Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease is persistent obstruction of the airways occurring with emphysema, chronic bronchitis, or both disorders.
In the United States, about 16 million people suffer from chronic obstructive pulmonary disease (COPD). It is second only to heart disease as a cause of disability that forces people to stop working. It is the fourth most common cause of death, accounting for more than 100,000 deaths per year in the United States; the number of deaths from COPD has increased by 40% over the last 20 years. More than 95% of all deaths from COPD occur in people older than age 55. COPD affects men more often than women and is more often fatal in men, although there has been a recent increase in the rate of deaths in women. COPD is also more often fatal in whites than in nonwhites and in blue-collar workers than in white-collar workers.
COPD leads to chronic airflow obstruction, which is defined as a persistent decrease in the rate of airflow through the lungs when the person breathes out (exhales). Both emphysema and chronic bronchitis contribute to the airflow obstruction of COPD. Emphysema is irreversible enlargement of many of the 300 million air sacs (alveoli) that make up the lungs and destruction of the air sac walls. Chronic bronchitis is characterized by a cough that produces sputum for 3 months or more during 2 successive years; the cough is not due to another lung disease.
The small airways of the lungs are normally held open by their alveolar wall attachments. In emphysema, the destruction of alveolar wall attachments results in collapse of the small airways, causing permanent airflow obstruction. In chronic bronchitis, the glands lining the bronchi enlarge, causing increased secretion of mucus. Inflammation of the small airways (bronchioles) develops and causes smooth muscle spasm and blockage by secretions. Asthma is also characterized by airflow obstruction (see Section 4, Chapter 44). However, in contrast with the airflow obstruction of COPD, the airflow obstruction of asthma is completely reversible in most people, either spontaneously or with treatment.
The airflow obstruction of COPD leads to an increase in the effort required for a person to breathe. The obstruction causes air to become trapped in the lungs, so that the amount of air remaining in the lungs after a full exhalation is increased. The number of capillaries in the walls of the alveoli decreases. These abnormalities impair the exchange of oxygen and carbon dioxide between the alveoli and the blood. In the earlier stages of COPD, oxygen levels in the blood are decreased, but carbon dioxide levels remain normal. In the later stages, carbon dioxide levels increase and oxygen levels fall even further. The decrease in oxygen levels in the blood stimulates the bone marrow to send more red blood cells into the bloodstream, a condition known as secondary polycythemia (see Section 14, Chapter 178).
Causes
Cigarette smoking is the most important cause of COPD, although only about 15 to 20% of smokers develop the disease. Pipe and cigar smokers develop COPD more often than nonsmokers but not as often as cigarette smokers. With age, susceptible cigarette smokers lose lung function more rapidly than nonsmokers. If a person stops smoking, there is little improvement in lung function. However, the rate of decline of lung function does return to that of nonsmokers when the person stops smoking, thus delaying the progression of symptoms.
COPD tends to occur more often in some families, so there may be an inherited tendency. Working in an environment polluted by chemical fumes or dust may increase the risk of COPD (see Section 4, Chapter 49). Exposure to air pollution and to smoke from nearby cigarette smokers (secondhand or passive smoke exposure) worsens a person's COPD and may cause COPD.
A rare cause of COPD is a hereditary condition in which the body produces a markedly decreased amount of the protein alpha1-antitrypsin. The main role of this protein is to prevent neutrophil elastase from damaging the alveoli. Consequently, emphysema develops by early middle age in people with severe alpha1-antitrypsin deficiency (see Section 10, Chapter 136), especially in those who also smoke.
Symptoms
In a person with COPD, a mild cough that produces clear sputum develops by around age 45, usually when the person first gets out of bed in the morning. Cough and sputum production persist for the next 10 years; shortness of breath may be noted with exertion. Sometimes, shortness of breath is first noted only with a lung infection, during which time the person coughs more and has an increased amount of sputum. The color of the sputum changes from clear to yellow or green.
By the time the person reaches his middle to late 60s, especially with continued smoking, shortness of breath with exertion becomes more troublesome. A lung infection may result in severe shortness of breath even when the person is at rest and may require hospitalization. Shortness of breath during activities of daily living, such as toileting, washing, dressing and sexual activity, may persist after the person has recovered from the lung infection.
About one third of people with severe COPD experience severe weight loss, in part because shortness of breath makes eating difficult and in part because of increased levels in the blood of a substance called tumor necrosis factor. Swelling of the legs often develops, which may be due to cor pulmonale (see Section 4, Chapter 54). People with COPD may intermittently cough up blood, which is usually due to inflammation of the bronchi, but which always raises the concern of lung cancer. Morning headaches may occur because breathing decreases during sleep, which causes increased retention of carbon dioxide.
As COPD progresses, some people, especially those who have emphysema, develop unusual breathing patterns. Some people breathe out through pursed lips. Others find it more comfortable to stand over a table with their arms outstretched and weight on their palms, a maneuver that improves the function of the diaphragm. Over time, many people develop a barrel chest as the size of the lungs increases because of trapped air. Low oxygen levels in the blood can give a blue tint to the skin (cyanosis). Clubbing of the fingers is rare (see Section 4, Chapter 39) and raises the suspicion of lung cancer.
Fragile areas in the lungs may rupture, permitting air to leak from the lung into the pleural space, a condition called pneumothorax (see Section 4, Chapter 52). This condition often causes sudden pain and shortness of breath and requires immediate intervention by a doctor to evacuate the air from the pleural space.
Symptoms may suddenly worsen during flare-ups of COPD. A flare-up is a worsening of symptoms of cough, increased sputum, and shortness of breath. Sputum color often changes from white to yellow or green, and fever and body aches sometimes occur. Shortness of breath may be present when the person is at rest and may be severe enough to require hospitalization. Severe air pollution, common allergens, and viral or bacterial infections may cause flare-ups.
Diagnosis
Chronic bronchitis is diagnosed by the history of a prolonged productive cough. Emphysema is diagnosed by a constellation of findings observed during a physical examination and on pulmonary function test results; however, by the time the doctor notices these abnormalities, emphysema is moderately severe. It is not important for doctors to differentiate between chronic bronchitis and emphysema; the most important determinant of how the person feels and functions is the severity of airflow obstruction.
In mild COPD, a doctor may find nothing during a physical examination. As the disease progresses, wheezes may be heard through the stethoscope, and prolonged expiration and decreased breathing sounds become apparent. Chest movement diminishes during breathing, and use of the neck and shoulder muscles in breathing may be noted.
In mild COPD, results of a chest x-ray are usually normal. As COPD worsens, the chest x-ray shows over-inflation of the lungs; decreased shadows of blood vessels denote the presence of emphysema.
Doctors can evaluate airflow obstruction with forced expiratory spirometry (see Section 4, Chapter 39). Decrease in the forced expiratory volume in 1 second (FEV1) and the ratio of the FEV1 to the forced vital capacity (FVC) are required to demonstrate airflow obstruction and to make the diagnosis.
A blood test may show an abnormally high level of red blood cells (polycythemia). Pulse oximetry or a sample of blood taken from an artery often shows low levels of oxygen. High levels of carbon dioxide in the arteries are seen late in the course of the disease.
If a person develops COPD at a young age, especially when the person has a family history of COPD, the alpha1-antitrypsin blood level is measured to determine whether the person has alpha1-antitrypsin deficiency. This genetic disorder is also suspected when COPD develops in someone who has never smoked.
Treatment
The most important treatment for COPD is to stop smoking. Stopping smoking when the airflow obstruction is mild or moderate often improves cough, reduces the amount of sputum, and slows the development of shortness of breath. Stopping smoking at any point in the disease process provides some benefit. The person should also try to avoid exposure to other airborne irritants, including secondhand smoke and air pollution.
If the person contracts influenza or pneumonia, COPD may worsen markedly. Therefore, a person with COPD should receive an influenza vaccination every year and a pneumococcal vaccination 5 years after an initial pneumococcal vaccination.
Treatment of Symptoms: Wheezing and shortness of breath are relieved when airflow obstruction improves. Although the airflow obstruction due to emphysema is not reversible, bronchial smooth muscle spasm, inflammation, and increased secretions are potentially reversible.
The anticholinergic drug ipratropium given by metered-dose inhaler 4 times daily is the drug of choice to help relieve shortness of breath. When symptoms are more severe, inhaled short-acting beta-adrenergic agonists, such as albuterol, more rapidly relieve shortness of breath than ipratropium. Salmeterol, a long-acting beta-adrenergic agonist with a delayed onset of action, can be given by inhalation every 12 hours. This drug is useful for prolonged relief of symptoms in some people, especially at night.
The combination of ipratropium and albuterol in a metered-dose inhaler has the advantage of decreasing the number of inhalers the person must use. People who have difficulty using metered dose inhalers benefit by inhaling the drug from a delivery device called a spacer (see Section 4, Chapter 44). Solutions of ipratropium and the beta-adrenergic agonists may also be given using nebulizers; this mode of therapy is reserved for people who have severe disease. A nebulizer creates a mist of drug, and its use does not have to be coordinated with breathing. Nebulizers are more portable than they were in the past; some units can even be plugged into a cigarette lighter in a car. Beta-adrenergic agonists are rarely given by mouth for people with COPD because they tend to work slower than the inhaled form and are more likely to cause side effects, including abnormal heart rhythms.
Theophylline acts by different mechanisms than ipratropium or the beta-adrenergic agonists. It is given only to people who do not respond to other drugs. The dose must be carefully controlled by the doctor, and levels of the drug in the blood must be measured periodically. A long-acting form of the drug permits twice-daily dosing in many people and helps to control shortness of breath at night.
Corticosteroids are helpful for many people with moderate and severe COPD whose symptoms cannot be controlled by the other drugs. Inhaled corticosteroids do not prevent decline of lung function over time. However, their use improves symptoms and results in decreased frequency of COPD flare-ups. Because of local delivery of drug to the lungs, inhaled corticosteroids produce fewer side effects than treatment given by mouth. However, high doses of inhaled corticosteroids can have effects throughout the body, such as worsening of osteoporosis. Corticosteroids given by mouth are largely restricted to treatment of COPD flare-ups or are given to people who continue to have symptoms from airflow obstruction and who are not responding to a simpler regimen.
There is no reliable therapy for thinning secretions so they can be coughed up more easily. However, avoiding dehydration may prevent thick secretions. A rule of thumb is to drink enough fluids to keep the urine pale except for that passed first in the morning. In severe COPD, respiratory therapy may help loosen secretions in the chest.
A doctor often uses spirometry and pulse oximetry during treatment to monitor the person's symptoms. Arterial blood gas measurements add information that is useful in severe disease.
Treatment of Flare-ups: Flare-ups should be treated by the doctor as soon as possible. If treatment fails, hospitalization may be needed. When bacterial infection is suspected by the doctor, a 7- to 10-day course of antibiotic treatment is often prescribed. Many doctors give people who have COPD a supply of an antibiotic and advise them to start taking the drug early in a flare-up. A number of antibiotics can be taken by mouth, including trimethoprim-sulfamethoxazole, doxycycline, amoxicillin-clavulanate, and ampicillin. Many doctors reserve the newer antibiotics, such as azithromycin, clarithromycin, and levofloxacin, for more severe lung infections or for people in whom treatment with the older and less expensive drugs has not worked. Although many people with COPD think they should take antibiotics to prevent flare-ups, there is no indication that these drugs do prevent flare-ups. Sometimes corticosteroids are given by mouth for 10 to 14 days to help reduce the severity and length of flare-ups.
Oxygen Therapy: Long-term oxygen therapy (see Section 4, Chapter 40) prolongs the life of people who have advanced COPD and severely reduced oxygen levels in the blood. Although round-the-clock therapy is best, using oxygen 12 hours a day also has some benefits. This therapy reduces the excess of red blood cells caused by low blood oxygen levels, improves mental functioning, and helps to relieve heart failure caused by COPD. Oxygen therapy may also improve shortness of breath during exercise.
Different devices are available for oxygen therapy. Electrically driven oxygen concentrators are used for people who are mainly homebound. The use of compressed oxygen in small tanks permits short periods outside the home for such people. Liquid oxygen systems are more expensive but are preferable for active people. They permit several hours away from the source reservoir by use of portable liquid oxygen containers. People must never use oxygen therapy near open flames or while smoking.
Pulmonary Rehabilitation: Pulmonary rehabilitation can help people who have COPD (see Section 4, Chapter 40). However, lung function does not improve with pulmonary rehabilitation. Programs encompass education about the disease, exercise, and nutritional and psychosocial counseling. These programs can improve the person's independence and quality of life, decrease the frequency and length of hospital stays, and improve the person's ability to exercise. Exercise programs can be carried out in the clinic and at home. Stationary bicycling, stair climbing, and walking are used to exercise the legs. Weight lifting is used for the arms. Often, oxygen is recommended during exercise. As with any exercise program, gains in conditioning are quickly lost if the person stops exercising. Special techniques are taught for decreasing shortness of breath during activities, such as cooking, engaging in hobbies, and sexual activity.
Other Treatments: For people with a severe alpha1-antitrypsin deficiency, the missing protein can be replaced. The treatment, which requires weekly intravenous infusions of the protein, is expensive. Single lung transplantation may be used in certain people who are usually younger than 55.
An experimental operation known as lung volume reduction surgery can be carried out in people who have severe emphysema in the upper portions of their lungs. In this operation, the most severely diseased portions of the lungs are removed, thus permitting the remaining portions of the lungs and the diaphragm to function better. It is not known how long the improvement lasts. People are required to stop smoking for at least 6 months before surgery, and they should undergo an intense rehabilitation program to be certain lung function has improved significantly before undertaking this operation, which carries a mortality rate of about 5 to 8%.
Prognosis and End-of-Life Issues
The prognosis for people with mild COPD is favorable, little worse than the prognosis for smokers without COPD; continued smoking, however, virtually assures that symptoms will worsen. With moderate and severe airway obstruction, the prognosis becomes progressively worse. People with an FEV1 between 35% and 50% of normal are still only slightly more likely to die within 10 years than a normal person. However, about 30% of people with more severe airway obstruction die in 1 year; 95% die in 10 years. Death may result from respiratory failure, pneumonia, pneumothorax, heart rhythm abnormalities (arrhythmias), or blockage of the arteries leading to the lungs (pulmonary embolism). People with COPD have a risk of lung cancer beyond that due to their use of cigarettes.
People in advanced stages of COPD are likely to need considerable help with medical care and with activities of daily living. People with end-stage disease who develop flare-ups may need an endotracheal tube and mechanical ventilation (see Section 4, Chapter 55). The period of mechanical ventilation may be prolonged and some people remain ventilator-dependent. It is important for people to consider with their doctors and loved ones whether or not they wish this kind of supportive therapy. The best way of assuring that the person's wishes are carried out is to have completed an advanced directive, preferably by the appointment of a health care proxy (see Section 1, Chapter 9).
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