Objectives

1. Be familiar with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.
2. Know that objective measurement of pulmonary function is essential for the diagnosis and assessment of COPD.
3. Review the medical therapy indicated for treatment of stable COPD and COPD exacerbations, and the medical therapy that is not indicated for treatment of COPD.
4. Emphasize importance and indications of home oxygen therapy in COPD patients.
5. Know the importance of noninvasive mechanical ventilation in treating patients with COPD exacerbations.

Key words

anticholinergics; bronchodilators; chronic bronchitis; COPD; COPD exacerbations; emphysema; inhaled corticosteroids; oxygen therapy; smoking; smoking cessation; spirometry

Abbreviations

AAT = a1-antitrypsin; GOLD = Global Initiative for Chronic Obstructive Lung Disease; NIPPV = noninvasive positive pressure ventilation

In late 2001, under the direction of the National Heart, Lung and Blood Institute and the World Health Organization, an expert panel released a set of new guidelines on the diagnosis and management of COPD, entitled the Global Initiative for Chronic Obstructive Lung Disease (GOLD).¹ The document presents an evidence-based approach to managing COPD. These guidelines define the classifications of COPD on the basis of both severity and type of symptoms, and explore all new information on the diagnosis and treatment of COPD. We will divide the report into a series of categories and discuss the clinical implications of the various components of the GOLD document. We have also added some pearls that are the result of new data in COPD patients published after the GOLD guidelines were finished.

General Knowledge Concerning COPD in the United States

The incidence of COPD has risen continuously over the last 30 years, and data-based information from a 1998 survey suggest that 13 million Americans have been diagnosed with COPD (3 million with emphysema and 10 million with chronic bronchitis).^2,3 Many more millions of patients are thought to be exhibiting early symptoms of COPD but have not yet been diagnosed or treated. COPD is the term used to refer to patients with airflow obstruction due to either emphysema, chronic bronchitis, or a combination of both disorders. COPD was the fourth leading cause of death in the United States in 1998, and death rates rose steadily between 1965 and 1998. The data from 1998 showed that COPD accounted for > 100,000 deaths and > 600,000 hospital discharges. The majority of patients are male, but an increasing prevalence of the disease in women has been noted in the last 5 years.

Emphysema is defined according to anatomical pathology as abnormal, permanent enlargement of airspaces distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis. This tissue destruction results in enlargement of proximal and distal airspaces and can ultimately form bullae out in the lung parenchyma. These bullae result in loss of surface area for gas exchange in the involved lungs.

Chronic bronchitis is defined as the presence of a chronic, productive cough for 3 months during each of 2 consecutive years, and for which other causes of chronic cough have been excluded.⁴ The other common causes of chronic cough include asthma, gastric reflux, or postnasal drip secondary to sinus disease.⁵ The pathologic findings of chronic bronchitis include enlargement of tracheobronchial mucus glands, as well as variable amounts of airway smooth-muscle hyperplasia, inflammation, and bronchial wall thickening. Abnormalities of small airways may also be present, and are accompanied by fibrosis and the presence of a mononuclear inflammatory process.

Pearl: The decrease in the pulmonary function FEV₁ of the patient is inversely proportional to the number of inflammatory cells in the airways.

Pearl: A genetically inherited form of emphysema occurs, resulting from a1-antitrypsin (AAT) deficiency. This disorder accounts for < 1 to 2% of COPD cases in the United States.¹ AAT is a protease inhibitor produced by the liver that circulates into tissues. Active proteases are released into the lung by lung macrophages and neutrophils, which can contribute to the development of emphysema.

Pearl: All patients developing emphysema who form bullae before age 45 should be evaluated for AAT deficiency. A normal serum level of AAT is > 11 mmol/L. Patients with low levels of AAT should be evaluated by a pulmonologist and may be candidates for AAT replacement therapy.

Evaluating Pulmonary Function

COPD is diagnosed by a combination of history and physical examination and the use of objective measurement of airway obstruction. The standard pulmonary function test used to measure airway obstruction is the forced expiratory spirogram. This test is useful in the evaluation of patients presenting with symptoms of COPD by providing measurements of FEV₁, FVC, and the ratio of FEV₁/FVC (which is also called the timed vital capacity). The FVC provides a measure of lung volume, and the FEV₁ and FEV₁/FVC provide a measure of obstruction. In most of these patients, other abnormal lung volumes that may exist include increases in both the total lung capacity and the residual volume. These increases in lung volumes are due to hyperinflation of the lungs.⁶

Pearl: In patients with emphysema, the specific diffusing capacity for carbon monoxide (corrected for lung volume) is often markedly decreased.

Pearl: Another pulmonary function test that can be useful in diagnosing COPD includes the maximum expiratory flow volume curve, which shows a decrease in the flow rates during the latter portion of the maximum expiratory flow volume curve which is effort independent. Flow depends on the resistance of the peripheral bronchi and the recoil pressure of the lung in the mid-vital capacity range.

Pearl: Healthy nonsmokers begin losing lung function after age 35 at a rate of about 30 mL/yr. The rate of lung function deterioration in patients who have begun to develop COPD rises to 50 to 100 mL/yr, and may have even greater declines when they have experienced exacerbations of their disease.⁷

GOLD Components of COPD Management

The management plan for patients who have COPD consists of four key components in the GOLD guidelines: (1) assess and monitor disease; (2) reduce risk factors; (3) manage stable COPD; and (4) manage exacerbations

Goals of management include (1) preventing disease progression, (2) relieving symptoms, (3) improving exercise tolerance, (4) improving health status, (5) preventing and treating complications, (6) preventing and treating exacerbations, and (7) reducing mortality. Side effects of various treatments are common in COPD patients because of the comorbidities they often exhibit.⁸

Pearl: Spirometric screening of the general population or smokers is not presently recommended. It is more important for the physician to ask about smoking, cough, sputum production, or breathlessness.

Pearl: Absence of a wheeze does not exclude COPD.

Assess and Monitor Disease

The diagnosis of COPD by the GOLD guidelines1 is defined as follows: “COPD is a disease state characterized by airflow limitation that is usually not fully reversible. The airflow limitation is often both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.” The diagnosis of COPD is made on the basis of symptoms, which may include those due to airway irritation (cough and sputum production) and those reflecting altered lung mechanics (breathlessness, wheezing, and sometimes chest pain). Cough and sputum production usually precede the development of airflow limitation by many years, although not all individuals with symptoms of cough and sputum production go on to develop COPD.¹

Pearl: The GOLD guidelines classify the severity of COPD into four stages.

Stage 0, At Risk. Characterized by symptoms of cough and sputum production not solely due to asthma, nasal disease, or gastric reflux. Lung function, as measured by spirometry, is still normal.

Stage I, Mild Risk. Characterized by mild airflow limitation (FEV₁/FVC < 70% but FEV₁ ≥ 80% predicted) and usually, but not always, by the continued presence of cough and sputum production. At this stage, the individual may not even be aware that his or her lung function is abnormal.

Stage II, Moderate COPD. Characterized by worsening airflow limitation (FEV₁/FVC < 70% and FEV₁ < 80% and ≥ 30% of predicted), and usually the progression of symptoms, with shortness of breath typically developing on exertion. Exacerbations may be troublesome and frequently lead to a significant decrease in the patient’s quality of life. Patients typically seek medical attention at this stage.

Stage III, Severe COPD. Characterized by severe airflow limitation (FEV₁/FVC < 70% and FEV₁ < 30% predicted) plus the presence of respiratory failure or clinical signs of right heart failure. At this stage, quality of life is appreciably impaired and exacerbations may occur three to four times per year and may be life-threatening.

Pearl: Use of accessory muscles of respiration, such as the abdominal rectus, on expiration is a sign of advanced disease. Physical findings of hyperinflation include an increased anteropsoterior diameter of the chest, tracheal tug, or pulsus paradoxus > 20 mm Hg.

Pearl: Arterial blood gas measurement is indicated in patients with FEV₁ < 40%, or in patients with signs of respiratory failure or right heart failure.

Reduce Risk Factors

Risk factors for the development of COPD include exposures of the lung to noxious agents and various host factors. Exposures include smoking (> 90% of cases), passive smoking, ambient air pol1ution, occupational dust and chemical exposures, and respiratory infections during childhood.

Host risk factors include AAT deficiency (< 1%), hyperresponsive airways, lung growth, and both sex and ethnicity (highest prevalence in the white male population).

Pearl: Smoking cessation is the single most effective—and cost-effective—intervention to reduce the risk of developing COPD and decreases its progression.

Pearl: Numerous studies indicate that nicotine replacement therapy in any form (nicotine gum, inhaler, nasal spray, transdermal patch, sublingual tablet, or lozenge) reliably increases long-term smoking abstinence rates. The antidepressants, bupropion and nortriptyline have also been shown to increase long-term quit rates. The antihypertensive drug clonidine can also be used to help a patient quit smoking, but side effects should be carefully reviewed with the patient.

Pearl: Special consideration should be given before using pharmacotherapy in selected populations, including people with medical contraindications, those smoking < 10 cigarettes/d, and pregnant or adolescent smokers.

Manage Stable COPD

The overall approach to managing stable COPD should be characterized by a stepwise increase in treatment, depending on the severity of the disease. A number of different types of pharmacologic agents are used to treat patients with COPD, and patients in GOLD Stage II or greater should receive daily bronchodilator therapy. Pharmacologic therapy is used to prevent and control symptoms, reduce the frequency and severity of exacerbations, improve health status, and improve exercise tolerance. Initial use should decrease airways obstruction and decrease dyspnea. None of the existing medications for COPD has been shown to alter the long-term decline in lung function that occurs with COPD. These various medications, however, can be used to decrease morbidity and may also delay disability and mortality in some patients. Medications may also decrease the number of exacerbations of COPD occurring each year.

Pearl: In general, nebulized therapy is not needed for a stable patient unless it has been demonstrated to be more effective than conventional metered-dose or dry powder inhaler dose therapy in that particular patient. It can also be considered for the patients who are unable to properly use inhalers.

Pearl: Combinations of bronchodilators with different mechanisms and durations of action tend to increase the degree of bronchodilation in COPD patients with increases in FEV₁, FEV₁/FVC, and peak expiratory flow. Changes in pulmonary function are not directly additive with an increasing number of bronchodilators being administered, but combinations usually do increase pulmonary function significantly more than administering each agent alone. Use of combination therapy is recommended as COPD advances beyond Stage II. Long-acting inhaled bronchodilators are more convenient to the patient.

Pearl: Tiotropium, a long-acting anticholinergic, has been shown in clinical trials to be more beneficial than ipratropium in improving exacerbations, dyspnea, quality of life, and lung function in patients with COPD.^8,9 It is expected to be approved by the Food and Drug Administration by July 2003.

Pearl: Mast cell stabilizers such as cromolyn sodium or nedocromil sodium should not be used to treat COPD. Leukotriene modifiers such as zileuton, zafirlukast, or montelukast also should not be used to treat COPD because there are no data to suggest efficacy.

Pearl: If you have a patient receiving theophylline, any time a new medication is added, someone in your office must review the new drug to make sure it does not cause hepatic P-450 inhibition, which could ultimately result in theophylline toxicity.

Pearl: Systemic steroids are clinically beneficial to patients hospitalized with a COPD exacerbation, and maximum effects of oral steroids after 3 days of IV steroids are achieved within 2 weeks. Longer tapering schedules increase steroid side effects without significantly improving lung function.

Pearl: In trials of inhaled steroids, there was a tendency for exacerbations of COPD to be less severe and exacerbation rates to have been decreased by as much as 25%. The use of inhaled corticosteroids in COPD does not decrease the rate of decline of the patient’s FEV₁ over time, but may decrease the decline in their health status.

Pearl: Inhaled corticosteroids may reduce the risks of repeated hospitalizations and death in elderly patients with COPD.¹⁰

Pearl: Inhaled corticosteroids should be considered for patients with repeated exacerbations requiring treatment with oral steroids, and/or patients with objective evidence (increase in FEV₁ > 200 mL and 15% above baseline) of response to a trial of inhaled corticosteroids (6 of 12 weeks). The FEV₁ in these patients should be < 50% of predicted.

Pearl: Influenza vaccination is recommended. It can reduce death and serious disease in patients with COPD.

Pearl: Antibiotics: The use of antibiotics, other than in treating infectious exacerbations of COPD or other bacterial infections, such as pneumonia, is not recommended. Antitussives: The regular use of antitussives is contraindicated in stable COPD. Mucolytic agents: Although a few patients with viscous sputum may benefit from mucolytics, the overall benefits seem to be very small. Therefore, the widespread use of these agents cannot be recommended on the basis of the present evidence. Narcotics: Narcotics are contraindicated in COPD because of their respiratory-depressant effects and potential to worsen hypercapnia. Clinical studies suggest that morphine use to control dyspnea may have serious adverse effects, but it may provide benefits to a limited number of patients.

Pearl: Long-term oxygen therapy is generally introduced in the GOLD Stage III patient who has: (1) PaO₂ ≤ 55 mm Hg or arterial oxygen saturation ≤ 88% on room air, with or without hypercapnia; or (2) PaO₂ < 60 mm Hg or arterial oxygen saturation ≤ 89% on room air, if there is evidence of pulmonary hypertension, peripheral edema suggesting congestive heart failure, or polycythemia (hematocrit > 55%). In these patients, long-term oxygen therapy improves survival.

Pearl: Pulmonary rehabilitation should be considered for patients with moderate or severe COPD. Exercise tolerance and symptoms improve with these programs.¹¹

Manage Exacerbations

Patients with COPD will have usually two to four exacerbations of their disease symptoms per year, with some requiring hospitalization. The most common causes of an exacerbation are pulmonary infections and air pollution, but the exact cause of about one third of severe exacerbations cannot be identified and may be related to reactive airway disease. Other conditions that may produce the symptoms of an acute exacerbation of COPD include pneumonia, myocardial ischemia, congestive heart failure, pneumothorax, pleural effusion, pulmonary embolism, cardiac arrhythmia, esophageal reflux, and noncompliance with medications. Treatment of exacerbations should consist of inhaled bronchodilators and systemic corticosteroids. Theophylline can be used in selected cases.

Pearl: An increase in sputum volume and purulence points to a bacterial cause. Green sputum has a high predictability for infection. Antibiotics should be administered.

Pearl: There is a high incidence of Haemophilus influenzae infections in patients with a COPD exacerbation due to infection. Other important bacterial causes include Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa.¹²

Pearl: Even if results of a barium swallow test are negative, 24-h pH measurements of the esophagus may still be needed to diagnose esophageal reflux. The pH measurement test is a better test of the presence of acid reflux. The normal DeMeester score is < 15 (95th percentile) when using pH measurement testing.

Pearl: Begin anticoagulant therapy immediately if you suspect pulmonary embolism during work-up of a patient, unless there is a specific contraindication for anticoagulation (document in the patient’s chart the reasoning for the contraindication).

Pearl: When the patient is admitted into the hospital, arterial blood gas measurement is essential to assessing the severity of the exacerbation.

Pearl: Noninvasive positive pressure ventilation (NIPPV) improves blood gases and pH, reduces hospital mortality, decreases the need for invasive mechanical ventilation, and decreases hospital stay. Not all patients are candidates for NIPPV.¹³

References

1. Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001; 163:1256–1276
2. Petty TL. A new national strategy for COPD. J Respir Dis 1997; 18:365–369
3. National Center for Health Statistics, National Health Interview Survey, 1982-1996, 1997-1998. Information cited in: Trends in chronic bronchitis and emphysema: morbidity and mortality. New York, NY: American Lung Association, Epidemiology and Statistics Units, December 2000
4. Calverley PMA. Chronic obstructive pulmonary disease: the key facts. London, UK: British Lung Foundation, 1998
5. Irwin RS, Curley FJ, French CL. Chronic cough: the spectrum and frequency of causes, key components of the diagnostic evaluation, and outcome of specific therapy. Am Rev Respir Dis 1990; 141:640–647
6. Jenkinson SG. Interpretation of pulmonary function tests. In: Pulmonary function testing: principles and practice. New York, NY: Churchill Livingstone, 1983; 205–224
7. Fassler HE, Wise RA. Lung volume reduction surgery. Am J Respir Crit Care Med 1999; 159:1031–1035
8. Casaburi R, Mahler DA, Jones PW, et al. A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease. Eur Respir J 2002; 19:217–224
9. Vincken W, van Noord JA, Greefhorst AP, et al. Improved health outcomes in patients with COPD during 1 yr’s treatment with tiotropium. Eur Respir J 2002; 19:209–216
10. Sin DD, Tu JV. Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164:580–584
11. Lacasse Y, Brosseau L, Milne S, et al. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2002; (3):CD003793
12. Monso E, Ruiz J, Rosell A, et al. Bacterial infection in chronic obstructive pulmonary disease: a study of stable and exacerbated outpatients using the protected specimen brush. Am J Respir Crit Care Med 1995; 152:1316–1320
13. Mehta S, Hill N. Non-invasive ventilation state of the art. Am J Respir Crit Care Med 2001; 163:540–577

Copyright ©2003 American College of Chest Physicians