For updates on diagnosis and management of coexisting conditions during the coronavirus disease (COVID-19) pandemic, see our topic "Management of coexisting conditions in the context of COVID-19".
The ultimate goals of treatment of COPD are to prevent and control symptoms, to reduce the severity and number of exacerbations, to improve respiratory capacity for increased exercise tolerance, and to reduce mortality.
There is a stepwise approach to therapy and treatment should be individualized for general health status and comorbid conditions.
The therapeutic approach involves reducing risk factor exposure, appropriate assessment of disease, patient education, pharmacologic and nonpharmacologic management of stable COPD, and prevention and treatment of acute COPD exacerbations.
The World Health Organization (WHO) has specified a minimum set of interventions for the management of stable COPD in primary care. WHO: package of essential noncommunicable (PEN) disease interventions for primary health care
Continuous assessment and monitoring of disease
Ongoing monitoring and assessment in COPD ensures that the goals of treatment are being met. Quality of life and patients' sense of wellbeing will improve, and hospital admissions will be significantly decreased in cases where self- or professional monitoring of disease is being utilized. Such assessment of the medical history should include:
Exposure to risk factors and preventive measures:
Indoor and outdoor air pollution
Occupational exposures (fumes, dust, etc.)
Influenza and pneumococcal vaccination.
Disease progression and development of complications:
Decline in exercise tolerance
Worsened sleep quality
Missed work or other activities.
Pharmacotherapy and other medical treatment:
How often rescue inhaler is used
Any new medicines
Compliance with medical regimen
Ability to use inhalers properly
Urgent care or emergency room visits
Recent oral corticosteroid bursts
Frequency, severity, and likely causes of exacerbations should be evaluated.
Assessment of coexisting medical problems (e.g., heart failure) which may add to symptoms and impact prognosis.
In addition, objective assessment of lung function should be obtained yearly, or more frequently if there is a substantial increase in symptoms.
Integrated disease management (IDM), in which several healthcare providers (physical therapist, pulmonologist, nurse, etc.) work together with patients, has been shown to improve quality of life and decrease hospital admissions. [ ]
An exacerbation of COPD is defined as an event characterized by a change in the patient's baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations and is acute in onset. See our topic on Acute exacerbation of chronic obstructive pulmonary disease for further information.
Chronic management: stepwise therapy according to GOLD group
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend that initial treatment is determined by the patient’s GOLD group at diagnosis:
Rescue short-acting bronchodilators should be prescribed to all patients for immediate symptom relief. Failure to respond to short-acting bronchodilator may signify an acute exacerbation.
For group A patients (few symptoms and low risk of exacerbations), a short-acting or a long-acting bronchodilator is 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. LABAs and LAMAs both significantly improve lung function, dyspnea, and health status and reduce exacerbation rates. [ ] [Evidence A] LAMAs have a greater effect on exacerbation reduction than LABAs. The effect of the bronchodilator should be evaluated. It should be continued if effective, otherwise it should be stopped and another class of bronchodilator or another inhaler device should be tried.
For group B patients (more symptoms and low risk of exacerbations), a long-acting bronchodilator should be offered first-line. Either a LAMA or a 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. For patients with severe breathlessness, initial treatment with two bronchodilators of different classes may be warranted.
For group C patients (few symptoms but higher risk of exacerbations), first-line treatment should be a LAMA, as LAMAs have a greater effect on exacerbation reduction than LABAs in patients with moderate to very severe COPD.
For group D patients (more symptoms and high risk of exacerbations), GOLD recommends starting therapy with a LAMA, a LABA/LAMA combination, or an inhaled corticosteroid (ICS)/LABA combination. A 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, and 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. 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. [ ]
Further treatment is determined by the patient’s dyspnea/exercise limitation symptom burden and frequency of exacerbations after review and is independent of the patient’s GOLD group at diagnosis. GOLD recommends different treatment pathways depending on whether the primary treatment goal is relieving dyspnea/exercise limitation symptoms or reducing exacerbations. If treatment is required for both purposes, clinicians should follow the exacerbation pathway. Patients should be reviewed for symptoms and exacerbation risk, and their inhaler technique and treatment adherence assessed, prior to any adjustment in treatment. The role of non-pharmacologic treatment should also be assessed. Adjustment of pharmacologic treatment can consist of escalation or de-escalation of therapy, as well as switching inhaler devices or molecules within the same drug class. If treatment is changed, then clinicians should review the patient for a clinical response, and for any potential side effects.
Recommended escalation therapy for patients with persistent dyspnea/exercise limitation after initial therapy is as follows:
Patients taking long-acting bronchodilator monotherapy should start a second long-acting bronchodilator from a different class. If symptoms do not improve, the second long-acting bronchodilator should be stopped. Changing inhaler device or molecules may be considered.
For patients taking LABA/ICS therapy, LAMA may be added (triple therapy). Alternatively, LABA/ICS may be switched to LABA/LAMA if the original indication for LABA/ICS was not appropriate, if the patient has not responded to ICS treatment, or if there are significant ICS adverse effects.
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.
Recommended escalation therapy for patients with persistent exacerbations after initial therapy is as follows:
Patients taking long-acting bronchodilator monotherapy should increase therapy to either LABA/LAMA or LABA/ICS. Blood eosinophil counts can identify patients who are more likely to respond to ICS. 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. Patients who have one exacerbation per year are more likely to respond to LABA/ICS if their peripheral eosinophil count is ≥300 cells/microliter. Patients who take a LABA or LAMA who have blood eosinophils <100 cells/microliter or who have contraindications to ICS should commence a LABA/LAMA.
Patients who take LABA/LAMA and whose blood eosinophils are ≥100 cells/microliter should escalate to triple therapy with LABA/LAMA/ICS. 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. American Thoracic Society guidelines recommend the use of triple therapy 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. UK guidelines recommend the use of triple therapy in patients who have an exacerbation requiring hospitalization, or two moderate exacerbations within a year, despite dual therapy with LABA/LAMA.
Patients who take a LABA/LAMA and whose blood eosinophils are <100 cells/microliter should add roflumilast or azithromycin.
Patients who take LABA/ICS should escalate to triple therapy by adding a LAMA. If ICS is ineffective or causing significant adverse effects, patients may switch to LABA/LAMA.
Patients who take LABA/LAMA/ICS may add roflumilast or azithromycin. Roflumilast may be considered in patients with forced expiratory volume in 1 second (FEV1) <50% predicted and chronic bronchitis, particularly if they have had at least one hospitalization for an exacerbation in the last year. The risk of developing antibiotic-resistant organisms should be considered when prescribing azithromycin. ICS can be discontinued if it is ineffective or causing adverse effects. Patients with blood eosinophils ≥300 cells/microliter are at greatest risk of exacerbations after withdrawing ICS.
All patients are candidates for education, vaccination, and smoking cessation interventions.
Beta-2 agonists are widely used in the treatment of COPD. They increase intracellular cAMP, leading to respiratory smooth muscle relaxation and reduced airway resistance. Muscarinic antagonists (anticholinergics) act as bronchodilators by blocking the cholinergic receptors on the respiratory smooth muscle. This causes muscle relaxation and reduces airflow limitation. Beta agonists and muscarinic antagonists, therefore, provide bronchodilator effects through different pathways. Both are available as short-acting and long-acting preparations.
Short-acting beta-2 agonists (e.g., albuterol, levalbuterol) and short-acting muscarinic antagonists (e.g., ipratropium) improve lung function and breathlessness and quality of life. Ipratropium may have a small benefit over short-acting beta-2 agonists in improving health-related quality of life. These agents can be used as rescue therapy when the patient is using long-acting bronchodilator therapy and may be used as initial treatment for patients in GOLD group A if patients only have occasional dyspnea. However, regular use of short-acting bronchodilators is not generally recommended.
Tiotropium, a LAMA, has been shown to reduce risk of exacerbation versus placebo or other maintenance treatments. [ ] Newer LAMAs, such as aclidinium, glycopyrrolate, and umeclidinium, have at least comparable efficacy to tiotropium, in terms of change from baseline in trough FEV1, transitional dyspnea index focal score, St George's Respiratory Questionnaire score, and rescue medication use. Revefenacin is a nebulized LAMA approved for the maintenance treatment of moderate to severe COPD. There is a suggestion of increased cardiovascular-related mortality in some studies of patients taking short-acting muscarinic antagonists and in some studies of patients taking LAMAs. One study concluded that aclidinium was not associated with an increase in major adverse cardiovascular events, compared with placebo. A population-based cohort study found that older men with COPD newly started on LAMAs are at increased risk of urinary tract infections.
LABAs and LAMAs both significantly improve lung function, dyspnea, and health status and reduce exacerbation rates. [ ] In cases of stable COPD, if the decision is made to use single-agent therapy, LAMA may be superior to LABA agents. LAMAs have a greater effect on exacerbation reduction than LABAs in patients with moderate to very severe COPD. The long-term safety of LAMA was demonstrated in the UPLIFT trial.
A LABA/LAMA combination may provide a better therapeutic effect without increasing the adverse effects of each class. 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. [ ] Compared to LABA/ICS, a LABA/LAMA combination has fewer exacerbations, a larger improvement of FEV1, a lower risk of pneumonia, and more frequent improvement in quality of life. A systematic review and network meta-analysis found that all LABA/LAMA fixed-dose combinations had a similar efficacy and safety.
Umeclidinium/vilanterol, glycopyrrolate/formoterol, indacaterol/glycopyrrolate, tiotropium/olodaterol, and aclidinium/formoterol are LABA/LAMA combinations approved for use in COPD. Indacaterol/glycopyrrolate showed superior efficacy compared with glycopyrrolate or tiotropium in patients with moderate to severe COPD, and compared with salmeterol/fluticasone in preventing COPD exacerbation. Umeclidinium/vilanterol decreases the risk of exacerbations in patients with mild/moderate COPD. [ ]
As outlined above, GOLD makes recommendations on the initial agent based on the patient’s risk group (A, B, C, or D). American Thoracic Society guidelines recommend initiating LABA/LAMA dual therapy in preference to monotherapy in patients with COPD who have dyspnea or exercise intolerance. UK guidelines recommend initiating dual therapy with a LABA/LAMA or LABA/ICS if a patient has symptoms or exacerbations despite nonpharmacologic treatment and using a short-acting bronchodilator as needed. The choice of initial drug regimen in the UK guidance is based on whether or not the patient has features of asthma or features suggesting corticosteroid responsiveness.
Inhaled corticosteroids are indicated in some patients with COPD who suffer from frequent exacerbations. They should always be prescribed in combination with long-acting bronchodilators. Inhaled corticosteroids are believed to be effective because of their anti-inflammatory effects. Long-term inhaled corticosteroid use reduces the need to use rescue therapy and reduces exacerbations, and may also decrease mortality. [ ]
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). Blood eosinophil count may predict the effectiveness of adding inhaled corticosteroids to regular long-acting bronchodilator treatment to prevent exacerbations. 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. These thresholds indicate approximate cut-off values which may help clinicians predict the likelihood of a treatment benefit. Former smokers are more corticosteroid-responsive than current smokers at any eosinophil count. 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.
Several studies have pointed to an increased risk of pneumonia in patients with COPD taking inhaled corticosteroids. This risk is slightly higher for fluticasone in comparison with budesonide. A systematic review and meta-analysis found that, despite a significant increase in unadjusted risk of pneumonia associated with use of inhaled corticosteroids, pneumonia fatality and overall mortality were not increased in randomized controlled trials and were decreased in observational studies. Therefore, an individualized treatment approach that assesses a patient's risk of pneumonia versus the benefit of decreased exacerbations should be implemented. Concern is also raised with regards to increased risk of tuberculosis and influenza in adult patients with COPD who are on inhaled corticosteroid therapy. ICS may also cause oropharyngeal candidiasis and hoarseness.
Clinicians should weigh the potential benefits and risks of prescribing ICS and discuss these with the patient. A history of hospitalization(s) for exacerbations of COPD, two or more moderate exacerbations per year despite regular long-acting bronchodilators, blood eosinophils of ≥300 cells/microliter, and/or previous or concomitant asthma all strongly favor initiating ICS. Repeated episodes of pneumonia, blood eosinophils <100 cells/microliter, and/or history of mycobacterial infection are all factors against the use of ICS. Use of ICS can be considered in patients with one moderate exacerbation of COPD per year despite regular long-acting bronchodilator therapy and/or peripheral eosinophils 100-300 cells/microliter.
Long-term use of oral corticosteroids in COPD is not recommended. Some patients with severe disease are unable to completely stop treatment after starting oral corticosteroids for an acute exacerbation. In this case, the dose should be kept as low as possible and consideration given to osteoporosis prophylaxis.
Combined bronchodilator and corticosteroid preparations
A combination preparation of a long-acting bronchodilator and an inhaled corticosteroid may be used for patients who require both these agents. [ ] This is convenient and may help with compliance in some patients. The choice of therapy in this class is based on availability and individual response and preference. Combination therapy with an inhaled corticosteroid and a LABA is superior to use of either agent alone. [ ] The combination may be provided in separate inhalers or a combination inhaler.
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. 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. One randomized controlled trial has reported a reduction in all-cause mortality in patients with FEV1 <50% and at least one exacerbation in the past year who take fluticasone furoate/umeclidinium/vilanterol, compared with patients taking umeclidinium/vilanterol. Patients with mild COPD and at least two moderate or one severe exacerbations in the last year also had reduced all-cause mortality when taking fluticasone furoate/umeclidinium/vilanterol, compared with umeclidinium/vilanterol. 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. The same study showed that increasing the dose of budesonide in triple therapy does not decrease the rate of exacerbations, compared with standard dose triple therapy. For both studies, there were no differences in mortality compared with LABA/ICS. 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.
Before prescribing triple therapy, clinicians should assess whether another physical or mental condition could be causing the patient’s symptoms. UK guidelines advise clinicians to review patients taking triple therapy for relief of daily symptoms after 3 months. Treatment should be changed to LABA/LAMA if the patient’s symptoms have not improved. The ICS may be withdrawn if the patient has had no exacerbations in the past year.
Roflumilast is an oral phosphodiesterase-4 inhibitor which inhibits the breakdown of cAMP. It may be considered in patients with FEV1 <50% predicted and chronic bronchitis who are taking LABA/LAMA/ICS, particularly if they have had at least one hospitalization for an exacerbation in the last year. Roflumilast offers benefit in improving lung function and reducing the likelihood of exacerbations. However, it has little impact on quality of life or symptoms.
Prophylactic antibiotics, such as macrolides, may be considered for reducing the risk of acute exacerbation, particularly in patients who have frequent exacerbations and are refractory to standard therapy. Use of prophylactic macrolide antibiotics decreases the frequency of exacerbations in patients with COPD but long-term azithromycin use is associated with clinically significant hearing loss, which in many cases was reversible. [ ] There are no data showing the efficacy or safety of chronic azithromycin treatment beyond 1 year of treatment.
Azithromycin therapy is believed to be most effective in preventing acute exacerbation, with greater efficacy seen in older patients and milder GOLD stages. Little evidence of treatment benefit is seen in current smokers. 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.
UK guidelines advise that prophylactic azithromycin could be considered for patients who have more than three acute exacerbations requiring corticosteroid therapy and at least one exacerbation requiring hospitalization per year. 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. ECG and liver tests should be repeated after 1 month of treatment. A head-to-head comparison of fluoroquinolones, tetracyclines, and macrolides given for 12 to 13 weeks to people with COPD did not identify a difference in efficacy or safety between antibiotic classes, but the sample sizes of included studies were small and the studies were of short duration; further research is required in this area.
Prophylactic antibiotic therapy should be reviewed at 6 and 12 months to determine whether there is a benefit in terms of exacerbation rates. If antibiotic therapy is not effective it should be stopped.
Theophylline (a methylxanthine agent) is a bronchodilator that acts by increasing cAMP and subsequent respiratory smooth muscle relaxation. It 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. GOLD advise that theophylline should only be used if other long-term bronchodilator treatments are unavailable or unaffordable. Experts may prescribe theophylline after a patient has exhausted all options for inhaled therapies.
Patient education and self-management
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. It is important to remember that 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.
One Cochrane review found that self-management interventions that include an action plan for acute exacerbations of COPD are associated with improvements in health-related quality of life and fewer admissions to the hospital for respiratory problems. An exploratory analysis found a small, but significantly higher, respiratory-related mortality rate for self-management compared to usual care, although no excess risk of all-cause mortality was seen. A randomized controlled trial showed that a 3-month program of self-management started in patients with COPD exacerbations recently discharged from hospital led to increases in COPD-related hospitalizations and emergency department visits over 6 months.
Self-management plans should include personalized advice on: breathlessness and stress management techniques, energy conservation, avoiding aggravating factors, how to monitor symptoms, how to manage worsening symptoms, and contact information to use in the event of an exacerbation.
Helping patients to self-manage should ideally address psychosocial concerns and patients’ personal beliefs about COPD and its management. Many patients report losses and limitations on their lifestyle and social interaction after a diagnosis of COPD. Symptoms of anxiety, depression, and frustration are common. A systematic review found a small beneficial effect of cognitive behavioral therapy-based psychological treatment and symptoms of depression, compared with education or no intervention, although the evidence was limited by heterogeneity between trials and inability to blind participants and researchers to the intervention.
One randomized controlled trial found that a telephone health coaching intervention to promote behavior change in patients with mild COPD in primary care led to improvements in self-management activities, but did not improve health-related quality of life. A meta-analysis found that health coaching that included goal setting, motivational interviewing, and COPD-related health education significantly improved health-related quality of life and reduced hospital admissions for an exacerbation of COPD, but did not decrease all-cause hospital admissions.
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. Poor technique is more likely when patients are using multiple devices or have never received inhaler technique training. Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique. Demonstration using a placebo device may be most effective for teaching inhaler technique to adults ages ≥65 years. Patients should be asked to bring their inhalers to clinic to facilitate a review of inhaler use. Pharmacist-led interventions and lay health coaching can improve inhaler technique and adherence in patients with COPD.
Metered dose inhaler
Metered dose inhaler plus spacer
Dry powder inhalers
Soft mist inhaler
Physical activity is recommended for all patients with COPD. One systematic review and meta-analysis of randomized controlled trials found that exercise training on its own can improve physical activity in COPD, and greater improvements can be made with the addition of physical activity counseling. Another systematic review and meta-analysis found that a combination of aerobic exercise and strength training was more effective than strength training or endurance training alone in increasing the 6-minute walking distance. A Cochrane review found limited evidence for improvement in physical activity with physical activity counseling, exercise training, and pharmacologic management of COPD. The authors commented that assessment of quality had been limited by lack of methodologic detail and the diverse range of interventions had primarily been assessed in single studies. The optimal timing, components, duration, and models for improving physical activity remain unclear. Meta-analyses suggest that yoga and Qigong can improve exercise capacity and pulmonary function in patients with COPD.
Smoking cessation and vaccination
Smoking cessation should be encouraged in all patients, in addition to guidance on avoiding exposure to occupational or environmental tobacco smoke and other irritants. Smoking cessation significantly reduces the rate of progression of COPD and risk of malignancies. It also reduces the risk of coronary and cerebrovascular diseases. Among different therapeutic modalities in COPD, the only two factors that improve survival are smoking cessation and oxygen supplementation.
Usual smoking cessation programs include counseling, group meetings, and drug therapy. Some patients may need frequent referrals to achieve success. Smoking cessation that includes pharmacotherapy and intensive counseling has a higher success rate and is cost effective in COPD, with low costs per quality-adjusted life year. The effectiveness and safety of e-cigarettes/vaping as an aid to smoking cessation is uncertain.
Motivational interviewing overview
Motivational interviewing: smoking cessation part 1
Motivational interviewing: smoking cessation part 2
Patients should be vaccinated against influenza virus and Streptococcus pneumoniae. Vaccination against influenza is associated with fewer exacerbations of COPD. [ ] Guidance from the Centers for Disease Control and Prevention (CDC) advises a single dose of pneumococcal 23-valent polysaccharide vaccine (PPSV23) for all patients with COPD who have not previously received the recommended pneumococcal vaccine. The CDC recommends shared decision-making regarding administration of the PCV13 (pneumococcal 13-valent conjugate vaccine) to people ages 65 years and older who do not have an immunocompromising condition, cerebrospinal fluid leak, or cochlear implant, and who have not previously received PCV13. If a decision to give PCV13 is made, PCV13 should be given first, followed by PPSV23 at least 1 year later.
The CDC also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.
Patients with the chronic bronchitis phenotype of COPD often produce thick sputum on a frequent basis. Mucolytic agents are not associated with an increase in adverse effects and may be beneficial during exacerbations of COPD. [ ] They 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. 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. Erdosteine and carbocysteine are not available in the US and some other countries. Treatment with mucolytic agents such as carbocysteine and acetylcysteine may be most beneficial for patients not on inhaled corticosteroids. However, erdosteine may have a significant effect on mild exacerbations whether or not the patient is taking inhaled corticosteroids.
Pulmonary rehabilitation compromises aerobic exercise, strength training, and education. It should be initiated for patients who remain symptomatic despite bronchodilator therapy and is recommended to start early in the course of the disease, when they start feeling shortness of breath with regular activity and walking on a level surface. GOLD guidelines recommend pulmonary rehabilitation for patient groups B to D.
Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent. Extensive pulmonary rehabilitation following hospital admission with an acute exacerbation of COPD decreases the risk of readmission, improves health-related quality of life, and reduces mortality. [ ] It also decreases the depression and anxiety related to this disease, and reduces hospitalization in patients with COPD. The benefit appears to subside after termination of the course unless patients follow a home exercise schedule. Benefits of home- or community-based pulmonary rehabilitation on respiratory symptoms and quality of life in patients with COPD could match those of the hospital-based rehabilitation programs. Early progressive exercise rehabilitation beyond current standard physical therapy practice during hospital admission for COPD is not recommended and could be associated with a higher 12-month mortality. There is evidence to support starting pulmonary rehabilitation within 1 month of an acute exacerbation.
Oxygen therapy and ventilatory support
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%).
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.
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.
Supplemental oxygen should be titrated to achieve SaO₂ ≥90%. The patient should be reassessed after 60 to 90 days to determine whether oxygen is still indicated and is therapeutic. Among different therapeutic modalities in COPD, the only two factors that improve survival are smoking cessation and oxygen supplementation.
There is some evidence that oxygen can relieve breathlessness when given during exercise to mildly hypoxemic and nonhypoxemic people with COPD who do not otherwise qualify for home oxygen therapy. 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. 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%).
Air travel is safe for most patients receiving long-term oxygen therapy. Patients with SaO₂ >95% at sea level and SaO₂ ≥84% after a 6-minute walk test may travel by air without further assessment. Supplemental oxygen is recommended for patients with SaO₂ 92% to 95% at sea level and SaO₂ <84% after a 6-minute walk test, and for patients with SaO₂ <92% at sea level. Hypoxia-altitude simulation testing should be performed for other patients.
For patients who have COPD and obstructive sleep apnea, ventilatory support with continuous positive airway pressure (CPAP) can improve survival and reduce hospital admissions. Noninvasive ventilation is occasionally used in patients with very severe but stable COPD, although the best selection criteria for candidates is unclear.
Surgical interventions (bullectomy, lung volume reduction surgery, [ ] 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. 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. [ ] 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.
Criteria for referral for lung transplantation include:
Progressive disease, despite maximal treatment including medication, pulmonary rehabilitation, and oxygen therapy.
Patient is not a candidate for endoscopic or surgical lung volume reduction surgery (LVRS). Simultaneous referral of patients with COPD for both lung transplant and LVRS evaluation is appropriate.
Body mass index, airflow Obstruction, Dyspnea, and Exercise (BODE) index of 5 to 6.
PaCO₂ >50 mmHg or 6.6 kPa and/or PaO₂ <60 mmHg or 8 kPa.
FEV1 <25% predicted.
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. Opioid analgesics, fans, neuromuscular electrical stimulation, and chest wall vibration can relieve dyspnea. Long-acting oral and parenteral opioids may be considered for treating dyspnea in patients with severe COPD. 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.
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.
Acupuncture and acupressure may also improve breathlessness and quality of life in patients with advanced COPD.
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