The GOLD guidelines emphasize that a COPD management plan should include four components, which are summarized in Table 42-2. In stages I and II of COPD, treatment will concentrate on avoiding risk factors and treating symptoms as needed with medications. In stages III and IV, treatment will require multiple disciplines and treatment approaches. The ultimate goal would be to prevent development of COPD altogether, but once it is diagnosed the goal is effective management.1 The goals of management are listed in Table 42-3.
Smoking cessation is the single most effective treatment for reducing the progression of COPD.1 Tobacco dependence is a chronic condition that warrants intensive and repeated treatment with both counseling and pharmacotherapy until continued abstinence is achieved.17
Pulmonary rehabilitation should be considered for patients with COPD, and it has been shown to have numerous benefits including improved exercise capacity, improved health-related quality of life, reduced number of hospitalizations, reduced anxiety and depression, and improved survival.1 A comprehensive pulmonary rehabilitation program will include exercise training, nutrition counseling, and education.
Oxygen therapy is often necessary for patients with stage IV COPD. Oxygen therapy for patients with chronic respiratory therapy has been shown to increase survival.18,19 Other benefits include improvement in exercise capacity, lung mechanics, and mental state.20 Oxygen therapy can also prevent the progression of pulmonary hypertension.21,22
All patients with COPD should receive the influenza vaccine annually.1 The 2008 GOLD guidelines only recommend the pneumococcal polysaccharide vaccination in COPD patients over the age of 65 and for patients less than 65 years of age with an FEV1 less than 40%.1 However, the more updated 2009 CDC recommendations state that all patients with chronic lung disease or who are chronic smokers should receive the pneumococcal vaccine.23
The medications available for COPD are effective for reducing or relieving symptoms, improving exercise tolerance, reducing the number and severity of exacerbations, and improving the quality of life. No medications presently available have been shown to slow the rate of decline in lung function.1
Bronchodilators are the mainstay of treatment for symptomatic COPD. They reduce symptoms and improve exercise tolerance and quality of life.1 Bronchodilator medications commonly utilized for COPD include β2-agonists, anticholinergics, and theophylline (theophylline would be considered a last-line agent because of potential adverse reactions). The inhaled route is the preferred route for β2-agonists and anticholinergics, but attention must be paid to proper inhaler technique.1 Clinicians should advise, counsel, and observe patient technique with the devices frequently and consistently. Combining different bronchodilator therapies improves efficacy and is preferred over increasing the dose of a single agent, due to increased risk of adverse drug reactions. Additionally, the dose-response relationship using FEV1 is relatively flat for single-agent therapy.1,24-31 Bronchodilators work by reducing the tone of airway smooth muscle (relaxation), thus minimizing airflow limitation.1,24 In patients with COPD, the clinical benefits of bronchodilators include increased exercise capacity, decreased air trapping in the lungs, and relief of symptoms. However, the use of bronchodilators may not be associated with significant improvements in pulmonary function measurements such as FEV1.1 The initial therapy for COPD patients who experience symptoms intermittently are short-acting bronchodilators. Among these agents, the choices are short-acting β2-agonists or an anticholinergic. Either class of agents has a rapid onset of action, relieves symptoms, and improves lung function. For patients with moderate to severe COPD who experience symptoms on a regular and consistent basis, or in whom short-acting therapies do not provide relief, long-acting bronchodilator therapies are recommended.1,24,32-33 Long-acting therapy may be administered as a β2-agonist or anticholinergic.
β2-Agonists cause airway smooth muscle relaxation by stimulating adenyl cyclase to increase the formation of cyclic adenosine monophosphate (cAMP).24-28 cAMP is responsible for mediating relaxation of bronchial smooth muscle, leading to bronchodilation. β2-Agonists are available in inhalation, oral, and parenteral dosage forms; the inhalation route is preferred because of fewer adverse reactions. β2-Agonists are available in short-acting, long-acting, and selective/nonselective formulations (Table 42-4). Short-acting β2-agonists are used for acute symptom relief and maintenance therapy. Short-acting β2-agonists require frequent dosing (albuterol 2 puffs every 6 hours when prescribed on a scheduled basis) and often lose effectiveness when used regularly for more than 3 months (tachyphylaxis). Long-acting β2-agonists (see Table 42-4) last at least 12 hours, allowing for twice daily dosing and have not been shown to lose effectiveness with regular use. Long-acting β2-agonists are more effective and convenient than short-acting β2-agonists for maintenance therapy, but more expensive. If a patient has a prescription for a long-acting β2-agonist, patients should also have a short-acting β2-agonists available for as-needed use (rescue). Less-selective β2-agonists (eg, metaproterenol, isoproterenol, and epinephrine) should not be used because of short duration of action and increased cardiostimulatory effects. Short-acting, selective β2-agonists (albuterol, levalbuterol, and pirbuterol) are preferred for therapy. Adverse effects of β2-agonists are dose-related and include palpitations, tachycardia, and tremor. Sleep disturbances may also occur and appear to be worse with higher doses of inhaled long-acting β2-agonists.24-28 Increasing doses beyond those clinically recommended is without benefit and could be associated with increased adverse effects.
TABLE 42-4 β2-Agonists for COPDa ||Download (.pdf)
TABLE 42-4 β2-Agonists for COPDa
|Generic Name||Brand Name||Selectivity||Formulations||Indication||Special Considerations|
|Albuterol||Proventil; Ventolin||β1< β2||Inhalation, nebulization, oral||Rescue and maintenance for COPD||Tachyphylaxis; requires frequent dosing for maintenance therapy. Adverse reactions: tachycardia, heart palpitations, tremor; use with caution in patients with cardiovascular disease, diabetes, hyperthyroidism, or hypokalemia.|
|Levalbuterol||Xopenex||β1< β2||Inhalation, nebulization||Rescue and maintenance for COPD||Tachyphylaxis; requires frequent dosing for maintenance therapy. Adverse reactions (less than albuterol): tachycardia, heart palpitations, tremor; use with caution in patients with cardiovascular disease, diabetes, hyperthyroidism, or hypokalemia.|
|Isoproterenol||Isuprel||β1 and β2||Injection, solution||Ventricular and brady arrhythmias||Sympathomimetic with significant stimulatory effect on β1 receptor (therefore no role in COPD). Adverse effects: cardiovascular—tachycardia, arrhythmias, hyper-/hypotension|
|Pirbuterol||Maxair||β1< β2||Inhalation||Rescue or maintenance for COPD||Same as albuterol|
|Epinephrine||Adrenalin; EpiPen; Epifrin; Primatene Mist||β1 and β2||Inhalation; injection; solution; ophthalmic solution||Cardiac arrest; open-angle glaucoma; acute treatment of bronchospasm||Same as isoproterenol|
|Formoterol||Foradil||β1< β2||Powder for oral inhalation||Maintenance for COPD||Should not be used as rescue inhaler. β2 (short- and long-acting) may increase risk of arrhythmias, decrease serum potassium, prolong QTc interval, or increase serum glucose. Use with caution in patients with cardiovascular disease, diabetes, hyperthyroidism, or hypokalemia. β-Agonists may cause elevation in blood pressure, heart rate, and result in CNS stimulation/excitation.|
|Salmeterol||Serevent||β1< β2||Powder for oral inhalation||Maintenance for COPD||Same as formoterol|
Ipratropium and tiotropium are inhaled anticholinergic medications commonly used for COPD. The anticholinergics produce bronchodilation by competitively blocking muscarinic receptors in bronchial smooth muscle.32-33 This activity blocks acetylcholine, with the net effect of a reduction in cyclic guanosine monophosphate. Cyclic guanosine monophosphate normally causes bronchial smooth muscle constriction. They may also decrease mucus secretion, although this effect is variable. Tiotropium dissociates from receptors extremely slowly resulting in a half-life longer than 36 hours, allowing for once-daily dosing.33 Ipratropium has an elimination half-life of about 2 hours, necessitating dosing every 6 to 8 hours.32 Inhaled anticholinergics are well-tolerated with the most common adverse effect being dry mouth. Occasional metallic taste has also been reported with ipratropium. Other anticholinergic adverse effects include constipation, tachycardia, blurred vision, urinary retention, and precipitation of narrow-angle glaucoma symptoms.32-33 Atropine is an anticholinergic available in oral and inhalation formulations. Atropine has a tertiary structure and is absorbed across the oral and respiratory mucosa, whereas ipratropium and tiotropium have quaternary structures that are poorly absorbed. The lack of systemic absorption of ipratropium and tiotropium greatly diminishes the anticholinergic side effects compared to atropine. Table 42-5 compares the inhaled anticholinergics.
TABLE 42-5 Inhaled Anticholinergics for COPD ||Download (.pdf)
TABLE 42-5 Inhaled Anticholinergics for COPD
|Generic Name||Brand Name||Formulation||Duration||Indication for COPD||Special Considerations|
|Ipratropium||Atrovent||Oral inhalation; nasal spray||Short||Maintenance therapy for COPD||Paradoxical bronchospasm may occur; not indicated for initial treatment of acute episodes of bronchospasm; use with caution in patients with myasthenia gravis, narrow-angle glaucoma, and benign prostatic hyperplasia|
|Tiotropium||Spiriva||Powder for oral inhalation||Long||Maintenance therapy for COPD||Same as ipratropium|
Methylxanthines, including theophylline and aminophylline, have been available for the treatment of COPD for decades and at one time was considered a first-line agent. Currently the role of methylxanthines has been limited to a patient not responding to β2-agonists, anticholinergics, or corticosteroids.1 Although theophylline is available in a variety of oral dosage forms, sustained relief preparations are most appropriate for the long-term management of COPD.1,34 These products have the advantage of improving patient compliance and achieving more consistent serum concentrations over rapid release theophylline and aminophylline preparations. However, caution must be used when switching from one sustained release preparation to another because there are considerable variations in sustained-release characteristics. Aside from IV aminophylline, there is no need to use any of the various salt forms of theophylline. Methylxanthines are nonspecific phosphodiesterase inhibitors that increase intracellular cAMP within airway smooth muscle resulting in bronchodilation.34 It has a modest bronchodilator effect and its use is limited due to a narrow therapeutic index, multiple-drug interactions, and adverse effects. Theophylline's bronchodilator effects are dependent upon achieving adequate serum concentrations, and therapeutic drug monitoring is needed to optimize therapy because of wide interpatient variability.34 If theophylline is used, serum concentrations in the range of 5 to 15 mg/L (28 to 83 μmol/L) provide adequate clinical response with a greater margin of safety than the traditionally recommended range of 10 to 20 mg/L (55 t o110 μmol/L).1 The most common adverse effects include heartburn, restlessness, insomnia, irritability, tachycardia, and tremor.34 Dose-related adverse effects include nausea and vomiting, seizures, and arrhythmias.34 Tobacco smoke contains a chemical that induce the cytochrome P-450 isoenzymes 1A1, 1A2, and 2E1.34 Theophylline is metabolized by 1A2 and 2E1, and therefore, smoking leads to increased clearance of theophylline.
Symptomatic patients with severe COPD (FEV1 less than 50% predicted) and frequent exacerbations should be considered for treatment with inhaled corticosteroids. Regular treatment with inhaled corticosteroids decreases the number of exacerbations per year and improves health status; however, corticosteroids therapy does not slow the long-term decline in pulmonary function.1 The anti-inflammatory mechanisms of corticosteroids include: (1) reduction in capillary permeability to decrease mucus, (2) inhibition of release of proteolytic enzymes from leukocytes, and (3) inhibition of prostaglandins.1,35-41 Currently, the appropriate situations to consider corticosteroids in COPD include (1) short-term systemic use for acute exacerbations and (2) inhalation therapy for chronic COPD.1 Long-term systemic corticosteroid use should be avoided due to an unfavorable risk/benefit ratio. The steroid myopathy that can result from long-term use of oral corticosteroids weakens muscles, further decreasing the respiratory drive in patients with advanced disease.1 Other long-term adverse effects of systemic corticosteroid therapy include osteoporosis, thinning of the skin, development of cataracts, and adrenal suppression and insufficiency.35-41 The use of chronic inhaled corticosteroid therapy has been of interest for the past decade. Their use has been common despite the lack of firm evidence about significant clinical benefit until recently. Inhaled corticosteroids have an improved risk-to-benefit ratio compared to systemic corticosteroid therapy. Upon discontinuation of inhaled corticosteroids, some patients experience deterioration in lung function and an increase in dyspnea and mild exacerbations; it is reasonable to reinstitute the medication in these patients. The most common adverse effects from inhaled corticosteroid therapy include oropharyngeal candidiasis and hoarse voice.35-41 These can be minimized by rinsing the mouth after use and by using a spacer device with metered-dose inhalers (MDI). Table 42-6 lists the inhaled corticosteroids and Table 42-7 lists formulations and doses for commonly used COPD medications.
TABLE 42-6 Inhaled Corticosteroidsa,b for COPD ||Download (.pdf)
TABLE 42-6 Inhaled Corticosteroidsa,b for COPD
|Generic Name||Brand Name||Formulations|
|Beclomethasone||Beconase AQ||Aerosol for inhalation; suspension (nasal)|
|Budesonide||Pulmicort||Powder for oral inhalation; suspension (nasal)|
|Ciclesonide||Alvesco||Aerosol for oral inhalation; suspension (nasal)|
|Flunisolide||AeroBid||Aerosol for oral inhalation; suspension (nasal)|
|Fluticasone||Flovent||Aerosol for oral inhalation; cream; lotion; ointment; powder for oral inhalation; suspension (nasal)|
|Mometasone||Asmanex||Powder for oral inhalation; suspension (nasal); cream; lotion; ointment|
|Triamcinolone||Azmacort||Aerosol for oral inhalation; cream; injection; lotion; paste; powder; suspension (nasal)|
TABLE 42-7 Formulations and Doses for Commonly Used COPD Medications ||Download (.pdf)
TABLE 42-7 Formulations and Doses for Commonly Used COPD Medications
|Generic/Brand Name||Formulation||Onset||Usual Dose|
|Albuterol||Nebulization||5-15 min||2.5 mg every 6-8 h (max: 30 mg/d)|
|Inhalation||5-15 min||MDI (90 μg/puff) 1-2 puffs every 4-6 h (max: 1080 μg/d)|
|Oral||7-30 min||2-4 mg three to four times per d; extended release: 4-8 mg every 12 h (max:32 mg/d)|
|Levalbuterol (Xopenex)||Nebulization||10-20 min||0.63-1.25 mg tid, 6-8 h apart (max: 3.75 mg/d)|
|Inhalation||5-10 min||MDI (45 μg/puff) 1-2 puffs every 4-6 h (max: 540 μg/d)|
|Long Acting β2-Agonists|
|Salmeterol (Serevent)||Inhalation||10 min-2 h||Powder (50 μg/inhalation) one inhalation every 12 h (max: 100 μg/d)|
|Formoterol (Foradil)||Inhalation||1-3 min||Powder 912 μg/inhalation) one inhalation every 12 h (max: 24 μg/d)|
|Beclomethasone||Inhalation||1-7 d||MDI (40, 80 μg/puff) 40-160 μg bid (max:640 μg/d)|
|Budesonide||Inhalation||1-7 d||Powder (200 μg/inhalation) one to two inhalations twice a d|
|Fluticasone||Inhalation||1-7 d||MDI (44, 110, 220 μg/puff) 88-440 μg twice a d (max: 1760 μg/d)|
|Triamcinolone||Inhalation||1-7 d||MDI (100 μg/puff) two puffs three to four times per d or four puffs twice a d (max: 1600 μg/d)|
|Theophylline||Oral||0.2-2 h||400-600 μg/d divided every 6-24 h based upon the formulation. Doses vary widely and should be based upon pharmacokinetic considerations and plasma theophylline concentrations. Aminophylline is the most widely used salt of theophylline. Aminophylline is usually administered by slow IV injection. The bronchodilation effects of theophylline are proportional to the log of the theophylline concentration. This means that as the theophylline concentration increases, there will be a less than proportional increase in bronchodilation. Patients should always be maintained at the lowest possible theophylline-plasma concentration that produces a satisfactory response. There are numerous factors or disease states that impact theophylline clearance (smoking, cirrhosis, heart failure, drug interactions). The formulation Theo-24 has been associated with dose-dumping when combined with a high-fat meal, other formulations have not been associated with dose dumping.|