Chronic Obstructive Pulmonary Disease: New Treatments Against an Old Foe

Chronic obstructive pulmonary disease (COPD) is characterized by long-standing airflow limitation that usually results from emphysema or chronic bronchitis. More than 16 million Americans have COPD, which is now the fourth leading cause of death in the United States. COPD is also a major cause of morbidity and a leading contributor to hospital admissions and office visits.¹

COPD is often not recognized until late in its course, when lung function is markedly reduced and the patient has become symptomatic. Early recognition and diagnosis can halt-or at least slow-the progression of this disease.

Here we focus on prevention and early identification of COPD; in our second article on page 30, we discuss drug therapy, pulmonary rehabilitation, lung volume reduction surgery, and transplantation.

PREVENTION: AN OVERVIEW

Smoking cessation and abstinence are key primary prevention strategies for COPD. Identifying high-risk groups, including smokers and those with a family history of premature COPD or alpha₁-antitrypsin deficiency, facilitates early detection and initiation of therapy (secondary prevention). Vaccination with the influenza and pneumococcal vaccines can reduce the risk of infection and consequent morbidity and mortality in patients with COPD.

SMOKING CESSATION

Cigarette smoking is the leading cause of COPD and promotes ongoing deterioration of lung function. The dictum "It's never too late to quit" continues to ring true. Smoking cessation remains one of the only interventions shown to reduce morbidity and mortality in patients with COPD. In contrast, continued smoking accelerates the ongoing decline in lung function, increases susceptibility to respiratory infections and bronchoconstriction, and contributes significantly to the development of other comorbid diseases in this (usually older) population.

Cigar smoking is also a known risk factor for COPD. Between 1993 and 2002, cigar consumption nearly doubled. A cohort study with approximately 18,000 men-encompassing several decades of follow-up-demonstrated an increased risk of COPD, coronary heart disease, upper aerodigestive tract disorders, and lung cancer in regular cigar smokers. This was a dose-response effect.²

During office visits, many smokers are not advised to quit or given smoking cessation assistance. Therefore, we recommend the following for every visit³:

Record tobacco-use status along with vital signs.

Offer simple smoking cessation advice and assistance to current smokers ("Ask, Advise, Assess, Assist").

Nicotine replacement therapy. These therapies can help patients cope with withdrawal symptoms, such as irritability and early morning craving, that commonly occur in those who smoke more than 10 cigarettes daily (Table 1). Exercise caution in recommending these products to patients with recent (within the previous 4 weeks) myocardial infarction, severe arrhythmias, or angina. Both the nicotine patch and gum are available over-the-counter in the United States; the patch is generally preferred because it is easier to use.

Two alternative formulations of nicotine replacement are the nasal spray and oral inhaler. The inhaler is a plastic rod that provides a nicotine vapor (when puffed) that may help with the oral fixation of smoking. These products may be considered for highly dependent smokers and are preferred by some patients; the delivery of nicotine is quicker than with other forms of nicotine replacement.

Bupropion. This antidepressant has been shown to improve smoking cessation rates at 1 year, either when used alone or with a nicotine patch.^4,5 Treatment is typically started 1 week before the quit date at a dosage of 150 mg/d for 3 days, then 150 mg twice daily for 7 to 12 weeks. The Treating Tobacco Use and Dependence (TTUD) guidelines advocate maintenance therapy for up to 6 months³; however, a clinical trial showed that extending treatment with bupropion to 52 weeks improved 1-year abstinence rates by approximately 13%.⁶ Major side effects are headache and insomnia. Exercise caution in recommending this medication to patients with a history of seizures.

Clonidine. Oral or transdermal administration of this centrally acting antihypertensive agent can diminish withdrawal symptoms (such as craving and anxiety) and improve cessation rates in severely addicted smokers. Use of this agent is limited by a high incidence of side effects, such as sedation, dry mouth, and dizziness (23% to 92%; median, 71%), compared with placebo (4% to 61%; median, 10%).³ The sedation may be useful in those with extreme agitation and anxiety that is unrelieved by nicotine replacement therapy.

Clonidine may be used in addition to, or in place of, nicotine replacement. Overall, it is considered second-line therapy and should be reserved for those with severe nicotine dependence and withdrawal symptoms in whom nicotine replacement therapy or bupropion has failed.³ It is best used for short-term therapy (3 to 10 weeks).

Frequently, many attempts are made before smoking cessation is successful. If one modality fails, encourage patients to try another. Combination therapy may be beneficial in difficult cases.

Resources for patients. Smoking cessation rates vary considerably but are highest when behavioral and supportive therapies are combined with nicotine replacement and/or treatment with bupropion. The key to success is close follow-up and support during the quitting period. Self-help resources are available through the American Lung Association (800-LUNG-USA [800-586-4872], www.lungusa.org), the American Cancer Society (800-227-2345, www.cancer.org), and the American Heart Association (800-242-8721, www. americanheart.org).

Some pharmaceutical companies offer telephone-based support that can help reduce the need for face-to-face encounters. The bottom line is that any method of smoking cessation can be successful-and with supportive counseling, quit rates can be doubled (from 15% to 30%) at 6 months.^3,7,8

VACCINATIONS

Influenza vaccine. Influenza virus type A and B epidemics usually begin early in the winter and end in the spring. The virus (particularly type A) mutates rapidly. A new formulation of the influenza vaccine is prepared each year and should be administered to high-risk persons, such as those with chronic lung disease. The risk of morbidity and mortality from acute respiratory infection is very high in patients with COPD and can be reduced through vaccination.

Nevertheless, recent surveys by the CDC have shown that vaccination rates in high-risk groups are as low as 30%. To ensure immunization compliance, it is essential to incorporate vaccinations into a standardized charting or care plan formula. Yearly influenza vaccinations are also recommended for health care workers and household contacts of patients with COPD.

Pneumococcal vaccine. Streptococcus pneumoniae is the most common cause of pneumonia in all age groups and is responsible for considerable morbidity and mortality, particularly in patients with COPD. A multivalent polysaccharide antigen vaccine against S pneumoniae provides immunity against the common S pneumoniae strains. The pneumococcal vaccine is recommended for high-risk patients and those older than 65 years (Table 2).⁹ Antibody titers wane with time, and reimmunization or booster injections with the vaccine are recommended after 6 years. The vaccine has been shown to reduce mortality in high-risk groups by 50%. Studies have indicated that side effects are minimal, with no systemic side effects and only mild to moderate local symptoms in 25% of patients.¹⁰

ALPHA₁-ANTITRYPSIN REPLACEMENT

A congenital form of emphysema, which typically occurs in younger adults, has been linked to alpha₁-antitrypsin deficiency. This genetic disorder is inherited in a codominant fashion (expressing alleles from both parents). Alpha₁-antitrypsin is a protein produced in the liver that inhibits neutrophil elastase (a proteolytic enzyme in the lung). When serum levels of alpha₁-antitrypsin drop below about 35% of predicted, elastase activity is not sufficiently inhibited, and there is a significantly increased risk of emphysema, primarily of the panacinar type.

The distribution of emphysema is characteristically at the lung bases, as opposed to the upper lobes (as in the typical form of "smoker's emphysema"). Chronic bronchitis and, rarely, bronchiectasis may also develop. Smoking can further reduce the activity of alpha₁-antitrypsin and can cause emphysema 10 to 15 years earlier than in nonsmokers. Alpha₁-antitrypsin deficiency may also increase the risk of cirrhosis and other liver disease, particularly in younger persons.

Although only a small minority of cases of COPD are caused by this deficiency, it is important to identify these cases (Table 3). This disorder may typically be found in young patients, usually smokers, who demonstrate severe basilar emphysema on chest radiographs; there may also be associated liver disease and a family history of the disorder.

A form of purified and isolated alpha₁-antitrypsin protein has been approved by the FDA for replacement therapy. This expensive treatment requires weekly intravenous infusion. A pulmonary consultation is appropriate (Table 4).

Early identification of appropriate candidates (by serum alpha₁-antitrypsin level and confirmation of emphysema) may decrease the rate of progression of the disease; however, to date, controlled studies have not been performed to demonstrate this benefit. Subgroup analysis of a national Alpha₁-Antitrypsin Deficiency Registry Study Group showed that the rate of decline of forced expiratory volume in 1 second and mortality are reduced in patients with moderate to severe COPD who receive replacement therapy.¹⁰

References:

REFERENCES:

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2. Iribarren C, Tekawa IS, Sidney S, Friedman GD. Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men. N Engl J Med. 1999;340:1773-1780.

3. Tobacco Use and Dependence Clinical Practice Guideline Panel Staff and Consortium Representatives. A clinical practice guideline for treating tobacco use and dependence: a US Public Health Service report. JAMA. 2000;283:3244-3254.

4. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999;340:685-691.

5. Hurt RD, Sachs DP, Glover ED, et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997;337: 1195-1202.

6. Hays JT, Hurt RD, Rigotti NA, et al. Sustained- release bupropion for pharmacologic relapse prevention after smoking cessation. A randomized, controlled trial. Ann Intern Med. 2001;135:423-433.

7. Fiore MC, Bailey SC, Cohen SJ, et al. Treating Tobacco Use and Dependence. Rockville, Md: US Dept of Health and Human Services, Public Health Service; 2000. AHRQ publication 00-0032.

8. Watts SA, Noble SL, Smith PO, Disco M. First-line pharmacotherapy for tobacco use and dependence. J Am Board Fam Pract. 2002;15:489-497.

9. Centers for Disease Prevention and Control. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 1997;46:1-24.

10. Nichol KL, MacDonald R, Hauge M. Side effects associated with pneumococcal vaccination. Am J Infect Control. 1997;25:223-228.

11. The Alpha₁-Antitrypsin Deficiency Registry Study Group. Survival and FEV₁ decline in individuals with severe deficiency of alpha₁-antitrypsin. Am J Respir Crit Care Med. 1998;158:49-59.

12. American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152:S77-S121.

13. COPD Guidelines Group of the Standards of Care Committee of the BTS. BTS guidelines for the management of chronic obstructive pulmonary disease. Thorax. 1997;52(suppl 5):S1-S28.