD: the evidence remains inconclusive. Lancet Respir Med. 2014;2(4):e3.
- Zheng JP, Wen FQ, Bai CX, et al. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014;2(3):187-194.
- Amazon.com. Amazon Search. 2015 06/1/2015].