CHAPTER 77

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease is persistent obstruction of the airways occurring with emphysema, chronic bronchitis, or both disorders.

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease.

People develop a cough and eventually become short of breath.

Diagnosis is made with chest x-rays and tests of lung function.

Stopping smoking and taking drugs that help keep airways open are important.

People who have severe disease may need to take other drugs, use oxygen, or have pulmonary rehabilitation.

In the United States, about 12 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 120,000 deaths per year in the United States. The number of deaths from COPD has increased more than 60% over the last 20 years, and more than 95% of all COPD-related deaths occur in people older than age 55. COPD affects men more often than women, but men and women die as a result of COPD at about equal rates. COPD is 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 from the lungs when the person breathes out (exhales). This airflow obstruction is partially reversible in most people, either spontaneously or with treatment. COPD includes the diagnoses of chronic obstructive bronchitis and emphysema. Many people have both disorders. Chronic bronchitis is defined as cough that produces sputum repeatedly during two successive years. When chronic bronchitis involves airflow obstruction, it qualifies as chronic obstructive bronchitis. Emphysema is defined as widespread and irreversible destruction of the alveolar walls (the cells that support the air sacs, or alveoli, that make up the lungs) and enlargement of many of the alveoli.

The small airways (bronchioles) of the lungs contain smooth muscles and are normally held open by their attachments to alveolar walls. In emphysema, the destruction of alveolar wall attachments results in collapse of the bronchioles, causing permanent airflow obstruction. In chronic bronchitis, the glands lining the larger airways (bronchi) of the lungs enlarge and increase their secretion of mucus. Inflammation of the bronchioles develops and causes smooth muscle to contract (spasm), further obstructing airflow. Inflammation also causes airflow to be blocked by secretions. Asthma is also characterized by airflow obstruction (see page 473). 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 causes air to become trapped in the lungs after a full exhalation, increasing the effort required to breathe. Also in COPD, 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 may be decreased, but carbon dioxide levels remain normal. In the later stages, carbon dioxide levels increase and oxygen levels fall.

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 box on page 1069). The decrease in oxygen levels in the blood also increases the pressure in the artery through which blood flows from the heart to the lungs (pulmonary artery). As a result of the increased pressure, pulmonary hypertension and cor pulmonale can occur (see box on page 523). People with COPD also have an increased risk of developing heart rhythm abnormalities (arrhythmias). For smokers, the risk of developing lung cancer is higher than it would be on the basis of cigarette smoking alone.

Causes

Cigarette smoking is the most important cause of COPD, although only about 15% of smokers develop the disease. Pipe and cigar smokers develop COPD more often than nonsmokers but not as often as cigarette smokers. With aging, susceptible cigarette smokers lose lung function more rapidly than nonsmokers. Lung function improves only a little if people stop smoking. However, the rate of decline of lung function returns to that of nonsmokers when people stop smoking, thus delaying development and 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 page 496). Exposure to air pollution and to smoke from nearby cigarette smokers (secondhand or passive smoke exposure) may cause COPD (and also worsens the disease).

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 (an enzyme in certain white blood cells) from damaging the alveoli. Consequently, emphysema develops by early middle age in people with severe alpha1-antitrypsin deficiency (also called alpha1-antiprotease inhibitor deficiency), especially in those who also smoke.

Symptoms

In people with COPD, a mild cough that produces clear sputum develops by around age 45. The cough usually occurs when the person first gets out of bed in the morning. Cough and sputum production persist. Shortness of breath may occur with exertion. Sometimes, shortness of breath first occurs 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 or white to yellow or green.

By the time people with COPD reach their middle to late 60s, especially if they continue smoking, shortness of breath with exertion becomes more troublesome. Pneumonia and other lung infections occur more often. They 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. 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 respiratory muscles. 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 page 453) 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 page 520). This condition often causes sudden pain and shortness of breath and requires immediate intervention by a doctor to remove the air from the pleural space.

A flare-up of COPD is a worsening of symptoms, usually cough, increased sputum, and shortness of breath. Sputum color often changes 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. During severe flare-ups, people may develop a life-threatening condition called acute respiratory failure. Among the possible symptoms are severe shortness of breath (a feeling likened to being drowned), severe anxiety, sweating, cyanosis, and confusion.

Diagnosis

Chronic bronchitis is diagnosed by the history of a prolonged productive cough. People with chronic obstructive bronchitis have chronic bronchitis and evidence of airflow obstruction on pulmonary function tests. Emphysema is diagnosed on the basis 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 obstructive bronchitis and emphysema. The most important determinant of how the person feels and functions is the severity of the airflow obstruction.

In mild COPD, a doctor may find nothing unusual during the physical examination. As the disease progresses, wheezes may be heard through the stethoscope, and prolonged expiration and decreased breath sounds become apparent. Chest movement diminishes during breathing, and use of the neck and shoulder muscles in breathing may occur.

In mild COPD, the chest x-ray is usually normal. As COPD worsens, the chest x-ray shows over-inflation of the lungs. Thinning of blood vessels suggests the presence of emphysema.

Doctors can evaluate airflow obstruction with forced expiratory spirometry (see page 454). 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 occur late in the course of the disease.

In people who develop COPD at a young age, especially when there is a family history of COPD, the alpha1-antitrypsin blood level is measured to determine whether alpha1-antitrypsin deficiency is present. This genetic disorder is also suspected when COPD develops in people who have never smoked.

Treatment

The most important treatment for COPD is to stop smoking. Stopping smoking when the airflow obstruction is mild or moderate often lessens 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. Trying several strategies at once is most likely to be effective. Among these strategies are committing to a specific date for quitting, using behavioral modification techniques (for example, making cigarettes difficult to obtain or rewarding oneself for abstaining for increasingly long periods of time), group counseling and support sessions, and nicotine replacement (for example, by chewing nicotine gum, wearing a nicotine skin patch, or using a nicotine inhaler, nicotine lozenge, or nicotine nasal spray). The drugs varenicline and bupropion may also help decrease tobacco craving. However, even with the most effective methods, less than half of people have quit smoking after one year.

People should also try to avoid exposure to other airborne irritants, including secondhand smoke and air pollution.

Contracting influenza or developing pneumonia may worsen COPD markedly. Therefore, all people with COPD should receive an influenza vaccination every year and a pneumococcal vaccination every 5 or 6 years.

Treatment of Symptoms: Wheezing and shortness of breath are relieved when airflow obstruction improves. Although airflow obstruction due to emphysema is not reversible, bronchial smooth muscle spasm, inflammation, and increased secretions are all potentially reversible.

Inhaled bronchodilators are given with a device that allows the user to spray a specific and consistent dose of a drug into the airways via the mouth and throat (metered-dose inhaler). Inhaled bronchodilators include anticholinergic and beta-adrenergic agonist drugs. Both relax muscles around the bronchioles. Anticholinergic drugs include ipratropium and tiotropium. Ipratropium is given about 4 times daily, and tiotropium is given once daily. Inhaled short-acting beta-adrenergic agonists, such as albuterol, more rapidly relieve shortness of breath than anticholinergic drugs and so can be most useful during flare-ups. 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.

Many people can use metered dose inhalers more effectively when they inhale the drug through a delivery device called a spacer (see art on page 476). Inhaled bronchodilators may also be given using nebulizers. This mode of therapy should be reserved for people who have severe disease or for those who cannot use a metered-dose inhaler properly. A nebulizer creates a mist of drug, and the timing of its inhalation 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 the cigarette lighter in a car.

Corticosteroids are helpful for many people with moderate and severe COPD whose symptoms cannot be controlled by the other drugs or for those who get frequent flare-ups despite the use of 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 the drug is delivered 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.

Theophylline is given only to people who do not respond to other drugs. The dose must be carefully controlled by the doctor, and, in some patients, levels of the drug in the blood must be measured periodically. A long-acting form of the drug permits once-daily or twice-daily dosing in many people and helps to control shortness of breath at night.

There is no reliable therapy for thinning secretions so they can be coughed up more easily. However, avoiding dehydration may prevent thickening of 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.

Spirometry and pulse oximetry are often used to monitor symptoms. Arterial blood gas measurements add information that is useful in severe disease.

Treatment of Flare-ups: Flare-ups should be treated as soon as possible. When bacterial infection is suspected, a 7- to 10-day course of antibiotic treatment is usually prescribed. Many doctors give people who have COPD a supply of an antibiotic to be kept on hand and taken 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 more expensive antibiotics, such as azithromycin, clarithromycin, and levofloxacin, for more severe lung infections, for people in whom treatment with the older and less expensive drugs has not worked, for those who have severe symptoms, and for those at risk of infection with organisms that are not likely to be eliminated by the older drugs (resistant bacteria). People whose immune system is suppressed or those who live in nursing homes are most likely to be infected with resistant bacteria.

People with severe flare-ups require hospitalization and treatment with short-acting beta-adrenergic agonist drugs and ipratropium, oral or intravenous corticosteroids, and oxygen. They may require machine-assistance with breathing (mechanical ventilation) and sometimes placement of an endotracheal (breathing) tube. Although many people with COPD think they should take antibiotics to prevent flare-ups, there is no indication that this practice is effective.

Oxygen Therapy: Long-term oxygen therapy (see page 460) prolongs the life of people who have advanced COPD and severely reduced oxygen levels in their 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 and helps to relieve cor pulmonale 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 when electrical outlets are available. Compressed oxygen is available in small tanks that permit people to travel outside of their homes for 2 to 6 hours. Liquid oxygen systems are more expensive but are preferable for active people as they permit several hours away from the source reservoir. People must never use oxygen therapy near open flames or while smoking.

Pulmonary Rehabilitation: Pulmonary rehabilitation can help people who have COPD (see page 459), but it does not improve lung function. Programs encompass education about the disease, exercise, and nutritional and psychosocial counseling. These programs can improve independence and quality of life, decrease the frequency and length of hospital stays, and improve the ability to exercise. Exercise programs can be carried out in an outpatient setting or at home. Walking (sometimes on a treadmill) is usually used to exercise the legs. Sometimes stationary bicycling and stair climbing are also used. 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: Over-the-counter cough suppressants usually help little and are not recommended. 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 60 and have severe airflow obstruction. The goal of lung transplantation is to improve quality of life, because survival time is rarely increased. Lifelong immunosuppression is required, placing people at risk of infections.

Lung volume reduction surgery can be carried out in people with 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. They should undergo an intense rehabilitation program to determine whether overall function can be improved significantly without surgery before undertaking this operation, which carries a risk of death of about 5%.

Prognosis and End-of-Life Issues

COPD itself usually does not cause death or severe symptoms if the person stops smoking at a time when airflow is only mildly obstructed. Continued smoking, however, virtually assures that symptoms will worsen. With moderate and severe airflow obstruction, the prognosis becomes progressively worse. People in advanced stages of COPD are likely to need considerable help with medical care and with activities of daily living. They may, for example, arrange to live on a single floor of their house, eat several small meals rather than one large meal, and avoid wearing shoes that must be tied. Death may result from respiratory failure, lung cancer, heart disorders (for example, heart failure or heart rhythm abnormalities), pneumonia, pneumothorax, or blockage of the arteries leading to the lungs (pulmonary embolism).

People with end-stage disease who develop flare-ups may need a breathing tube and mechanical ventilation. The duration of mechanical ventilation may be prolonged, and some people remain ventilator-dependent until death. It is important for people to consider with their doctors and loved ones whether or not they wish this kind of supportive therapy and to do so before a flare-up occurs. The best way to ensure that the person’s wishes regarding prolonged mechanical ventilation are carried out is to prepare an advance directive (see page 69) and appoint a health care proxy (see page 70).

Alpha1-Antitrypsin Deficiency

Alpha1-antitrypsin deficiency is a hereditary disorder in which a lack or low level of the enzyme alpha1-antitrypsin damages the lungs and liver.

Alpha1-antitrypsin deficiency is caused by an inherited gene mutation.

Infants may develop jaundice and cirrhosis.

Adults commonly develop emphysema, with shortness of breath, wheezing, and coughing; some adults develop cirrhosis.

Tests that measure the amount of the enzyme in the blood and that detect the gene mutations are used for diagnosis.

People with emphysema take drugs to improve breathing and sometimes receive infusions of alpha1-antitrypsin by vein.

Some people need lung or liver transplants.

Alpha1-antitrypsin is an enzyme produced by the liver that inhibits the action of other enzymes called proteases. Proteases break down proteins as part of normal tissue repair. Alpha1-antitrypsin protects the lungs from the damaging effects of proteases.

Alpha1-antitrypsin deficiency results from an inherited mutation in the gene that controls production and release of the enzyme. There are many subtypes of alpha1-antitrypsin deficiency, but in all, levels of active enzyme in the blood are insufficient, the enzyme is structurally abnormal (and thus functions poorly), or both. Whites are affected more often than blacks or Asians.

The most common problems caused by the deficiency are

Liver damage

Emphysema

If the enzyme is structurally abnormal, it may clump in the liver, causing the liver to malfunction. In some people, liver malfunction leads to cirrhosis (see page 222) and to an increased risk of liver cancer.

The low levels of alpha1-antitrypsin allow proteases to damage the lungs, resulting in emphysema (see page 480). Emphysema is more common (and worse) in people who smoke. Emphysema in nonsmokers is often caused by alpha1-antitrypsin deficiency.

Disorders of other organs sometimes occur. These disorders include inflammation of fat under the skin (panniculitis), life-threatening hemorrhage, aneurysms, ulcerative colitis, vasculitis, and kidney disease.

Symptoms

Symptoms may first appear during infancy, childhood, or adulthood. About 20% of affected people have symptoms during infancy. Affected infants develop yellowing of the skin and the whites of the eyes (jaundice) and an enlarged liver during the first week of life. Jaundice disappears at about age 2 to 4 months. However, about 20% of these infants later develop cirrhosis, and some die before reaching adulthood.

Adults commonly develop emphysema, with progressively increasing shortness of breath, difficulty breathing, coughing, and wheezing. Emphysema rarely develops before age 25. It develops earlier and is more severe in smokers than in nonsmokers. The severity of symptoms also varies depending on the form of the deficiency, other disorders people have, environmental exposure to lung irritants, and other factors. If people have never smoked, their symptoms tend to be moderate, and most have a normal life expectancy.

Even if they did not have liver problems during infancy, about 10% of adults develop cirrhosis, which may eventually lead to liver cancer.

People with panniculitis have painful, tender bumps or discolored patches on the lower abdomen, buttocks, and thighs. The bumps may feel hard to the touch.

Diagnosis

Alpha1-antitrypsin deficiency is suspected in the following:

Infants who have typical symptoms

Smokers who develop emphysema before age 45

Nonsmokers who develop emphysema at any age

People with an unexplained liver disorder

Because the deficiency is inherited, doctors usually ask whether any family members have had emphysema or cirrhosis with no known cause.

The deficiency is often confirmed by genetic testing, which also can determine the specific form of the deficiency. Doctors also usually do blood tests to measure the level of alpha1-antitrypsin.

Treatment

Emphysema: People who smoke are advised to stop. Bronchodilators such as albuterol may help ease breathing and relieve cough. Lung infections that develop are treated promptly.

Alpha1-antitrypsin may be given by vein to replace the deficient enzyme. It is collected from a group of donors and screened for bloodborne disorders. Thus, it is expensive and is most beneficial to people who have only moderate symptoms due to emphysema and do not smoke. This treatment is thought to prevent further damage but does not reverse damage already done.

If people are younger than 60 and have severe symptoms, lung transplantation may be done. A few medical centers sometimes do transplantations in highly selected people as old as 70.

Liver Damage: Taking alpha1-antitrypsin does not treat or prevent liver damage because liver damage is caused by production of an abnormal enzyme, not by enzyme deficiency. If the liver is severely damaged, liver transplantation may be done (see page 1132). The transplanted liver does not become damaged because the alpha1-antitrypsin it produces is normal and thus does not accumulate in the liver.

Panniculitis: Doctors may give corticosteroids, antimalarial drugs, or certain antibiotics (tetracyclines) to relieve inflammation. But whether these drugs are effective is unclear.