US Pharm.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) remains the third leading cause of death in the United States, and the number of COPD deaths is projected to increase by 30% within the next 10 years. Exacerbations of COPD are associated with a more rapid decline in lung function. However, prevention, early detection, and prompt treatment can greatly improve patients’ health status and quality of life. Recent updates to the Global Initiative for Chronic Obstructive Lung Disease guidelines provide recommendations for the diagnosis and management of COPD exacerbations. Pharmacists can be instrumental in educating patients and can serve as a resource for multidisciplinary teams in the setting of COPD exacerbations.

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung characterized by progressive airflow limitation that is not fully reversible.1 There are two subtypes of COPD: emphysema and chronic bronchitis. Emphysema is a destruction of the alveolar surfaces that results in the inability to perform efficient gas exchange. Chronic bronchitis, a chronic cough caused by mucosal hypersecretion, is formally defined as the presence of a cough and sputum production for >3 months in two consecutive years. Most patients with COPD have elements of both emphysema and chronic bronchitis. The term COPD is now used more frequently, since it encompasses both conditions.2,3

Approximately 12 million people in the United States have been diagnosed with COPD, and it is estimated that another 12 million are undiagnosed.2 COPD is currently the third leading cause of death in the U.S.4 In 2005, more than 3 million people died of COPD, and it is projected that the total number of deaths from COPD will increase by >30% within the next 10 years.5

COPD development is due to environmental exposures and various other factors. Cigarette smoking is the most common risk factor for COPD.2 Other common risk factors include gender, age >40 years, socioeconomic status, occupational dust, indoor and outdoor air pollution, respiratory infections, and genetic predisposition. In recent years, studies have shown an increase in the prevalence of COPD among women; this increase is due to a rise in the number of women who smoke, changes in occupational trends, and possibly greater susceptibility.6,7

Exacerbations of COPD cause a more rapid decline in lung function and result in increased hospital admissions and mortality, which are associated with a greater financial burden. People with known COPD average 1.3 exacerbations per year.8 The estimated cost of COPD exacerbations in the U.S. is $73 billion each year.9 Prevention, early detection, and prompt treatment of COPD exacerbations are important for improving patients’ health status and quality of life. This article will highlight the management of acute COPD exacerbations.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has developed a set of evidence-based recommendations for managing patients with COPD. The GOLD Committee, which was formed in 1998, is a multidisciplinary team of healthcare providers and scientists who are working to promote COPD awareness and provide strategies for effective patient care. The GOLD guidelines were most recently updated in January 2014. This article will discuss some of the GOLD recommendations.3

Causes and Diagnosis

A COPD exacerbation is an acute event that is associated with worsening of a patient’s respiratory symptoms beyond normal day-to-day variations and may necessitate a change in medication.10 Exacerbations are associated with an increased systemic inflammatory response in the lungs and airway that leads to increased ventilation-perfusion imbalance. This imbalance can cause hyperinflation, hypercapnia, or hypoxemia, depending upon the severity of the exacerbation. Exacerbations may be precipitated by several factors. Respiratory infections—either viral or bacterial—cause approximately 70% of exacerbations.11 Air pollutants, cigarette smoke, other respiratory irritants, and interruption of maintenance therapy can result in exacerbations. However, in more than one-third of exacerbations, the cause is not identified.9

Currently, exacerbations are diagnosed based upon the patient’s clinical presentation. The three cardinal symptoms of COPD exacerbation are increased dyspnea, cough, and purulent sputum production. An exacerbation is acute in nature and is associated with a change in symptoms that is beyond normal day-to-day variation. Patients experiencing exacerbations should receive a thorough medical assessment including medical history, exposure history, clinical signs of severity, comorbidities, and additional laboratory tests. Laboratory assessments include comparison of pulse oximetry with the patient at rest and during activity if the patient can ambulate, chest radiographs, electrocardiogram, electrolytes, and whole blood count. Spirometry is not recommended during exacerbations because the readings are inaccurate and the task is difficult for patients to perform.10


Management of exacerbations may occur in the inpatient or outpatient setting, depending upon the severity of the exacerbation and other patient-specific factors and circumstances. Hospitalization may be indicated for patients who experience frequent exacerbations, have significant comorbid conditions, or cannot be managed easily in the outpatient setting. A worsening of clinical status, including the development of new physical signs or a pronounced increase in symptom intensity, also may warrant hospitalization. The goals of exacerbation therapy are to decrease symptoms to baseline and prevent subsequent exacerbations. Pharmacologic treatment of exacerbations involves bronchodilators, corticosteroids, and antibiotics.3

Short-Acting Bronchodilators: Short-acting beta2-agonists (e.g., albuterol, levalbuterol) with or without short-acting anticholinergics (e.g., ipratropium) are usually the preferred bronchodilators for exacerbation management. In a meta-analysis examining improvement of airflow obstruction with use of short-acting bronchodilators, the change in forced expiratory volume in 1 second (FEV1) did not differ significantly between metered-dose inhalers (MDIs) and nebulizers.12 Nebulizers are commonly used in patients with more serious illness, since they may be easier to administer than MDIs. Methylxanthines (theophylline and aminophylline) are considered second-line IV therapy in patients having an insufficient response to short-acting bronchodilators.10 Methylxanthines are not commonly administered but are an option, depending upon the patient’s needs.

Although inhaled long-acting beta-agonists, long-acting anticholinergics, and corticosteroids are the mainstay of COPD maintenance therapy, they are not appropriate for the treatment of COPD exacerbations. High doses of short-acting beta-agonists, short-acting anticholinergics, and systemic corticosteroids are better suited to decreasing acute respiratory symptoms, whereas long-acting agents are indicated for reducing day-to-day symptoms, preventing exacerbations, and limiting disease progression. If these agents are used concomitantly during an exacerbation, the patient has a higher likelihood of experiencing adverse effects, since the medication classes are very similar. For these reasons, the use of long-acting agents should be suspended until the patient’s condition significantly improves and he or she can be transitioned back to an appropriate maintenance regimen.3

Corticosteroids: The benefits of systemic corticosteroid use as a component of COPD exacerbation treatment have been well established. However, the optimal dosage and duration have yet to be determined. Systemic corticosteroids have been shown to shorten length of hospital stay, decrease recovery time, improve FEV1, and improve arterial hypoxemia.3,13-15 In addition, they are associated with a reduced risk of early relapse and treatment failure.3,16 Oral therapy is preferred, as it is not associated with worse outcomes compared with IV therapy.3,17,18 A Cochrane review of seven studies involving patients with COPD exacerbations found no significant differences in clinical outcomes when shorter treatment durations ( <7 days) were compared with longer durations (>7 days).19

In the past, the GOLD guidelines suggested the use of prednisolone 30 to 40 mg daily for 10 to 14 days. However, the most recent update recommends oral prednisone 40 mg daily for 5 days, based on results from the REDUCE (Reduction in the Use of Corticosteroids in Exacerbated COPD) trial.3,20 This randomized noninferiority trial involving 314 patients found that a 5-day course of prednisone 40 mg daily was noninferior to a 14-day course of therapy with respect to reexacerbation within 6 months. In addition, there were no significant differences in mortality, need for mechanical ventilation, short-term adverse effects, recovery of lung function, or improvement of disease-related symptoms. However, patients receiving the shorter course of corticosteroids had a significant reduction in corticosteroid exposure and a shortened length of hospital stay.20

At this time, the GOLD guidelines note that nebulized budesonide may be used as an alternative to systemic corticosteroids.3

Antibiotics: Antibiotic use in the management of exacerbations remains controversial. The microorganisms associated with exacerbations are shown in TABLE 1.21 The GOLD guidelines recommend the use of antibiotics in patients who have all three cardinal symptoms (increased dyspnea, sputum volume, and sputum purulence); have two of these cardinal symptoms, one of them being increased sputum purulence; or require mechanical ventilation (invasive or noninvasive). Antibiotic resistance is an increasing problem worldwide. The choice of the antibiotic should be based on the local pattern of bacterial resistance. Studies support the use of antibiotics when the patient has signs of bacterial infection. The recommended length of treatment is 5 to 10 days.3

Oxygen: Oxygen therapy is commonly used during COPD exacerbations. Supplemental oxygen should be titrated to maintain arterial saturation of 88% to 92%. Titrated oxygen is associated with less acidosis, a lower need for ventilation, and reduced mortality compared with the use of high-flow oxygen during exacerbations.3,22

Ventilatory Support: Some patients may require noninvasive (nasal cannula or facial mask) or invasive ( orotracheal tube or tracheostomy) ventilatory support in order to maintain proper oxygenation. Criteria for the use of noninvasive ventilation and invasive mechanical ventilation are given in TABLE 2. It may be appropriate to allow a trial of noninvasive methods prior to advancing support, as these modalities are associated with improvement in clinical signs, a decreased need for escalation to invasive mechanical ventilation, and reduced mortality. Although ventilatory support may seem necessary, it is important to take patient preferences into consideration and to be mindful of the risks.3 Complications of noninvasive support include aspiration, gastric distention, and facial pressure sores, whereas invasive support carries the risks of infection with multidrug-resistant ventilator-associated microorganisms and inability to wean ventilation.3,23 Both types of support may cause hypotension and barotrauma.3,23

Hospital Discharge

There is not an established optimal length of hospitalization for patients with COPD exacerbations. Prior to discharge, patients should be clinically stable for a minimum of 12 to 24 hours and should need inhaled short-acting beta2-agonists no more than every 4 hours. A plan for effective home management and follow-up should be coordinated and clearly communicated to the patient and his or her caregivers and healthcare providers. It is imperative that discharge planning include medication counseling to ensure patient and caregiver comprehension and proper medication use.24

Despite efforts to prevent COPD exacerbations, the rate of readmission remains quite high, which has caught the attention of the Joint Commission and the Centers for Medicare and Medicaid Services in recent years. The 30-day readmission rate among patients with COPD is approximately 7% with COPD as the primary diagnosis; however, the all-cause 30-day readmission rate is three times higher (21%).24 The likelihood of readmission appears to be greater in patients with a history of prior hospitalizations, use of oral corticosteroids, use of long-term oxygen therapy, poor health-related quality of life, and lack of physical activity.25 The involvement of pharmacists in discharge planning may effectively reduce the rate of readmission through medication reconciliation, medication counseling, and thoughtful selection of affordable medication options.26,27


The frequency and severity of COPD exacerbations have been associated with poor prognosis and increased mortality. Pharmacists can counsel patients about how to prevent future COPD exacerbations, including disease education, smoking cessation, pneumococcal and annual influenza vaccinations, and proper inhaler technique for maintenance therapy.3,28 Patients should schedule regular physician follow-ups to optimize maintenance therapy in order to minimize the occurrence of COPD exacerbations and prevent future hospital admissions.


1. Decramer M, Janssens W, Miravitlles M. Chronic obstructive pulmonary disease. Lancet. 2012;379: 1341-1351.
2. National Institutes of Health. Fact sheet: chronic obstructive pulmonary disease (COPD). Accessed February 21, 2013.
3. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (updated 2014). Accessed February 21, 2013.
4. Schulman, Ronca and Bucuvalas, Inc (SRBI). Confronting COPD in America, 2000 [published survey]; 2001.
5. World Health Organization. Chronic obstructive pulmonary disease fact sheet. Accessed February 20, 2013.
6. Sorheim IC, Johannessen A, Gulsvik A, et al. Gender differences in COPD: are women more susceptible to smoking effects than men? Thorax. 2010;65:480-485.
7. Aryal S, Diaz-Guzman E, Mannino DM. COPD and gender differences: an update. Transl Res. 2013;162: 208-218.
8. Singh JM, Palda VA, Stanbrook MB, Chapman KR. Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review. Arch Intern Med. 2002;162:2527-2536.
9. Halpern MT, Stanford RH, Borker R. The burden of COPD in the U.S.A.: results from the Confronting COPD survey. Respir Med. 2003;97(suppl C):S81-S89.
10. Lange P, Marott JL, Vestbo J, et al. Prediction of the clinical course of chronic obstructive pulmonary disease, using the new GOLD classification: a study of the general population. Am J Respir Crit Care Med. 2012;186:975-981.
11. Papi A, Bellettato CM, Braccioni F, et al. Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med. 2006;173:1114-1121.
12. Turner MO, Patel A, Ginsburg S, FitzGerald JM. Bronchodilator delivery in acute airflow obstruction. A meta-analysis. Arch Intern Med. 1997;157:1736-1744.
13. Davies L, Angus RM, Calverley PM. Oral corticosteroids in patients admitted to hospital with exacerbations of chronic obstructive pulmonary disease: a prospective randomised controlled trial. Lancet. 1999;354:456-460.
14. Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 1999;340:1941-1947.
15. Thompson WH, Nielson CP, Carvalho P, et al. Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med. 1996;154(2 pt 1):407-412.
16. Alía I, de la Cal MA, Esteban A, et al. Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support. Arch Intern Med. 2011;171:1939-1946.
17. de Jong YP, Uil SM, Grotjohan HP, et al. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest. 2007;132:1741-1747.
18. Lindenauer PK, Pekow PS, Lahti MC, et al. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303:2359-2367.
19. Walters JA, Wang W, Morley C, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2011;(10):CD006897.
20. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-2231.
21. Miravitlles M, Anzueto A. Antibiotics for acute and chronic respiratory infections in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;188:1052-1057.
22. Austin M, Wills K, Blizzard L, et al. Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial. BMJ. 2010;341:c5462.
23. Gay PC. Complications of noninvasive ventilation in acute care. Respir Care. 2009;54:246-257.
24. Bahadori K, FitzGerald JM. Risk factors of hospitalization and readmission of patients with COPD exacerbation—systematic review. Int J Chron Obstruct Pulmon Dis. 2007;2:241-251.
25. Elixhauser A, Au D, Podulka J. Readmissions for Chronic Obstructive Pulmonary Disease, 2008. HCUP Statistical Brief #121. Rockville, MD: Agency for Healthcare Research and Quality; September 2011.
26. Eisenhower C. Impact of pharmacist-conducted medication reconciliation at discharge on readmissions of elderly patients with COPD. Ann Pharmacother. 2014;48:203-208.
27. Pal A, Babbott S, Wilkinson ST. Can the targeted use of a discharge pharmacist significantly decrease 30-day readmissions? Hosp Pharm. 2013;48:380-388.
28. Sehatzadeh S. Influenza and pneumococcal vaccinations for patients with chronic obstructive pulmonary disease (COPD): an evidence-based review. Ont Health Technol Assess Ser. 2012;12:1-64.

To comment on this article, contact