Death rates from COPD are on the rise. Pharmacotherapy and nonsurgical therapy are options in short- and long-term treatment.

Chronic obstructive pulmonary disease (COPD) is a spectrum of chronic pulmonary diseases characterized by shortness of breath, coughing, sputum production, airflow limitation, and impaired gas exchange.¹ Most patients with COPD have either chronic bronchitis or emphysema (or elements of both). Collectively, these diseases affect between 15 million and 35 million people in the United States,^1-4 and they represent the fifth leading cause of death.^2,5,6

The death rate from COPD has increased 22% during the past decade.^6,7 The mortality rate 10 years after diagnosis is greater than 50%, and this percentage is rising.⁷ Cigarette smoking is perhaps the most important etiologic factor. Prevalence, incidence, and mortality increase with age, and are greater in men than in women.⁶ Prevalence, however, is increasing more rapidly in females, largely as a result of increased cigarette smoking by women.^2,6

COPD is characterized by permanent, abnormal airspace enlargement. This enlargement occurs distal to the terminal bronchioles and is associated with destruction of the airspace walls. Chronic bronchitis is characterized by chronic cough, sputum production, and inflammation of the mucosal surfaces of the larger airways.⁸

Case Report
On April 12, 2003, a 62-year-old man presented to his primary care physician in Chicago, with moderate shortness of breath and a chronic cough productive of large volumes of purulent sputum. His medical history was significant for recurrent respiratory infections over the previous 2 years, with one episode requiring hospitalization and intravenous antibiotics. The patient was unable to perform normal daily activities because of his symptoms. He had been a heavy smoker since his early teen years, and his smoking history was estimated at 70 pack-years. He stopped smoking 2 years before this office visit, when the respiratory infections began.

Physical examination revealed diminished breath sounds bilaterally, with prominent expiratory wheezing. Chest radiography showed prominent bronchial markings consistent with chronic bronchitis. Pulmonary function testing revealed a forced vital capacity that was 55% of the predicted value, a forced expiratory volume in 1 second that was 25% of the predicted value, a residual volume that was 188% of the predicted value, and a total lung capacity that was 118% of the predicted value. A diagnosis of COPD was established.

The patient was admitted to the University of Chicago Hospital for a course of aerosolized beta2-agonist treatment, intravenous theophylline, intravenous antibiotics, oxygen therapy, and pulmonary toilet. After 7 days, the patient’s condition stabilized; he was discharged with prescriptions for inhaled albuterol, inhaled ipratropium, sustained-release oral theophylline, and nocturnal use of home supplemental oxygen. During a routine follow-up visit with his primary care physician 1 month later, the patient reported that his symptom control had been maintained with the current treatment regimen.

Management Principles
As this case illustrates, the general principles of management of the patient with COPD are to slow disease progression, to prevent infection, to treat reversible symptoms, and to educate patients. The RT is intimately involved in all four cornerstones of care.

If end-stage (completely irreversible) disease is not yet present, the progression of disease can be slowed through smoking cessation, reduction of exposure to environmental or occupational irritants, and therapy with supplemental oxygen. Patients with COPD should be encouraged to undergo annual influenza vaccinations.^9,10 Some authorities¹¹ also recommend vaccination against pneumococcal disease. Many bacterial and other organisms have been found in the sputum of patients with chronic pulmonary disease. These include Haemophilus influenzae, Streptococcus pneumoniae and Streptococcus viridans, Klebsiella species, Moraxella (formerly called Branhamella) catarrhalis, Staphylococcus aureus and Staphylococcus epidermidis, and Candida albicans (a fungus). Broad-spectrum antibiotic prophylaxis has not been shown to decrease the frequency of infection, but it may decrease the severity and duration of symptoms.

Education should be an integral part of COPD management. Patients and their families should be given basic facts about the disease process and offered a list of resources, in the event that they desire additional information. Medication issues should be addressed. If appropriate, the subjects of intubation and resuscitative intervention should be reviewed, and the patient’s desires should be delineated.

Pharmacotherapy
Pharmacological agents for managing reversible bronchospasm associated with COPD include theophylline, beta-agonists, corticosteroids, anticholinergic agents, mucolytic agents, and, if appropriate, alpha1-antitrypsin.

Although theophylline has limited bronchodilatory effects, it may cause improved peripheral ventilation, resulting in a fall in trapped gas volume and an increase in exercise tolerance. It can improve mucociliary clearance and lessen the overall work of breathing. Theophylline augments central respiratory drive and may also improve diaphragm-muscle activity and decrease vascular and pulmonary bronchiolar resistance. There is some evidence that theophylline may provide protection against episodic bronchospasm. Animal studies^4,8 suggest a possible anti-inflammatory effect. Long-acting preparations taken in the early evening have the added advantages of controlling nocturnal symptoms and increasing compliance.¹²

Selective beta2-agonists cause vasodilation of peripheral and pulmonary vessels.¹³ Cardiovascular effects include reflex tachycardia and a reduced biventricular afterload in patients with severe COPD. A major problem with potent beta2-agonists is their action on muscle receptors; they accelerate the relaxation phase of slow-contracting fibers, thus producing tremor. The use of inhaled beta-agonists may reduce systemic effects such as tremor.¹⁴ Beta-agonists may also improve mucociliary clearance, but tolerance may be a problem. Another difficulty limiting the efficacy of beta-agonists is inadequate dosage resulting from inefficient use.

For patients with COPD, inhaled beta2-agonist bronchodilators are used either as needed for relief of acute respiratory distress or for long-term maintenance treatment. Agents with a rapid onset of action (such as albuterol) are used for relief as needed, and those with a long duration of action (such as salmeterol) are used for maintenance therapy. No single beta2-agonist available in the United States to date has been effective for both purposes. One inhaled bronchodilator, formoterol, is a highly selective beta2-agonist that has the unique combination of a rapid onset of bronchodilation (within 1 to 3 minutes, comparable to that of albuterol) and a long duration of action (more than 12 hours, comparable to that of salmeterol).

Inhaled corticosteroid treatment is sometimes used for long-term maintenance treatment in COPD; however, the efficacy of these agents is the subject of controversy. Some patients with COPD do improve with inhaled corticosteroid treatment, and it is possible that these patients have coexistent asthma. Corticosteroids do not reduce the inflammatory response in COPD, and are not believed to be useful in preventing the progression of disease.^15,16

Inhaled anticholinergic agents such as ipratropium are now an integral part of COPD therapy, and are considered first-line agents by many practitioners. Inhaled ipratropium has been shown to provide the same (or even greater) bronchodilation as beta2-agonists.¹⁷ In inhaled forms, anticholinergics have few adverse effects because of minimal systemic absorption. Use of a combination product, such as an ipratropium-albuterol mixture, may simplify the medication regimen, thereby facilitating compliance.

Nonpharmacological Therapy
Smoking cessation is, perhaps, the single most important nonpharmacological therapy. Usually, long-term cessation will allocate for the reversible portion of obstructive disease. Supplemental oxygen may sustain PaO2 levels in late-stage or end-stage patients. Oxygen therapy may also improve health-related quality of life¹⁸ and prolong survival.¹⁹ Lung-volume reduction surgery and lung transplantation may offer hope for improved quality of life and prolonged life in selected patients with severe COPD. With refinements in surgical technique has come a renewed interest in using these surgical modalities as a therapeutic adjunct to medical therapy.

A structured, outpatient pulmonary rehabilitation program improves functional capacity in certain patients with COPD. Services may include general exercise training; administration of oxygen and nutritional supplements, intermittent mechanical ventilatory support, and continuous positive airway pressure therapy; and training in relaxation, breathing exercises and techniques (such as pursed-lip breathing), and methods for mobilizing and removing secretions.

John D. Zoidis, MD, is a contributing writer for RT.

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