Chronic obstructive pulmonary disease (COPD)
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
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: (15.6 micrograms/capsule inhaler) 15.6 micrograms (1 capsule) twice daily; (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device
Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A patients are characterized by few symptoms and low risk of exacerbations.
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 occasional dyspnea.[1] LABAs and LAMAs both significantly improve lung function, dyspnea, and health status and reduce exacerbation rates.
[ 
]
LAMAs have a greater effect on exacerbation reduction than LABAs.[60][61]
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.[77]
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.
[ ]
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.
Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), and coronavirus disease 2019 (COVID-19).[1][169] Vaccination against influenza is associated with fewer exacerbations of COPD.[170][171]
[ ]
The Centers for Disease Control and Prevention (CDC) also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence, and varicella-zoster virus (shingles) for adults with COPD ages 50 years and over.[169]
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.[144][145] Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[147]
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]
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: (15.6 micrograms/capsule inhaler) 15.6 micrograms (1 capsule) twice daily; (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device
OR
LAMA
revefenacin inhaled: 175 micrograms nebulized once daily
Global Initiative for Chronic Obstructive Lung Disease (GOLD) group B patients are characterized by more symptoms and low risk of exacerbations.
Either a long-acting muscarinic antagonist (LAMA) or a long-acting beta-2 agonist (LABA) may be prescribed. 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.
[ ]
For patients with severe breathlessness, initial treatment with two bronchodilators of different classes may be warranted.[1]
LABAs include salmeterol, arformoterol, and olodaterol. LAMAs include tiotropium, umeclidinium, aclidinium, and glycopyrrolate.
[ ]
Revefenacin is a nebulized LAMA approved for the maintenance treatment of moderate to severe COPD.
Treatment recommended for ALL patients in selected patient group
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
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.[77] 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.
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.
Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), and coronavirus disease 2019 (COVID-19).[1][169] Vaccination against influenza is associated with fewer exacerbations of COPD.[170][171]
[ ]
The Centers for Disease Control and Prevention (CDC) also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence, and varicella-zoster virus (shingles) for adults with COPD ages 50 years and over.[169]
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.[144][145] Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[147]
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]
Treatment recommended for ALL patients in selected patient group
Pulmonary rehabilitation compromises aerobic exercise, strength training, and education, and should be started early in the disease course. GOLD guidelines recommend pulmonary rehabilitation for patient groups B to D.[1]
Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[176]
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.[179][180] However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[181]
Primary options
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: (15.6 micrograms/capsule inhaler) 15.6 micrograms (1 capsule) twice daily; (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device
OR
revefenacin inhaled: 175 micrograms nebulized once daily
Global Initiative for Chronic Obstructive Lung Disease (GOLD) Group C patients have few symptoms and a higher risk of exacerbations.
GOLD recommends starting a long-acting muscarinic antagonist (LAMA) in this group.[1] LAMAs have a greater effect on exacerbation reduction than long-acting beta-2 agonists (LABAs) in patients with moderate to very severe COPD.[60][61]
Treatment recommended for ALL patients in selected patient group
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
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.[77]
Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[77] SAMAs should not be prescribed with a LAMA. 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.
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.
Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), and coronavirus disease 2019 (COVID-19).[1][169] Vaccination against influenza is associated with fewer exacerbations of COPD.[170][171]
[ ]
The Centers for Disease Control and Prevention (CDC) also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence, and varicella-zoster virus (shingles) for adults with COPD ages 50 years and over.[169]
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.[144][145] Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[147]
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]
Treatment recommended for ALL patients in selected patient group
Pulmonary rehabilitation compromises aerobic exercise, strength training, and education, and should be started early in the disease course. GOLD guidelines recommend pulmonary rehabilitation for patient groups B to D.[1]
Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[176]
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.[179][180] However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[181]
Primary options
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: (15.6 micrograms/capsule inhaler) 15.6 micrograms (1 capsule) twice daily; (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device
OR
LAMA
revefenacin inhaled: 175 micrograms nebulized once daily
OR
LABA/LAMA
umeclidinium/vilanterol inhaled: (62.5/25 micrograms/dose inhaler) 1 puff once daily
OR
LABA/LAMA
glycopyrrolate/formoterol fumarate 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 fumarate inhaled: (400/12 micrograms/dose inhaler) 1 puff twice daily
OR
LABA/ICS
fluticasone furoate/vilanterol inhaled: (100/25 micrograms/dose inhaler) 1 puff once daily
OR
LABA/ICS
fluticasone propionate/salmeterol inhaled: (250/50 micrograms/dose inhaler) 1 puff twice daily
OR
LABA/ICS
budesonide/formoterol inhaled: (160/4.5 micrograms/dose inhaler) 2 puffs twice daily
OR
LABA/ICS
mometasone/formoterol inhaled: (100/5 micrograms/dose inhaler; 200/5 micrograms/dose inhaler) 2 puffs twice daily
Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D patients are characterized by more symptoms and high risk of exacerbations.
GOLD recommends starting therapy with a long-acting muscarinic antagonist (LAMA), a long-acting beta-2 agonist (LABA)/LAMA combination, or an inhaled corticosteroid (ICS)/LABA combination.[1]
LAMA is the first choice for most patients. A LABA/LAMA combination should be considered if the patient is highly symptomatic (COPD assessment test [CAT] score >20), especially if the patient has significant dyspnea and/or exercise limitation.[1]
An ICS/LABA combination should be considered if the patient’s blood eosinophil count is ≥300 cells/microliter or the patient has a history of asthma.[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).[68][70][98] Blood eosinophil count may predict the effectiveness of adding inhaled corticosteroids to regular long-acting bronchodilator treatment to prevent exacerbations.[99][63][64] 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.[62][73] These thresholds indicate approximate cut-off values which 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.[117] Former smokers are more corticosteroid-responsive than current smokers at any eosinophil count.[99] 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.[70][100]
Combination therapy with an inhaled corticosteroid and a LABA is superior to use of either agent alone.[115][116]
[ ]
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.
[ ]
LAMAs include tiotropium, umeclidinium, aclidinium, and glycopyrrolate.
[ ]
Umeclidinium/vilanterol, glycopyrrolate/formoterol, tiotropium/olodaterol, and aclidinium/formoterol are LABA/LAMA combinations approved for use in COPD.[212][98] Umeclidinium/vilanterol decreases the risk of exacerbations in patients with mild/moderate COPD.[92]
[ ]
LABA/ICS combinations include fluticasone furoate/vilanterol, fluticasone propionate/salmeterol, budesonide/formoterol, and mometasone/formoterol.
Treatment recommended for ALL patients in selected patient group
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
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.[77]
Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[77] 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.
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.
Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), and coronavirus disease 2019 (COVID-19).[1][169] Vaccination against influenza is associated with fewer exacerbations of COPD.[170][171]
[ ]
The Centers for Disease Control and Prevention (CDC) also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence, and varicella-zoster virus (shingles) for adults with COPD ages 50 years and over.[169]
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.[144][145] Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[147]
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]
Treatment recommended for ALL patients in selected patient group
Pulmonary rehabilitation compromises aerobic exercise, strength training, and education, and should be started early in the disease course. GOLD guidelines recommend pulmonary rehabilitation for patient groups B to D.[1]
Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[176]
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.[179][180] However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[181]
Primary options
LABA/LAMA
umeclidinium/vilanterol inhaled: (62.5/25 micrograms/dose inhaler) 1 puff once daily
OR
LABA/LAMA
glycopyrrolate/formoterol fumarate 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 fumarate 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: (15.6 micrograms/capsule inhaler) 15.6 micrograms (1 capsule) twice daily; (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device
Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A patients are characterized by few symptoms and low risk of exacerbations; group B by more symptoms and low risk of exacerbations; group C by few symptoms and a higher risk of exacerbations; and group D by more symptoms and high risk of exacerbations.[1]
GOLD advise 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, the second long-acting bronchodilator should be stopped. 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.[85][88][89][90] Combination therapy with a LABA/LAMA reduces exacerbation rate compared with monotherapy. Once-daily LABA/LAMA delivered via a combination inhaler is more associated with a clinically significant improvement in lung function and health-related quality of life in patients with mild/moderate COPD, compared with placebo.[92]
[ ]
Patients with persistent dyspnea/exercise limitation while on combined LABA and inhaled corticosteroid (ICS) therapy may switch to LABA/LAMA/ICS. The indication for ICS should be reviewed. If the original indication was not appropriate, or if the patient has not responded to ICS treatment or experienced significant adverse effects, ICS should be withdrawn and the patient switched to a LABA/LAMA.[1] The combination may be provided in separate inhalers or a combination inhaler.
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.
Treatment recommended for ALL patients in selected patient group
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
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.[77]
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.
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.
Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), and coronavirus disease 2019 (COVID-19).[1][169] Vaccination against influenza is associated with fewer exacerbations of COPD.[170][171]
[ ]
The Centers for Disease Control and Prevention (CDC) also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence, and varicella-zoster virus (shingles) for adults with COPD ages 50 years and over.[169]
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.[144][145] Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[147]
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]
Treatment recommended for SOME patients in selected patient group
Pulmonary rehabilitation compromises aerobic exercise, strength training, and education, and should be started early in the disease course. GOLD guidelines recommend pulmonary rehabilitation for patient groups B to D.[1]
Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[176]
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.[179][180] However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[181]
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 7.5-7.9 kPa (56-59 mmHg) or SpO₂ of 89% plus one of the following: edema, hematocrit ≥55%, or P pulmonale on an ECG.[189]
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.[189]
Supplemental oxygen should be titrated to achieve SaO₂ ≥90%.[1] The patient should be reassessed after 60 to 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][46]
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.[189] 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%-93%).[189]
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][192] 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][193]
Guidelines from the American Thoracic Society suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD.[196] The European Respiratory Society and Canadian Thoracic Society have issued similar guidance.[197][198]
Treatment recommended for SOME patients in selected patient group
Primary options
acetylcysteine: consult specialist for guidance on dose
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.[173] 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.[174] 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.[175] 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.
Treatment recommended for SOME patients in selected patient group
Primary options
theophylline: consult specialist for guidance on dose
Theophylline (a methylxanthine agent) is not commonly used because of limited potency, narrow therapeutic window, high-risk profile, and frequent drug-drug interactions. Theophylline is indicated for persistent symptoms if inhaled therapy is insufficient to relieve airflow obstruction. Theophylline has modest effects on lung function in moderate to severe COPD.[133] A large randomized controlled trial found no effect of oral theophylline alone or with prednisone on exacerbations of severe COPD.[134] GOLD advise that theophylline should only be used if other long-term bronchodilator treatments are unavailable or unaffordable.[1] Experts may prescribe theophylline after a patient has exhausted all options for inhaled therapies. Toxicity is dose-related.
Treatment recommended for SOME patients in selected patient group
Surgical interventions (bullectomy, lung volume reduction surgery,[199][200]
[ ]
and lung transplant) are the last step in the management of COPD. They are used to improve lung dynamics, exercise adherence, and quality of life.[200] 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.[199]
[ ]
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.[201] 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.[202][201][203] 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%).[204] The most common adverse events associated with endobronchial valve insertion are pneumothorax and exacerbation.[201]
Criteria for referral for lung transplantation include:[205]
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 ]
Lung transplantation has been shown to improve quality of life and functional capacity.[200] However, lung transplantation does not appear to confer a survival benefit.[206]
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.[1] 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.[207] 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.[208] 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.[209]
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.[210]
Acupuncture and acupressure may also improve breathlessness and quality of life in patients with advanced COPD.[211]
Primary options
LABA/LAMA
umeclidinium/vilanterol inhaled: (62.5/25 micrograms/dose inhaler) 1 puff once daily
OR
LABA/LAMA
glycopyrrolate/formoterol fumarate 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 fumarate inhaled: (400/12 micrograms/dose inhaler) 1 puff twice daily
OR
LABA/ICS
fluticasone furoate/vilanterol inhaled: (100/25 micrograms/dose inhaler) 1 puff once daily
OR
LABA/ICS
fluticasone propionate/salmeterol inhaled: (250/50 micrograms/dose inhaler) 1 puff twice daily
OR
LABA/ICS
budesonide/formoterol inhaled: (160/4.5 micrograms/dose inhaler) 2 puffs twice daily
OR
LABA/ICS
mometasone/formoterol inhaled: (100/5 micrograms/dose inhaler; 200/5 micrograms/dose inhaler) 2 puffs 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: (15.6 micrograms/capsule inhaler) 15.6 micrograms (1 capsule) twice daily; (25 micrograms/vial nebulizer inhalation solution) 25 micrograms nebulized twice daily using Magnair® nebulizer device
Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A patients are characterized by few symptoms and low risk of exacerbations; group B by more symptoms and low risk of exacerbations; group C by few symptoms and a higher risk of exacerbations; and group D by more symptoms and high risk of exacerbations.[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 either LABA/LAMA or LABA/inhaled corticosteroid (ICS).
Blood eosinophil counts can identify patients who are more likely to respond to ICS.[62][63][64] LABA/ICS may be considered in patients with two or more moderate exacerbations per year, or at least one severe exacerbation needing hospital admission in the previous year, and an eosinophil count ≥100 cells/microliter, or if the history/clinical findings are suggestive of asthma.[1] Patients who have one exacerbation per year are more likely to respond to LABA/ICS if their peripheral eosinophil count is ≥300 cells/microliter.[65] 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.[117] Former smokers are more corticosteroid-responsive than current smokers at any eosinophil count.[99]
Patients on LABA or LAMA who experience persistent exacerbations and who have blood eosinophils <100 cells/microliter or who have contraindications to ICS should commence a LABA/LAMA.[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.[66][67][68][69][70][71][72][73][74] 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.[118] 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.[74][119] For both studies, there were no differences in mortality compared with LABA/ICS.[74][118][119] 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 non-significant trend for lower mortality with triple therapy compared with non-ICS treatments.[120] 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.[121]
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.[75] 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]
Patients who take LABA/ICS and who experience persistent exacerbations should switch to LABA/LAMA/ICS.[1] If ICS is ineffective or causing significant adverse effects, patients may switch to LABA/LAMA. Patients with blood eosinophils ≥300 cells/microliter are at greatest risk of exacerbations after withdrawing ICS.[76]
Treatment recommended for ALL patients in selected patient group
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
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.[77] Ipratropium, a SAMA, may have a small benefit over SABAs in improving health-related quality of life.[77] 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.
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.
Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), and coronavirus disease 2019 (COVID-19).[1][169] Vaccination against influenza is associated with fewer exacerbations of COPD.[170][171]
[ ]
The Centers for Disease Control and Prevention (CDC) also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence, and varicella-zoster virus (shingles) for adults with COPD ages 50 years and over.[169]
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.[144][145] Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[147]
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]
Treatment recommended for SOME patients in selected patient group
Pulmonary rehabilitation compromises aerobic exercise, strength training, and education, and should be started early in the disease course. GOLD guidelines recommend pulmonary rehabilitation for patient groups B to D.[1]
Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[176]
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.[179][180] However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[181]
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 7.5-7.9 kPa (56-59 mmHg) or SpO₂ of 89% plus one of the following: edema, hematocrit ≥55%, or P pulmonale on an ECG.[189]
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.[189]
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][46]
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.[189] 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%-93%).[189]
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][192] 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][193][213]
Guidelines from the American Thoracic Society suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD.[196] The European Respiratory Society and Canadian Thoracic Society have issued similar guidance.[197][198]
Treatment recommended for SOME patients in selected patient group
Primary options
roflumilast: 500 micrograms orally once daily
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]
Treatment recommended for SOME patients in selected patient group
Primary options
azithromycin: 250 mg orally once daily; or 500 mg orally three times weekly
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.[130] 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 optimised, and bronchiectasis should be excluding with a CT scan.[2][131] 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.[131] If antibiotic therapy is not effective it should be stopped.
Treatment recommended for SOME patients in selected patient group
Primary options
acetylcysteine: consult specialist for guidance on dose
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.[173] 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.[174] 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.[175] 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.
Treatment recommended for SOME patients in selected patient group
Primary options
theophylline: consult specialist for guidance on dose
Theophylline (a methylxanthine agent) is not commonly used because of limited potency, narrow therapeutic window, high-risk profile, and frequent drug-drug interactions. Theophylline is indicated for persistent symptoms if inhaled therapy is insufficient to relieve airflow obstruction. Theophylline has modest effects on lung function in moderate to severe COPD.[133] A large randomized controlled trial found no effect of oral theophylline alone or with prednisone on exacerbations of severe COPD.[134] GOLD advise that theophylline should only be used if other long-term bronchodilator treatments are unavailable or unaffordable.[1] Experts may prescribe theophylline after a patient has exhausted all options for inhaled therapies. Toxicity is dose-related.
Treatment recommended for SOME patients in selected patient group
Surgical interventions (bullectomy, lung volume reduction surgery,[199][200]
[ ]
and lung transplant) are the last step in the management of COPD. They are used to improve lung dynamics, exercise adherence, and quality of life.[200] 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.[199]
[ ]
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.[201] 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.[202][201][203] 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%).[204] The most common adverse events associated with endobronchial valve insertion are pneumothorax and exacerbation.[201]
Criteria for referral for lung transplantation include:[205]
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 ]
Lung transplantation has been shown to improve quality of life and functional capacity.[200] However, lung transplantation does not appear to confer a survival benefit.[206]
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.[1] 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.[207] 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.[208] 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.[209]
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.[210]
Acupuncture and acupressure may also improve breathlessness and quality of life in patients with advanced COPD.[211]
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