Management Of Stable COPD

Description #

This unit is designed to help health care professionals develop a better understanding of the pharmacological and non-pharmacological management of stable Chronic Obstructive Pulmonary Disease (COPD).

Learning Objectives #

By the end of this unit, you should be able to:

1. Explain the goals of COPD management

2. Explain the stepwise approach to the management of stable COPD

3. Explain smoking cessation in terms of importance and strategies available

4. Identify the inhaled medications and delivery devices used in COPD management

5. Describe the indications and benefits of long-term oxygen therapy

6. Explain the role of exercise and pulmonary rehabilitation in COPD management

7. .Describe the selection criteria for lung volume reduction surgery and and lung transplantation

Management Intro #

Summary #

• COPD is emerging as a major cause of morbidity and mortality in the United States. COPD currently is the fourth leading cause of death among Americans.
• COPD is under-recognized overall, as is α₁-antitrypsin deficiency, a genetic predisposition to COPD.
• Among the available therapies for COPD, many can improve symptoms (e.g., bronchodilators, pulmonary rehabilitation). Three treatments—smoking cessation, supplemental oxygen used 24 hours a day, and lung volume reduction surgery—have been shown to prolong life in appropriately selected COPD patients.

If we are to begin to make inroads on the enormous burden that COPD poses to patients and the health service, we need to make the diagnosis and initiate treatment, particularly smoking cessation interventions, earlier.

We need to think of it as a possibility when we consult with smokers.

In addition, the general public need to be made more aware of COPD and smokers need to be encouraged to present earlier with symptoms.

All of the options listed may have a significant impact on a COPD patient’s quality of life, depending on the severity of the condition and the personal circumstances. The nature of the disease means that little improvement in lung function can be expected, and it should not be sought.

Appropriate therapeutic interventions can, however, have a considerable impact on disability and health status.

It is therefore important to assess these aspects of COPD in order to determine a baseline from which to assess the effectiveness of our interventions and monitor disease progression.

Goal of treatment is to slow progression

• Optimize acute care…

• Decrease readmission rate and length of stay

• Improve symptoms; self-management*

• Improve activity levels

• Enhance quality of life

The management of COPD requires a step-wise approach where therapy is intensified in accordance with the

increasing severity of symptoms and disability as outlined in CTS guidelines. The goals of management of COPD are as follows:

1. To prevent disease progression (smoking cessation).

2. To alleviate breathlessness and other respiratory symptoms.

3. To improve exercise tolerance.

4. To prevent and treat exacerbations.

5. To improve health status.

6. To reduce mortality.

Early detection and early treatment and Smoking cessation can slow COPD and improve quality of life.

– Aggressive management makes a difference.

– Advances in therapies can improve survival or quality of life

1. Assess and monitor disease
2. Reduce risk factors
3. Manage stable COPD

Education

lPharmacologic

 Non-pharmacologic

Manage exacerbations (see unit xx)

Treatment Goals:

•Relieve symptoms

•Prevent disease progression

•Improve exercise tolerance

•Improve health status

•Prevent and treat complications

•Prevent and treat exacerbations

•Reduce mortality

Treatment Approach:

Smoking cessation

Pharmacotherapy

Nonpharmacologic

interventions

Nonpharmacologic treatment of COPD includes pulmonary rehabilitation, long-term oxygen therapy, ventilatory support, and lung volume reduction surgery (LVRS).

MOH:

The therapeutic goals of management of COPD are to:2

• prevent disease progression (smoking cessation)
• alleviate breathlessness and other respiratory symptoms
• improve exercise tolerance and daily activity
• reduce frequency and severity of exacerbations
• treat exacerbations and complications of the disease
• improve health status
• reduce mortality

A management strategy including pharmacotherapy and non-pharmacotherapeutic approaches can improve symptoms, activity levels and quality of life even in patients with severe COPD. The following table of severity can help guide the management of the disease. (Stepwise approach chart)

Indications for specialist referral

• The diagnosis is uncertain.
• A young patient with COPD and limited smoking history or those with severe symptoms and disability which is disproportionate to their lung function decline.
• There are signs and symptoms of hypoxemic or hypercarbic respiratory failure.
• There are severe or recurrent exacerbations and treatment failure.
• The patient has severe COPD and disability requiring more intensive interventions including surgical therapies.
• More intensive co-morbidity assessment and management is required.
• Difficulty in assessing home oxygen or sleep disorders.

The projected increase in the prevalence of COPD will have major implications for Canadians and for health care delivery and provision of community services. Improved medical and public health interventions that target the risk factors for COPD and aim for earlier diagnosis and treatment are needed to decrease the extensive and growing costs associated with COPD in Canada.

Key aims of the National COPD Strategy include:

• Increased public education regarding the importance of good health and the factors that affect it (e.g. smoking, pollution)
• Increased education and action to increase early recognition of symptoms and removal of causative factors
• Earlier recognition of disease by opportunistically screening or case-finding in high risk patients (e.g. smokers aged over 40)
• Diagnosis confirmed by quality-assured spirometry
• Equitable access to high quality pharmacological and non-pharmacological management (especially pulmonary rehabilitation)
• Patients with acute exacerbation of COPD should receive specialist respiratory inpatient care and timely post-discharge review
• Improved access to end-of-life services

Education #

Disease education Tailored to individual patients and families should be offered

The following interventions are recommended for all patients with COPD, regardless of severity:

• Smoking cessation advice: patients who smoke should understand that quitting is the most important thing they can do to improve their health. Help to quit smoking should be offered by all health care providers at every possible opportunity.
• Patient education/self management
• Assess co-morbidity
• Assess BMI: Dietary Advice >25
• Exercise promotion
• Pneumococcal vaccination
• Annual influenza vaccination
• Specialist Dietary Referral if BMI <20

Disease pathophysiology and rationale for treatments:

Reduce Risk Factors:

• Reduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD
• Reduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD
• Smoking cessation is the single most effective — and cost effective — intervention in most people to reduce the risk of developing COPD and stop its progression
• Reducing the risk from indoor and outdoor air pollution is feasible and requires a combination of public policy and protective steps taken by individual patients
• Reduction of exposure to smoke from biomass fuel, particularly among women and children, is a crucial goal to reduce the prevalence of COPD worldwide
• Smoking cessation is the single most effective — and cost effective — intervention in most people to reduce the risk of developing COPD and
• stop its progression (see COPD-004 Patient Self-Management Education) Al smokers should be advised to quit. many COPD patients are heavily addicted and find it difficult to quit; lost lung function cannot be regained but smoking cessation can slow down the rate of decline of lung function and disease progression; Key message: it’s never too late to quit, but earlier is better
• Influenza and pneumococcal vaccination should be offered depending on local guidelines. Shot (vaccines) can help protect you against some strains of flu and pneumonia. Flu and pneumonia shots can lower your chances of getting a flare-up and needing hospital care. You need to take a flu shot every year, usually in the fall. Most people with COPD need to take the pneumonia shot every 5- 10 years. Vaccinations: COPD patients with influenza have a significant risk of hospitalization. The CTS guidelines recommend annual influenza vaccination for all COPD patients who do not have a contraindication. It has been shown to reduce hospitalization by as much as 39% in COPD patients. The CTS also recommends that all patients with COPD be given the pneumococcal vaccine at least once in their lives; and that consideration be given to repeating the vaccination in 5–10 years in high risk patients. Yearly prophylactic immunization with the influenza vaccine has been shown to reduce the incidence of influenza by 76% and is strongly recommended.51-53 Immunization once with the 23-polyvalent pneumococcal vaccine in patients with COPD or, in the special case of patients with immunodeficiency or those with splenectomy, every 5 years, is also recommended.53 The role of different pneumococcal vaccine preparations is being examined as part of the COPD Network, a multicenter consortium sponsored by the National Institutes of Health.

Remain Active:

encourage exercise

Identification of Educational and Support Resources:

help the patient identify resources and a support team (e.g. physician, pharmacist, nurse, dietitian as appropriate)

• refer the patient to a pulmonary rehabilitation program where available and to community respiratory services
• encourage patients to stay indoors when air quality is poor, as air quality may have a significant effect on COPD

Disease Self-Management Education:

Inhaler technique, early recognition of symptoms and action plan use, techniques to control breathlessness

Topics in patient disease self-management are covered in greater detail in the next unit, COPD-004

Medications #

Table X. Common COPD medications and their method of delivery.

– Appropriate pharmacologic therapy can reduce COPD symptoms, reduce the frequency and severity of exacerbations, and improve health status and exercise tolerance.

– None of the existing medications for COPD has been shown conclusively to modify the long-term decline in lung function.

Bronchodilators: Short and long acting bronchodilators 

Inhaled bronchodilators are preferable to oral therapy. The drugs work quicker, making them more suitable for rapid symptom relief, and there are fewer side effects. 

Most patients can cope with a hand-held inhaler, if the right device is selected for them and they are carefully taught how to use it. Nebulisers are rarely necessary and should not be given for regular use without specialist assessment.

 Inhaler technique, once taught, needs to be regularly checked and inhaler checks are incentivised under QOF. There may be some special considerations for inhaler selection in some patients.

The algorithm opposite illustrates the NICE recommendations (2010) for inhaled pharmacotherapy in COPD. 

If you have COPD, your main symptom is probably shortness of breath. You might get short of breath when you exercise, when you do chores, when you feel upset, or for no reason at all.

Bronchodilator medicines open up the airways (breathing tubes) in your lungs. When your airways are more open, it’s easier to breathe. Doctors may prescribe more than one kind of bronchodilator to treat COPD.

Some bronchodilators act very quickly (within 5 minutes) and are known as Rescue Medications. They are used as needed for fast relief symptoms. Others are used regularly to keep symptoms under control. They are known as controllers.

There are two main types of bronchodilators that come in inhalers:

• Beta-2 agonists, for example: salbutamol (Ventolin ®) terbutaline (Bricanyl ®) formoterol (Oxeze ®) salmeterol (Serevent ®)
• Some side effects: fast heartbeat, irregular heartbeat, irritability (feeling cranky), difficulty sleeping, muscle cramps, and shaky hands. More serious side effects are rare. Side effects are usually less noticeable as time goes on.
• Anticholinergics, for example: ipratropium bromide (Atrovent ®) tiotropium (Spiriva ®)
• Some side effects: occasional dry mouth. Men who have trouble with their prostate gland may have difficulty urinating. 

COPD Medications: (GOLD)

  – Bronchodilator medications are central to the  symptomatic management of COPD.

  – Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reducesymptoms. 

– The principal bronchodilator treatments are beta2-agonists, anticholinergics, theophylline or combination therapy.

– The choice of treatment depends on the availability of medications and each patient’s individual response in terms of symptom relief and side effects..

  – Long-acting inhaled bronchodilators are convenient and more effective for symptom relief than short-acting bronchodilators. 

 –  Long-acting inhaled bronchodilators reduce exacerbations and related hospitalizations and  improve symptoms and health status. 

 – Combining bronchodilators of different pharmacological classes may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator. 

– An inhaled corticosteroid combined with a long-acting beta2-agonist is more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD.

– Combination therapy is associated with an increased risk of pneumonia.

– Addition of a long-acting beta2-agonist/inhaled glucorticosteroid combination to an anticholinergic (tiotropium) appears to provide additional benefits.

– Chronic treatment with systemic corticosteroids should be avoided because of an unfavorable benefit-to-risk ratio.

– In patients with severe and very severe COPD (GOLD 3  and 4) and a history of exacerbations and chronic bronchitis, the phospodiesterase-4 inhibitor (PDE-4), roflumilast, reduces exacerbations treated with oral glucocorticosteroids.

– Theophylline is less effective and less well tolerated than inhaled long-acting bronchodilators and is not recommended if those drugs are available and affordable. 

There is evidence for a modest bronchodilator effect and some symptomatic benefit compared with placebo in stable COPD.  Addition of theophylline to salmeterol produces a greater increase in FEV1 and breathlessness than salmeterol alone. 

Low dose theophylline reduces exacerbations but does not improve post-bronchodilator lung function.

– Alpha-1 antitrypsin augmentation therapy: not recommended for patients with COPD that is unrelated to the genetic deficiency.

– Mucolytics:    Patients with viscous sputum may benefit from mucolytics; overall benefits are very small.

– Antitussives:  Not recommended.

Rapid-onset bronchodilators (also called quick-relief medicines) act quickly and start to relieve shortness of breath within minutes. They are often used as needed, to help relieve sudden shortness of breath. Quick-relief medicines usually come in a blue puffer.

Some rescue medicines are short-acting and last for 4-6 hours (like Ventolin ® or Bricanyl ®). Some are long-acting and last for up to 12 hours (like Oxeze ®).

Slow-onset bronchodilators take longer to act. Some last for 4 to 6 hours (like Atrovent ®), and some last up to 12 hours (like Serevent ®). One slow-onset bronchodilator lasts for 24 hours (Spiriva ®).

If you’re short of breath and need help right away, take a quick-relief medicine like Ventolin ®, Bricanyl ®, or Oxeze ®. Quick-relief medicines usually come in a blue puffer. Keep your quick-relief medicine with you at all times, so it’s there when you need it.

All the bronchodilators listed above come in puffers (inhalers). Learn how to use puffers (inhalers) and other devices.

There’s another kind of bronchodilator that opens your airways. This one is in pill form:

Xanthines or theophyllines (such as Uniphyl® or Theodur ®)

Xanthines or theophyllines are slow-onset bronchodilator pills. They don’t open your airways as well as inhaled bronchodilators, and they can have serious side effects and drug interactions. For these reasons, xanthines/ theophyllines are not commonly used. When they are used, it’s usually in combination with other bronchodilators.

Some side effects: nausea, heartburn, restlessness and fast heartbeat.

Xanthines/theophyllines can interact with food and other medicines. Make sure your doctor and pharmacist knows all the other medicines you are taking. If you are taking these pills, your doctor will give you regular blood tests to monitor how much of the medicine is in your body. 

The next three pages take a more detailed look at the different kinds of medications used in the management of stable COPD.

Bronchodilators #

Many patients do not obtain all of the benefits from their inhaled medications because they do not use them correctly, and this can lead to poor asthma control.1

Guidelines recommend that healthcare professionals repeatedly check their patient’s inhaler technique and provide training as required. 

•         Ventolin

– Short-acting

– 2-4 times/day

– Prevents/relieves smooth muscle constriction

•         Serevent (salmeterol)

– Long-acting

– 2 times/day

•         Atrovent

– Prevents/relieves smooth muscle constriction

– 4 times/day 

•         Tiotropium (Spiriva)

– Long-acting

– Once per day    

 Tailoring treatment with bronchodilator medications is the first-line therapy for COPD. Bronchodilators form the mainstay of drug therapy for COPD. They work by decreasing airway smooth muscle tone, thus improving expiratory flow and lung emptying with each breath. Inhaled therapy is preferable to oral therapy because inhaled drugs target the airways directly and are less likely to cause systemic adverse effects. Three major classes of bronchodilators available are:

Beta₂-Agonist

Anticholinergics

Methylxanthines (Theophyllines). Theophyllines are not routinely recommended in patients with COPD but may be considered in some individuals whose symptoms are not controlled by inhaled bronchodilators. They should be used cautiously due to high risk of side effects and drug interactions.

 There are 2 subgroups of Beta Agonists and what is generally prescribed for COPD patients are Beta₂ Agonists. 

“Beta₁-agonists receptors are in the heart. These increase cardiac activity, Increase HR, increase BP

 “Beta₂-agonist receptors are in the lung. These relax smooth muscle—i.e. therefore open the airway and allow the patient to breathe more easily.

Bronchodilators #

Bronchodilators are a mainstay of COPD treatment and include β-adrenergic agonists, anticholinergics, and methylxanthines. β-Adrenergic agonists are effective in alleviating symptoms and improving exercise capacity, and they can produce significant increases in FEV₁.5,6 Their effect is achieved through smooth-muscle relaxation, resulting in improved lung emptying, reduced thoracic gas volume and residual volume, and lessened dynamic hyperinflation. It is believed that the increase in exercise tolerance and reduction in symptoms of breathlessness are primarily a result of an improvement in inspiratory capacity rather than an increase in FEV₁. Oral theophylline has been shown to lessen dyspnea and improve the health-related quality of life despite lack of significant rise in FEV₁, with improvements believed to be a result of increased respiratory muscle performance. However, the narrow therapeutic index of methylxanthines and their potential for adverse drug-drug interactions have hindered their widespread use. Long-acting formulations have allowed more-consistent and stable plasma levels, thereby mitigating the problem.

Phosphodiesterase Inhibitors #

Newly developed oral, highly selective phosphodiesterase 4 (PDE4) inhibitors roflumilast32 and cilomilast,33 have shown promise in the management of stable COPD. Specifically, a randomized, double-blind study involving more than 1400 patients with moderate-to-severe COPD compared patients assigned to receive 250 µg of roflumilast, 500 µg of roflumilast, or placebo over a period of 24 weeks. The primary end points were post-bronchodilator FEV₁ and health-related quality of life. Secondary end points included the rate of COPD exacerbations. Although there was no significant difference in the post-bronchodilator FEV₁ in the treatment arms, both were superior to placebo (P < .0001). Similar findings were reported in the health-related quality of life and rate of exacerbations with an acceptable safety profile.32

Similarly, cilomilast was compared with placebo in a double-blind, placebo-controlled, parallel group trial. Here, patients were assigned to cilomilast 15 mg orally twice daily versus placebo, and followed for 24 weeks. Change from baseline FEV₁ and St. George’s Respiratory Questionnaire (SGRQ) scores were the primary end points, with the rate of COPD exacerbations as the main secondary end point. Again, cilomilast was statistically superior to placebo in all study end points, with mild-to-moderate adverse events that were self-limited.33 As promising as these studies seem, more studies are needed before these new PDE4 inhibitors become part of standard therapy for the stable COPD patient.5,33

β-Adrenergic Agonists #

In the early stages of COPD (e.g., stage I), a short-acting β-adrenergic agonist (e.g., albuterol, terbutaline) or an anticholinergic is used on an as-needed basis. As the disease progresses (e.g., stages II and III), regular use of one or more bronchodilators is often recommended. Some data suggest that a combination of albuterol and ipratropium bromide provides better bronchodilation than either agent alone.5,34-36

In 2004, the United States Food and Drug Administration approved a new anticholinergic agent, tiotropium, for the long-term, once daily, maintenance treatment of bronchospasm associated with stable COPD, including chronic bronchitis and emphysema.37 Although this is the same indication granted to ipratropium, tiotropium has shown significant advantages over ipratropium, both pharmacologically and clinically. Specifically, tiotropium blocks the M₁ to M₅ muscarinic receptors with a 6- to 20-fold greater affinity than ipratropium and for a longer period38-40 and dissociates more rapidly from the M₂ receptor associated with acetylcholine release, thereby conferring theoretical advantages over ipratropium.

These advantages were shown in clinical trials comparing the two agents. Specifically, tiotropium demonstrated significantly greater bronchodilation than ipratropium, and users experienced less dyspnea, fewer acute exacerbations, reduced albuterol use, and improved nocturnal oxygen saturation.39-42 When compared with long-acting β₂-agonists, tiotropium provided greater bronchodilation and more-reduced dyspnea than salmeterol. A large double-blind, placebo-controlled trial showed a significantly greater reduction in yearly incidence as well as delay to first COPD exacerbation compared with either salmeterol or placebo.42

Results of a large randomized, controlled trial (called UPLIFT) comparing the efficacy of tiotropium have shown that tiotropium conferred benefits of a lower exacerbation frequency but neither slowing of FEU₁ decline nor a lower mortality rate.43 

COPD Medications: (GOLD)

  – Bronchodilator medications are central to the  symptomatic management of COPD.

  – Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms. 

– The principal bronchodilator treatments are beta2-agonists, anticholinergics, theophylline or combination therapy.

– The choice of treatment depends on the availability of medications and each patient’s individual response in terms of symptom relief and side effects..

  – Long-acting inhaled bronchodilators are convenient and more effective for symptom relief         than short-acting bronchodilators. 

 –  Long-acting inhaled bronchodilators reduce exacerbations and related hospitalizations and  improve symptoms and health status. 

 – Combining bronchodilators of different pharmacological classes may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

– In patients with severe and very severe COPD (GOLD 3  and 4) and a history of exacerbations and chronic bronchitis, the phospodiesterase-4 inhibitor (PDE-4), roflumilast, reduces exacerbations treated with oral glucocorticosteroids. 

– Theophylline is less effective and less well tolerated than inhaled long-acting bronchodilators and is not recommended if those drugs are available and affordable. 

There is evidence for a modest bronchodilator effect and some symptomatic benefit compared with placebo in stable COPD.  Addition of theophylline to salmeterol produces a greater increase in FEV1 and breathlessness than salmeterol alone. 

Low dose theophylline reduces exacerbations but does not improve post-bronchodilator lung function.

•         Bronchodilator medications are central to the symptomatic management of COPD (Evidence A).

They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms.

•         The principal bronchodilator treatments are beta2-agonists, anticholinergics, theophylline, and a combination of these drugs (Evidence A).

•         Long-acting inhaled bronchodilators are more convenient (Evidence A) .

•         Combinations of bronchodilators may improve efficacy and reduce risk of side effects vs. increasing dose of a single agent

•         1) Physiologic Effects

–        a) ASM relaxation

–        Bronchodilation: FEV1

–        Decreased air trapping and dynamic hyperinflation

–        b) Non-bronchodilator Effects (LABAs, Theophylline) 

•         2) Clinical Effects

–        ¯ Breathlessness (¯ Raw, ¯ hyperinflation)

–        ­ Exercise tolerance (¯ dynamic hyperinflation)

–        ­ Sleep quality (¯ nocturnal bronchospasm)

–        ­ Health-related quality of life

–        ¯ Frequency of acute exacerbations 

MOH:

Bronchodilators are the mainstay of COPD pharmacotherapy. Pharmacological treatment of COPD has not been shown to reverse, slow, or prevent progressive decline in lung function, but can improve symptoms, reduce exacerbations and hospitalizations, and improve quality of life. Bronchodilators reduce air trapping, dyspnea, and improve quality of life even if improvement is not seen on spirometry.

• Patients with mild COPD should be prescribed a short-acting inhaled beta₂ agonist or ipratropium to be used as needed.
• If symptoms persist, then consider regular use of ipratropium or a long-acting bronchodilator (tiotropium or a long-acting beta₂ agonist (LABA)).
• If the patient continues to be symptomatic despite the addition of tiotropium or LABA, the other may be added.
• Concurrent use of tiotropium and ipratropium is not recommended.
• Regular use of inhaled corticosteroids could be added to combination tiotropium and LABA therapy for patients with moderate to severe COPD with a history of exacerbations (one or more per year, on average, for two consecutive years) to reduce exacerbations,2 or if asthma coexists. Long term oral corticosteroid therapy is not recommended.
• If indications for both a LABA and an inhaled corticosteroid exist, then consider a combination product containing both medications.
• Theophylline may be useful in select patients with persistent symptoms despite optimal inhaled therapy.
• Evaluate the patient’s inhaler technique regularly. Consider prescribing a spacer for metered dose inhalers. Dry powder inhalers are not used with a spacer.

ACP:

There is limited and conflicting evidence of health benefits resulting from initiation of inhaled bronchodilators (anticholinergics or long-acting
-agonists) in symptomatic patients with FEV1 between 60% and 80% predicted as documented by spirometry. Individual patients may benefit from the therapy and may show improvement in their respiratory symptoms. However, the duration of maintenance therapy and the frequency of reevaluation once a patient is receiving therapy are unknown because evidence is limited. Further research is needed to evaluate the health benefits of inhaled therapies (anticholinergics orlong-acting
-agonists) in symptomatic patients with FEV1 between 60% and 80% predicted. This recommendation does not address the occasional use of short-acting inhaled bronchodilators for acute symptom relief.

Patients who benefit the most from inhaled bronchodilators (anticholinergics or long-acting
-agonists) seem to be those who have respiratory symptoms and airflow

obstruction with an FEV1 less than 60% predicted. The mean FEV1 was less than 60% predicted in the majority of the trials that evaluated the management of COPD. This recommendation does not address the occasional use of short-acting inhaled bronchodilators for acute symptom relief.

Monotherapy with a long-acting inhaled
-agonist or a long-acting inhaled anticholinergic is beneficial in reducing exacerbations and improving health-related quality of life. Evidence was inconclusive regarding the effect of inhaled agents (anticholinergics and long-acting
-agonists) on mortality, hospitalizations, and dyspnea. Although data support that inhaled corticosteroids are superior to placebo in reducing exacerbations, concerns about their side effect profile (thrush, potential for bone loss, and moderate to severe easy bruisability) and less biologic rationale, in contrast to the rationale that supports the use of inhaled steroids as anti-inflammatory monotherapy in asthma, led to our recommendation that inhaled corticosteroids are not a preferred monotherapy for patients with stable COPD.

Adverse effects related to inhaled long-acting anticholinergics or long-acting
-agonists range from mild (for example, dry mouth) to potentially serious (for example, cardiovascular events). Pooled analyses of results from trials of monotherapy show no statistically significant differences in outcomes among various monotherapies. However, some of the large recent trials have shown that different monotherapies may have a greater effect on certain outcomes. These observed effects need to be confirmed with further comparative effectiveness studies. Clinicians should base selection of treatment from among various monotherapies on individual patient preferences, cost, and adverse effect profile.

Corticosteroids #

The CTS guidelines recommend that oral corticosteroids not be used in COPD, given the absence of benefit and the risk of adverse systemic effects. Adverse events include adrenal suppression, osteoporosis, cataract formation, dermal thinning, muscle weakness, hypertension, diabetes and hyperadrenocorticism. The following are the recommendations of the CTS regarding inhaled corticosteroids (ICS):

1.   ICS should not be used as first line medication in COPD because no consistent effects have been demonstrated on airway inflammatory cells and related inflammatory mediators

2.   Regular use of high dose ICS alone should only be considered in patients with moderate to severe COPD who have recurrent, acute exacerbations (i.e., 3 exacerbations or more per year, especially those requiring the use of oral corticosteroids.

3.   The panel further suggests that the potential for limited benefits in many patients contrasts sharply with the high likelihood of adverse effects when

ICS are used in high doses for prolonged periods of time, particularly in the elderly. 

– Regular treatment with inhaled corticosteroids (ICS) improves symptoms, lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV1 < 60% predicted.

– Inhaled corticosteroid therapy is associated with an increased risk of pneumonia 

ICS should not be used alone in COPD. They should only be prescribed with a LABA.

Long-term treatment with oral corticosteroids is not recommended.

– An inhaled corticosteroid combined with a long-acting beta2-agonist is more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD.

– Combination therapy is associated with an increased risk of pneumonia.

– Addition of a long-acting beta2-agonist/inhaled glucorticosteroid combination to an anticholinergic (tiotropium) appears to provide additional benefits.

– Chronic treatment with systemic corticosteroids should be avoided because of an unfavorable benefit-to-risk ratio.

Corticosteroids #

Although widely used, oral and inhaled corticosteroids have a limited role in managing patients with stable COPD. Several groups suggest brief trials of oral corticosteroids for patients with stable COPD. For example, the BTS suggests a course of oral prednisone (e.g., 30 mg daily) taken for 2 weeks, or a course of inhaled steroid (e.g., beclomethasone 500 µg twice daily or the equivalent) taken for 6 weeks.7 Similarly, the ERS suggests a trial of corticosteroids (e.g., 0.4-0.6 mg/kg/day) taken for 2 to 4 weeks. Patients with significant FEV₁ responses are considered candidates for long-term inhaled corticosteroids.6 At the same time, four randomized, placebo-controlled trials of inhaled corticosteroids in patients with COPD have shown no effect on the rate of FEV₁ decline,27,44-47 although one study suggested that steroid recipients experienced fewer COPD exacerbations than nonrecipients.46

A more-recent trial was conducted comparing the effect of the salmeterol-fluticasone combination with either agent alone and with placebo. It found that the combination therapy was significantly more effective than sole therapy with the long-acting bronchodilator, or fluticasone, or placebo in patients with COPD. The TRISTAN study, a 52-week, randomized, placebo-controlled study involving 1465 patients with moderate-to-severe COPD, showed significant improvement in FEV₁ in the salmeterol-fluticasone combination versus salmeterol (treatment difference of 73 mL, P < 0.0001), fluticasone (treatment difference of 95 mL, P < 0.0001),48 and placebo (treatment difference of 133 mL, P < 0.0001). Other benefits included a decrease in the use of rescue medications in the combination group and a significant improvement in health status as defined by the St. George’s Respiratory Questionnaire compared with the fluticasone group but not the salmeterol group. The rate of moderate and severe exacerbations was reduced by 25% in the combination group compared with placebo.48

This finding becomes all the more significant in the context that severe acute exacerbations have an independent negative impact on prognosis, with increased mortality associated with the frequency of severe exacerbations.49 In a prospective cohort of 304 men with severe COPD (mean FEV₁, 46% of predicted), older age, Pco ₂, and acute exacerbation of COPD represented independent indicators of poor prognosis, and patients with three or more exacerbations showed the greatest mortality risk.49 Whether the combination of an inhaled corticosteroid and long-term bronchodilator enhances survival in patients with COPD is the subject of ongoing research.50

Several randomized, controlled clinical trials have assessed the role of inhaled corticosteroids (e.g., called Euroscop, ISOLDE, Copenhagen City, Lung Health Study, and OPTIMAL) and of inhaled steroids combined with long-acting β agonists in exacerbation frequency, quality of life, rate of change of FEV₁, and, in one study (TORCH), mortality. The weight of evidence suggests that inhaled corticosteroids can lessen the frequency of acute exacerbations of COPD, but (with the exception of the TORCH trial) inhaled steroids do not appear to affect the rate of FEV₁ decline. The combination of inhaled fluticasone and salmeterol appears better than placebo in enhancing health-related quality of life and lessening exacerbation frequency. The one trial (TORCH) that examined mortality as a primary outcome measure showed that the combination of inhaled fluticasone and salmeterol (500 µg/50 µg, respectively, twice daily) conferred a 2.6% absolute reduction in mortality (15.2%-12.6%; 17.5% relative reduction), although this difference missed statistical significance (P = 0.052).

Currently, inhaled corticosteroids are widely used, especially for patients with frequent exacerbations of COPD, although recent concerns about excess pneumonia risk in users of inhaled steroids have spurred some controversy and will certainly receive prospective scrutiny.

ACP:

Many symptomatic patients with stable COPD and an FEV1 less than 60% predicted may benefit from combination therapy, but when to use combination therapy instead of monotherapy has not been clearly established. The longterm benefit of combination therapy compared to monotherapy in 2 recent large clinical trials (TORCH and UPLIFT) was moderate for COPD exacerbations and of borderline statistical significance for mortality, but was not consistently seen in earlier trials. In some studies, combination therapy has been associated with a modest increase in the risk for adverse events, whereas other studies have not found this. Thus, the evidence is insufficient to support a strong recommendation for the broad use of combination therapy, and clinicians will need to weigh the potential benefits and harms of combination therapy on a case-by-case basis. The combination therapy that has been most studied to date is long-acting inhaled
-agonists plus inhaled corticosteroids.

Other Medications #

Phosphodiesterase 4 (PDE4) enzyme inhibitor:

Daxas® (roflumilast) is an orally administered selective phosphodiesterase 4 (PDE4) enzyme inhibitor, which has been shown to inhibit COPD related inflammation with a novel mode of action. Daxas, a once-a-day oral tablet, is the first drug in a new class of treatment for COPD and the first oral anti-inflammatory treatment for COPD patients. Other pharmacological treatments for COPD patients include the use of inhaled bronchodilators and inhaled corticosteroids.

Methylxanthines:

Oral Theophylline  

– Alpha-1 antitrypsin augmentation therapy: not recommended for patients with COPD that is unrelated to the genetic deficiency.

– Mucolytics:    Patients with viscous sputum may benefit from mucolytics; overall benefits are very small.

– Antitussives:  Not recommended.

– Vasodilators:  Nitric oxide is contraindicated in stable COPD.  The use of endothelium-modulating agents for the treatment of pulmonary hypertension associated with COPD is not recommended.

Mucokinetic Agents #

Mucoactive agents are varied and include ambroxol, erdosteine, carbocysteine, iodinated glycerol, N-acetylcysteine, surfactant, and others, all of which have been studied with conflicting results. However, a Cochrane systematic review of 23 randomized, controlled trials in Europe and the United States associates the long-term use (>2 months) of oral mucolytics with a reduction in acute COPD exacerbations and days of illness and suggests considering these agents in patients with recurrent, prolonged, severe COPD exacerbations.54 Still, the latest guidelines by the ATS and BTS do not recommend the routine use of mucoactive agents in the management of chronic COPD.5-8

Pulmonary rehabilitation #

What is Pulmonary Rehabilitation?

Pulmonary rehabilitation is a coordinated program of exercise, education and psychosocial support for patients with chronic lung disease. Patients with COPD often avoid exercise in order to avoid feeling short of breath. This reduction in activity leads to deconditioning and generalized weakness resulting in dyspnea occurring at lower activity levels and a progressive reduction in excercise tolerance. Pulmonary rehabilitation programs are aimed at breaking this cycle of disability and returning patients to acceptable levels of daily activity.

Physicians should consider prescribing pulmonary rehabilitation for any patient with COPD who remains symptomatic or limited in their exercise capacity despite optimal pharmacological treatment. However, patients at all stages of disease appear to benefit from participating in pulmonary rehabilitation programs.

Benefits of Pulmonary Rehabilitation

All COPD patients benefit from pulmonary rehabilitation programs with improvements in exercise capacity, dyspnea and fatigue. Rehabiliation provides patients with a sense of control over their disease which can lessen the psychological impact of their disease. Other benefits of pulmonary rehabilitation include improved health-related quality of life, fewer hospitalization days, fewer exacerbations, and decreased health care utilization.

Following participation in a pulmonary rehabilitation program, the benefits of reduced symptoms can be sustained for several months However all patients should be encouraged to continue with an active lifestyle through a maintenance exercise programs.

Structure of a Pulmonary Rehabilitation Program

Effective pulmonary rehabilitation programs can be based in hospitals, in the community or in the home. More formal hospital and community based programs are often operated by multidisciplinary staff and sessions are generally conducted in groups. The benefits of pulmonary rehabilitation are dose dependent, with longer programs resulting in greater benefit. Most programs are 4-8 weeks in duration, but patients should have the option to continue for longer. The components of pulmonary rehabilitation programs vary, but typically include exercise training, disease management education, and psychosocial support.

Excercise Training: The exercise component of a pulmonary rehabilitation program has the greatest effect on improving symptoms, exercise capacity and health-related quality of life in COPD patients. Excercise training can provide also provide patients with the added benefits of increased energy, improved sleep habits, increased muscle and bone mass, stronger connective tissue and maintaining a healthy weight.

Aerobic exercise is the foundation of pulmonary rehabilitation with lower extremity training provided through walking, treadmill, bicycle ergometry or rowing. Upper extremity exercise, respiratory muscle training, and strength training might also be offered. While exercise training is known to improve the functional status of patients with COPD, the optimal duration, frequency, and intensity of the each type of training remains poorly defined and these variables are different from program to program.

If exercise training is maintained at home following completion of a pulmonary rehabilitation program, the patient’s health status remains above pre-rehabilitation levels.

Disease Management Education: In combination with exercise training, most pulmonary rehabilitation programs provide patients and their families with disease management education. Self-management education that is tailored to each patient is an important aspect COPD management as it provides the skills necessary for patients to reduce their risk factors, reduce exacerbations, and cope with their illness. Topics in disease management education program might also include breathing and relaxation techniques, sexuality, nutrition, and end-of-life care .

The next unit in this course (COPD-OO4) takes a closer look at topics in patient disease self-management.

Psychosocial Support: The cycle of dyspnea and inactivity in COPD patients who avoid exercise has not only physical consequences but emotional consequences as well. COPD patients can experience depression and anxiety as they become socially isolated and less able to cope with daily activities. By increasing their mobility and independence, pulmonary rehabilitation programs can lead to improved mood and self- efficacy.

Many programs also provide access to supportive counseling and social support networks to encourage patients to connect with others suffering from COPD. A strong support system is an important component of pulmonary rehabilitation.

Oxygen Therapy #

Hypoxemia in COPD

Hypoxemia is defined as an abnormally low blood oxygen level. It is common among patients with COPD, and the severity of hypoxemia tends to correlate with the severity of lung function impairment. Chronic hypoxemia caused by COPD can lead to conditions such as pulmonary hypertension, right ventricular dilatation, and cardiac arrhythmias. It can also cause peripheral muscle impairment, neurologic and cognitive problems and polycythemia. Patients with chronic hypoxemia will likely experience shortness of breath, a reduced excercise tolerance and an overall reduced quality of life.

Long Term Oxygen Therapy (LTOT)

While it does not improve lung function, LTOT is one of the few therapeutic interventions that increases survival in COPD patients. It is shown to be effective in severely hypoxemic patients when used for at least 15 hours per day to achieve a saturation of 90% or greater. As well as prolonging life, when used in appropriate patients LTOT has been shown to improve cognitive function, reduce shortness of breath, improve exercise tolerance and reduce hospital admissions.

Oxygen is a drug. It is prescribed by a physician for eligible patients who agree to have oxygen in the home. It is prescribed in litres/minute for rest, exertion and sleep. The prescribed oxygen flow is determined by arterial blood gas values, walking oximetry tests and overnight oximetry studies.

Assessment of Hypoxemia

 Shortness of breath alone is not a good indicator of hypoxemia. Generally, the measurement of arterial blood gases is required to assess arterial oxygenation and the need for oxygen therapy. Under certain circumstances, noninvasive monitoring using pulse oximetry may be appropriate in the assessment of hypoxemia, such as during sleep, or during ambulation.

In order to accurately determine the need for LTOT, assessment should occur when a patient is stable, rather than during or immediately following an exacerbation. However, in-hospital home oxygen assessments are routinely done in order to faciliate the discharge of a patient who is remains hypoxic on room air, but is otherwise ready to go home. Patients should be receiving optimal medical management for COPD before they are assessed for the need for oxygen therapy.

Patients discharged home with oxygen will be re-evaluated by a home-care clinician periodically to determine if they are still suitable for LTOT. 

Criteria for Oxygen Therapy

In Canada, home oxygen therapy is funded by provincial governments according to a set of eligibility criteria that are similar in most health regions.

In general, the patients are eligible for LTOT when they have a resting [?]PaO₂[/?] of 55 mmHg or less, or when their resting PaO₂ is less than 60mmHg in the presence of bilateral ankle edema, cor pulmonale, or polycythemia. Patients may also qualify if they show a desaturation below 88% (>1 minute) during ambulation, as long as there is an improvement in exercise tolerance with oxygen.

In patients experiencing isolated desaturations at night, nocturnal oxygen therapy is not currently indicated. In these patients, a sleep study should be considered to rule out the presence of sleep apnea.

Specific criteria for LTOT eligibility vary across health regions in Canada.  This PDF shows an example of the home oxygen program criteria in place at Vancouver Coastal Health (February 2012).

Considerations

• Patients on oxygen therapy and their family should receive education on the role of oxygen, and how to use it safely and as prescribed.
• Although oxygen is relatively safe, it does support combustion. It should only be used in a smoke-free environment and kept away from open flames, sparks, direct heat sources and oil-based lubricants such as Vaseline.
• There are a variety of oxygen delivery systems available for home use. The system provided will depend on factors such as patient mobility and lifestyle, and the flow rate of oxygen required.

Surgical Treatment #

Surgical treatment for COPD is usually reserved for those patients with advanced disease and severe symptoms unrelieved by maximal medical therapy. The two main surgical procedures used in COPD management include lung volume reduction surgery (LVRS) and lung transplantation.

Lung Volume Reduction Surgery

Lung Volume Reduction Surgery (LVRS) is a potentially effective treatment option for some COPD patients. LVRS involves the excision of lung tissue from patients with diffuse emphysema and hyperinflation. In patients who meet specific criteria, this procedure may improve lung function, exercise capacity, dyspnea, and quality of life. It may also improve survival among some patients. (insert Table)

Lung Transplantation:

Lung transplantation, a procedure in which one or both diseased lungs are replaced with healthy lungs from a human donor, is also an option for some patients with severe COPD. In appropriately selected patients, lung transplantation has been shown to improve exercise tolerance and quality of life. (insert Table)

A major complication of lung transplantation is chronic graft rejection, however survival rates for patients with COPD undergoing lung transplantation tend to be better than for patients with other conditions. Despite the steady increase in the number of lung transplants performed in Canada, the number of patients on waiting lists for the procedure continues to rise. 

AAT Deficiency Treatment #

As you recall from Unit COPD-102, alpha1-antitrypsin (A1AT) deficiency is a hereditary disorder accounting for 1-2% of all cases of emphysema. It is a well-studied genetic cause of COPD, in which individuals have a 50-80% chance of developing emphysema. Patients with this deficiency may also develop liver disease (cirrhosis).

A1AT deficiency is a disease in which there are low serum and lung levels of A1AT. A1AT is a natural protein, produced by the liver, that protects the lung tissue by controlling elastase levels. Elastase is a protein released by white blood cells which digests bacteria and other foreign irritants in the lungs. When a person with A1AT deficiency is exposed to respiratory irritants or infection, elastase is released in the lung unchecked, eventually destroying healthy lung tissue as well. This lung structure degradation leads to emphysema. The damage to the lung is faster and more pronounced in patients who smoke .

COPD caused by A1AT deficiency should be treated with the same modalities as COPD of other causes. Depending on disease severity, management of A1AT deficiency may include short- and long-acting bronchodilators, inhaled corticosteroids, antibiotics, pulmonary rehabilitation, oxygen, and oral corticosteroids.

As well, quitting smoking is essential in the management of A1AT deficiency. All patients with A1AT deficiency should be offered smoking cessation counseling and pharmacotherapy. These patients should also be advised to minimize occupational and environmental exposure to fumes and other lung irritants.

Certain patients suffering from emphysema as a result of A1AT deficiency are also treated with augmentation therapy. By replacing the missing A1AT protein, the A1AT level in the bloodstream is raised, protecting the lungs against the elastase. This can slow the loss of lung function in people with A1AT related emphysema. This treatment is typically given intravenously, once weekly, and is continued for life.

Indications for A1AT Augmentation Therapy:

Patients who do not smoke that are diagnosed with emphysema and have:

• FEV1 25% to 80% predicted
• A1AT level ≤11 μmol/L
• Optimal management of emphysema already in place.

Treatment for AAT deficiency also involves management of cirrhosis when appropriate.

References #

1. O’Donnell DE, Aaron S, Bourbeau J, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease – 2007 update. Can Respir J. 2007;14(Suppl B):5B-32B.
2. O’Donnell DE, Hernandez P, Caplan A, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease – 2008 update – highlights for primary care. Can Respir J. 2008;15(Suppl A):1A-8A.
3. Marciniuk D, Hernandez P, Balter M, et al; Canadian Thoracic Society COPD Clinical Assembly Alpha-1 Antitrypsin Deficiency Expert Working Group. Alpha-1 antitrypsin deficiency target testing and augmentation therapy: A Canadian Thoracic Society clinical practice guideline. Can Respir J 2012;19(2):109-116.