The report of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines chronic obstructive pulmonary disease (COPD) as “a common preventable and treatable disease ... characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients.”1 The report, developed to increase awareness of COPD and standardize patient care, is updated regularly and has become the standard of care for managing COPD. Despite these well-recognized guidelines, however, clinical practice continues to vary. One study found that 66% of patients with COPD were not treated according to the GOLD guidelines, resulting in additional costs of $3,000 to $10,000 per patient.2
COPD was the third leading cause of death in the United States in 2010, according to the CDC.3 In addition to constituting a significant overall disease burden, COPD particularly affects hospitals. For example, in 2011, more than 600,000 patients were discharged with a principal diagnosis of COPD.4 From an economic standpoint, the estimated direct costs of COPD in the United States were more than $53 billion in 2008.5 Despite its cost and prevalence, however, COPD remains both underrecognized and undertreated by patients and providers. For example, one study found that just over half of the surveyed primary care physicians were informed about COPD guidelines, and more than a third of patients with COPD considered themselves poorly informed about their diagnosis.6
Lack of insight into the disease process means that patients are more likely to be undertreated, which increases the risk for hospitalization. Once hospitalized, patients with COPD have an increase in both short-term and long-term mortality. For example, studies have found that patients admitted with COPD exacerbations have an in-hospital mortality between 8% and 11%.7,8 One study of more than 1,000 patients admitted with a COPD exacerbation found that they had a 50% chance of readmission within the following 6 months and a 2-year postdischarge mortality of nearly 50%.7
This article reviews the management of hospitalized patients with COPD with an emphasis on evidence-based evaluation and treatment of COPD exacerbations.
SPIROMETRIC DIAGNOSIS OF COPD
Spirometry is used to establish a diagnosis and determine the stage of COPD. In general, patients with COPD have decreased forced expiratory volume in 1 second (FEV1) and diffusing capacity of the lung for carbon monoxide with increased total lung capacity and residual volumes. Patients with COPD also have an FEV1 to forced vital capacity ratio (FEV1/FVC) of less than 70%, which is the defining spirometric feature of COPD. The FEV1 value defines the stage of COPD, which in turn directs management. As the severity of COPD increases, the likelihood of exacerbations and hospitalizations also increases. Despite its importance, only 10% of patients with COPD know their FEV1.9
The GOLD report defines a COPD exacerbation as “an acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication.”1 Patients with exacerbations typically experience an increase in their baseline dyspnea, cough, and/or sputum production. In a study looking at 504 patients with COPD exacerbations, the most frequently reported symptom was dyspnea (64%), followed by increased sputum production (42%) and increased wheezing/increased coryza (both 35%).10 Extrapulmonary symptoms can include mental status changes, fever, malaise, and fatigue.
The initial step in the physical examination of patients with COPD exacerbations is a primary survey to rule out acute respiratory failure that would require noninvasive positive-pressure ventilation or mechanical ventilation. Patients requiring ventilatory assistance typically demonstrate significant hypoxia and/or hypercarbia, tachypnea, and shallow, pursed-lip breathing. In stable patients, common physical examination findings include decreased breath sounds, wheezing, and a prolonged expiratory phase. For patients with more advanced COPD, a barrel-shaped chest, cyanosis, and clubbing may be seen, but these are not reliable physical findings.
Common precipitating causes of COPD exacerbations include infections, exposure to pollutants, and medication nonadherence. In about one-third of severe COPD exacerbations, the cause is never determined.1
Viral or bacterial infections are the most common causes of COPD exacerbations. Viral infections account for up to one-third of exacerbations with the most common pathogen being rhinovirus.11 Although influenza is not thought to play a major role in exacerbations, it is a risk factor for development of secondary bacterial pneumonia, specifically pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA).11,12 Bacterial infections are responsible for up to 50% of COPD exacerbations with the most common pathogens being Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.11Pseudomonas aeruginosa is more prevalent in patients with Stage 3 or 4 COPD, defined as an FEV1 of less than 50% predicted value.1 Risk factors for P. aeruginosa include a low FEV1, chronic use of systemic corticosteroids, and antibiotic use within the last 3 months.13 Many patients with COPD may be colonized with bacteria, which then leads to an inflammatory reaction triggering an exacerbation.14
The differential diagnosis of COPD exacerbations is extensive. Patients often have multiple comorbid conditions that can be the actual cause of the presenting symptoms or can precipitate an exacerbation. The differential diagnosis includes conditions such as pneumonia, heart failure, pulmonary embolism (PE), and pneumothorax. A 2006 study showed a 25% prevalence of PE in hospitalized patients with severe COPD exacerbations of unknown origin.15 Factors that were associated with positive predictability for PE in patients with a COPD exacerbation included a history of venous thromboembolism, underlying malignancy, and a decrease in PaCO2 of at least 5 mm Hg.15
Although a COPD exacerbation is typically a clinical diagnosis, the diagnostic evaluation has a significant role. Begin with a thorough physical examination, including pulse oximetry measurements, which can estimate the patient's degree of hypoxia as well as his or her response to oxygen supplementation and breathing treatments. According to the GOLD report, arterial blood gas (ABG) analysis is not routinely recommended but can be useful in patients with acute or acute-on-chronic respiratory failure in order to determine pH, PaO2, and PaCO2.1 Patients with severe COPD exacerbations typically have ABG findings consistent with hypercapnia, hypoxia, and respiratory acidosis. Obtaining serial ABGs is helpful if the initial ABG analysis is abnormal in order to track treatment effectiveness and the need for noninvasive positive-pressure ventilation or mechanical ventilation. Also, having a baseline ABG analysis to compare with subsequent ABGs is ideal, specifically when determining the patient's baseline PaCO2.
A chest radiograph can help exclude alternative diagnoses, such as pneumonia, pneumothorax, fluid overload from heart failure, or a pleural effusion. CT of the thorax is not routinely recommended unless a diagnosis is in question. For example, if PE is suspected then a CT of the thorax would be indicated.
The evidence regarding the need for bacterial or viral sputum culture with sensitivities is conflicting. Studies have shown that cultures can be positive in more than 30% of patients with COPD exacerbations, but whether this represents an acute pathogen or colonization is unclear.16 Obtain bacterial and viral sputum cultures in patients with comorbid conditions and those who require mechanical ventilation.17 If the exacerbation does not improve after initial antibiotic treatment, obtain a sputum culture with sensitivities.1
Laboratory studies, such as a complete blood cell count, also are helpful for detecting polycythemia, anemia, or leukocytosis. An ECG can identify underlying cardiac disorders. Additional diagnostic tests, such as an influenza swab, nasal MRSA swab, S. pneumoniae urinary antigen, and Legionella pneumophila urinary antigen, may be indicated, depending on the clinical situation. Spirometry is not recommended during a COPD exacerbation because measurements may not accurately represent true lung capacity.1
INDICATIONS FOR HOSPITAL ADMISSION
After the patient's initial diagnostic evaluation in the ED, determine if the patient can be managed as an outpatient or if hospitalization is warranted. An estimated 80% of patients with COPD exacerbations can be treated in the outpatient setting, but patients with severe underlying disease or severe exacerbations may require inpatient care.1
Although inpatient mortality for patients with COPD exacerbations is about 5%, the 1-year mortality after hospitalization is 27%. Patients admitted to the ICU have up to a 13% mortality and higher long-term mortality than those admitted for non-COPD conditions.18 Age, male sex, previous hospitalizations, hypercapnia, and heart failure are all independent predictors of higher mortality.19 This does not suggest that hospitalization leads to worse outcomes but rather that patients who are hospitalized have more severe disease or comorbidities. In the future, hospitalization may serve as a measure for risk stratification and prognostic indicator in patients with severe COPD.
Indications for hospitalization include severe signs or symptoms, severe comorbidities, and inadequate home support.1 Also consider admission for patients with severe underlying COPD or those who have not responded to initial outpatient treatment. Older adults also should be treated on an inpatient basis.
Depending on the severity of the patient's exacerbation and the need for noninvasive ventilation, admission to the ICU may be warranted. The use of noninvasive ventilation in managing acute respiratory failure secondary to COPD exacerbation has been well documented.20 Specifically, noninvasive positive-pressure ventilation has been shown to be successful in 80% to 85% of patients with respiratory distress from COPD, and patients on this type of ventilation can avoid many of the complications of endotracheal intubation.1 Patients who continue to show a pattern of deterioration as demonstrated by persistent or worsening hypoxemia (PaO2 of less than 40 mm Hg), worsening respiratory acidosis (pH less than 7.25), and failure of noninvasive ventilation require evaluation for intubation and mechanical ventilation.
Other criteria for admission to the ICU based on GOLD guidelines include a change in mental status or hemodynamic instability.1
Patients in respiratory distress due to a COPD exacerbation should be given oxygen supplementation aimed at increasing their oxygen saturation to between 88% and 92%. Perform clinical examinations and obtain serial ABGs to monitor for signs and symptoms of carbon dioxide retention, including altered mental status and lethargy. Although monitoring for signs of hypercapnia is important, remember that tissue oxygenation should be the primary concern; treat resultant hypercapnia with noninvasive positive-pressure ventilation or mechanical ventilation.17
Oral roflumilast is used as a maintenance treatment to reduce exacerbations in patients with severe COPD and chronic bronchitis. Given daily, this phosphodiesterase-4 inhibitor increases intracellular adenosine monophosphate, causing an overall reduction in inflammatory cells involved in the pathogenesis of COPD.1
Bronchodilator therapy has been shown to significantly improve FEV1. Commonly used bronchodilators include short-acting beta2 agonists such as albuterol and levalbuterol, and anticholinergics such as ipratropium bromide. Short-acting beta-agonists with or without short-acting anticholinergics are the standard of care for COPD exacerbations.1 FEV1 does not differ whether short-acting bronchodilators are delivered by metered-dose inhaler or small-volume nebulizer.1
No clinical data exist comparing long-acting bronchodilators with or without inhaled corticosteroids during a COPD exacerbation. Therefore, long-acting bronchodilators are not recommended for patients with COPD exacerbations.1
These drugs are the mainstay of treatment for COPD exacerbations. Compared with placebo, patients treated with corticosteroids had a 46% decrease in treatment failure, 1.4 days decrease in length of hospital stay, and 0.13 L increase in FEV1 3 days after therapy.21 The main controversy surrounding the use of corticosteroids is the proper route of administration and length of therapy. One study found that low-dose oral corticosteroids and IV corticosteroids produced similar clinical outcomes (noninferiority study).22 Higher doses and longer treatment duration of IV corticosteroids have been associated with more complications, including hyperglycemia and hypertension.23
According to the GOLD report, the recommended corticosteroid regimen is prednisone 40 mg daily for 5 days.1 Supporting this, the 2013 REDUCE randomized clinical trial found that when evaluating patients for a recurrent exacerbation within 6 months, a 5-day course of 40 mg of prednisone was noninferior to a 14-day course.24 A 5-day course of treatment was also shown to be associated with a shorter hospital stay.24 Overall, the use of corticosteroids in patients with COPD exacerbations is associated with improved lung function, decreased recovery time, and fewer treatment failures.
The use of antibiotics is recommended for COPD exacerbations if the patient has signs or symptoms, including increased dyspnea, excessive sputum, or purulent sputum, that suggest an underlying infectious cause.1 Initiate antibiotic therapy if only two of the three previously mentioned symptoms are present, and one is purulent sputum. All patients requiring mechanical ventilation should receive antibiotics. According to a meta-analysis, when compared with placebo, patients treated with antibiotics had a 46% decrease in treatment failure and a 78% decrease in inpatient mortality.21 A large retrospective study in 2013 found that adding antibiotics to corticosteroids for the treatment of COPD resulted in lower mortality and readmission rates.25
The GOLD report recommends empiric antibiotic treatment with aminopenicillin with or without clavulanic acid, macrolides, or tetracyclines, but local bacterial resistance patterns should be considered when selecting antibiotics.1 Oral antibiotics are preferred, but IV antibiotics may be necessary, depending on the patient's ability to take oral antibiotics. Interestingly, a study by Stefan and colleagues found that choice of antibiotic did not affect outcome in patients with COPD.25
Special considerations for antibiotic coverage include determining the need for gram-negative coverage, specifically for P. aeruginosa. Patients considered at risk for infection with P. aeruginosa include those who have severe airflow limitation (Stage 3 or 4 COPD), recent hospitalization for COPD, and previous P. aeruginosa infection.26 The recommended duration of antibiotic treatment for COPD exacerbations is 5 to 10 days.1
Determining if patients are ready for hospital discharge can be complicated and often is determined by subjective criteria. Clinical stability is the key to a successful discharge transition, and vital signs and ABG results should be stable for 12 to 24 hours before discharge. Patients should be able to ambulate near their baseline function. Short-acting beta2 agonists should be used no more often than every 4 hours, and patients should be transitioned to long-acting bronchodilators. In addition to inhalers, discharge prescriptions should include antibiotics to complete a 5- to 10-day course and corticosteroids to complete a 5-day course. Arranging appropriate home and follow-up care is imperative to prevent future exacerbations and readmission.1 Ultimately, patients, family members/caregivers, and providers should feel comfortable that patients are stable and ready to be discharged from the hospital to the outpatient setting.
Interventions that help to reduce the frequency of COPD exacerbations include smoking cessation, self-management education and pulmonary rehabilitation, and vaccination against influenza and pneumonia. Of these, only smoking cessation has been found to reliably slow the progression of COPD.26 Smoking cessation education should begin in the inpatient setting, although the effectiveness of these efforts is unclear. In outpatient settings, healthcare providers have about a 3% success rate in simply telling patients to quit.27 Tips for improving rates of smoking cessation include reporting lung age to patients, explaining spirometry results, and combining behavioral and pharmacologic therapies.27
Pulmonary rehabilitation is often underused but has been found to be an effective treatment for many patients with COPD. Pulmonary rehabilitation can decrease respiratory symptoms, improve quality of life, and reduce patient anxiety related to COPD symptoms.28,29 Most pulmonary rehabilitation programs include nutrition advice, psychological counseling, and education, in addition to exercise training. Finally, all patients with COPD should be actively encouraged to keep up-to-date on the influenza and pneumonia vaccines.
COPD exacerbations are associated with inpatient morbidity and mortality. Providers should implement appropriate medical evaluation and management to reduce this risk. Assessing patients with COPD exacerbations should include a thorough physical examination and diagnostic evaluation, including laboratory studies and imaging. Patient management should consist of oxygen administration, antibiotics, corticosteroids, small-volume nebulizers, and noninvasive positive-pressure ventilation, when indicated.
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