Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

GOLD group A: initial treatment

1st line – short- or long-acting bronchodilator

Back
ACUTE
|
GOLD group A: initial treatment
1st line – 

short- or long-acting bronchodilator

Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A patients are characterized by few symptoms (Modified British Medical Research Council [mMRC] 0-1 or COPD Assessment Test [CAT] <10) and low risk of exacerbations (0-1 exacerbations per year, not requiring hospitalization).[1]

A short-acting bronchodilator or long-acting bronchodilator should be offered first-line. Long-acting beta-2 agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are preferred over short-acting bronchodilators, except for patients with only very occasional dyspnea.[1] LABAs and LAMAs both significantly improve lung function, dyspnea, and health status and reduce exacerbation rates. [ Cochrane Clinical Answers logo ] [Evidence A]​​​ LAMAs have a greater effect on exacerbation reduction than LABAs.[100][101]

If a long-acting bronchodilator is prescribed, a short-acting bronchodilator should also be prescribed for rescue therapy. Regular use of short-acting bronchodilators is not generally recommended.

Short-acting beta-2 agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) improve lung function and breathlessness and quality of life. Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[91]

SAMAs should be discontinued if a LAMA is prescribed.

SABAs include albuterol and levalbuterol. Ipratropium is a SAMA. LABAs include salmeterol, arformoterol, and olodaterol. LAMAs include tiotropium, umeclidinium, aclidinium, and glycopyrrolate. [ Cochrane Clinical Answers logo ]

Primary options

SABA

albuterol inhaled: (90 micrograms/dose inhaler) 90-180 micrograms (1-2 puffs) every 4-6 hours when required

OR

SABA

levalbuterol inhaled: (45 micrograms/dose inhaler) 45-90 micrograms (1-2 puffs) every 4-6 hours when required

OR

SAMA

ipratropium bromide inhaled: (17 micrograms/dose inhaler) 34 micrograms (2 puffs) up to four times a day when required, maximum 204 micrograms/day

OR

LABA

salmeterol inhaled: (50 micrograms/dose inhaler) 50 micrograms (1 puff) twice daily

OR

LABA

arformoterol inhaled: 15 micrograms nebulized twice daily

OR

LABA

olodaterol inhaled: (2.5 micrograms/dose inhaler) 5 micrograms (2 sprays) once daily

OR

LAMA

tiotropium inhaled: (18 micrograms/capsule inhaler) 18 micrograms (1 capsule) once daily; (2.5 micrograms/dose inhaler) 5 micrograms (2 sprays) once daily

OR

LAMA

umeclidinium inhaled: (62.5 micrograms/dose inhaler) 62.5 micrograms (1 puff) once daily

OR

LAMA

aclidinium bromide inhaled: (400 micrograms/dose inhaler) 400 micrograms (1 puff) twice daily

OR

LAMA

glycopyrrolate inhaled: (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device

Plus – supportive care and advice

Back
ACUTE
|
GOLD group A: initial treatment
Plus – 

supportive care and advice

Treatment recommended for ALL patients in selected patient group

Smoking cessation should be encouraged in all patients, in addition to guidance on avoiding exposure to occupational or environmental tobacco smoke and other irritants.[1][2]​​ Smoking cessation significantly reduces the rate of progression of COPD and risk of malignancies. See Smoking cessation (Treatment algorithm).

Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), respiratory syncytial virus, and coronavirus disease 2019 (COVID-19).[1][181]​​ Vaccination against influenza is associated with fewer exacerbations of COPD.[182][183] [ Cochrane Clinical Answers logo ] ​​ The Centers for Disease Control and Prevention recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.[181]

Patients who use inhaled therapies should receive training on inhaler device technique. The majority of patients make at least one error in using their inhaler, and incorrect inhaler use is associated with worse disease control.[155][156]​ Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[158]

All patients should be well educated about the disease course and symptoms of exacerbation or decompensation. Their expectation of the disease, treatment, and prognosis should be realistic. No medication has been shown to modify the long-term decline in lung function, and the primary goal of pharmacotherapy is to control symptoms and prevent complications. Self-management education should include provision of a written action plan. Physical activity is recommended for all patients with COPD.[1]

GOLD group B: initial treatment

1st line – LABA/LAMA

Back
ACUTE
|
GOLD group B: initial treatment
1st line – 

LABA/LAMA

Global Initiative for Chronic Obstructive Lung Disease (GOLD) group B patients are characterized by more symptoms (Modified British Medical Research Council [mMRC] ≥2 or COPD Assessment Test [CAT] ≥10) and low risk of exacerbations (0-1 exacerbations per year, not requiring hospitalization).[1]

Long-acting muscarinic antagonist (LAMA)/long-acting beta-2 agonist (LABA) combination treatment should be offered first-line in the absence of issues with adverse effects or availability.[1]

Umeclidinium/vilanterol, glycopyrrolate/formoterol, tiotropium/olodaterol, and aclidinium/formoterol are LABA/LAMA combinations approved for use in COPD.[113][227]​​ Umeclidinium/vilanterol decreases the risk of exacerbations in patients with mild/moderate COPD.[107] [ Cochrane Clinical Answers logo ] ​​ 

Primary options

LABA/LAMA

umeclidinium/vilanterol inhaled: (62.5/25 micrograms/dose inhaler) 1 puff once daily

OR

LABA/LAMA

glycopyrrolate/formoterol inhaled: (9/4.8 micrograms/dose inhaler) 2 puffs twice daily

OR

LABA/LAMA

tiotropium/olodaterol inhaled: (2.5/2.5 micrograms/dose inhaler) 2 puffs once daily

OR

LABA/LAMA

aclidinium bromide/formoterol inhaled: (400/12 micrograms/dose inhaler) 1 puff twice daily

Plus – short-acting bronchodilator

Back
ACUTE
|
GOLD group B: initial treatment
Plus – 

short-acting bronchodilator

Treatment recommended for ALL patients in selected patient group

All patients diagnosed with COPD should be prescribed a short-acting bronchodilator for immediate symptom relief.[1]​ Short-acting beta-2 agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) improve lung function and breathlessness and quality of life.

Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[91] SAMAs should be discontinued if a LAMA is prescribed. SABAs include albuterol and levalbuterol.

Regular use of short-acting bronchodilators is not generally recommended. Failure to respond to short-acting bronchodilator may signify an acute exacerbation.

Primary options

albuterol inhaled: (90 micrograms/dose inhaler) 90-180 micrograms (1-2 puffs) every 4-6 hours when required

OR

levalbuterol inhaled: (45 micrograms/dose inhaler) 45-90 micrograms (1-2 puffs) every 4-6 hours when required

OR

ipratropium bromide inhaled: (17 micrograms/dose inhaler) 34 micrograms (2 puffs) up to four times a day when required, maximum 204 micrograms/day

Plus – supportive care and advice

Back
ACUTE
|
GOLD group B: initial treatment
Plus – 

supportive care and advice

Treatment recommended for ALL patients in selected patient group

Smoking cessation should be encouraged in all patients, in addition to guidance on avoiding exposure to occupational or environmental tobacco smoke or other irritants.[1][2]​​ Smoking cessation significantly reduces the rate of progression of COPD and risk of malignancies. See Smoking cessation (Treatment algorithm).

Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), respiratory syncytial virus, and coronavirus disease 2019 (COVID-19).[1][181]​​ Vaccination against influenza is associated with fewer exacerbations of COPD.[182][183] [ Cochrane Clinical Answers logo ] ​​ The Centers for Disease Control and Prevention recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.[181]

Patients who use inhaled therapies should receive training on inhaler device technique. The majority of patients make at least one error in using their inhaler, and incorrect inhaler use is associated with worse disease control.[155][156]​ Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[158]

All patients should be well educated about the disease course and symptoms of exacerbation or decompensation. Their expectation of the disease, treatment, and prognosis should be realistic. No medication has been shown to modify the long-term decline in lung function, and the primary goal of pharmacotherapy is to control symptoms and prevent complications. Self-management education should include provision of a written action plan. Physical activity is recommended for all patients with COPD.[1]

Plus – pulmonary rehabilitation

Back
ACUTE
|
GOLD group B: initial treatment
Plus – 

pulmonary rehabilitation

Treatment recommended for ALL patients in selected patient group

Pulmonary rehabilitation comprises aerobic exercise, strength training, and education, and should be started early in the disease course.[1][189][190]​​ GOLD guidelines recommend pulmonary rehabilitation for patient groups B and E.[1]​​

Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[191]

A large US cohort study found that initiation of pulmonary rehabilitation within 90 days of hospital discharge following an acute exacerbation of COPD was significantly associated with lower mortality risk at 1 year and fewer rehospitalizations at 1 year.[194][195]​ However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[196]

2nd line – LABA or LAMA

Back
ACUTE
|
GOLD group B: initial treatment
2nd line – 

LABA or LAMA

Global Initiative for Chronic Obstructive Lung Disease (GOLD) group B patients are characterized by more symptoms (Modified British Medical Research Council [mMRC] ≥2 or COPD Assessment Test [CAT] ≥10) and low risk of exacerbations (0-1 exacerbations per year, not requiring hospitalization).[1]

If there are issues with adverse effects or availability, monotherapy with either a LAMA or a LABA may be prescribed.[1]​ There is no evidence to recommend one class of long-acting bronchodilator over another for initial treatment in this group of patients. The choice should depend on the patient's perception of symptom relief.[1]

LABAs and LAMAs both significantly improve lung function, dyspnea, and health status and reduce exacerbation rates. [ Cochrane Clinical Answers logo ] ​ 

LABAs include salmeterol, arformoterol, and olodaterol. LAMAs include tiotropium, umeclidinium, aclidinium, and glycopyrrolate. [ Cochrane Clinical Answers logo ] ​ Revefenacin is a nebulized LAMA approved for the maintenance treatment of moderate to severe COPD.

Primary options

LABA

salmeterol inhaled: (50 micrograms/dose inhaler) 50 micrograms (1 puff) twice daily

OR

LABA

arformoterol inhaled: 15 micrograms nebulized twice daily

OR

LABA

olodaterol inhaled: (2.5 micrograms/dose inhaler) 5 micrograms (2 sprays) once daily

OR

LAMA

tiotropium inhaled: (18 micrograms/capsule inhaler) 18 micrograms (1 capsule) once daily; (2.5 micrograms/dose inhaler) 5 micrograms (2 sprays) once daily

OR

LAMA

umeclidinium inhaled: (62.5 micrograms/dose inhaler) 62.5 micrograms (1 puff) once daily

OR

LAMA

aclidinium bromide inhaled: (400 micrograms/dose inhaler) 400 micrograms (1 puff) twice daily

OR

LAMA

glycopyrrolate inhaled: (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device

OR

LAMA

revefenacin inhaled: 175 micrograms nebulized once daily

Plus – short-acting bronchodilator

Back
ACUTE
|
GOLD group B: initial treatment
Plus – 

short-acting bronchodilator

Treatment recommended for ALL patients in selected patient group

All patients diagnosed with COPD should be prescribed a short-acting bronchodilator for immediate symptom relief.[1] Short-acting beta-2 agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) improve lung function and breathlessness and quality of life.

Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[91] SAMAs should be discontinued if a LAMA is prescribed. SABAs include albuterol and levalbuterol.

Regular use of short-acting bronchodilators is not generally recommended. Failure to respond to short-acting bronchodilator may signify an acute exacerbation.

Primary options

albuterol inhaled: (90 micrograms/dose inhaler) 90-180 micrograms (1-2 puffs) every 4-6 hours when required

OR

levalbuterol inhaled: (45 micrograms/dose inhaler) 45-90 micrograms (1-2 puffs) every 4-6 hours when required

OR

ipratropium bromide inhaled: (17 micrograms/dose inhaler) 34 micrograms (2 puffs) up to four times a day when required, maximum 204 micrograms/day

Plus – supportive care and advice

Back
ACUTE
|
GOLD group B: initial treatment
Plus – 

supportive care and advice

Treatment recommended for ALL patients in selected patient group

Smoking cessation should be encouraged in all patients, in addition to guidance on avoiding exposure to occupational or environmental tobacco smoke or other irritants.[1][2]​​ Smoking cessation significantly reduces the rate of progression of COPD and risk of malignancies. See Smoking cessation (Treatment algorithm).

Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), respiratory syncytial virus and coronavirus disease 2019 (COVID-19).[1][181]​​​​ Vaccination against influenza is associated with fewer exacerbations of COPD.[182][183] [ Cochrane Clinical Answers logo ] The CDC also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.[181]

Patients who use inhaled therapies should receive training on inhaler device technique. The majority of patients make at least one error in using their inhaler, and incorrect inhaler use is associated with worse disease control.[155][156]​ Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[158]

All patients should be well educated about the disease course and symptoms of exacerbation or decompensation. Their expectation of the disease, treatment, and prognosis should be realistic. No medication has been shown to modify the long-term decline in lung function, and the primary goal of pharmacotherapy is to control symptoms and prevent complications. Self-management education should include provision of a written action plan. Physical activity is recommended for all patients with COPD.[1]

Plus – pulmonary rehabilitation

Back
ACUTE
|
GOLD group B: initial treatment
Plus – 

pulmonary rehabilitation

Treatment recommended for ALL patients in selected patient group

Pulmonary rehabilitation comprises aerobic exercise, strength training, and education, and should be started early in the disease course.[1][189][190]​​ GOLD guidelines recommend pulmonary rehabilitation for patient groups B and E.[1]

Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[191]

A large US cohort study found that initiation of pulmonary rehabilitation within 90 days of hospital discharge following an acute exacerbation of COPD was significantly associated with lower mortality risk at 1 year and fewer rehospitalizations at 1 year.[194][195]​ However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[196]

GOLD group E: initial treatment

1st line – LABA/LAMA or LABA/LAMA/ICS

Back
ACUTE
|
GOLD group E: initial treatment
1st line – 

LABA/LAMA or LABA/LAMA/ICS

Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E patients are characterized by a high risk of exacerbations (≥2 exacerbations per year, or ≥1 requiring hospitalization) and any level of symptoms.[1]

GOLD recommends starting therapy with a long-acting beta-2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination.[1]

Addition of an inhaled corticosteroid (ICS) to a LABA/LAMA combination should be considered if the patient's blood eosinophil count is ≥300 cells/microliter.[1] The effect of treatment regimens containing ICS is higher in patients at higher risk of exacerbations (two or more exacerbations and/or one hospitalization for an exacerbation in the previous year).[84][86][113]​​ Blood eosinophil count may predict the effectiveness of adding inhaled corticosteroids to regular long-acting bronchodilator treatment to prevent exacerbations.[71][72][73]​​ Little or no effect is seen at blood eosinophil counts of <100 cells/microliter, while maximal effect is seen at blood eosinophil counts of ≥300 cells/microliter.[70][74]​​ These thresholds indicate approximate cut-off values that may help clinicians predict the likelihood of a treatment benefit.[1] Use of ICS also slows the rate of decline in lung function following an exacerbation in patients with mild to moderate COPD and elevated blood eosinophils.[128] Former smokers are more corticosteroid-responsive than current smokers at any eosinophil count.[73] Both current and former smokers with COPD can benefit from ICS in terms of lung function and rates of exacerbations, although the effect is smaller for heavy or current smokers compared with light or former smokers.[86][114]

ICS increases the risk of developing pneumonia in some patients, so should only be used as initial therapy after the possible clinical risks and benefits have been evaluated.

Umeclidinium/vilanterol, glycopyrrolate/formoterol, tiotropium/olodaterol, and aclidinium/formoterol are LABA/LAMA combinations approved for use in COPD.[113][227]​ Umeclidinium/vilanterol decreases the risk of exacerbations in patients with mild/moderate COPD.[107] [ Cochrane Clinical Answers logo ]

Fluticasone/umeclidinium/vilanterol (a LABA/LAMA/ICS combination) is available as a proprietary combination inhaler.

Primary options

LABA/LAMA

umeclidinium/vilanterol inhaled: (62.5/25 micrograms/dose inhaler) 1 puff once daily

OR

LABA/LAMA

glycopyrrolate/formoterol inhaled: (9/4.8 micrograms/dose inhaler) 2 puffs twice daily

OR

LABA/LAMA

tiotropium/olodaterol inhaled: (2.5/2.5 micrograms/dose inhaler) 2 puffs once daily

OR

LABA/LAMA

aclidinium bromide/formoterol inhaled: (400/12 micrograms/dose inhaler) 1 puff twice daily

Secondary options

LABA/LAMA/ICS

fluticasone furoate/umeclidinium/vilanterol inhaled: (100/62.5/25 micrograms/dose inhaler) 1 puff once daily

OR

LABA/LAMA/ICS

fluticasone furoate/vilanterol inhaled: (100/25 micrograms/dose inhaler) 1 puff once daily

or

fluticasone propionate/salmeterol inhaled: (250/50 micrograms/dose inhaler) 1 puff twice daily

or

budesonide/formoterol inhaled: (160/4.5 micrograms/dose inhaler) 2 puffs twice daily

or

mometasone/formoterol inhaled: (100/5 micrograms/dose inhaler; 200/5 micrograms/dose inhaler) 2 puffs twice daily

-- AND --

tiotropium inhaled: (18 micrograms/capsule inhaler) 18 micrograms (1 capsule) once daily; (2.5 micrograms/dose inhaler) 5 micrograms (2 sprays) once daily

or

umeclidinium inhaled: (62.5 micrograms/dose inhaler) 62.5 micrograms (1 puff) once daily

or

aclidinium bromide inhaled: (400 micrograms/dose inhaler) 400 micrograms (1 puff) twice daily

or

glycopyrrolate inhaled: (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device

Plus – short-acting bronchodilator

Back
ACUTE
|
GOLD group E: initial treatment
Plus – 

short-acting bronchodilator

Treatment recommended for ALL patients in selected patient group

All patients diagnosed with COPD should be prescribed a short-acting bronchodilator for immediate symptom relief.[1] Short-acting beta-2 agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) improve lung function and breathlessness and quality of life.[91]

Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[91] SAMAs should be discontinued if a LAMA is prescribed. SABAs include albuterol and levalbuterol.

Regular use of short-acting bronchodilators is not generally recommended. Failure to respond to short-acting bronchodilator may signify an acute exacerbation.

Primary options

albuterol inhaled: (90 micrograms/dose inhaler) 90-180 micrograms (1-2 puffs) every 4-6 hours when required

OR

levalbuterol inhaled: (45 micrograms/dose inhaler) 45-90 micrograms (1-2 puffs) every 4-6 hours when required

OR

ipratropium bromide inhaled: (17 micrograms/dose inhaler) 34 micrograms (2 puffs) up to four times a day when required, maximum 204 micrograms/day

Plus – supportive care and advice

Back
ACUTE
|
GOLD group E: initial treatment
Plus – 

supportive care and advice

Treatment recommended for ALL patients in selected patient group

Smoking cessation should be encouraged in all patients, in addition to guidance on avoiding exposure to occupational or environmental tobacco smoke or other irritants.[1][2]​​ Smoking cessation significantly reduces the rate of progression of COPD and risk of malignancies. See Smoking cessation (Treatment algorithm).

Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), respiratory syncytial virus, and coronavirus disease 2019 (COVID-19).[1][181]​​ Vaccination against influenza is associated with fewer exacerbations of COPD.[182][183] [ Cochrane Clinical Answers logo ] ​​ The Centers for Disease Control and Prevention recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.[181]

Patients who use inhaled therapies should receive training on inhaler device technique. The majority of patients make at least one error in using their inhaler, and incorrect inhaler use is associated with worse disease control.[155][156]​ Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[158]

All patients should be well educated about the disease course and symptoms of exacerbation or decompensation. Their expectation of the disease, treatment, and prognosis should be realistic. No medication has been shown to modify the long-term decline in lung function, and the primary goal of pharmacotherapy is to control symptoms and prevent complications. Self-management education should include provision of a written action plan. Physical activity is recommended for all patients with COPD.[1]

Plus – pulmonary rehabilitation

Back
ACUTE
|
GOLD group E: initial treatment
Plus – 

pulmonary rehabilitation

Treatment recommended for ALL patients in selected patient group

Pulmonary rehabilitation comprises aerobic exercise, strength training, and education, and should be started early in the disease course.[1][189][190]​​ GOLD guidelines recommend pulmonary rehabilitation for patient groups B and E.[1]

Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[191]

A large US cohort study found that initiation of pulmonary rehabilitation within 90 days of hospital discharge following an acute exacerbation of COPD was significantly associated with lower mortality risk at 1 year and fewer rehospitalizations at 1 year.[194][195]​ However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[196]

ONGOING

GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy

1st line – LABA/LAMA

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
1st line – 

LABA/LAMA

Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A patients are characterized by few symptoms (Modified British Medical Research Council [mMRC] 0-1 or COPD Assessment Test [CAT] <10) and low risk of exacerbations (0-1 exacerbations per year, not requiring hospitalization); group B by more symptoms (mMRC ≥2 or CAT ≥10) and low risk of exacerbations (0-1 exacerbations per year, not requiring hospitalization); and group E by a high risk of exacerbations (≥2 exacerbations per year, or ≥1 requiring hospitalization) and any level of symptoms.[1]

GOLD advises that if a patient has both persistent symptoms and exacerbations after initial therapy, clinicians should follow the pathway for treating persistent exacerbations.[1]

Patients with persistent dyspnea/exercise limitation while on a long-acting beta-2 agonist (LABA) or a long-acting muscarinic antagonist (LAMA) alone should switch to dual long-acting bronchodilator therapy with a LABA/LAMA combination. If symptoms do not improve, changing inhaler device or molecules may be considered.[1] 

A LABA/LAMA combination may provide a better therapeutic effect without increasing the adverse effects of each class.[99][103][104][105][106]​​​ Systematic reviews and meta-analyses have found that combination therapy with a LABA/LAMA:

reduces exacerbation rate compared with monotherapy;

is associated with a clinically significant improvement in lung function and health-related quality of life in patients with mild/moderate COPD, compared with placebo;[107] [ Cochrane Clinical Answers logo ]

improves FEV₁ and modestly reduces risk of pneumonia in patients with stable chronic obstructive pulmonary disease, but increases odds of all-cause death from 1% to 1.4%.[108] [ Cochrane Clinical Answers logo ] ​ 

Dyspnea due to other causes should be considered, investigated, and treated. Inhaler technique and adherence should also be re-assessed, as these may have led to an inadequate response to treatment.

Primary options

LABA/LAMA

umeclidinium/vilanterol inhaled: (62.5/25 micrograms/dose inhaler) 1 puff once daily

OR

LABA/LAMA

glycopyrrolate/formoterol inhaled: (9/4.8 micrograms/dose inhaler) 2 puffs twice daily

OR

LABA/LAMA

tiotropium/olodaterol inhaled: (2.5/2.5 micrograms/dose inhaler) 2 puffs once daily

OR

LABA/LAMA

aclidinium bromide/formoterol inhaled: (400/12 micrograms/dose inhaler) 1 puff twice daily

Plus – short-acting bronchodilator

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Plus – 

short-acting bronchodilator

Treatment recommended for ALL patients in selected patient group

All patients diagnosed with COPD should be prescribed a short-acting bronchodilator for immediate symptom relief.[1] 

Short-acting beta-2 agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) improve lung function and breathlessness and quality of life.[91]

Regular use of short-acting bronchodilators is not generally recommended. Failure to respond to short-acting bronchodilator may signify an acute exacerbation.

SAMAs should not be prescribed with a LAMA. SABAs include albuterol and levalbuterol.

Primary options

albuterol inhaled: (90 micrograms/dose inhaler) 90-180 micrograms (1-2 puffs) every 4-6 hours when required

OR

levalbuterol inhaled: (45 micrograms/dose inhaler) 45-90 micrograms (1-2 puffs) every 4-6 hours when required

Plus – supportive care and advice

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Plus – 

supportive care and advice

Treatment recommended for ALL patients in selected patient group

Smoking cessation should be encouraged in all patients, in addition to guidance on avoiding exposure to occupational or environmental tobacco smoke or other irritants.[1][2]​​ Smoking cessation significantly reduces the rate of progression of COPD and risk of malignancies. See Smoking cessation (Treatment algorithm).

Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), respiratory syncytial virus, and coronavirus disease 2019 (COVID-19).[1][181]​​ Vaccination against influenza is associated with fewer exacerbations of COPD.[182][183] [ Cochrane Clinical Answers logo ] ​​ The Centers for Disease Control and Prevention recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.[181]

Patients who use inhaled therapies should receive training on inhaler device technique. The majority of patients make at least one error in using their inhaler, and incorrect inhaler use is associated with worse disease control.[155][156]​ Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[158]

All patients should be well educated about the disease course and symptoms of exacerbation or decompensation. Their expectation of the disease, treatment, and prognosis should be realistic. No medication has been shown to modify the long-term decline in lung function, and the primary goal of pharmacotherapy is to control symptoms and prevent complications. Self-management education should include provision of a written action plan. Physical activity is recommended for all patients with COPD.[1]

Consider – pulmonary rehabilitation

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Consider – 

pulmonary rehabilitation

Treatment recommended for SOME patients in selected patient group

Pulmonary rehabilitation comprises aerobic exercise, strength training, and education, and should be started early in the disease course.[1][189][190]​​ GOLD guidelines recommend pulmonary rehabilitation for patient groups B and E.[1]

Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[191]

A large US cohort study found that initiation of pulmonary rehabilitation within 90 days of hospital discharge following an acute exacerbation of COPD was significantly associated with lower mortality risk at 1 year and fewer rehospitalizations at 1 year.[194][195]​ However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[196]

Consider – oxygen therapy and/or ventilatory support

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Consider – 

oxygen therapy and/or ventilatory support

Treatment recommended for SOME patients in selected patient group

GOLD guidelines recommend long-term oxygen therapy in stable patients who have: PaO₂ ≤7.3 kPa (55 mmHg) or SaO₂ ≤88%, with or without hypercapnia confirmed twice over a 3-week period; or PaO₂ between 7.3 kPa (55 mmHg) and 8.0 kPa (60 mmHg) or SaO₂ of 88%, if there is evidence of pulmonary hypertension, peripheral edema suggesting congestive cardiac failure, or polycythemia (hematocrit >55%).[1]

Guidelines from the American Thoracic Society (ATS) recommend prescribing long-term oxygen therapy for at least 15 hours per day in adults with COPD who have severe chronic resting room air hypoxemia. The ATS defines severe hypoxemia as either: PaO₂ ≤7.3 kPa (55 mmHg) or oxygen saturation as measured by pulse oximetry (SpO₂) ≤88%; or PaO₂ 7.5 to 7.9 kPa (56-59 mmHg) or SpO₂ of 89% plus one of the following: edema, hematocrit ≥55%, or P pulmonale on an ECG.[204]

For patients prescribed home oxygen therapy, the ATS recommends that the patient and their caregivers should receive instruction and training on the use and maintenance of all oxygen equipment and education on oxygen safety, including smoking cessation, fire prevention, and tripping hazards.[204]

Supplemental oxygen should be titrated to achieve SaO₂ ≥90%.[1] The patient should be reassessed after 60-90 days to determine whether oxygen is still indicated and is therapeutic.[1] Among different therapeutic modalities in COPD, the only two factors that improve survival are smoking cessation and oxygen supplementation.

Oxygen therapy helps minimize pulmonary hypertension by decreasing pulmonary artery pressure, and improves exercise tolerance and quality of life. It has been shown to improve survival.[1][61]

The ATS suggests prescribing ambulatory oxygen (oxygen delivered during exercise or activities of daily living) in adults with COPD who have severe exertional room air hypoxemia.[204] However, the ATS suggests not prescribing long-term oxygen therapy in adults with COPD who have moderate chronic resting room air hypoxemia (SpO₂ of 89% to 93%).[204]

For patients who have COPD and obstructive sleep apnea, ventilatory support with continuous positive airway pressure (CPAP) can improve survival and reduce hospital admissions.[1][67]​ Noninvasive ventilation is occasionally used in patients with very severe but stable COPD, although the optimal timing for initiation and best selection criteria for candidates is unclear.[1][208]

Guidelines from the ATS suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD.[211] The European Respiratory Society and Canadian Thoracic Society have issued similar guidance.[212][213]

Consider – mucolytic

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Consider – 

mucolytic

Treatment recommended for SOME patients in selected patient group

Patients with the chronic bronchitis phenotype of COPD often produce thick sputum on a frequent basis. Mucolytic agents result in a small reduction in the frequency of acute exacerbations and in days of disability per month, but do not improve lung function or quality of life.[186] One meta-analysis comparing erdosteine, carbocysteine, and acetylcysteine concluded that erdosteine had the most favorable safety and efficacy profile. Erdosteine reduced the risk of hospitalization due to an acute exacerbation, and erdosteine and acetylcysteine reduced the duration of an acute exacerbation.[187] Erdosteine is therefore the preferred option in countries where it is available. Another meta-analysis found that acetylcysteine significantly reduced the frequency of exacerbations compared with placebo, without increasing the risk of adverse effects. The authors concluded that 3 months of treatment with a low dosage was effective.[188] Treatment with mucolytic agents such as carbocysteine and acetylcysteine may reduce exacerbations and modestly improve health status in patients not receiving ICS.[1] However, erdosteine may have a significant effect on mild exacerbations whether or not the patient is taking inhaled corticosteroids.[1] Erdosteine and carbocysteine are not available in the US.

Primary options

acetylcysteine: consult specialist for guidance on dose

Consider – theophylline

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Consider – 

theophylline

Treatment recommended for SOME patients in selected patient group

Theophylline (a methylxanthine agent) is not commonly used because of limited potency, narrow therapeutic window, high-risk profile, and frequent drug-drug interactions. Theophylline has modest effects on lung function in moderate to severe COPD.[144] A large randomized controlled trial found no effect of oral theophylline alone or with prednisone on exacerbations of severe COPD.[145] Experts may prescribe theophylline after a patient has exhausted all options for inhaled therapies. Toxicity is dose-related. Theophylline is not recommended unless other long-term bronchodilator treatments are unavailable or unaffordable.[1]

Primary options

theophylline: consult specialist for guidance on dose

Consider – bronchoscopic intervention or surgery

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Consider – 

bronchoscopic intervention or surgery

Treatment recommended for SOME patients in selected patient group

Surgical interventions are the last step in the management of COPD, and include bullectomy, lung volume reduction surgery, and lung transplant.[214][215] [ Cochrane Clinical Answers logo ] ​​​ They are used to improve lung dynamics, exercise adherence, and quality of life.[215] Lung volume reduction surgery is indicated in patients with very severe airflow limitation, and especially in patients with localized upper lobe disease and lower than normal exercise capacity.[214] [ Cochrane Clinical Answers logo ] ​​​ One meta-analysis found an increased risk of early mortality in patients who underwent lung volume reduction surgery compared to standard care; however, no significant difference was observed in overall mortality.[216] Bullectomy is an option in COPD patients with dyspnea in whom CT reveals huge bullae occupying at least 30% of the hemithorax. Severely poor functional status and severe decrease in FEV₁ (<500 mL) make these options less favorable. Endobronchial valve insertion can produce clinically meaningful improvements in appropriately selected patients with COPD.[216][217][218]​​​ The procedure may be most beneficial in patients whose dyspnea is primarily due to hyperinflation and air trapping in the air spaces distal to the terminal bronchioles, which manifests as emphysema with markedly increased residual volume. Contraindications include active lung infection and incomplete lobar fissures (<80%).[219] The most common adverse events associated with endobronchial valve insertion are pneumothorax and exacerbation.[216]

Criteria for referral for lung transplantation include:[220]

Body mass index, airflow Obstruction, Dyspnea, and Exercise (BODE) score 5-6 with additional factor(s) present suggestive of increased risk of mortality: frequent acute exacerbations, increase in BODE score >1 over past 24 months, pulmonary artery to aorta diameter >1 on CT scan, and/or FEV₁ 20% to 25% predicted.

Clinical deterioration despite maximal treatment including medication, pulmonary rehabilitation, oxygen therapy, and, as appropriate, nocturnal noninvasive positive pressure ventilation.

Poor quality of life unacceptable to the patient.

For a patient who is a candidate for bronchoscopic or surgical lung volume reduction (LVR), simultaneous referral for both lung transplant and LVR evaluation is appropriate.

[ BODE Index for COPD Survival Prediction Opens in new window ]

Lung transplantation has been shown to improve quality of life and functional capacity.[215] However, lung transplantation does not appear to confer a survival benefit.[221]

Consider – palliative care

Back
ONGOING
|
GOLD group A, B, or E: persistent dyspnea/exercise limitation after initial therapy
Consider – 

palliative care

Treatment recommended for SOME patients in selected patient group

Palliative therapies to improve symptoms of dyspnea, offer nutritional support, address anxiety and depression, and reduce fatigue may benefit patients with COPD who experience these despite optimal medical therapy. End-of-life care and hospice admission should be considered for patients with very advanced disease. Patient and family should be well educated about the process, and it is suggested that discussions should be held early in the course of the disease before acute respiratory failure develops.[1][222]​ Opioid analgesics, fans, neuromuscular electrical stimulation, and chest wall vibration can relieve dyspnea.[1] One study has suggested that low doses of an opioid analgesic and a benzodiazepine are safe and are not associated with increased hospital admissions or mortality.[223] Another study found that regular, low-dose, oral sustained-release morphine for 4 weeks improved disease-specific health status in patients with COPD and refractory breathlessness.[224]

One Cochrane review concluded that there is no evidence for or against benzodiazepines for the relief of breathlessness in people with advanced cancer and COPD.[225]

Acupuncture and acupressure may also improve breathlessness and quality of life in patients with advanced COPD.[226]

GOLD group A, B, or E: persistent exacerbations after initial therapy

1st line – LABA/LAMA or LABA/LAMA/ICS

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
1st line – 

LABA/LAMA or LABA/LAMA/ICS

Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A patients are characterized by few symptoms (Modified British Medical Research Council [mMRC] 0-1 or COPD Assessment Test [CAT] <10) and low risk of exacerbations (0-1 exacerbations per year, not requiring hospitalization); group B by more symptoms (mMRC ≥2 or CAT ≥10) and low risk of exacerbations (0-1 exacerbations per year, not requiring hospitalization); and group E by a high risk of exacerbations (≥2 exacerbations per year, or ≥1 requiring hospitalization) and any level of symptoms.[1]

Patients taking a long-acting beta-2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) alone and who experience persistent exacerbations should increase therapy to LABA/LAMA.

Blood eosinophil counts can identify patients who are more likely to respond to an inhaled corticosteroid (ICS).[70][71][72]​​ Use of ICS also slows the rate of decline in lung function following an exacerbation in patients with mild to moderate COPD and elevated blood eosinophils.[128] Former smokers are more corticosteroid-responsive than current smokers at any eosinophil count.[73]

Escalation to triple therapy with LABA/LAMA/ICS may be considered for patients on long-acting bronchodilator monotherapy if their peripheral eosinophil count is ≥300 cells/microliter. ICS is unlikely to be beneficial in patients whose blood eosinophil count is <100 cells/microliter.[1]

Patients who take LABA/LAMA who experience persistent exacerbations and whose blood eosinophils are ≥100 cells/microliter should escalate to LABA/LAMA/ICS.[1] Multiple studies support triple therapy with LABA/LAMA/ICS as being superior to single- or double-agent therapy with LABA/LAMA or LABA/ICS regarding rate of moderate to severe COPD exacerbations and rate of hospitalization.[74][82][83][84][85][86][87][88]​​​[89]​​ One randomized controlled trial has reported a reduction in all-cause mortality in patients at risk of exacerbations who take fluticasone furoate/umeclidinium/vilanterol, compared with umeclidinium/vilanterol.[129] Another randomized controlled trial had similar findings in terms of mortality in the triple therapy arm (budesonide/glycopyrrolate/formoterol), but only at the higher dose of ICS.[89][130]​​​ For both studies, there were no differences in mortality compared with LABA/ICS.[89][129][130] A post hoc pooled analysis of three trials of triple therapy in patients with COPD and severe airflow limitation and a history of exacerbations showed a nonsignificant trend for lower mortality with triple therapy compared with non-ICS treatments.[131] These results are strengthened by findings from a meta-analysis of over 200 studies: triple therapy provided a significant reduction in mortality versus dual therapy, although was associated with greater risk of pneumonia. No differences were observed between regimens in lung function or health-related quality of life.[132]

American Thoracic Society guidelines recommend the use of LABA/LAMA/ICS in patients who have had one or more exacerbations requiring oral corticosteroids, antibiotics, or hospitalization in the past year and who have symptoms of dyspnea or reduced exercise tolerance despite LABA/LAMA dual therapy.[90] UK guidelines recommend the use of LABA/LAMA/ICS in patients who have an exacerbation requiring hospitalization, or two moderate exacerbations within a year, despite dual therapy with LABA/LAMA.[2]

LABA/ICS is not recommended by GOLD. However, if a patient with COPD and no features of asthma has received this treatment and is well controlled, they may continue on LABA/ICS. If the patient has further exacerbations, they should be escalated to triple therapy by adding a LAMA. If they have significant symptoms, patients may switch to LABA/LAMA. Patients with blood eosinophils ≥300 cells/microliter are at greatest risk of exacerbations after withdrawing ICS.[75]

Primary options

LABA/LAMA

umeclidinium/vilanterol inhaled: (62.5/25 micrograms/dose inhaler) 1 puff once daily

OR

LABA/LAMA

glycopyrrolate/formoterol inhaled: (9/4.8 micrograms/dose inhaler) 2 puffs twice daily

OR

LABA/LAMA

tiotropium/olodaterol inhaled: (2.5/2.5 micrograms/dose inhaler) 2 puffs once daily

OR

LABA/LAMA

aclidinium bromide/formoterol inhaled: (400/12 micrograms/dose inhaler) 1 puff twice daily

OR

LABA/LAMA/ICS

fluticasone furoate/umeclidinium/vilanterol inhaled: (100/62.5/25 micrograms/dose inhaler) 1 puff once daily

OR

LABA/LAMA/ICS

fluticasone furoate/vilanterol inhaled: (100/25 micrograms/dose inhaler) 1 puff once daily

or

fluticasone propionate/salmeterol inhaled: (250/50 micrograms/dose inhaler) 1 puff twice daily

or

budesonide/formoterol inhaled: (160/4.5 micrograms/dose inhaler) 2 puffs twice daily

or

mometasone/formoterol inhaled: (100/5 micrograms/dose inhaler; 200/5 micrograms/dose inhaler) 2 puffs twice daily

-- AND --

tiotropium inhaled: (18 micrograms/capsule inhaler) 18 micrograms (1 capsule) once daily; (2.5 micrograms/dose inhaler) 5 micrograms (2 sprays) once daily

or

umeclidinium inhaled: (62.5 micrograms/dose inhaler) 62.5 micrograms (1 puff) once daily

or

aclidinium bromide inhaled: (400 micrograms/dose inhaler) 400 micrograms (1 puff) twice daily

or

glycopyrrolate inhaled: (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device

Plus – short-acting bronchodilator

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Plus – 

short-acting bronchodilator

Treatment recommended for ALL patients in selected patient group

All patients diagnosed with COPD should be prescribed a short-acting bronchodilator for immediate symptom relief.[1] 

Short-acting beta-2 agonists (SABAs) and short-acting muscarinic antagonists (SAMAs) improve lung function and breathlessness and quality of life.[91] Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[91] SAMAs should be discontinued if a LAMA is prescribed. SABAs include albuterol and levalbuterol.

Regular use of short-acting bronchodilators is not generally recommended. Failure to respond to short-acting bronchodilator may signify an acute exacerbation.

Primary options

albuterol inhaled: (90 micrograms/dose inhaler) 90-180 micrograms (1-2 puffs) every 4-6 hours when required

OR

levalbuterol inhaled: (45 micrograms/dose inhaler) 45-90 micrograms (1-2 puffs) every 4-6 hours when required

OR

ipratropium bromide inhaled: (17 micrograms/dose inhaler) 34 micrograms (2 puffs) up to four times a day when required, maximum 204 micrograms/day

Plus – supportive care and advice

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Plus – 

supportive care and advice

Treatment recommended for ALL patients in selected patient group

Smoking cessation should be encouraged in all patients, in addition to guidance on avoiding exposure to occupational or environmental tobacco smoke or other irritants.[1][2]​​ Smoking cessation significantly reduces the rate of progression of COPD and risk of malignancies. See Smoking cessation (Treatment algorithm).

Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), respiratory syncytial virus, and coronavirus disease 2019 (COVID-19).[1][181]​​ Vaccination against influenza is associated with fewer exacerbations of COPD.[182][183] [ Cochrane Clinical Answers logo ] ​​ The Centers for Disease Control and Prevention recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.[181]

Patients who use inhaled therapies should receive training on inhaler device technique. The majority of patients make at least one error in using their inhaler, and incorrect inhaler use is associated with worse disease control.[155][156]​ Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[158]

All patients should be well educated about the disease course and symptoms of exacerbation or decompensation. Their expectation of the disease, treatment, and prognosis should be realistic. No medication has been shown to modify the long-term decline in lung function, and the primary goal of pharmacotherapy is to control symptoms and prevent complications. Self-management education should include provision of a written action plan. Physical activity is recommended for all patients with COPD.[1]

Consider – pulmonary rehabilitation

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

pulmonary rehabilitation

Treatment recommended for SOME patients in selected patient group

Pulmonary rehabilitation comprises aerobic exercise, strength training, and education, and should be started early in the disease course.[1][189][190]​​ GOLD guidelines recommend pulmonary rehabilitation for patient groups B and E.[1]

Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[191]

A large US cohort study found that initiation of pulmonary rehabilitation within 90 days of hospital discharge following an acute exacerbation of COPD was significantly associated with lower mortality risk at 1 year and fewer rehospitalizations at 1 year.[194][195]​ However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[196]

Consider – oxygen therapy and/or ventilatory support

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

oxygen therapy and/or ventilatory support

Treatment recommended for SOME patients in selected patient group

GOLD guidelines recommend long-term oxygen therapy in stable patients who have: PaO₂ ≤7.3 kPa (55 mmHg) or SaO₂ ≤88%, with or without hypercapnia confirmed twice over a 3-week period; or PaO₂ between 7.3 kPa (55 mmHg) and 8.0 kPa (60 mmHg) or SaO₂ of 88%, if there is evidence of pulmonary hypertension, peripheral edema suggesting congestive cardiac failure, or polycythemia (hematocrit >55%).[1]

Guidelines from the American Thoracic Society (ATS) recommend prescribing long-term oxygen therapy for at least 15 hours per day in adults with COPD who have severe chronic resting room air hypoxemia. The ATS defines severe hypoxemia as either: PaO₂ ≤7.3 kPa (55 mmHg) or oxygen saturation as measured by pulse oximetry (SpO₂) ≤88%; or PaO₂ 7.5 to 7.9 kPa (56-59 mmHg) or SpO₂ of 89% plus one of the following: edema, hematocrit ≥55%, or P pulmonale on an ECG.[204]

For patients prescribed home oxygen therapy, the ATS recommends that the patient and their caregivers should receive instruction and training on the use and maintenance of all oxygen equipment and education on oxygen safety, including smoking cessation, fire prevention, and tripping hazards.[204]

Supplemental oxygen should be titrated to achieve SaO₂ ≥90%.[1] The patient should be reassessed after 60-90 days to determine whether oxygen is still indicated and is therapeutic.[1] Among different therapeutic modalities in COPD, the only two factors that improve survival are smoking cessation and oxygen supplementation.

Oxygen therapy helps minimize pulmonary hypertension by decreasing pulmonary artery pressure, and improves exercise tolerance and quality of life. It has been shown to improve survival.[1][61]

The ATS suggests prescribing ambulatory oxygen (oxygen delivered during exercise or activities of daily living) in adults with COPD who have severe exertional room air hypoxemia.[204] However, the ATS suggests not prescribing long-term oxygen therapy in adults with COPD who have moderate chronic resting room air hypoxemia (SpO₂ of 89% to 93%).[204]

For patients who have COPD and obstructive sleep apnea, ventilatory support with continuous positive airway pressure (CPAP) can improve survival and reduce hospital admissions.[1][67]​ Noninvasive ventilation is occasionally used in patients with very severe but stable COPD, although the optimal timing for initiation and best selection criteria for candidates is unclear.[1][208][209]

Guidelines from the ATS suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD.[211] The European Respiratory Society and Canadian Thoracic Society have issued similar guidance.[212][213]

Consider – roflumilast

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

roflumilast

Treatment recommended for SOME patients in selected patient group

Roflumilast, an oral phosphodiesterase-4 inhibitor, may be prescribed for patients taking LABA/LAMA who have persistent exacerbations and whose blood eosinophils are <100 cells/microliter, and for patients taking LABA/LAMA/ICS who have persistent exacerbations.[1]

Roflumilast should be considered in patients with FEV₁ <50% predicted and chronic bronchitis, particularly if they have had at least one hospitalization for an exacerbation in the last year.[1]

Primary options

roflumilast: 500 micrograms orally once daily

Consider – azithromycin

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

azithromycin

Treatment recommended for SOME patients in selected patient group

Azithromycin may be prescribed for patients taking LABA/LAMA who have persistent exacerbations and whose blood eosinophils are <100 cells/microliter, and for patients taking LABA/LAMA/ICS who have persistent exacerbations.[1]

Azithromycin increases the risk of colonization with macrolide-resistant organisms and should not be prescribed for patients with hearing impairment, resting tachycardia, or apparent risk of QTc prolongation.[141] Azithromycin should be considered preferentially, but not only, in former smokers with persistent exacerbations despite appropriate therapy.[1]

Before starting prophylactic antibiotics, baseline ECG and liver function tests should be performed, a sputum sample obtained for culture and sensitivity (including tuberculosis testing), the patient's sputum clearance technique should be optimized, and bronchiectasis should be excluded with a CT scan.[2][142]​ ECG and liver tests should be repeated after 1 month of treatment. Prophylactic antibiotic therapy should be reviewed at 6 and 12 months to determine whether there is a benefit in terms of exacerbation rates.[142] If antibiotic therapy is not effective it should be stopped.

Primary options

azithromycin: 250 mg orally once daily; or 500 mg orally three times weekly

Consider – mucolytic

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

mucolytic

Treatment recommended for SOME patients in selected patient group

Patients with the chronic bronchitis phenotype of COPD often produce thick sputum on a frequent basis. Mucolytic agents result in a small reduction in the frequency of acute exacerbations and in days of disability per month, but do not improve lung function or quality of life.[186] One meta-analysis comparing erdosteine, carbocysteine, and acetylcysteine concluded that erdosteine had the most favorable safety and efficacy profile. Erdosteine reduced the risk of hospitalization due to an acute exacerbation, and erdosteine and acetylcysteine reduced the duration of an acute exacerbation.[187] Erdosteine is therefore the preferred option in countries where it is available. Another meta-analysis found that acetylcysteine significantly reduced the frequency of exacerbations compared with placebo, without increasing the risk of adverse effects. The authors concluded that 3 months of treatment with a low dosage was effective.[188] Treatment with mucolytic agents such as carbocysteine and acetylcysteine may reduce exacerbations and modestly improve health status in patients not receiving ICS.[1] However, erdosteine may have a significant effect on mild exacerbations whether or not the patient is taking inhaled corticosteroids.[1] Erdosteine and carbocysteine are not available in the US. 

Primary options

acetylcysteine: consult specialist for guidance on dose

Consider – theophylline

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

theophylline

Treatment recommended for SOME patients in selected patient group

Theophylline (a methylxanthine agent) is not commonly used because of limited potency, narrow therapeutic window, high-risk profile, and frequent drug-drug interactions. Theophylline has modest effects on lung function in moderate to severe COPD.[144] A large randomized controlled trial found no effect of oral theophylline alone or with prednisone on exacerbations of severe COPD.[145] Experts may prescribe theophylline after a patient has exhausted all options for inhaled therapies. Toxicity is dose-related. Theophylline is not recommended unless other long-term bronchodilator treatments are unavailable or unaffordable.[1]

Primary options

theophylline: consult specialist for guidance on dose

Consider – bronchoscopic intervention or surgery

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

bronchoscopic intervention or surgery

Treatment recommended for SOME patients in selected patient group

Surgical interventions are the last step in the management of COPD, and include bullectomy, lung volume reduction surgery, and lung transplant.[214][215] [ Cochrane Clinical Answers logo ] ​​ They are used to improve lung dynamics, exercise adherence, and quality of life.[215] Lung volume reduction surgery is indicated in patients with very severe airflow limitation, and especially in patients with localized upper lobe disease and lower than normal exercise capacity.[214] [ Cochrane Clinical Answers logo ] ​​ One meta-analysis found an increased risk of early mortality in patients who underwent lung volume reduction surgery compared to standard care; however, no significant difference was observed in overall mortality.[216] Bullectomy is an option in COPD patients with dyspnea in whom CT reveals huge bullae occupying at least 30% of the hemithorax. Severely poor functional status and severe decrease in FEV₁ (<500 mL) make these options less favorable. Endobronchial valve insertion can produce clinically meaningful improvements in appropriately selected patients with COPD.[216][217][218]​​ The procedure may be most beneficial in patients whose dyspnea is primarily due to hyperinflation and air trapping in the air spaces distal to the terminal bronchioles, which manifests as emphysema with markedly increased residual volume. Contraindications include active lung infection and incomplete lobar fissures (<80%).[219] The most common adverse events associated with endobronchial valve insertion are pneumothorax and exacerbation.[216]

Criteria for referral for lung transplantation include:[220]

Body mass index, airflow Obstruction, Dyspnea, and Exercise (BODE) score 5-6 with additional factor(s) present suggestive of increased risk of mortality: frequent acute exacerbations, increase in BODE score >1 over past 24 months, pulmonary artery to aorta diameter >1 on CT scan, and/or FEV₁ 20% to 25% predicted.

Clinical deterioration despite maximal treatment including medication, pulmonary rehabilitation, oxygen therapy, and, as appropriate, nocturnal noninvasive positive pressure ventilation.

Poor quality of life unacceptable to the patient.

For a patient who is a candidate for bronchoscopic or surgical lung volume reduction (LVR), simultaneous referral for both lung transplant and LVR evaluation is appropriate.

[ BODE Index for COPD Survival Prediction Opens in new window ]

Lung transplantation has been shown to improve quality of life and functional capacity.[215] However, lung transplantation does not appear to confer a survival benefit.[221]

Consider – palliative care

Back
ONGOING
|
GOLD group A, B, or E: persistent exacerbations after initial therapy
Consider – 

palliative care

Treatment recommended for SOME patients in selected patient group

Palliative therapies to improve symptoms of dyspnea, offer nutritional support, address anxiety and depression, and reduce fatigue may benefit patients with COPD who experience these despite optimal medical therapy. End-of-life care and hospice admission should be considered for patients with very advanced disease. Patient and family should be well educated about the process, and it is suggested that discussions should be held early in the course of the disease before acute respiratory failure develops.[1][222]​ Opioid analgesics, fans, neuromuscular electrical stimulation, and chest wall vibration can relieve dyspnea.[1] One study has suggested that low doses of an opioid analgesic and a benzodiazepine are safe and are not associated with increased hospital admissions or mortality.[223] Another study found that regular, low-dose, oral sustained-release morphine for 4 weeks improved disease-specific health status in patients with COPD and refractory breathlessness.[224]

One Cochrane review concluded that there is no evidence for or against benzodiazepines for the relief of breathlessness in people with advanced cancer and COPD.[225]

Acupuncture and acupressure may also improve breathlessness and quality of life in patients with advanced COPD.[226]

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer