Chronic obstructive pulmonary disease (COPD)

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

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.[1] One systematic review looking at nine studies found that, compared with placebo, pharmacologic treatment for COPD can reduce the rate of decline in FEV₁. Overall, the systematic review showed a reduction in the rate of decline in FEV₁ of 5.0 mL/year for active treatment arms compared with placebo. For studies with inhaled corticosteroid-containing treatment arms, the difference in decline was 7.3 mL/year compared with placebo, whereas the difference between treatment arms containing long-acting bronchodilator and placebo was 4.9 mL/year.[76] However, further research is needed to find out which patients are most likely to benefit.[1]

There is a stepwise approach to therapy, and treatment should be individualized for general health status and comorbid conditions. If a patient with COPD has concomitant asthma, they should primarily be managed according to asthma guidelines.[1] See Asthma in adults. For details on the management of alpha-1 antitrypsin deficiency, see Alpha-1 antitrypsin deficiency.

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 Opens in new window

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, when self- or professional monitoring of disease is being utilized.[77] Such assessment of the medical history should include:

Exposure to risk factors and preventive measures:

Tobacco smoke
Indoor and outdoor air pollution
Occupational exposures (fumes, dust, etc.)
Influenza and pneumococcal vaccination.

Disease progression and development of complications:

Decline in exercise tolerance
Increased symptoms
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
Adverse effects.

Exacerbation history:

Urgent care or emergency room visits
Recent oral corticosteroid bursts
Frequency, severity, and likely causes of exacerbations should be evaluated.

Comorbidities:

Assessment of coexisting medical problems (e.g., heart failure) that 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.

One Cochrane review found that integrated disease management (IDM), in which several healthcare providers (physical therapist, pulmonologist, nurse, etc.) work together with patients, probably results in improvement in disease‐specific quality of life, exercise capacity, hospital admissions, and hospital days per person.[78] [ ] [Evidence A]

Acute exacerbations

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 Acute exacerbation of chronic obstructive pulmonary disease.

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:[1]

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 [Modified British Medical Research Council {mMRC} 0-1 or COPD Assessment Test {CAT} <10] and low risk of exacerbations [0-1 exacerbations per year, not requiring hospitalization]), 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 very occasional dyspnea.
For group B patients (more symptoms [mMRC ≥2 or CAT ≥10] and low risk of exacerbations [0-1 exacerbations per year, not requiring hospitalization]), LABA/LAMA combination treatment should be offered first-line in the absence of issues with adverse effects or availability. Otherwise, monotherapy with either a LAMA or a LABA may be prescribed. There is no evidence to recommend one class of long-acting bronchodilator over another for bronchodilator monotherapy. The choice should depend on the patient's perception of symptom relief. Patients in group B may have comorbidities that add to their symptoms and impact their prognosis, and so any potential comorbidities should be considered and investigated.
For group E patients (high risk of exacerbations [≥2 exacerbations per year, or ≥1 requiring hospitalization] and any level of symptoms), LABA/LAMA combination treatment is first-line therapy in the absence of issues with adverse effects or availability. Addition of an inhaled corticosteroid (ICS) to a LABA/LAMA combination may be considered if the patient's blood eosinophil count is ≥300 cells/microliter (triple therapy). Use of ICS with LABA alone is not recommended.

[Figure caption and citation for the preceding image starts]: Initial pharmacological management of COPDGlobal Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2023 report); reproduced with permission [Citation ends]. com.bmj.content.model.Caption@6143adbf

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.[1]

Before any adjustment in treatment, patients should be reviewed for symptoms and exacerbation risk, and their inhaler technique and treatment adherence should be assessed. The role of nonpharmacologic treatment should also be assessed. If the patient's response to initial treatment is appropriate, then the initial treatment can be maintained. 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 adverse effects.[1]

Recommended escalation therapy for patients with persistent dyspnea/exercise limitation after initial therapy is as follows:[1]

Patients taking long-acting bronchodilator monotherapy should start a second long-acting bronchodilator. If symptoms do not improve, switching inhaler device or molecules may be considered.
Dyspnea due to other causes should be considered, investigated, and treated. Inhaler technique and adherence should also be reassessed, 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:[1]

Patients taking long-acting bronchodilator monotherapy should increase therapy to LABA/LAMA. Blood eosinophil counts can identify patients who are more likely to respond to ICS.[68][69][70] Escalation to triple therapy with LABA/LAMA/ICS may be considered for patients on long-acting bronchodilator monotherapy if their peripheral eosinophil count is ≥300 cells/microliter. ICS is unlikely to be beneficial in patients whose blood eosinophil count is <100 cells/microliter.
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.[72][79][80][81][82][83][84][85][86] 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.[87] 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.[2]
Patients who take a LABA/LAMA and whose blood eosinophils are <100 cells/microliter should add roflumilast or azithromycin.
LABA/ICS is not recommended by GOLD. However, if a patient with COPD and no features of asthma has received this treatment and is well controlled, they may continue on LABA/ICS. If the patient has further exacerbations, they should be escalated to triple therapy by adding a LAMA. If they have significant symptoms, patients may switch to LABA/LAMA.
Patients 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.[73]

All patients are candidates for education, vaccination, and smoking cessation interventions.

[Figure caption and citation for the preceding image starts]: Escalation therapy for patients with COPD. Definition of abbreviations: ICS: inhaled corticosteroids; LABA: long-acting beta-2 agonists; LAMA: long-acting muscarinic antagonistsGlobal Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2023 report); reproduced with permission [Citation ends]. com.bmj.content.model.Caption@5208c295

Bronchodilators

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.[88] 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.[1][89] 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.[90] [ ] 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.[91] 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.[92][93] One study concluded that aclidinium was not associated with an increase in major adverse cardiovascular events, compared with placebo.[94] A population-based cohort study found that older men with COPD newly started on LAMAs are at increased risk of urinary tract infections.[95]

LABAs and LAMAs both significantly improve lung function, dyspnea, and health status and reduce exacerbation rates. [ ] [Evidence A] In cases of stable COPD, if the decision is made to use single-agent therapy, LAMA may be superior to LABA agents.[96] LAMAs have a greater effect on exacerbation reduction than LABAs in patients with moderate to very severe COPD.[97][98] The long-term safety of LAMA was demonstrated in the UPLIFT trial.[99]

A LABA/LAMA combination may provide a better therapeutic effect without increasing the adverse effects of each class.[96][100][101][102][103] 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.[104] [ ] 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.[105] [ ] One systematic review and network meta-analysis found that all LABA/LAMA fixed-dose combinations had a similar efficacy and safety.[106]

Umeclidinium/vilanterol, glycopyrrolate/formoterol, tiotropium/olodaterol, and aclidinium/formoterol are LABA/LAMA combinations approved for use in COPD. Umeclidinium/vilanterol decreases the risk of exacerbations in patients with mild/moderate COPD.[104] [ ]

As outlined above, GOLD makes recommendations on the initial agent based on the patient's risk group (A, B, or E).[1] American Thoracic Society guidelines recommend initiating LABA/LAMA dual therapy in preference to monotherapy in patients with COPD who have dyspnea or exercise intolerance.[87] 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.[2]

Inhaled corticosteroids (ICS)

When indicated in patients with COPD, ICS should always be prescribed in combination with long-acting bronchodilators. ICS are believed to be effective because of their anti-inflammatory effects. Long-term ICS use reduces the need to use rescue therapy and reduces exacerbations, and may also decrease mortality.[107][108][109] [ ]

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).[81][83][110] Blood eosinophil count may predict the effectiveness of adding ICS to regular long-acting bronchodilator treatment to prevent exacerbations.[69][70][71] 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.[68][72] These thresholds indicate approximate cut-off values that may help clinicians predict the likelihood of a treatment benefit.[1] Former smokers are more corticosteroid-responsive than current smokers at any eosinophil count.[71] 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.[83][111] Short-term ICS use (≤1 year) may be associated with greater improvements in FEV₁ than long-term use, although further studies are needed to better understand the effect of treatment on lung function.[112]

Several studies have pointed to an increased risk of pneumonia in patients with COPD taking ICS.[113] [ ] This risk is higher for fluticasone in comparison with budesonide.[114][115][116] A study in a large cohort of Danish patients found the risk of acquiring Pseudomonas aeruginosa, a common cause of hospital-acquired pneumonia, to be dose-dependent, with high-dose ICS associated with the greatest risk. The study also found that patients with P aeruginosa were more likely to have a lower BMI and FEV₁ than P aeruginosa-negative patients.[117] One systematic review and meta-analysis found that, despite a significant increase in unadjusted risk of pneumonia associated with use of ICS, pneumonia fatality and overall mortality were not increased in randomized controlled trials and were decreased in observational studies.[118] Therefore, an individualized treatment approach that assesses a patient's risk of pneumonia versus the benefit of decreased exacerbations should be implemented.[113][119][120] Concern is also raised with regards to increased risk of tuberculosis and influenza in adult patients with COPD who are on ICS therapy, although one meta-analysis found that less than 1% of all assessed tuberculosis cases were attributable to ICS exposure.[121][122] ICS may also cause oropharyngeal candidiasis and hoarseness.[113] [ ]

Although there have been reports of ICS use either increasing or decreasing the risk of lung cancer, the available data do not appear to support either conclusion; further studies are needed.[1]

Clinicians should weigh the potential benefits and risks of prescribing ICS and discuss these with the patient.[2] 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.[123] Repeated episodes of pneumonia, blood eosinophils <100 cells/microliter, and/or history of mycobacterial infection are all factors against the use of ICS.[123] 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.[123]

The European Respiratory Society has produced a guideline on the withdrawal of inhaled corticosteroids in COPD.[124]

Long-term use of oral corticosteroids in COPD is not recommended.[87] 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.[2]

Combined bronchodilator and corticosteroid preparations

A combination preparation of a long-acting bronchodilator and an ICS 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.[125] 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.[72][79][80][81][82][83][84][85][86] 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.[126] 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.[127] 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.[86][128] 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.[86] For both studies, there were no differences in mortality compared with LABA/ICS.[86][127][128] A post hoc pooled analysis of three trials of triple therapy in patients with COPD and severe airflow limitation and a history of exacerbations showed a nonsignificant trend for lower mortality with triple therapy compared with non-ICS treatments.[129] 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.[130]

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.[2] The ICS may be withdrawn if the patient has had no exacerbations in the past year.[87] One systematic review of data from real-world studies found little to no evidence of worsened outcomes when ICS was withdrawn and followed by appropriate pharmacologic management in patients with moderate to severe COPD.[131]

Phosphodiesterase-4 inhibitors

Roflumilast is an oral phosphodiesterase-4 inhibitor that 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.[1] Roflumilast offers benefit in improving lung function and reducing the likelihood of exacerbations. However, it has little impact on quality of life or symptoms.[132] [ ]

Antibiotics

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.[133][134][135][136] One Cochrane review ranked macrolides first in reducing exacerbations and serious adverse events, and improving quality of life, above fluoroquinolones and tetracyclines.[136] 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.[137] [ ] 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.[138] 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.[139] Azithromycin should be considered preferentially, but not only, in former smokers with persistent exacerbations despite appropriate therapy.[1]

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.[140] Before starting prophylactic antibiotics, baseline ECG and liver function tests should be performed, a sputum sample obtained for culture and sensitivity (including tuberculosis testing), the patient's sputum clearance technique should be optimized, and bronchiectasis should be excluded with a CT scan.[2][140] ECG and liver tests should be repeated after 1 month of treatment. A head-to-head comparison of fluoroquinolones, tetracyclines, and macrolides given for 12-13 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.[141]

Prophylactic antibiotic therapy should be reviewed at 6 and 12 months to determine whether there is a benefit in terms of exacerbation rates.[140] If antibiotic therapy is not effective it should be stopped.

Methylxanthines

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 has modest effects on lung function in moderate to severe COPD.[142] A large randomized controlled trial found no effect of oral theophylline alone or with prednisone on exacerbations of severe COPD.[143] Experts may prescribe theophylline after a patient has exhausted all options for inhaled therapies. Theophylline is not recommended unless other long-term bronchodilators are unavailable or unaffordable.[1]

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.[144] A randomized controlled trial showed that a 3-month program of self-management started in patients with COPD exacerbations recently discharged from the hospital led to increases in COPD-related hospitalizations and emergency department visits over 6 months.[145]

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.[1]

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. It is estimated that patients with COPD are 1.9 times more likely to die from suicide than those without COPD, and symptoms of anxiety, depression, and frustration are common.[146][147] Studies have found a beneficial effect of cognitive behavioral therapy (CBT) on outcomes including symptoms of depression and anxiety, quality of life, and frequency of emergency department visits.[148][149][150] Further research is warranted into the effects of high-resource-intensive versus low-resource-intensive CBT.[150]

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.[151] 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.[152]

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.[153][154] Poor technique is more likely when patients are using multiple devices or have never received inhaler technique training.[155] Demonstration of inhaler use by a clinician, device selection, and reviewing technique at subsequent appointments can improve inhaler technique.[156] Demonstration using a placebo device may be most effective for teaching inhaler technique to adults ages ≥65 years.[157] Patients should be asked to bring their inhalers to clinic to facilitate a review of inhaler use.[1] Pharmacist-led interventions and lay health coaching can improve inhaler technique and adherence in patients with COPD.[158][159] Inhaler device attributes such as rapid onset of symptom relief and small size have been recorded in patient preference studies.[160][161]

Metered dose inhaler

A principal pharmacist shows a patient how to use a metered dose inhaler and discusses ways of improving inhaler technique.

Metered dose inhaler plus spacer

A principal pharmacist shows a patient how to use a metered dose inhaler plus a spacer and discusses ways of improving inhaler technique.

Dry powder inhalers

A principal pharmacist shows a patient how to use dry powder devices and discusses ways of improving inhaler technique.

Soft mist inhaler

A principal pharmacist shows a patient how to use a soft mist inhaler and discusses ways of improving inhaler technique.

Physical activity is recommended for all patients with COPD.[1] 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.[162] 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.[163] Other studies have demonstrated improvements in peak oxygen uptake, perceived fatigue, and health-related quality of life following adherence to supervised and unsupervised exercise programs.[164][165][166] One 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.[167] [ ] The optimal timing, components, duration, and models for improving physical activity remain unclear. Meta-analyses suggest that yoga, Qigong, and other home-based breathing exercises can improve exercise capacity and pulmonary function in patients with COPD.[168][169][170] Tai Chi has been shown to improve exercise capacity compared with usual care.[171]

Dietary advice and oral supplements have been found to improve body weight, quality of life, respiratory muscle strength, and 6-minute walk distance.[172][173] However, nutritional support has not been consistently found to improve lung function.[173]

Smoking cessation

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. 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.[174] 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.[175][176][177]

The use of electronic nicotine delivery systems (ENDS), including e-cigarette and vaping products, as tobacco cessation aids is controversial. Evidence from observational studies does not currently support the use of ENDS as an aid to smoking cessation in people with COPD.[178] See Smoking cessation (Management approach).

Motivational interviewing overview

A professor of healthcare communication provides an overview of motivational interviewing.

Motivational interviewing: smoking cessation part 1

Demonstration, with a professor of healthcare communication, of conducting a motivational interview with a patient about smoking cessation (part 1 of 2).

Motivational interviewing: smoking cessation part 2

Demonstration, with a professor of healthcare communication, of conducting a motivational interview with a patient about smoking cessation (part 2 of 2).

Vaccination

Depending on local guidelines, patients should be vaccinated against influenza virus, Streptococcus pneumoniae, pertussis (whooping cough), varicella-zoster virus (shingles), respiratory syncytial virus (RSV), and coronavirus disease 2019 (COVID-19).[1][179]

Vaccination against influenza is associated with fewer exacerbations of COPD.[180][181] [ ] Guidance from the Centers for Disease Control and Prevention (CDC) advises a single dose of pneumococcal 15-valent pneumococcal conjugate vaccine (PCV15) or 20-valent PCV (PCV20) for all patients with COPD who have not previously received PCV or whose vaccination history is unknown. Patients receiving PCV15 should have a single dose of 23-valent polysaccharide vaccine (PPSV23) at least 1 year later.[182]

The CDC recommends the RSV vaccine for adults with COPD ages ≥60 years and/or with chronic lung or heart disease.[183] The CDC also recommends the tetanus/diphtheria/pertussis vaccine in people with COPD who were not vaccinated in adolescence.[179]

Mucolytics

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.[184] 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.[185] 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.[186] Erdosteine and carbocysteine are not available in the US and some other countries. 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 ICS.[1]

Pulmonary rehabilitation

Pulmonary rehabilitation comprises 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.[1][187][188] GOLD guidelines recommend pulmonary rehabilitation for patients with high symptom burden and risk of exacerbation (i.e., groups B and E).[1]

Pulmonary rehabilitation relieves dyspnea and fatigue, improves emotional function, and enhances a sense of control to a moderately large and clinically significant extent.[189] 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. [ ] There is evidence to support starting pulmonary rehabilitation within 1 month of an acute exacerbation.[190][191]

A large US cohort study found that initiation of pulmonary rehabilitation within 90 days of hospital discharge was significantly associated with lower mortality risk at 1 year and fewer rehospitalizations at 1 year.[192][193] Less than 2% of the patient cohort initiated rehabilitation within this timeframe, highlighting the need to develop more effective strategies to encourage patient participation.[192] However, starting pulmonary rehabilitation before hospital discharge could be associated with a higher 12-month mortality, so is not recommended.[194]

Pulmonary rehabilitation also decreases the depression and anxiety related to COPD, and reduces hospitalization.[195]

The benefit of pulmonary rehabilitation appears to subside after termination of the course unless patients follow a home exercise schedule.[196] Maintenance pulmonary rehabilitation, defined as ongoing supervised exercise at a lower frequency than the original rehabilitation program, may have a role in preserving the benefits of pulmonary rehabilitation over time. Findings from one Cochrane review indicate that supervised maintenance programs may improve health-related quality of life and exercise capacity at 6-12 months compared with usual care.[197] [ ]

Benefits of home- or community-based pulmonary rehabilitation on respiratory symptoms and quality of life in patients with COPD can match those of the hospital-based rehabilitation programs.[198][199][200] One Cochrane review concluded that both primary and maintenance telerehabilitation achieved similar outcomes to in-person rehabilitation with no safety issues. Limitations of the review include small patient numbers and heterogeneity in telerehabilitation models.[201]

Oxygen therapy and ventilatory support

GOLD guidelines recommend long-term oxygen therapy in stable patients who have:[1]

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:[202]

PaO₂ ≤7.3 kPa (55 mmHg) or oxygen saturation as measured by pulse oximetry (SpO₂) ≤88%; or
PaO₂ 7.5 to 7.9 kPa (56-59 mmHg) or SpO₂ of 89% plus one of the following: edema, hematocrit ≥55%, or P pulmonale on an ECG.

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.[202]

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][60]

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.[203] 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.[202] However, the ATS suggests not prescribing long-term oxygen therapy in adults with COPD who have moderate chronic resting room air hypoxemia (SpO₂ of 89% to 93%).[202]

Air travel is safe for most patients receiving long-term oxygen therapy, although patients should be able to tolerate short periods without oxygen as it is likely there will be times it is unavailable.[1][204] Patients with SaO₂ >95% at sea level and SaO₂ ≥84% after a 6-minute walk test may travel by air without further assessment.[1][204][205] 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.[205] Hypoxia-altitude simulation testing (also known as hypoxic challenge testing) should be performed for other patients.[204][205] For patients on long-term oxygen therapy, the British Thoracic Society recommends considering in-flight oxygen at 2L/minute more than the patient's usual prescription.[204]

For patients who have COPD and obstructive sleep apnea, ventilatory support with continuous positive airway pressure (CPAP) can improve survival and reduce hospital admissions.[1][65] Noninvasive ventilation (NIV) 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][206][207] One Cochrane review found that chronic NIV delivered via a facial mask improved survival and conferred short-term health-related quality of life benefit in stable COPD. Chronic NIV also improved duration of hospital admission-free survival in patients with persistent hypercapnia following an exacerbation.[207] Another study reported a significant decrease in exacerbation frequency with NIV versus control therapy, although no improvements were observed in mortality, PaO₂, PaCO₂, or pH.[208]

Guidelines from the ATS suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD.[209] The European Respiratory Society and Canadian Thoracic Society have issued similar guidance.[210][211]

Surgery

Surgical interventions are the last step in the management of COPD, and include bullectomy, lung volume reduction surgery, and lung transplant.[212][213] [ ] They are used to improve lung dynamics, exercise adherence, and quality of life.[213] 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.[212] [ ] 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.[214] 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.[214][215][216] 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%).[217] The most common adverse events associated with endobronchial valve insertion are pneumothorax and exacerbation.[214]

Criteria for referral for lung transplantation include:[218]

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
- FEV₁ 20% to 25% predicted.
Clinical deterioration despite maximal treatment including medication, pulmonary rehabilitation, oxygen therapy, and, as appropriate, nocturnal noninvasive positive pressure ventilation
Poor quality of life unacceptable to the patient
For a patient who is a candidate for bronchoscopic or surgical lung volume reduction (LVR), simultaneous referral for both lung transplant and LVR evaluation is appropriate.

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

Lung transplantation has been shown to improve quality of life and functional capacity.[213] However, lung transplantation does not appear to confer a survival benefit.[219]

Palliative care

Palliative therapies to improve symptoms of dyspnea, offer nutritional support, address anxiety and depression, and reduce fatigue may benefit patients with COPD who experience these despite optimal medical therapy. End-of-life care and hospice admission should be considered for patients with very advanced disease. Patient and family should be well educated about the process, and it is suggested that discussions should be held early in the course of the disease before acute respiratory failure develops.[1][220] 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.[221] 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.[222]

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.[223]

Acupuncture and acupressure may also improve breathlessness and quality of life in patients with advanced COPD.[224]

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