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Chronic Obstructive Pulmonary Disease

Davoren A. Chick , MD, Paul J. Grant , MD, R. Van Harrison , PhD, Amal Othman , MD, Sarah E. Roark , MD, MeiLan K. Han , MD, MS, Tami L. Remington , PharmD, and Noah Leja , PharmD.

Authors

Davoren A. Chick , MD, Paul J. Grant , MD, R. Van Harrison , PhD, Amal Othman , MD, Sarah E. Roark , MD, MeiLan K. Han , MD, MS, Tami L. Remington , PharmD, and Noah Leja , PharmD.

Affiliations

Except where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-sa/4.0/

Patient population: Adults with chronic obstructive pulmonary disease (COPD).

Provide a framework for management of chronic COPD and for the treatment of mild to moderate acute exacerbations.

Improve symptoms, quality of life and lung function while reducing morbidity and mortality for patients with COPD.

COPD is underdiagnosed and misdiagnosed. See Table 1 for an overview of diagnosis and management of COPD.

Table 1

Overview of Diagnosis and Management of Patients with COPD.

Do not perform population-wide screening for COPD. [III-C]

Appropriate comprehensive treatment can improve symptoms and quality of life. [I-A]

Consider COPD in any patient with dyspnea, chronic cough or sputum production. [I-C] Consider early diagnostic case finding in persons with a history of inhalation exposures known to be risk factors for COPD. [I-D]

Pulmonary function testing with post-bronchodilator assessment demonstrating a reduced FEV₁/FVC ratio is required for diagnosis. [I-C]

Assess COPD severity by determining extent of airflow limitation (spirometry), symptom severity, and exacerbation history (Table 5). [I-C]

Table 5

Aspects of COPD Severity.

Smoking cessation is the single most important intervention to slow the rate of lung function decline, regardless of disease severity. [I-C]

Chronic medication management includes:

Bronchodilators (beta-2 agonists and anticholinergics), selected based on symptoms and severity (Figure 1 and Table 7), with the goal of improving symptoms and functioning and reducing exacerbations. [I-A]

Inhaled corticosteroids – consider adding to bronchodilators for patients with frequent exacerbations despite bronchodilator therapy [I-A], or with an eosinophil count ≥ 300 cells/μL [I-B], or with features suggestive of asthma-COPD overlap. [II-D]

Figure 1

Overview of COPD Management: Patient Education, Preventive Care, Pharmacologic Therapy, and Pulmonary Rehabilitation. Note: Adapted and expanded from the COPD Pocket Consultant, COPD Foundation Guide for Management of COPD, 2020. Abbreviations: CAT = (more. )

Table 7

Medications Commonly Used in Chronic Obstructive Pulmonary Disease.

Acute exacerbation medication management includes bronchodilators (beta-2 agonists and anticholinergics) [I-C], systemic corticosteroid therapy [I-A], and antibiotics [II-A] based on clinical indications (Table 9). Empiric antibiotics are recommended for patients with increased sputum purulence plus either increased dyspnea or increased sputum volume. [I-A] Sputum culture is not routinely recommended. [III-D]

Table 9

Acute Exacerbation: Commonly Used Medications and Doses.

Pulmonary rehabilitation should be considered for all patients with functional impairment. [I-A]

Surgical and minimally invasive options include bullectomy, lung volume reduction procedures, and lung transplantation. [II-B] Life expectancy should be incorporated into shared decision making regarding the potential benefits of surgery. [II-D] Pulmonary consultation is recommended prior to consideration of invasive options. [I-D]

Palliative care should be discussed with patients with advanced COPD. Doing so may help limit unnecessary and burdensome personal and societal costs and invasive approaches. [I-C]

Clinical Background and Rationale for Recommendations

Epidemiology and Impact

COPD is the third-leading cause of death in the United States, accounting for over 147,000 deaths 8 and 700,000 hospitalizations annually. 9 COPD can have a long pre-symptomatic phase. About 15.7 million Americans have been diagnosed with COPD, but an estimated 50% of those with COPD are undiagnosed, so the actual number affected is probably much higher. 10

Etiology

The pulmonary manifestations of COPD include an abnormal inflammatory response to noxious inhaled particles or gases. 9 The most common causal agent is cigarette smoke, and cigarette smoking is the single largest risk factor for COPD. 11 Second-hand smoke is also a recognized risk factor, 12 as are environmental and occupational air pollutants. 9,13 Deficiency of alpha-1 antitrypsin is a treatable cause of abnormal inflammatory response. While uncommon, it can be an important etiologic factor in early onset and severe disease. 14

Prognosis

COPD is a chronic disease characterized by acute exacerbations. While the disease is heterogeneous with a variable course, airflow limitation is usually progressive, and life expectancy falls as disease progresses. Continued smoking predicts worse prognosis. 15 Persons with frequent exacerbations (two or more per year) experience worse quality of life, more rapid loss of lung function, more frequent hospitalization, and increased mortality. 16,17

While FEV₁ (the forced expiratory volume in the first second) is commonly used to assess airflow limitation, FEV₁ does not always directly correlate with symptom burden, functional status, or quality of life, and it is imperfect for predicting prognosis. Multiple dimensions of disease severity (airflow limitation, symptom severity, exacerbation risk) should help guide management.

Management Issues

Both physicians and patients under-recognize the potential benefits of appropriate disease management for COPD. The lack of a large FEV₁ response to bronchodilation may contribute to a sense of skepticism regarding the benefits of treatment. However, COPD is a chronic inflammatory disease with systemic manifestations that affect patient function, quality of life, rate of lung function decline and the development of comorbidities. FEV₁ is not the sole measure of disease response. COPD is responsive to multiple treatments. Appropriate comprehensive treatment can improve patients’ quality of life and prognosis.

Screening for COPD

Recommendation

Do not perform population-wide screening for COPD.

Although about half of the individuals with COPD in the United States are undiagnosed, 8 no direct evidence quantifies the benefits and harms of COPD screening with questionnaires or handheld spirometry, nor does evidence exist to estimate the treatment benefits in screen-detected populations. Screening in older populations may lead to over-diagnosis in “never” smokers. The United States Preventive Services Task Force recommends against population-based screening. 18

Diagnosis of COPD (Table 1)

Risk Factors and Clinical History

Recommendation

Consider a diagnosis of COPD in any patient who has dyspnea, chronic cough or sputum production.

Consider early diagnostic case finding in any patient with risk factors for the disease.

While routine population screening cannot be recommended, early diagnostic case finding is encouraged for persons at risk. 18 Risk factors for COPD include exposure to chronic tobacco smoke, 19 occupational dusts and chemicals, 20 and smoke from home cooking and heating fuels (Table 2). 21 The likelihood of a COPD diagnosis also increases with age.

Table 2

Symptoms and Signs Suggesting COPD.

Early diagnosis is encouraged, as the most effective therapy for COPD, in terms of slowing the decline of lung function, is smoking cessation. 19,22 Also, case finding may improve smoking cessation rates. 23

Recent evidence suggests that explaining a patient’s pulmonary function to them in terms of relative “lung-age” enhances smoking cessation rates. 23

Differential diagnosis considerations for patients with chronic cough and dyspnea can be found in Tables 3 and 4.

Table 3

Alternative Diagnoses for Chronic Cough and Dyspnea.

Table 4

Factors Differentiating Asthma and COPD .

Symptoms and Signs on Physical Exam (Table 2)

Recommendation

Dyspnea, often preceded by a chronic cough with sputum production, may lead patients to seek care. Physical exam is typically helpful only for patients with more severe disease.

Dyspnea is the symptom that most frequently leads patients to seek medical attention, and dyspnea worsens with increasing disease severity. 24 With severe disease, dyspnea can be debilitating. Chronic cough, often accompanied by sputum production, may precede the onset of dyspnea. Dyspnea frequently begins as an intermittent symptom, but later becomes persistent. Wheezing and chest tightness are nonspecific symptoms that may or may not be present. In patients with more severe disease, anorexia and anxiety may also develop.

Physical examination is typically unhelpful in the diagnosis of COPD. 25 Early airflow limitation is typically detectable via spirometry before it is evident on physical exam. In patients with more severe disease, the physical exam may reveal decreased breath sounds, decreased air movement, wheezing, and rhonchi. Hyperinflation, as indicated by a “barrel” chest, accessory muscle use and weight loss, typically indicates more advanced disease.

Spirometry

Recommendation

Perform spirometry to diagnose COPD.

Spirometry is the diagnostic “gold standard” because it is the most reproducible, standardized, and objective way of measuring airflow limitation. 26 Spirometry should be ordered with bronchodilator, and the post-bronchodilator values should be used to assess both the presence of airflow obstruction and its severity. A post-bronchodilator FEV₁/FVC < 0.70 confirms the presence of airflow limitation that is not fully reversible (FVC is the forced vital capacity). The severity of post-bronchodilator airflow obstruction is defined by the FEV₁ (Table 5). 27

While reversibility with bronchodilator (defined as an increase in FEV₁ of ≥ 200 mL and ≥ 12% absolute value) is commonly associated with asthma as opposed to COPD, post-bronchodilator FEV₁ improvement of 12% can also be seen in COPD. In such cases of COPD with FEV₁ bronchodilation response, the post-bronchodilator FEV₁/FVC by definition remains < 0.70 due to persistent airflow limitation. Therefore, FEV₁ response to bronchodilator should not be solely relied upon to distinguish between asthma and COPD (Table 4).

While diffusion capacity and lung volumes obtained using plethysmography can aid in patient characterization, these results are not required for making the diagnosis of COPD.

Differentiating COPD, Asthma, and Overlap Syndrome

Recommendation

Use the clinical history and spirometry to differentiate COPD, asthma, and overlap syndrome.

Distinguishing between COPD and asthma is important because they differ in first-line therapies and chronic management. A set of clinical factors to help guide clinicians in distinguishing between asthma and COPD can be found in Table 4.

Fixed airflow obstruction must be demonstrated to make a diagnosis of COPD. Many patients with a diagnosis of COPD have not undergone confirmatory testing, suggesting that both under-diagnosis and misdiagnosis are common. 2 Unfortunately, no single test can reliably distinguish asthma from COPD.

Some patients have features of both asthma and COPD. The Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) recognize Asthma COPD Overlap (ACO) or Asthma COPD Overlap Syndrome (ACOS) as characterized by “persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD.” 1

Imaging

Recommendation

Do not image to diagnose early or moderate COPD.

Generally, COPD can be documented by spirometry before it is seen on chest radiograph. A chest radiograph may suggest a diagnosis of COPD, particularly if it demonstrates hyperinflation, but it should not be considered diagnostic of the disease.

Current evidence is not sufficient to recommend routine chest imaging with computed tomography (CT) in early or moderate COPD. In patients with severe disease, high resolution CT is required to evaluate the appropriateness of therapies such as lung volume reduction surgery or transplant. The utility of chest CT in patients with COPD is an area of active investigation. 2 However, it should be noted that many individuals with COPD also meet criteria for lung cancer screening with CT, due to their smoking history. 18

Alpha-1 Antitrypsin

Recommendation

Perform alpha-1 antitrypsin testing in patients with early onset COPD or a family history of early onset COPD. Consider alpha-1 antitrypsin testing in the presence of prominent basilar lucency, unexplained liver disease, or the absence of other risk factors for COPD.

While alpha-1 antitrypsin deficiency has some association with COPD, 28 testing is controversial. Some of the controversy derives from quality of data regarding efficacy of treatment with alpha-1 antitrypsin augmentation therapy.

In the absence of clear empirical data, we recommend following the GOLD Guidelines to test alpha-1 antitrypsin in persons with COPD who: 2

Consider broader testing based on clinician judgment. The American Thoracic Society and European Respiratory Society joint statement recommends testing for: 29

symptomatic adults with emphysema, COPD, or asthma with airflow obstruction that is incompletely reversible after aggressive treatment with bronchodilators

Assess COPD Severity

Recommendation

Assess the extent of airflow limitation (using spirometry), symptom severity, and exacerbation risk (Table 5) to monitor patient status and guide therapy.

Separately assessing airflow limitation, symptom severity, and exacerbation risk helps individualize planning for each patient. 2 While these dimensions of COPD severity are somewhat interrelated, individuals vary appreciably on their status across these dimensions and on progression along each of these dimensions. All of these dimensions should be considered when assessing disease severity in an individual patient.

The upper part of Table 5 shows levels of airflow limitation (mild to very severe) by spirometry.

The middle part of Table 5 shows two approaches to assessing symptom severity. Patients use the Modified Medical Research Council (mMRC) Dyspnea Scale to rate their shortness of breath. 3,30 Patients use the COPD Assessment Test (CAT) to rate their health status impairment in 8 areas likely to be affected by COPD, and then the score is totaled. 4,31 Either method of assessing symptom severity can be used, although the mMRC Dyspnea Scale has a narrower focus. The choice can be made based on local preference and likely relevance to a specific patient.

The lower part of Table 5 addresses exacerbation risk and other aspects of severity. Having had ≥ 2 exacerbations in the past year or ≥ 1 exacerbation resulting in hospitalization is associated with increased risk for future exacerbations. 17 Other aspects of severity include oxygen therapy and comorbid conditions.

Recognition of Comorbid Diseases

Comorbid Disease

Recommendation

Recognize and diagnose comorbid diseases affecting the management and health of patients with COPD.

Patients with COPD are frequently at increased risk for:

Cigarette smoking, an established risk factor for COPD, also places patients at risk for other diseases due to its systemic effects.

COPD itself is an independent risk factor for cardiovascular disease, even after controlling for smoking. 33 This risk may be related to systemic inflammation.

Cardiovascular Conditions

Recommendation

Beta-blockers necessary for cardiovascular conditions can be prescribed for most patients with comorbid COPD.

Data from several studies demonstrate that beta-blockers necessary for cardiovascular conditions can be safely prescribed for most patients with COPD, particularly beta-1 cardioselective blockers (eg, atenolol, metoprolol) or combined beta and alpha blockers (eg, carvedilol). 34,35

Heart Failure

Recommendation

For inpatients with COPD, a low BNP ( < 100) can help rule out heart failure and a high BNP (>500) can help rule in heart failure.

Clinicians may have difficulty distinguishing between heart failure and COPD in certain clinical settings. Baseline BNP measurements may be elevated in COPD patients compared to those without COPD, but are not as high as measurements in patients with heart failure. In patients with COPD, a low BNP (less than 100) can help rule out significant heart failure, while a very high BNP (greater than 500) can help rule in heart failure. 36,37 Values between 100 and 500 must be interpreted with caution, keeping in mind the entire clinical picture. For further guidance regarding the management of heart failure, see the University of Michigan Health System (UMHS) Heart Failure Clinical Guideline.

Diabetes and Osteoporosis

Recommendation

Inhaled corticosteroids have only a small effect on serum glucose in diabetics and on bone mineral density related to osteoporosis.

Inhaled corticosteroid use is associated with only a small (approximately 2 mg/dL) dose-dependent increase in serum glucose concentration in diabetic patients. For further guidance regarding diabetes management, see the UMHS Diabetes Clinical Guideline.

While inhaled corticosteroids may carry a theoretical risk for decreasing bone mineral density (BMD), several studies following BMD over 3 years indicate the risk is minimal. 38 For further guidance regarding osteoporosis management, see the UMHS Osteoporosis Clinical Guideline.

Psychiatric Disorders

Recommendation

Identify psychiatric disorders in COPD patients and treat with cognitive behavioral therapy, mind-body interventions, and non-sedating therapies when possible.

Depression and anxiety are highly prevalent in COPD patients, and both predict a worse quality of life. 39 Cognitive behavioral therapy may improve psychological outcomes, and mind-body interventions (such as mindfulness, yoga, and relaxation) may decrease physical suffering. 40 Due to the risk of respiratory suppression, non-selective benzodiazepine anxiolytic sedation should be avoided when possible. 41 For further guidance regarding depression management, see the UMHS Depression Clinical Guideline.

Management

Overview of COPD Management

Managing COPD includes patient education, preventive care, medications, pulmonary rehabilitation, and oxygen therapy. Using symptoms and exacerbations as a guide, Figure 1 provides an approach to incorporating all of these management activities except oxygen therapy, which is addressed separately below. The rationale for each recommendation is explained in the relevant sections below.

Patient Education

Recommendation

Provide patient-focused education to support disease self-management including: smoking cessation, avoidance of exacerbations, appropriate inhaler technique, healthy behaviors, and end-of-life planning (Table 6).

Table 6

Patient Education Overview.

While evidence for clinical benefit due to self-management support is lacking, 42 patients should understand their disease, risk factors for progression, and their roles in optimizing their health and wellness. Education should include identification and reduction of exposures to inhalant irritants and appropriate use of inhalers. 2 Patients should be informed that smoking cessation has the greatest capacity to influence the natural history of COPD. Prospective end-of-life discussions help patients understand advance directives and therapies near the end of life.

Patients enrolled in pulmonary rehabilitation at UMHS receive instruction in self-management skills that enhance self-efficacy and support chronic disease management.

Preventive Care

Preventive care focuses on avoiding irritants that can aggravate COPD. The most common “triggers” are smoking, second-hand smoke, occupational fumes and chemicals, indoor air pollution (eg, cooking with biomass fuels), outdoor air pollution, and infections.

Smoking cessation and second-hand smoke

Recommendation

Advise smokers to quit and assist them in quitting. Assess for exposure to second-hand smoke and counsel its avoidance.

Smoking cessation is the single most important intervention to slow the rate of lung decline and reduce respiratory symptoms, regardless of the severity of the patient’s disease. The beneficial impact of smoking cessation on the natural history of COPD is greater the earlier in the disease that cessation is achieved. 22

Smoking cessation should be encouraged at each visit. The combination of pharmacologic and psychosocial treatment for smoking cessation has been shown to be superior to psychosocial treatment alone in patients with COPD. 43 Smoking cessation counseling is a billable diagnosis for patients with COPD. 44 For further guidance on smoking cessation, see the UMHS Tobacco Treatment Guideline.

Second-hand smoke exposure appears to have an adverse impact on health outcomes in COPD, independent of personal smoking. 45 It is a modifiable risk factor.

Occupational fumes and air pollution

Recommendation

Advise patients to identify and avoid occupational fumes and air pollution.

Occupational pulmonary irritant exposure causes 12–17% of COPD cases. 46 Therefore, limiting exposure to industrial fumes and dust is recommended. Limiting exposure can help slow the progression of disease and improve symptoms. Occupational exposures include organic and inorganic dusts, chemical agents, and fumes.

Patients with COPD should be counseled to avoid exposure to high air pollution to the extent that avoidance is reasonable. Emergency room visits have been shown to increase among patients with COPD following days of high air pollution. Long-term exposure to air pollution may be associated with increased risk for both COPD hospitalizations and COPD mortality. 47

Patients should be counseled to avoid indoor air pollution as well. Use of biomass fuels (eg, wood, crop materials, coal, animal dung) for indoor cooking is a significant risk factor for COPD, especially in developing countries. 48

Vaccination

Recommendation

Provide annual influenza vaccination to all COPD patients. Provide 23-valent pneumococcal vaccine at the time of COPD diagnosis. At age 65, provide 13-valent pneumococcal vaccine (at least 1 year after 23-valent vaccination.) Provide 23-valent booster pneumococcal vaccination at least 1 year after 13-valent vaccination and at least 5 years after the initial 23-valent vaccination.

Patients with COPD are at increased risk for complications from pulmonary infections (eg, hospitalization, increased use of antibiotics). Therefore, the CDC Advisory Committee on Immunization Practices recommends all patients receive pneumococcal and influenza vaccines beginning at the time of diagnosis. 49

Injectable polyvalent pneumococcal vaccination reduces risk for community acquired pneumonia and disease exacerbation in patients with COPD. 50

Inactivated influenza vaccination significantly reduces exacerbations and influenza-related respiratory infections. 51 Influenza vaccine reduces serious illness and death from influenza in COPD patients by approximately 50%. 52

Medications for Chronic Care

Figure 1 presents an overview of medical management for COPD based on symptom severity and exacerbation risk. It focuses on commonly used medications: short- and long-acting bronchodilators and inhaled corticosteroids. Specific recommendations regarding their use and the use of additional medications are presented below.

Benefits of medication

Recommendation

Medical therapy improves symptoms and functional status. However, no existing medications for COPD have been shown to modify long-term decline in lung function. Oxygen is the only treatment proven to impact mortality.

Medications commonly used in COPD include bronchodilators (both short- and long-acting beta-2 agonists and anticholinergics) and anti-inflammatory agents (inhaled corticosteroid). Detailed dosing and cost information by drug is presented in Table 7.

Beta-2 agonists and anticholinergics

Recommendation

Treatment with bronchodilators provides clinical benefit despite limited change in spirometric measures.

Both beta-2 agonists and anticholinergics are bronchodilators. They are indicated in the treatment of any COPD patient who is symptomatic. Current evidence suggests that the long-acting muscarinic antagonist (LAMA) anticholinergics should be considered first-line agents for baseline bronchodilator control, particularly in patients with severe airflow obstruction. 53,54

Dual bronchodilator therapy should be considered for patients who have persistent symptoms despite use of a single bronchodilator, and for patients with frequent exacerbations. 2 Combining different types of bronchodilators may increase the degree of bronchodilation with equivalent or fewer side effects. 55 Several combinations of long-acting beta agonist with long-acting muscarinic antagonist (LABA/LAMA) bronchodilators are now available. Evidence suggests lung function and quality of life improvements are greater for combination than for single agent bronchodilators. 2,56 Dual LABA/LAMA bronchodilators have also been demonstrated to reduce exacerbation frequency to a greater extent than inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combination therapy.

To treat asthma-COPD overlap patients, avoid monotherapy with long-acting beta agonists and consider earlier introduction of inhaled corticosteroid therapy in conjunction with a LABA and/or a LAMA.

Data from several studies demonstrate that beta-blockers necessary for cardiovascular conditions can be safely prescribed for most patients with COPD, particularly beta-1 cardioselective blockers (eg, atenolol, metoprolol) or combined beta and alpha blockers (eg, carvedilol). 34,35

Both long-acting beta-2 agonists and anticholinergics have safety concerns.

Long-acting beta-2 agonists (LABA). An FDA advisory panel recommended that LABAs not be used as single-agent therapy in asthma (see UMHS Asthma Guideline). However, for patients with COPD, LABAs may still be used as single-agent therapy without an inhaled corticosteroid. While LABAs may increase blood pressure and heart rate, data for COPD patients from the TORCH study 57 (a three-year trial in COPD patients of fluticasone proprionate and salmeterol combination versus fluticasone alone, salmeterol alone, or placebo), found no increased risk of all-cause death or cardiovascular death in the salmeterol group. These data further underscore the importance of distinguishing asthma from COPD.

Anticholinergics. Anticholinergic drugs may worsen symptoms and signs associated with narrow-angle glaucoma, prostatic hyperplasia, or bladder-neck obstruction and should be used with caution in patients with any of these conditions. Concerns about cardiovascular effects have diminished. Initially a meta-analysis suggested that inhaled anticholinergics (ipratropium and tiotropium) were associated with significantly increased risk of cardiovascular death, MI, or stroke among patients with COPD. 58 However, since then, data from the UPLIFT study (a four-year, placebo controlled trial of tiotropium) found no significant increase in myocardial infarction or stroke in the tiotropium treated group. 59

Inhaled corticosteroids

Recommendation

Add an inhaled corticosteroid (ICS) to bronchodilator therapy in patients with features of asthma overlap. Consider adding ICS in patients with an eosinophil count ≥ 300 cells/μL or with frequent (at least annual) severe COPD exacerbations despite maximal bronchodilation.

Inhaled corticosteroids (ICS) should not be used as monotherapy in COPD. However, ICS can provide additive benefit to bronchodilators in reducing the frequency of exacerbations and improving health status. 60 Withdrawal from treatment with ICS can lead to a short term increase in exacerbations in some patients. 2

Elevated blood eosinophil counts have been shown to predict the efficacy of adding ICS to maintenance bronchodilator therapy in preventing future exacerbations. 100–105 Patients with a blood eosinophil count ≥ 300 cells/μL have the highest likelihood of treatment benefit with ICS. Patients with an eosinophil count ≥ 100 cells/μL and who have a history of ≥ 2 moderate exacerbations (or, at least one exacerbation requiring hospitalization) in the past year demonstrated a favorable response to ICS. Patients with an eosinophil count < 100 cells/μL are less likely to receive benefit from ICS. 2

An increase in the frequency of pneumonia has been reported in COPD patients using ICS, particularly in patients age 65 and older. 2,61,62 The frequency of reported pneumonia appears to be approximately double in several studies comparing ICS/LABA combinations versus placebo in COPD. However, in the largest published mortality study in COPD, no increase in pulmonary related deaths was noted in the ICS/LABA combination therapy group as compared to placebo. 63 In patients with COPD being treated with ICS, particularly those age 65 and older, consider the possible increased risk of pneumonia and maintain a lower threshold for considering a diagnosis of pneumonia when patients present with increased symptoms.

ICS may also increase a patient’s risk for cataracts or glaucoma. 2 Consider regular eye exams for patients using these medications. Patients using ICS should also be warned about the possibility of oral candidiasis and vocal changes. Rinsing the mouth after administration of ICS should be encouraged.

Decrease in bone density is a theoretical risk of this class of medication, but available long-term data suggest there is no meaningful association between ICS use and decreased bone mineral density in this patient population. 38

Phosphodiesterase-4 inhibitors (roflumilast)

Recommendation

Consider roflumilast to reduce the frequency of acute exacerbations in patients with chronic bronchitis, recognizing that side effects may limit adherence.

Evidence is developing regarding both the role of phosphodiesterase-4 inhibitors in stable COPD management and which patients are most likely to benefit, including patients with a history of chronic bronchitis and frequent or severe exacerbations. 2 Roflumilast should be considered in conjunction with consultation with a pulmonologist. Discuss side effects including GI intolerance prior to prescribing.

Antibiotics

Recommendation

Do not routinely use prophylactic antibiotics, but consider referral to a COPD specialist for chronic macrolide therapy in selected patients.

Chronic macrolide therapy with oral azithromycin has been shown to decrease the frequency of COPD exacerbations. 64 A follow-up systematic review also suggests an improvement in acute exacerbations and decreased hospitalization with chronic macrolide therapy. 65 In patients with persistent exacerbations despite maximal inhaled therapies, consider referral to a specialist in COPD management (eg, pulmonologist) for consideration of additional therapies including macrolide antibiotics.

Leukotriene modifiers

Recommendation

Consider using leukotriene modifiers in patients with asthma/COPD overlap syndrome.

Leukotriene modifiers have not been adequately tested in COPD and cannot be recommended solely for COPD at this time.

Oral corticosteroids

Recommendation

Do not routinely use oral corticosteroids for treatment of chronic COPD. However, they can be used for acute exacerbations of COPD, as discussed below.

Theophylline

Recommendation

Do not routinely use theophylline for control of chronic COPD symptoms.

Theophylline is effective for symptom control in COPD. However, due to its narrow therapeutic window and side effect profile, inhaled bronchodilators are preferred.

Pulmonary Rehabilitation

Recommendation

Consider pulmonary rehabilitation for any patient with COPD who experiences significant dyspnea or exercise limitation, regardless of severity of airflow limitation.

The American Thoracic Society and European Respiratory Society 66 define pulmonary rehabilitation as “a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors.”

Pulmonary rehabilitation improves exercise capacity, dyspnea, and quality of life. 67 Pulmonary rehabilitation after a recent hospitalization for COPD has been shown to decrease hospital readmissions, decrease mortality, and improve both exercise capacity and health related quality of life. 68

Medicare covers pulmonary rehabilitation for patients with COPD who have moderate or greater disease severity, based on FEV₁ % predicted. (Table 5.) Medicare patients who continue to smoke must also be enrolled in a smoking cessation program.

Oxygen Therapy

Continuous oxygen

Recommendation

Provide continuous oxygen therapy for COPD patients if resting oxygen saturation is ≤ 88% and confirmed twice over a 3-week period.

The primary goal of oxygen therapy is to maintain vital organ function by ensuring adequate oxygen delivery. This is achieved by increasing the baseline PaO₂ to at least 60 mm Hg (or resting oxygen saturation to at least 90%). 67,69

In patients with very severe COPD, long-term oxygen therapy has been shown to improve the following outcomes: 70–73

Indications for continuous oxygen use are summarized in Table 8. Once oxygen therapy is initiated, if the clinical picture changes, oxygen requirement may need to be reevaluated. Medicare requires annual recertification of a patient’s continuing need for oxygen therapy.

Table 8

Indications for Continuous Use of Oxygen Therapy for Very Severe COPD .

Currently the Center for Medicare and Medicaid Services covers oxygen use both for patients who meet the evidence-based criteria in Table 8, as well as for individuals with PaO₂ ≤ 55 mm Hg (resting oxygen saturation ≤ 88%) either with activity or at night. For these patients with moderate hypoxemia but significant breathlessness despite maximizing other medical therapies, a trial of oxygen therapy may be appropriate.

Exercise and nocturnal oxygen therapy

Recommendation

Oxygen therapy during exercise or during sleep may benefit selected patients.

Follow Up Chronic Care

Frequency

Recommendation

Initial chronic care visits should occur at least every 6 months. Visits may be once a year for currently nonsmoking patients with mild disease who are stable on treatment and only rarely have exacerbations.

No consensus exists on the recommended frequency of office visits for chronic COPD care. Frequency of follow-up may be guided by:

Factors to Reassess

Recommendation

At follow-up visits, reassess:

Symptoms: severity, control, new, stable or worsening (eg, sputum production, dyspnea, cough, activities of daily living)

Evidence regarding comprehensive self-management is limited. One study that compared self-management to routine monitoring did not demonstrate long-term benefits in terms of quality of life or self-efficacy over usual care alone in COPD patients in general practice. 75

Spirometry

Recommendation

Monitor symptoms and functional status to guide spirometry use in disease monitoring.

No clear consensus exists on the appropriate frequency of spirometry to guide therapy after the initial diagnosis of COPD. Systematic reviews found insufficient evidence for using spirometry to guide therapy. When patients report symptomatic changes, follow-up spirometry may be warranted to detect clinically significant changes of lung function that may alter clinical therapeutic options.

Medication Management

Recommendation

Adjust medical therapy based on symptom severity as summarized in Figure 1 and as described above under “Medications for Chronic Care.”

If patients remain symptomatic at subsequent follow-up visits despite adherence to medications, intensifying pharmacotherapy should be considered.

Oxygen Therapy Management

Recommendation

Reassess patients who are on oxygen for resting hypoxemia (resting oxygen saturation ≤ 88%).

For patients on long-term oxygen therapy, an annual reevaluation of oxygen saturation is recommended to determine if oxygen is therapeutic and still clinically indicated.

All patients prescribed oxygen must be recertified every 12 months in order to qualify for Medicare and Medicaid coverage. Recertification includes an in-person encounter with the treating physician, a documented exam, and a resting oxygen saturation of < 88%, with improvement of the hypoxemia on oxygen. 76

Functional Assessment and Rehabilitation

Recommendation

If not already initiated, consider pulmonary rehabilitation for all patients with significant dyspnea or exercise limitation.

Nutrition

Recommendation

For patients with COPD and malnourishment, consider a referral for nutritional counseling and supplementation.

Insurance coverage for dietician referral for this purpose varies.

Reassessment after Severe Acute Exacerbation

Recommendation

Reassess patients after hospital discharge for an acute COPD exacerbation.

Assessment should include:

Spirometry about 3 months after the patient’s return to stability. Significant declines in baseline lung function can occur with exacerbations.

Acute Exacerbation in the Outpatient Setting

This guideline focuses on management of an exacerbation treated in the outpatient setting. For information regarding exacerbation in the inpatient setting, see Care of the Hospitalized Patient with Acute Exacerbation of COPD.

Diagnosis

Recommendation

Diagnose an acute exacerbation of COPD based on clinical findings. Consider causes of COPD exacerbation and alternate diagnoses.

No single definition of acute COPD exacerbation is universally accepted. However, it can reasonably be described as an acute change in a patient’s baseline dyspnea, cough, or sputum that is beyond the normal day-to-day variability and is sufficient to warrant a change in medication.

Causes of acute COPD exacerbation include: 2,77

Alternate diagnoses need to be considered, including:

Assessment

Recommendation

Assess the patient’s clinical history, physical exam, and oxygen saturation.

Do not routinely perform a chest radiograph or a sputum gram stain and culture.

Outpatient assessment for an acute exacerbation of COPD starts with the clinical history and physical examination. Obtaining an oxygen saturation via pulse oximetry is recommended.

Ordering a chest radiograph is generally not recommended. However, it may be reasonable for patients who are age 65 or older, use inhaled steroids, or have fever.

The utility of sputum gram stain and culture in the outpatient setting is limited given the length of time before results are available as well as the low reliability of the results. 2 Patients who have recently been on antibiotics or who are not responding to therapy may be exceptions.

Spirometry, arterial blood gas, and electrocardiogram are generally not recommended in the outpatient assessment of a patient with an acute COPD exacerbation.

Pharmacotherapy

Recommendation

Outpatient management of acute COPD exacerbation involves treatment with bronchodilators, systemic corticosteroids, and antibiotics.

Specific drugs and dosing are described in Table 9. Their use is summarized below.

Bronchodilators

Recommendation

Use bronchodilators as first-line therapy.

Bronchodilators improve respiratory symptoms and FEV₁ during acute COPD exacerbations. The dose and/or frequency of short-acting beta-2 agonists, either via inhaler or nebulizer, should be increased. The inhaled anticholinergic ipratropium, which is a short-acting muscarinic antagonist (SAMA), can be added if not already used, although the effectiveness of combination therapy in the setting of acute exacerbation is questionable. 78 The clinical response to medication administration via MDI with spacer is similar to that for inhalation via nebulizer for persons who can adequately demonstrate bronchodilator technique (even while dyspneic). 79

Systemic corticosteroids

Recommendation

Provide oral corticosteroids to reduce recovery time, improve lung function (FEV1), and improve hypoxemia (PaO2).

Prednisone 40 mg orally daily is recommended for not more than 5–7 days, 2,80 particularly in patients with an FEV₁ < 50% predicted.

Antibiotics

Recommendation

Treat selected patients with empiric antibiotic therapy.

The benefit of antibiotics for patients with severe COPD exacerbations requiring mechanical ventilation is well established. The role of antibiotics for the treatment of moderate exacerbations in the outpatient setting is more controversial. A few studies have shown that antibiotics reduce treatment failure rate and may increase the time to the next exacerbation. 2,81 Some studies suggest that patients who present with purulent sputum may benefit most from antibiotic treatment. COPD guideline documents vary in their recommendations.

For treatment of outpatients with a COPD exacerbation, we recommend using antibiotics in patients with increased sputum purulence and an increase in at least one of the following:

Antibiotic choice should be selected for presumptive therapy based on local resistance patterns. Sputum cultures are generally not recommended unless the patient has recently been taking antibiotics. For patients who meet the above criteria for antibiotics, the selection of a specific antibiotic depends on risk factors for poor outcomes with narrower spectrum antibiotics (eg, age ≥ 65, FEV₁ < 50% predicted, ≥ 2 exacerbations/year, presence of comorbid diseases) and unusual circumstances (Table 9).

Indications for hospitalization

Recommendation

Initiate an emergency department evaluation or hospital admission based on clinical judgment of COPD exacerbation severity, lack of response to treatment, history, and contextual factors.

Consider emergency department evaluation or hospital admission based on clinical judgment:

Significant comorbidities (eg, older age, pneumonia, congestive heart failure, diabetes mellitus, renal or liver failure)