Treatment of Stable COPD

Beta-agonists relax bronchial smooth muscle and increase mucociliary clearance. Albuterol aerosol, 2 puffs (90 to 100 mcg/puff) inhaled from a metered-dose inhaler 4 to 6 times a day as needed, is usually the drug of choice.

Long-acting beta-agonists are preferable for patients with nocturnal symptoms or for those who find frequent dosing inconvenient. Options include salmeterol powder, 1 puff (50 mcg) inhaled twice a day, indacaterol 1 puff (75 mcg) inhaled once a day (150 mcg once a day in Europe), and olodaterol 2 puffs once a day at the same time each day. Vilanterol is available in combination with an inhaled corticosteroid. Also available are nebulized forms of arformoterol and formoterol. The dry-powder formulations may be more effective for patients who have trouble coordinating use of a metered-dose inhaler.

Patients should be taught the difference between short-acting and long-acting drugs, because long-acting drugs that are used as needed or more than twice a day increase the risk of cardiac arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more .

Adverse effects commonly result from use of any beta-agonist and include tremor, anxiety, tachycardia, and mild, temporary hypokalemia.

Anticholinergics (antimuscarinics) relax bronchial smooth muscle through competitive inhibition of muscarinic receptors (M1, M2, and M3).

Ipratropium is a short-acting anticholinergic; dose is 2 to 4 puffs (17 mcg/puff) from a metered-dose inhaler every 4 to 6 hours. Ipratropium has a slower onset of action (within 30 minutes; peak effect in 1 to 2 hour), so a beta-agonist is often prescribed with it in a single combination inhaler or as a separate as-needed rescue drug.

Tiotropium is a long-acting quaternary anticholinergic inhaled as a powder formulation (18 mcg/puff) and soft mist inhaler (2.5 mcg/puff). Dose is 1 puff (18 mcg) once a day by dry powder inhaler and 2 puffs (5 mcg) once a day by soft mist inhaler. Aclidinium bromide is available as a multidose dry-powder inhaler. Dose is 1 puff (400 mcg/puff) twice a day. Aclidinium is also available in combination with a long-acting beta-agonist as a dry-powder inhaler. Umeclidinium can be used as a once a day combination with vilanterol (a long-acting beta-agonist) in a dry-powder inhaler. Glycopyrrolate (an anticholinergic) can be used twice a day in combination with indacaterol or formoterol (long-acting beta-agonists) in a dry-powder or metered-dose inhaler. Revefenacin is given once a day via nebulizer.

Adverse effects of all anticholinergics are pupillary dilation (and risk of triggering or worsening acute angle closure glaucoma Angle-Closure Glaucoma Angle-closure glaucoma is glaucoma associated with a physically obstructed anterior chamber angle, which may be chronic or, rarely, acute. Symptoms of acute angle closure are severe ocular pain... read more ), urinary retention, and dry mouth.

Corticosteroids are often part of treatment. Inhaled corticosteroids seem to reduce airway inflammation, reverse beta-receptor down-regulation, and inhibit leukotriene and cytokine production. They do not alter the course of pulmonary function decline in patients with COPD who continue to smoke, but they do relieve symptoms and improve short-term pulmonary function in some patients, are additive to the effect of bronchodilators, and diminish the frequency of COPD exacerbations. They are indicated for patients who have repeated exacerbations or symptoms despite optimal bronchodilator therapy. Inhaled corticosteroids are of greatest benefit in patients who have eosinophilia Eosinophilia Eosinophilia is defined as a peripheral blood eosinophil count > 500/mcL (> 0.5 × 10⁹/L). Causes and associated disorders are myriad but often represent an allergic reaction or... read more . In patients with exacerbations, addition of an inhaled corticosteroid reduces exacerbation frequency and prolongs survival (1, 2 Drug therapy references Chronic obstructive pulmonary disease (COPD) management involves treatment of chronic stable COPD and treatment of exacerbations. Treatment of chronic stable COPD aims to prevent exacerbations... read more ). Dose depends on the drug; examples include fluticasone 500 to 1000 mcg/day and beclomethasone 400 to 2000 mcg/day.

The long-term risks of inhaled corticosteroids in older people are not proved but probably include osteoporosis Osteoporosis Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more , cataract formation Cataract A cataract is a congenital or degenerative opacity of the lens. The main symptom is gradual, painless vision blurring. Diagnosis is by ophthalmoscopy and slit-lamp examination. Treatment is... read more , and an increased risk of nonfatal pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more . Long-term users therefore should undergo periodic ophthalmologic and bone densitometry screening if indicated (eg, by a history of changes in night vision, frailty, or bone fractures) and should possibly receive supplemental calcium, vitamin D, and a bisphosphonate as indicated.

De-escalation of inhaled corticosteroid therapy may be necessary if patients develop pneumonia or do not respond to treatment.

Combinations of a long-acting beta-agonist and an inhaled corticosteroid are more effective than either drug alone in the treatment of chronic stable disease.

Oral or systemic corticosteroids should usually not be used to treat chronic stable COPD.

Theophylline plays only a small role in the treatment of chronic stable COPD now that safer, more effective drugs are available. Theophylline decreases smooth muscle spasm, enhances mucociliary clearance, improves right ventricular function, and decreases pulmonary vascular resistance and arterial pressure. Its mode of action is poorly understood but appears to differ from that of beta-2-agonists and anticholinergics. Its role in improving diaphragmatic function and dyspnea during exercise is controversial.

Theophylline can be used for patients who have not adequately responded to inhaled drugs and who have shown symptomatic benefit from a trial of the drug. Serum levels need not be monitored unless the patient does not respond to the drug, develops symptoms of toxicity, or is questionably adherent; slowly absorbed oral theophylline preparations, which require less frequent dosing, enhance adherence.

Toxicity is common and includes sleeplessness and gastrointestinal upset, even at low blood levels. More serious adverse effects, such as supraventricular and ventricular arrhythmias and seizures, tend to occur at blood levels > 20 mg/L (111 micromol/L).

Hepatic metabolism of theophylline varies greatly and is influenced by genetic factors, age, cigarette smoking, hepatic dysfunction, diet, and some drugs, such as macrolide and fluoroquinolone antibiotics and nonsedating histamine 2 blockers.

Phosphodiesterase-4 inhibitors are more specific than theophylline for pulmonary phosphodiesterase and have fewer adverse effects. They have anti-inflammatory properties and are mild bronchodilators. Phosphodiesterase-4 inhibitors such as roflumilast can be used in addition to other bronchodilators for reduction of exacerbations in patients who have COPD with chronic bronchitis. Roflumilast should be started at a oral dose of 250 mcg once a day and increased to 500 mcg once a day as tolerated.

Common adverse effects include nausea, headache, and weight loss, but these effects may subside with continued use.

Long-term azithromycin therapy is an effective adjunct to prevent COPD exacerbations in patients who are prone to repeated or severe exacerbations, particularly those who are not currently smoking. A dose of 250 mg orally once a day has demonstrated efficacy. Erythromycin 250 mg orally twice or 3 times a day has also been found effective.

Oxygen is administered by nasal cannula at a flow rate sufficient to achieve a PaO2 > 60 mm Hg (oxygen saturation > 90%), usually ≤ 3 L/minute at rest (frequently higher at higher altitudes, such as in Denver). Oxygen is supplied by electrically driven oxygen concentrators, liquid oxygen systems, or cylinders of compressed gas. Stationary concentrators, which limit mobility but are the least expensive, are preferable for patients who spend most of their time at home. Such patients require small oxygen tanks for backup in case of an electrical failure and for portable use. Portable concentrators that allow mobility can be used for patients who do not require high flow rates.

A liquid system is preferable for patients who spend much time out of their home. Portable canisters of liquid oxygen are easier to carry and have more capacity than portable cylinders of compressed gas. Large compressed oxygen cylinders are the most expensive way of providing oxygen and should be used only if no other source is available. All patients must be taught the dangers of smoking during oxygen use.

Various oxygen-conserving devices can reduce the amount of oxygen used by the patient, either by using a reservoir system or by permitting oxygen flow only during inspiration. Systems with these devices may correct resting hypoxemia as effectively as continuous flow devices. However, intermittent flow devices may not be as effective as continuous flow for exercise-associated hypoxemia.

Lung volume reduction surgery consists of resecting nonfunctioning emphysematous areas. The procedure improves lung function, exercise tolerance, and quality of life in patients with severe, predominantly upper-lung emphysema who have low baseline exercise capacity after pulmonary rehabilitation. Mortality is increased in the first 90 days after lung volume reduction surgery, but survival is higher at 5 years.

The effect on arterial blood gas measurements is variable and not predictable, but most patients who require oxygen therapy before surgery continue to need it. Improvement is less than that with lung transplantation. The mechanism of improvement is believed to be enhanced lung recoil and improved diaphragmatic function.

Operative mortality is about 5%. The best candidates for lung volume reduction surgery are patients with an FEV1 20 to 40% of predicted, a DLCO > 20% of predicted, significantly impaired exercise capacity, heterogeneous pulmonary disease on CT with an upper-lobe predominance, PaCO2 < 50 mm Hg, and absence of severe pulmonary hypertension and coronary artery disease.

Rarely, patients have extremely large bullae that compress the functional lung. These patients can be helped by surgical resection of these bullae, with resulting relief of symptoms and improved pulmonary function. Generally, resection is most beneficial for patients with bullae affecting more than one third of a hemithorax and an FEV1 about half of the predicted normal value. Improved pulmonary function is related to the amount of normal or minimally diseased lung tissue that was compressed by the resected bullae. Serial chest x-rays and CT scans are the most useful procedures for determining whether a patient’s functional status is due to compression of viable lung by bullae or to generalized emphysema. A markedly reduced DLCO (< 40% predicted) indicates widespread emphysema and suggests a poorer outcome from surgical resection.

Lung transplantation Lung and Heart-Lung Transplantation Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. (See also Overview... read more can be single or double. Perioperative complications tend to be lower with single-lung transplantation, but some evidence shows that survival time is increased with double-lung transplantation. Candidates for transplantation are patients < 65 years with an FEV1 < 25% predicted after bronchodilator therapy or with severe pulmonary hypertension. The goal of lung transplantation is to improve quality of life, because survival time is not necessarily increased. The 5-year survival after transplantation for emphysema is 45 to 60%. Lifelong immunosuppression is required, with the attendant risk of opportunistic infections.

Endobronchial valves that cause atelectasis of emphysematous target regions of the lung in selected patients who do not have collateral ventilation to these regions are available in selected centers. Placement of an endobronchial valve is an alternative to lung volume reduction surgery in some patients. Surgical lung volume reduction is usually bilateral, whereas bronchoscopic procedures are usually unilateral and therefore result in less improvement.