Treatment of Stable Chronic Obstructive Pulmonary Disease: the GOLD Guidelines



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Am Fam Physician. 2013 Nov 15;88(10):655-663.

  Related editorial: Choosing the Right Inhaled Medication Device for COPD

  Patient Information: A handout on this topic is available at http://familydoctor.org/familydoctor/en/diseases-conditions/chronic-obstructive-pulmonary-disease/treatment.html.

This version of the article contains supplemental content.

This clinical content conforms to AAFP criteria for continuing medical education (CME). See the CME Quiz.

Author disclosure: No relevant financial affiliations.

Chronic obstructive pulmonary disease (COPD) is a common problem in primary care. COPD is diagnosed with spirometry only in clinically stable patients with a postbronchodilator forced expiratory volume in one second/forced vital capacity ratio of less than 0.70. All patients with COPD who smoke should be counseled about smoking cessation. Influenza and pneumococcal vaccinations are recommended for all patients with COPD. The Global Initiative for Chronic Obstructive Lung Disease assigns patients with COPD into four groups based on the degree of airflow restriction, symptom score, and number of exacerbations in one year. Pulmonary rehabilitation is recommended for patients in groups B, C, and D. Those in group A should receive a short-acting anticholinergic or short-acting beta2 agonist for mild intermittent symptoms. For patients in group B, long-acting anticholinergics or long-acting beta2 agonists should be added. Patients in group C or D are at high risk of exacerbations and should receive a long-acting anticholinergic or a combination of an inhaled corticosteroid and a long-acting beta2 agonist. For patients whose symptoms are not controlled with one of these regimens, triple therapy with an inhaled corticosteroid, long-acting beta2 agonist, and anticholinergic should be considered. Prophylactic antibiotics and oral corticosteroids are not recommended for prevention of COPD exacerbations. Continuous oxygen therapy improves mortality rates in patients with severe hypoxemia and COPD. Lung volume reduction surgery can improve survival rates in patients with severe, upper lobe–predominant COPD with heterogeneous emphysema distribution.

Chronic obstructive pulmonary disease (COPD) is a common problem in primary care. The estimated prevalence is 6.3% (15 million persons) in the United States,1 with more than 126,000 deaths each year.2 COPD treatments aim to improve quality of life and control symptoms while reducing exacerbation risk, which can lead to increased morbidity and mortality.

This article summarizes expert consensus guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) for nonpharmacologic and pharmacologic interventions for patients with stable COPD.3 The GOLD guidelines are widely used in the management of COPD. (Disclosure: the GOLD program is funded by pharmaceutical companies that make medications for COPD, and the board of directors, committee members, and reviewers have ties to the pharmaceutical industry. See http://www.goldcopd.org/disclosure-statements.html.)

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References

Suspected COPD should be confirmed by spirometry in stable patients with a postbronchodilator forced expiratory volume in one second/forced vital capacity ratio of less than 0.70.

C

3

Smoking cessation is recommended for all patients with COPD who smoke.

C

14, 15

Patients in GOLD group A should be treated with a short-acting anticholinergic or short-acting beta2 agonist on an as-needed basis.

A

1921

Patients in GOLD group B should be treated with a long-acting anticholinergic or long-acting beta2 agonist.

A

2229

Patients in GOLD group C or D should be treated with a long-acting anticholinergic or a combination of an inhaled corticosteroid and long-acting beta2 agonist.

B

3, 24, 28, 34, 37, 38

Long-term oxygen therapy improves mortality rates in patients with severe hypoxemia and COPD.

A

42, 43


COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

View Table

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References

Suspected COPD should be confirmed by spirometry in stable patients with a postbronchodilator forced expiratory volume in one second/forced vital capacity ratio of less than 0.70.

C

3

Smoking cessation is recommended for all patients with COPD who smoke.

C

14, 15

Patients in GOLD group A should be treated with a short-acting anticholinergic or short-acting beta2 agonist on an as-needed basis.

A

1921

Patients in GOLD group B should be treated with a long-acting anticholinergic or long-acting beta2 agonist.

A

2229

Patients in GOLD group C or D should be treated with a long-acting anticholinergic or a combination of an inhaled corticosteroid and long-acting beta2 agonist.

B

3, 24, 28, 34, 37, 38

Long-term oxygen therapy improves mortality rates in patients with severe hypoxemia and COPD.

A

42, 43


COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

Although some of the GOLD recommendations are derived from outcome-oriented evidence, the guidelines have not been shown to provide better clinical outcomes than other guidelines on COPD management, such as those from the National Institute for Health and Care Excellence4 or the joint guidelines from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society.5  A comparison of treatment guidelines is shown in Table 1.35 The joint guideline from the American College of Physicians uses the forced expiratory volume in one second (FEV1) to guide treatment decisions, whereas the National Institute for Health and Care Excellence guideline focuses on symptoms of breathlessness and exacerbations. The GOLD guideline combines the subjective and objective components of COPD to classify severity and guide treatment recommendations.

Table 1.

Comparison of Recommendations for Treatment of Chronic Obstructive Pulmonary Disease

American College of Physicians/American College of Chest Physicians/American Thoracic Society/European Respiratory Society guideline5

FEV1 = 60% to 80% predicted: inhaled bronchodilators may be used

FEV1 < 60% predicted: long-acting anticholinergic or long-acting beta2 agonist recommended; combination therapy may be used (long-acting anticholinergic, long-acting beta2 agonist, or inhaled corticosteroid)

Global Initiative for Chronic Obstructive Lung Disease guideline3

Patient group A*: short-acting anticholinergic or short-acting beta2 agonist as needed

Patient group B*: long-acting anticholinergic or long-acting beta2 agonist

Patient group C or D*: long-acting anticholinergic or combination of long-acting beta2 agonist plus inhaled corticosteroid

National Institute for Health and Care Excellence guideline4

Patients with breathlessness and exercise limitation: short-acting beta2 agonist or short-acting anticholinergic as needed

Patients with persistent breathlessness and exacerbations despite therapy above:

FEV1 ≥ 50% predicted: long-acting anticholinergic or long-acting beta2 agonist

FEV1 < 50% predicted: long-acting anticholinergic or combination of long-acting beta2 agonist and inhaled corticosteroid

Patients with persistent breathlessness or exacerbations despite therapy above:

FEV1 ≥ 50% predicted: long-acting beta2 agonist plus inhaled corticosteroid, or combination of long-acting anticholinergic, long-acting beta2 agonist, and inhaled corticosteroid

FEV1 < 50% predicted: long-acting anticholinergic, long-acting beta2 agonist, and inhaled corticosteroid


FEV1 = forced expiratory volume in one second.

*—See Figure 1 for definition of patient groups.

Information from references 3 through 5.

Table 1.   Comparison of Recommendations for Treatment of Chronic Obstructive Pulmonary Disease

View Table

Table 1.

Comparison of Recommendations for Treatment of Chronic Obstructive Pulmonary Disease

American College of Physicians/American College of Chest Physicians/American Thoracic Society/European Respiratory Society guideline5

FEV1 = 60% to 80% predicted: inhaled bronchodilators may be used

FEV1 < 60% predicted: long-acting anticholinergic or long-acting beta2 agonist recommended; combination therapy may be used (long-acting anticholinergic, long-acting beta2 agonist, or inhaled corticosteroid)

Global Initiative for Chronic Obstructive Lung Disease guideline3

Patient group A*: short-acting anticholinergic or short-acting beta2 agonist as needed

Patient group B*: long-acting anticholinergic or long-acting beta2 agonist

Patient group C or D*: long-acting anticholinergic or combination of long-acting beta2 agonist plus inhaled corticosteroid

National Institute for Health and Care Excellence guideline4

Patients with breathlessness and exercise limitation: short-acting beta2 agonist or short-acting anticholinergic as needed

Patients with persistent breathlessness and exacerbations despite therapy above:

FEV1 ≥ 50% predicted: long-acting anticholinergic or long-acting beta2 agonist

FEV1 < 50% predicted: long-acting anticholinergic or combination of long-acting beta2 agonist and inhaled corticosteroid

Patients with persistent breathlessness or exacerbations despite therapy above:

FEV1 ≥ 50% predicted: long-acting beta2 agonist plus inhaled corticosteroid, or combination of long-acting anticholinergic, long-acting beta2 agonist, and inhaled corticosteroid

FEV1 < 50% predicted: long-acting anticholinergic, long-acting beta2 agonist, and inhaled corticosteroid


FEV1 = forced expiratory volume in one second.

*—See Figure 1 for definition of patient groups.

Information from references 3 through 5.

Diagnosis

A diagnosis of COPD should be considered in patients with progressive dyspnea, chronic cough, or increased sputum production with risk factors (e.g., smoking). COPD can be diagnosed with spirometry only in stable patients (i.e., those not experiencing an acute exacerbation of symptoms) with a postbronchodilator FEV1/forced vital capacity ratio of less than 0.70.3 The diagnosis of COPD and interpretation of spirometry results have been reviewed previously.6,7

Assessment

GOLD classifies persons with COPD into four groups based on the severity of disease, as assessed by the following criteria: the degree of airflow restriction, a patient symptom score, and the number of exacerbations in one year (Figure 1).8 This grading system uses objective spirometry data and subjective symptoms because the degree of airflow restriction does not always correlate well with symptoms.9  The degree of airflow restriction is graded as mild, moderate, severe, or very severe (Table 2).8 Persons with mild or moderate airflow restriction are assigned to group A or B, whereas those with severe or very severe airflow restriction are assigned to group C or D.

Combined Assessment of COPD

Figure 1.

Combined assessment of COPD. (CAT = COPD Assessment Test; COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease; mMRC = modified Medical Research Council Dyspnea Scale.)

Reprinted with permission from the Global Strategy for the Diagnosis, Management and Prevention of COPD, 2013, © Global Initiative for Chronic Obstructive Lung Disease (GOLD), all rights reserved. http://www.goldcopd.org/other-resources-gold-teaching-slide-set.html. Accessed August 20, 2013.

View Large

Combined Assessment of COPD


Figure 1.

Combined assessment of COPD. (CAT = COPD Assessment Test; COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease; mMRC = modified Medical Research Council Dyspnea Scale.)

Reprinted with permission from the Global Strategy for the Diagnosis, Management and Prevention of COPD, 2013, © Global Initiative for Chronic Obstructive Lung Disease (GOLD), all rights reserved. http://www.goldcopd.org/other-resources-gold-teaching-slide-set.html. Accessed August 20, 2013.

Combined Assessment of COPD


Figure 1.

Combined assessment of COPD. (CAT = COPD Assessment Test; COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease; mMRC = modified Medical Research Council Dyspnea Scale.)

Reprinted with permission from the Global Strategy for the Diagnosis, Management and Prevention of COPD, 2013, © Global Initiative for Chronic Obstructive Lung Disease (GOLD), all rights reserved. http://www.goldcopd.org/other-resources-gold-teaching-slide-set.html. Accessed August 20, 2013.

Table 2.

Classification of Severity of Airflow Limitation in Chronic Obstructive Pulmonary Disease*

In patients with FEV1/FVC < 0.70:

GOLD 1 (mild): FEV1 ≥ 80% predicted

GOLD 2 (moderate): 50% ≤ FEV1 < 80% predicted

GOLD 3 (severe): 30% ≤ FEV1 < 50% predicted

GOLD 4 (very severe): FEV1 < 30% predicted


FEV1= forced expiratory volume in one second; FVC = forced vital capacity; GOLD = Global Initiative for Chronic Obstructive Lung Disease.

*—Based on postbronchodilator FEV1.

Reprinted with permission from the Global Strategy for the Diagnosis, Management and Prevention of COPD, 2013, © Global Initiative for Chronic Obstructive Lung Disease (GOLD), all rights reserved. http://www.goldcopd.org/other-resources-gold-teaching-slide-set.html. Accessed August 20, 2013.

Table 2.   Classification of Severity of Airflow Limitation in Chronic Obstructive Pulmonary Disease*

View Table

Table 2.

Classification of Severity of Airflow Limitation in Chronic Obstructive Pulmonary Disease*

In patients with FEV1/FVC < 0.70:

GOLD 1 (mild): FEV1 ≥ 80% predicted

GOLD 2 (moderate): 50% ≤ FEV1 < 80% predicted

GOLD 3 (severe): 30% ≤ FEV1 < 50% predicted

GOLD 4 (very severe): FEV1 < 30% predicted


FEV1= forced expiratory volume in one second; FVC = forced vital capacity; GOLD = Global Initiative for Chronic Obstructive Lung Disease.

*—Based on postbronchodilator FEV1.

Reprinted with permission from the Global Strategy for the Diagnosis, Management and Prevention of COPD, 2013, © Global Initiative for Chronic Obstructive Lung Disease (GOLD), all rights reserved. http://www.goldcopd.org/other-resources-gold-teaching-slide-set.html. Accessed August 20, 2013.

COPD symptoms are assessed subjectively using one of two validated patient symptom questionnaires.10 Because FEV1 does not necessarily correlate with patient symptoms, and because improvement of a patient's health status and reduction in symptoms are the goals of treatment, the inclusion of symptom questionnaires allows for the diagnostic assessment to match treatment goals, similar to the guidelines from the National Institute for Health and Care Excellence.3  GOLD recommends the use of the COPD Assessment Test (CAT) or the modified Medical Research Council Dyspnea Scale (mMRC, Table 3).11 The CAT is available at http://www.catestonline.org/ (eFigure A), and the CAT and the mMRC are available in the smartphone app COPD Pocket Consultant Guide (http://bit.ly/1aTrkIs). Patients with a CAT score less than 10 or an mMRC score of 0 or 1 are assigned to group A or C. Those with a CAT score of 10 or more or an mMRC score of 2 or more are assigned to group B or D.

COPD Assessment Test

eFigure A.

 Download in PDF format

Reprinted with permission from GlaxoSmithKline. COPD assessment test. http://catestonline.org/english/indexEN.htm. Accessed August 20, 2013. Copyright © GlaxoSmithKline group of companies. All rights reserved..

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COPD Assessment Test


eFigure A.

 Download in PDF format

Reprinted with permission from GlaxoSmithKline. COPD assessment test. http://catestonline.org/english/indexEN.htm. Accessed August 20, 2013. Copyright © GlaxoSmithKline group of companies. All rights reserved..

COPD Assessment Test


eFigure A.

 Download in PDF format

Reprinted with permission from GlaxoSmithKline. COPD assessment test. http://catestonline.org/english/indexEN.htm. Accessed August 20, 2013. Copyright © GlaxoSmithKline group of companies. All rights reserved..

Table 3.

Modified Medical Research Council Dyspnea Scale

Score Description of breathlessness

0

I get breathless only with strenuous exercise.

1

I get short of breath when hurrying on level ground or walking up a slight hill.

2

On level ground, I walk slower than other people my age because of breathlessness, or I have to stop for breath when walking at my own pace.

3

I stop for breath after walking about 100 yards or after a few minutes on level ground.

4

I am too breathless to leave the house, or I am breathless when dressing.


Information from reference 11.

Table 3.   Modified Medical Research Council Dyspnea Scale

View Table

Table 3.

Modified Medical Research Council Dyspnea Scale

Score Description of breathlessness

0

I get breathless only with strenuous exercise.

1

I get short of breath when hurrying on level ground or walking up a slight hill.

2

On level ground, I walk slower than other people my age because of breathlessness, or I have to stop for breath when walking at my own pace.

3

I stop for breath after walking about 100 yards or after a few minutes on level ground.

4

I am too breathless to leave the house, or I am breathless when dressing.


Information from reference 11.

The third component used to determine the GOLD group is the number of COPD exacerbations in one year. GOLD defines an exacerbation as an acute event characterized by worsening of respiratory symptoms beyond normal day-to-day variations that leads to a change in medication.3 Exacerbations are associated with higher mortality.12,13 Patients with no or one exacerbation per year are assigned to group A or B, and those with two or more are assigned to group C or D. If there is a discrepancy when all three components are considered, the patient should be assigned to the higher-risk group.

Patients with COPD should be reassessed every two to three months. Symptom questionnaires (e.g., CAT, mMRC), smoking cessation (if applicable), and exacerbation history should be reviewed. Repeat spirometry is recommended on a yearly basis.3

Treatment

COPD treatment is guided by the patient group assignment. As disease severity increases, long-acting inhalers and combination therapies are added to provide additional symptom control and reduce the risk of exacerbations.

SMOKING CESSATION

Patients who smoke should be assisted with smoking cessation through counseling and effective medications.14,15 The American Academy of Family Physicians' Ask and Act Tobacco Cessation Program provides online resources for physicians and patients (http://bit.ly/1fV71eZ).

IMMUNIZATIONS

Influenza vaccination reduces COPD exacerbations and is recommended yearly.16 The Centers for Disease Control and Prevention recommends pneumococcal vaccination for all adults 19 years and older who have chronic lung disease, including COPD. However, a meta-analysis of seven studies did not show a decrease in pneumonia rates, hospital admissions, or emergency department visits in patients with COPD who received the pneumococcal vaccine.17

PULMONARY REHABILITATION

Pulmonary rehabilitation has been shown to improve exercise tolerance, reduce dyspnea, and improve health-related quality of life in patients similar to those in GOLD groups B through D.18

INHALED MEDICATIONS

For patients in group A, a short-acting anticholinergic (e.g., ipratropium [Atrovent HFA]) or short-acting beta2 agonist (e.g., albuterol, levalbuterol [Xopenex HFA], pirbuterol [Maxair Autohaler]) is recommended on an as-needed basis for mild intermittent symptoms. A meta-analysis of 13 studies found that short-acting beta2 agonists improved lung function, dyspnea, and fatigue, and decreased breathlessness compared with placebo.19 A 2006 Cochrane review that included 3,912 patients showed a small benefit in quality of life and lung function in those receiving ipratropium compared with albuterol.20 Combination therapy with scheduled albuterol and ipratropium has been shown to increase FEV1 but does not affect patient symptom scores.21 It is not known if as-needed dosing is more or less effective than scheduled administration.

For patients in group B, long-acting inhaled medications should be used. Options include long-acting anticholinergics (e.g., tiotropium [Spiriva], aclidinium [Tudorza Pressair]) or long-acting beta2 agonists (e.g., arformoterol [Brovana], formoterol [Foradil], indacaterol [Arcapta], salmeterol [Serevent Diskus]). Tiotropium has been shown to improve quality-of-life scores, with a number needed to treat of 14 to prevent one exacerbation and 30 to prevent one hospitalization over one year.22 If tiotropium is prescribed, patients should be switched from ipratropium or ipratropium/albuterol (Combivent) to albuterol alone as short-acting rescue medication.

Long-acting beta2 agonists reduce exacerbation risk and improve FEV1 and daily symptom scores.23 A randomized, double-blind trial of 6,112 patients with moderate to severe COPD showed that salmeterol improved FEV1 and decreased exacerbation risk, but did not reduce mortality.24 Indacaterol is a once-daily long-acting beta2 agonist that improves FEV1 and reduces rescue use of albuterol.25 In patients with comorbid asthma or an unclear diagnosis, monotherapy with a long-acting beta2 agonist is contraindicated because it may increase cardiovascular mortality.26

Tiotropium reduces exacerbations and COPD-related hospitalizations compared with long-acting beta2 agonists, but does not affect mortality.27 For patients whose symptoms are not controlled with tiotropium or a long-acting beta2 agonist alone, a combination of tiotropium and a long-acting beta2 agonist is recommended based on short-term outcomes of improved symptom scores and higher FEV1.28,29

A 2008 meta-analysis found an association between the use of inhaled anticholinergics (ipratropium and tiotropium) and cardiovascular mortality in patients with COPD.30 However, a subsequent randomized, double-blind trial with 5,993 patients demonstrated decreased cardiovascular and overall mortality with tiotropium after four years of follow-up.31 A large cohort study of U.S. veterans showed an increased risk of cardiovascular events with the use of ipratropium in the previous six months.32 Given this association, ipratropium should be avoided in patients with cardiovascular disease.

Patients in GOLD groups C and D should be prescribed a long-acting anticholinergic or a combination of an inhaled corticosteroid and long-acting beta2 agonist.3 Compared with tiotropium alone, fluticasone/salmeterol (Advair) improved daily symptom scores and decreased mortality (number needed to treat = 40), but increased the incidence of pneumonia (number needed to harm = 25) and did not change the rate of exacerbations.33 Patients with poorly controlled symptoms should start triple therapy with an inhaled corticosteroid, long-acting anticholinergic, and long-acting beta2 agonist. The data for triple therapy are inconsistent, with studies showing improvement in lung function and symptom scores but conflicting results regarding reduction in exacerbation rates compared with tiotropium alone.28,34  A summary of initial treatment options and common medications is presented in Table 48and Table 5,35 and patient instructions for inhaler use are reviewed in eFigure B.

Table 4.

Initial Pharmacologic Management of Chronic Obstructive Pulmonary Disease

Patient group* First choice Second choice Alternatives

A

Short-acting anticholinergic as needed (e.g., ipratropium [Atrovent HFA])

or

Short-acting beta2 agonist (e.g., albuterol) as needed

Long-acting anticholinergic (e.g., tiotropium [Spiriva])

or

Long-acting beta2 agonist (e.g., salmeterol [Serevent Diskus])

or

Short-acting beta2 agonist and short-acting anticholinergic

Theophylline

B

Long-acting anticholinergic

or

Long-acting beta2 agonist

Long-acting anticholinergic and long-acting beta2 agonist

Short-acting anticholinergic as needed and/or short-acting beta2 agonist as needed

Theophylline

C

Inhaled corticosteroid(e.g., fluticasone [Flovent]) and long-acting beta2 agonist

or

Long-acting anticholinergic

Long-acting anticholinergic and long-acting beta2 agonist

Phosphodiesterase-4 inhibitor (e.g., roflumilast [Daliresp])

Short-acting anticholinergic as needed agonist as and/or short-acting beta2 needed

Theophylline

D

Inhaled corticosteroid and long-acting beta2 agonist

or

Long-acting anticholinergic

Inhaled corticosteroid and long-acting anticholinergic

or

Inhaled corticosteroid and long-acting beta2 agonist and long-acting anticholinergic

or

Inhaled corticosteroid and long-acting beta2 agonist and phosphodiesterase-4 inhibitor

or

Long-acting anticholinergic and long-acting beta2 agonist

or

Long-acting anticholinergic and phosphodiesterase-4 inhibitor

Short-acting anticholinergic as needed and/or short-acting beta2 agonist as needed

Theophylline


*—See Figure 1 for definition of patient groups.

Information from reference 8.

Table 4.   Initial Pharmacologic Management of Chronic Obstructive Pulmonary Disease

View Table

Table 4.

Initial Pharmacologic Management of Chronic Obstructive Pulmonary Disease

Patient group* First choice Second choice Alternatives

A

Short-acting anticholinergic as needed (e.g., ipratropium [Atrovent HFA])

or

Short-acting beta2 agonist (e.g., albuterol) as needed

Long-acting anticholinergic (e.g., tiotropium [Spiriva])

or

Long-acting beta2 agonist (e.g., salmeterol [Serevent Diskus])

or

Short-acting beta2 agonist and short-acting anticholinergic

Theophylline

B

Long-acting anticholinergic

or

Long-acting beta2 agonist

Long-acting anticholinergic and long-acting beta2 agonist

Short-acting anticholinergic as needed and/or short-acting beta2 agonist as needed

Theophylline

C

Inhaled corticosteroid(e.g., fluticasone [Flovent]) and long-acting beta2 agonist

or

Long-acting anticholinergic

Long-acting anticholinergic and long-acting beta2 agonist

Phosphodiesterase-4 inhibitor (e.g., roflumilast [Daliresp])

Short-acting anticholinergic as needed agonist as and/or short-acting beta2 needed

Theophylline

D

Inhaled corticosteroid and long-acting beta2 agonist

or

Long-acting anticholinergic

Inhaled corticosteroid and long-acting anticholinergic

or

Inhaled corticosteroid and long-acting beta2 agonist and long-acting anticholinergic

or

Inhaled corticosteroid and long-acting beta2 agonist and phosphodiesterase-4 inhibitor

or

Long-acting anticholinergic and long-acting beta2 agonist

or

Long-acting anticholinergic and phosphodiesterase-4 inhibitor

Short-acting anticholinergic as needed and/or short-acting beta2 agonist as needed

Theophylline


*—See Figure 1 for definition of patient groups.

Information from reference 8.

Table 5.

Medications Commonly Used for Treating Chronic Obstructive Pulmonary Disease

Medication Dosage Cost* Potential adverse effects

Short-acting anticholinergic

Ipratropium (Atrovent HFA)

Two puffs every six hours as needed

$236 per inhaler

Anaphylaxis, angioedema, bronchospasm (paradoxical), glaucoma (narrow-angle), hypersensitivity reaction, laryngospasm

Short-acting beta2 agonists

Albuterol

Two puffs every four to six hours as needed

$33 per inhaler (generic)

Angina, angioedema, arrhythmias, bronchospasm (paradoxical), hypertension, hypokalemia, QT-interval prolongation, seizures

Levalbuterol (Xopenex HFA)

Two puffs every four to six hours as needed

$55 per inhaler

Anaphylaxis, arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypertension, hypokalemia, metabolic acidosis, paresthesia, syncope

Pirbuterol (Maxair Autohaler)

One or two puffs every four to six hours as needed

$450 per inhaler

Arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypertension, hypokalemia, seizures

Long-acting anticholinergics

Aclidinium (Tudorza Pressair)

One dose twice per day

$237 for 60 doses

Atrioventricular block, bronchospasm (paradoxical), cardiopulmonary arrest, heart failure, hypersensitivity reaction

Tiotropium (Spiriva)

One dose per day

$282 for 30 doses

Angioedema, bronchospasm (paradoxical), glaucoma, hypersensitivity reaction

Long-acting beta2agonists

Arformoterol (Brovana)

15 mcg twice per day (nebulizer only)

$249 for 30 vials (15 mcg per vial)

Arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypokalemia, lung cancer

Formoterol (Foradil)

One dose every 12 hours

$200 for 60 doses

Anaphylaxis, arrhythmias, asthma exacerbation, atrial fibrillation, bronchospasm (paradoxical), hypertension, hypokalemia, metabolic acidosis

Indacaterol (Arcapta)

One capsule per day

$187 for 30 capsules

Arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypokalemia, seizure disorder

Salmeterol (Serevent Diskus)

One puff every 12 hours

$205 per inhaler

Anaphylaxis, angioedema, arrhythmias, bronchospasm (paradoxical), fever, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, paresthesia, pelvic inflammatory disease, vasculitis

Inhaled corticosteroids

Beclomethasone (Qvar, 40 to 80 mcg per puff)

40 to 320 mcg twice per day

$176 per inhaler

Anaphylaxis, angioedema, bronchospasm, hypersensitivity reaction, glaucoma, suicidal ideation

Budesonide (Pulmicort, 90 to 180 mcg per puff)

180 to 360 mcg twice per day

$120 to $135 per inhaler, depending on dosage

Adrenal insufficiency, angioedema, benign intracranial hypertension, bronchospasm, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, leukocytosis

Ciclesonide (Alvesco, 80 to 160 mcg per puff)

80 to 160 mcg twice per day

$188 per inhaler

Angioedema, bronchospasm (paradoxical), elevated liver enzymes, increased intraocular pressure

Fluticasone (Flovent HFA, 44 to 220 mcg per puff; Flovent Diskus, 100 to 250 mcg per puff)

44 to 500 mcg twice per day

$130 to $275 per inhaler, depending on dosage and delivery system

Anaphylaxis, angioedema, asthma exacerbation, bronchospasm (paradoxical), Churg-Strauss syndrome, fever, hypersensitivity reaction, muscle injury, vasculitis, wheezing

Mometasone (Asmanex, 220 mcg per puff)

One or two puffs per day

$181 per inhaler

Anaphylaxis, angioedema, bronchospasm, fever, hypersensitivity reaction, increased intraocular pressure, wheezing

Combination medications

Budesonide/formoterol (Symbicort)

Two puffs twice per day

$222 to $253, depending on dosage

Anaphylaxis, angioedema, arrhythmias, bronchospasm, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, hypotension, increased intraocular pressure, tachycardia

Fluticasone/salmeterol (Advair)

One puff twice per day (Diskus); two puffs twice per day (HFA)

$235 to $380 per inhaler, depending on dosage and delivery system

Anaphylaxis, angioedema, arrhythmias, asthma exacerbation, bronchospasm, hypertension, hypokalemia, myocardial ischemia, stridor, tachycardia, wheezing

Ipratropium/albuterol (Combivent Respimat)

One or two puffs every six hours as needed

$280 per inhaler

Anaphylaxis, angioedema, arrhythmias, exacerbation of chronic obstructive pulmonary disease, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, increased intraocular pressure, metabolic acidosis, myocardial ischemia, tachycardia

Mometasone/formoterol (Dulera)

Two puffs twice per day

$241 per inhaler

Adrenal suppression, angioedema, arrhythmias, asthma exacerbation, bronchospasm, glaucoma, hypersensitivity reaction, hypokalemia, seizures, vasculitis

Other

Roflumilast (Daliresp)

500 mcg per day

$215 for 30 500-mcg tablets

Arrhythmias, elevated liver enzymes, hypersensitivity reaction, lung cancer, paresthesia, prostate cancer, renal failure, suicidal ideation

Theophylline (extended-release)

300 mg per day initially, then titrate by serum levels

$10 (generic) for 30 300-mg tablets

Arrhythmias, hyperthyroidism, intractable vomiting, peptic ulcer disease, seizures, status epilepticus


*—Estimated retail price based on information obtained at http://www.goodrx.com and http://www.drugpriceinfo.com (accessed August 20, 2013).

Information from reference 35.

Table 5.   Medications Commonly Used for Treating Chronic Obstructive Pulmonary Disease

View Table

Table 5.

Medications Commonly Used for Treating Chronic Obstructive Pulmonary Disease

Medication Dosage Cost* Potential adverse effects

Short-acting anticholinergic

Ipratropium (Atrovent HFA)

Two puffs every six hours as needed

$236 per inhaler

Anaphylaxis, angioedema, bronchospasm (paradoxical), glaucoma (narrow-angle), hypersensitivity reaction, laryngospasm

Short-acting beta2 agonists

Albuterol

Two puffs every four to six hours as needed

$33 per inhaler (generic)

Angina, angioedema, arrhythmias, bronchospasm (paradoxical), hypertension, hypokalemia, QT-interval prolongation, seizures

Levalbuterol (Xopenex HFA)

Two puffs every four to six hours as needed

$55 per inhaler

Anaphylaxis, arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypertension, hypokalemia, metabolic acidosis, paresthesia, syncope

Pirbuterol (Maxair Autohaler)

One or two puffs every four to six hours as needed

$450 per inhaler

Arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypertension, hypokalemia, seizures

Long-acting anticholinergics

Aclidinium (Tudorza Pressair)

One dose twice per day

$237 for 60 doses

Atrioventricular block, bronchospasm (paradoxical), cardiopulmonary arrest, heart failure, hypersensitivity reaction

Tiotropium (Spiriva)

One dose per day

$282 for 30 doses

Angioedema, bronchospasm (paradoxical), glaucoma, hypersensitivity reaction

Long-acting beta2agonists

Arformoterol (Brovana)

15 mcg twice per day (nebulizer only)

$249 for 30 vials (15 mcg per vial)

Arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypokalemia, lung cancer

Formoterol (Foradil)

One dose every 12 hours

$200 for 60 doses

Anaphylaxis, arrhythmias, asthma exacerbation, atrial fibrillation, bronchospasm (paradoxical), hypertension, hypokalemia, metabolic acidosis

Indacaterol (Arcapta)

One capsule per day

$187 for 30 capsules

Arrhythmias, bronchospasm (paradoxical), hypersensitivity reaction, hypokalemia, seizure disorder

Salmeterol (Serevent Diskus)

One puff every 12 hours

$205 per inhaler

Anaphylaxis, angioedema, arrhythmias, bronchospasm (paradoxical), fever, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, paresthesia, pelvic inflammatory disease, vasculitis

Inhaled corticosteroids

Beclomethasone (Qvar, 40 to 80 mcg per puff)

40 to 320 mcg twice per day

$176 per inhaler

Anaphylaxis, angioedema, bronchospasm, hypersensitivity reaction, glaucoma, suicidal ideation

Budesonide (Pulmicort, 90 to 180 mcg per puff)

180 to 360 mcg twice per day

$120 to $135 per inhaler, depending on dosage

Adrenal insufficiency, angioedema, benign intracranial hypertension, bronchospasm, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, leukocytosis

Ciclesonide (Alvesco, 80 to 160 mcg per puff)

80 to 160 mcg twice per day

$188 per inhaler

Angioedema, bronchospasm (paradoxical), elevated liver enzymes, increased intraocular pressure

Fluticasone (Flovent HFA, 44 to 220 mcg per puff; Flovent Diskus, 100 to 250 mcg per puff)

44 to 500 mcg twice per day

$130 to $275 per inhaler, depending on dosage and delivery system

Anaphylaxis, angioedema, asthma exacerbation, bronchospasm (paradoxical), Churg-Strauss syndrome, fever, hypersensitivity reaction, muscle injury, vasculitis, wheezing

Mometasone (Asmanex, 220 mcg per puff)

One or two puffs per day

$181 per inhaler

Anaphylaxis, angioedema, bronchospasm, fever, hypersensitivity reaction, increased intraocular pressure, wheezing

Combination medications

Budesonide/formoterol (Symbicort)

Two puffs twice per day

$222 to $253, depending on dosage

Anaphylaxis, angioedema, arrhythmias, bronchospasm, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, hypotension, increased intraocular pressure, tachycardia

Fluticasone/salmeterol (Advair)

One puff twice per day (Diskus); two puffs twice per day (HFA)

$235 to $380 per inhaler, depending on dosage and delivery system

Anaphylaxis, angioedema, arrhythmias, asthma exacerbation, bronchospasm, hypertension, hypokalemia, myocardial ischemia, stridor, tachycardia, wheezing

Ipratropium/albuterol (Combivent Respimat)

One or two puffs every six hours as needed

$280 per inhaler

Anaphylaxis, angioedema, arrhythmias, exacerbation of chronic obstructive pulmonary disease, glaucoma, hypersensitivity reaction, hypertension, hypokalemia, increased intraocular pressure, metabolic acidosis, myocardial ischemia, tachycardia

Mometasone/formoterol (Dulera)

Two puffs twice per day

$241 per inhaler

Adrenal suppression, angioedema, arrhythmias, asthma exacerbation, bronchospasm, glaucoma, hypersensitivity reaction, hypokalemia, seizures, vasculitis

Other

Roflumilast (Daliresp)

500 mcg per day

$215 for 30 500-mcg tablets

Arrhythmias, elevated liver enzymes, hypersensitivity reaction, lung cancer, paresthesia, prostate cancer, renal failure, suicidal ideation

Theophylline (extended-release)

300 mg per day initially, then titrate by serum levels

$10 (generic) for 30 300-mg tablets

Arrhythmias, hyperthyroidism, intractable vomiting, peptic ulcer disease, seizures, status epilepticus


*—Estimated retail price based on information obtained at http://www.goodrx.com and http://www.drugpriceinfo.com (accessed August 20, 2013).

Information from reference 35.

Asthma Basics Booklet

eFigure B.

 Download in PDF format

Directions for appropriate inhaler use. (MDI = metered-dose inhaler.)

View Large

Asthma Basics Booklet


eFigure B.

 Download in PDF format

Directions for appropriate inhaler use. (MDI = metered-dose inhaler.)

Asthma Basics Booklet


eFigure B.

 Download in PDF format

Directions for appropriate inhaler use. (MDI = metered-dose inhaler.)

ORAL MEDICATIONS

Theophylline can be added or used as an alternative in patients whose symptoms are not controlled with triple therapy or who cannot afford inhaler therapy. Theophylline requires drug level monitoring and improves lung function parameters, but has uncertain effects on symptoms and exacerbations.36

Roflumilast (Daliresp), an oral phosphodiesterase-4 inhibitor approved for use in patients with COPD and chronic bronchitis symptoms, can also be added to long-acting bronchodilators in patients in group C or D. Studies have demonstrated improvement in FEV1 but inconsistent results regarding reduction of exacerbation rates.37,38

Prophylactic antibiotic therapy is not recommended to prevent COPD exacerbations. Although erythromycin and azithromycin (Zithromax) have shown a reduced risk of exacerbations,39,40 there are insufficient data about the effects on macrolide resistance and long-term adverse effects to recommend their use.

Oral corticosteroids do not improve quality of life or reduce exacerbation rates, and are not recommended for patients with stable COPD.41

OXYGEN

Long-term oxygen therapy is recommended for patients with COPD and severe hypoxemia (oxygen saturation less than 88% or partial arterial oxygen pressure less than 55 mg Hg). Supplemental oxygen improves endurance and exercise capacity in patients with moderate to severe COPD.42 A multicenter randomized trial with 203 patients who had hypoxemia and COPD demonstrated that continuous oxygen therapy had benefits on survival rates compared with nocturnal oxygen therapy.43 The goal oxygen saturation should be approximately 90% to avoid respiratory acidosis.44

SURGERY

Lung volume reduction surgery improves five-year survival rates in patients with severe COPD and heterogeneous distribution of emphysema with upper lobe predominance.45 Conversely, patients with severe COPD and FEV1 less than 20%, homogenous emphysema, or low carbon monoxide diffusion capacity have increased 30-day mortality after lung volume reduction surgery.46

Lung transplantation may improve quality of life and functional capacity in selected patients with severe COPD. Criteria for referral include a score greater than 5 on the BODE (body mass index, obstruction, dyspnea, exercise) Index3 (Table 647).

Table 6.

BODE Index for Predicting Mortality in Patients with Chronic Obstructive Pulmonary Disease

Component Points
0 1 2 3

Body mass index (kg per m2)

> 21

≤ 21

Obstruction: percentage of predicted FEV1

≥ 65

50 to 64

36 to 49

≤ 35

Dyspnea: mMRC score (Table 3)

0 or 1

2

3

4

Exercise: distance walked in six minutes (meters)

≥ 350

250 to 349

150 to 249

≤ 149


NOTE: Scores range from 0 to 10; higher scores indicate a greater risk of death. Patients with scores of 6 or greater meet criteria for referral for lung transplantation.

FEV1 = forced expiratory volume in one second; mMRC = modified Medical Research Council Dyspnea Scale.

Adapted from Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1007.

Table 6.   BODE Index for Predicting Mortality in Patients with Chronic Obstructive Pulmonary Disease

View Table

Table 6.

BODE Index for Predicting Mortality in Patients with Chronic Obstructive Pulmonary Disease

Component Points
0 1 2 3

Body mass index (kg per m2)

> 21

≤ 21

Obstruction: percentage of predicted FEV1

≥ 65

50 to 64

36 to 49

≤ 35

Dyspnea: mMRC score (Table 3)

0 or 1

2

3

4

Exercise: distance walked in six minutes (meters)

≥ 350

250 to 349

150 to 249

≤ 149


NOTE: Scores range from 0 to 10; higher scores indicate a greater risk of death. Patients with scores of 6 or greater meet criteria for referral for lung transplantation.

FEV1 = forced expiratory volume in one second; mMRC = modified Medical Research Council Dyspnea Scale.

Adapted from Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350(10):1007.

Data Sources: A PubMed search was completed in Clinical Queries using the key terms COPD treatment and COPD therapy. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Also searched were EBSCO Host Academic Search Premier, DynaMed, Essential Evidence Plus, and UpToDate. Search Date: October 2012.

The Authors

HOBART LEE, MD, is the program director and an assistant professor of family medicine at Loma Linda (Calif.) University School of Medicine.

JEFFREY KIM, MD, is the assistant program director and an assistant professor of family medicine at Loma Linda University School of Medicine.

KARINE TAGMAZYAN, MD, is a fourth-year combined family medicine and preventive medicine resident at Loma Linda Inland Empire Consortium for Healthcare Education.

Address correspondence to Hobart Lee, MD, Loma Linda University School of Medicine, 25455 Barton Rd., Ste. 209B, Loma Linda, CA 92354 (e-mail: holee@llu.edu). Reprints are not available from the authors.

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