Introduction

Chronic obstructive lung disease (COLD), also known as chronic obstructive pulmonary disease (COPD), is characterized by a limitation of the airflow in the lung, which develops over time and is not totally reversible.

COLD is associated with a set of breathing-related symptoms:

• Chronic cough
• Spitting or coughing mucus (phlegm)
• Being out of breath when doing physical activities

The ability to exhale (breath out) gets worse over time.

The lungs are located in the chest cavity and are responsible for respiration. The alveoli are small sacs where oxygen is exchanged in the lungs.

The two major diseases in this category are emphysema and chronic bronchitis, both covered in this report. Asthmatic bronchitis, the other major COLD, is a condition that develops when a person with asthma is exposed to irritants, such as smoking, and develops a chronic cough. [For more information, see In-Depth Report #04, Asthma in adults.]

Because smoking is overwhelmingly the cause of both emphysema and chronic bronchitis, they often develop together and frequently require similar treatments and approaches. As chronic bronchitis often coincides with emphysema, it is frequently difficult for a physician to distinguish between the two.

Emphysema

Emphysema is a disease marked by destruction in the alveoli, grapelike clusters of air sacs at the end of the smallest airways (the bronchioles) in the lung. It generally takes the following course:

• The walls of the alveoli become inflamed and damaged; over time they lose elasticity (the ability to stretch and shrink), and pockets of dead air (called bullae) form in the injured areas. These pockets are formed by damaged alveoli that merged, and have become irregular in shape.
• The pockets interfere with the normal working of the lungs, making breathing out more difficult.
• Inhalation (breathing in) is not impaired. Until the late stages of the disease, oxygen and carbon dioxide levels are normal.

Click the icon to see an image of emphysema.

Chronic Bronchitis

Chronic bronchitis is defined as coughing and overproduction of mucus for at least 3 months, during at least 2 consecutive years. In chronic bronchitis, the disease process is generally marked by the following characteristics:

• Irritation of the bronchial tubes (from smoking, air pollution, etc.) causes mucus production. The mucus is cleared through coughing.
• Constant coughing causes damage to the bronchial tubes. The tubes swell and thicken, leaving less room for air flow.
• The reduced airflow into the lungs usually leads to lung damage that results in emphysema.

Click the icon to see an image depicting bronchitis.

Click the icon to see an image of normal lungs.

Causes

Cigarette smoke accounts for over 80% of all cases of chronic obstructive lung disease. It contains irritants that inflame the air passages, setting off a cascade of biochemical events that damage cells in the lung, increasing the risk both for COLD and lung cancer. Different effects of smoking can lead to emphysema or chronic bronchitis, but smokers generally have signs of both conditions. The diagnosis of a specific type of COLD depends on which disease process predominates.

Causes of Emphysema

Smoking is the major cause of emphysema. In some rare inherited disorders, emphysema can develop even in nonsmokers.

The Disease Process Leading to Emphysema. The key process leading to emphysema is destruction of a protein in the lung called elastin, which is essential for the "springy" quality of many tissues in the body. This protein is specifically important in the lungs for maintaining flexibility in the alveoli -- the tiny sacs at the end of the airways.

An imbalance in the following chemicals may be important in this process:

• Proteases, particularly those known as elastase and trypsin. Proteases are enzymes released by white blood cells called neutrophils. Under normal circumstances, these enzymes are important for fighting infection and injury. In excess, however, these enzymes can degrade or destroy elastin.
• Alpha 1-antitrypsin (AAT). The AAT protein neutralizes proteases and therefore protects elastin from destruction.

An excess of protease coupled with impaired or deficient AAT can lead to emphysema. Eventually, the imbalance in these factors produces the inelastic walls of the alveoli and the pockets of dead air characteristic of emphysema. Any condition that causes an imbalance in any of these substances may trigger emphysema. Smoking is the major culprit, but genetic factors can also cause this imbalance.

Smoking and Biologic Factors Leading to Emphysema. Emphysema caused by smoking most often occurs in the upper lobes of the lungs. Some experts believe that smoking causes an imbalance between AAT and proteases in the following way:

• Heavy smoking can over-stimulate the immune system, so that proteases are overproduced.
• In addition, cigarette smoke triggers the release of damaging particles called oxygen free radicals (or oxidants) that deactivate AAT and make it ineffective.

Emphysema, then, can develop in smokers who have sufficient and even high amounts of AAT.

Only 15 - 20% of all smokers develop emphysema, however. Other factors, such as genetic abnormalities, may need to be present to increase susceptibility to airway damage. Some genetic factors being investigated are the following: Researchers identified a group of patients who might have an inherited susceptibility to the effects of smoking, so that severe COLD develops at an earlier age than usual.

• Some people may have genetic factors that cause the lungs to be hyper-reactive to stimulants and allergens.
• Some evidence points to genetic abnormalities in an important enzyme called microsomal epoxide hydrolase, which is responsible for the breakdown of harmful oxidants found in cigarette smoke.
• Researchers are also studying a variant of the gene for tumor necrosis factor, an immune factor responsible for inflammatory damage in a number of diseases.

Alpha 1-Antitrypsin (AAT) Deficiency. An estimated 70,000 Americans have an inherited condition called alpha 1-antitrypsin deficiency (A1AD), which causes emphysema in 20,000 to 40,000 of them. This disorder results in inadequate amounts of the protective enzyme AAT. Without adequate amounts of AAT, early and progressive damage occurs in both the walls of the alveoli and the airways leading to them. Because smoke is a major toxin and deactivates any residual amounts of AAT, smokers with AAT deficiency have almost no chance of escaping emphysema. Nonsmokers are also at high risk, however. Emphysema in people with A1AD develops in people as young as 30 years old, who are usually of Northern European descent.

Screening tests are now available to detect the genetic defect that causes A1AD. Couples in which one or both partners have a family history of the disease may wish to be tested for the deficiency, so they may take protective measures for themselves and any future children they may have. If the condition is present in the family, testing the children is important.

Causes of Chronic Bronchitis

Biologic Factors and Smoking in Chronic Bronchitis. In chronic bronchitis, smoking triggers inflammation that causes damage in the airways. The processes involved are less clearly understood than those in emphysema, but most likely include the following:

• Damage to the cilia, the hair-like waving projections that move bacteria and foreign particles out of the lungs -- when cilia are injured, such agents become trapped in the lungs and can cause infections that lead to chronic bronchitis.
• Enlargement of the mucus glands in the large airways of the lungs is also involved in the disease process.
• Overgrowth in the smooth muscle cells in the airway.

Bacteria and Viruses. Certain bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, are common in the lower airways of nearly half of chronic bronchitis patients. However, the role of bacteria, viruses, and other organisms in causing chronic symptoms, and inflammation is unclear. Some experts believe that a low-level infection in the lungs may trigger an inflammatory reaction that continues to produce subsequent acute attacks.

Symptoms

The hallmark symptom of chronic obstructive lung disease is progressive shortness of breath, frequently accompanied by a phlegm-producing cough, with episodes of wheezing. Symptoms may vary, however, or others may be present depending on which disease predominates.

Symptoms of Emphysema

Typically, first symptoms of emphysema occur in heavy smokers in their mid-50s. Emphysema patients have typically lost between 50 - 70% of their lung tissue by the time symptoms begin to appear:

• The predominant early symptom is shortness of breath with light physical activity. Coughing is usually minor, and there is little sputum (phlegm).
• Late, severe symptoms include rapid, labored breathing and persistent air hunger even during rest or after minimal physical activity.
• People with severe emphysema tend to have pinkish skin and barrel-shaped chests due to overinflated lungs (lungs that are bigger than normal size, due to lost elasticity and trapped air).
• In some cases, involuntary weight loss may be a symptom of emphysema.

Symptoms of A1AD-related emphysema tend to appear between the ages of 30 and 40. As with standard emphysema, they include shortness of breath after physical activity, wheezing, and inability to exercise.

Symptoms of Chronic Bronchitis

Chronic bronchitis usually causes the following symptoms:

• Coughing with excessive sputum on most days for at least 3 months of the year, over 2 successive years -- these symptoms in this time frame are the standard minimums for a diagnosis.
• Shortness of breath occurs, but it may not be as severe during rest as it is in emphysema.
• Lying down at night worsens symptoms in advanced conditions, so patients must sleep sitting up.

In late, severe stages, lack of oxygen causes the skin to have a blue cast (cyanosis), and the body is swollen from fluid accumulation caused by congestive heart failure. Such patients often have emphysema as well.

Diseases with Similar Symptoms

Several diseases have similar symptoms -- and may accompany COLD.

Acute Bronchitis

Acute bronchitis is usually caused by a virus, and in most cases does not require treatment. The cough it causes typically lasts for about a week to 10 days. In about half of patients, however, coughing can last up to 3 weeks, and 25% of patients continue to cough for over 1 month. Although acute bronchitis is usually not considered a serious problem, one 1999 study reported that a third of patients who had acute bronchitis later developed either chronic bronchitis or asthma. Acute bronchitis, then, may serve as a marker for future problems in some patients.

Asthma

The classic symptoms of an asthma attack are coughing, wheezing, and shortness of breath (dyspnea). Wheezing when breathing out is usually present during an attack. Typically, the attack begins with wheezing and rapid breathing, and as it becomes more severe, all breathing muscles become visibly active. Irritation of the nose and throat, thirst, and the need to urinate are common symptoms and may occur before an asthma attack begins. Some people first experience chest tightness or pain or a nonproductive cough that is not associated with wheezing. Chest pain occurs in about three quarters of patients; it can be very severe and its intensity is unrelated to the severity of the asthma attack itself. The end of an attack is often marked by a cough that produces a thick, stringy mucus.

Lung Cancer

There are usually no symptoms of lung cancer until the disease is advanced. Frequent bouts of pneumonia or a lung infection that does not clear up in a seemingly healthy adult may be the first signs of lung cancer. Signs of advanced lung cancer can include coughing, weight loss, fever, shortness of breath, bloody sputum, or chest pain.

Bronchiectasis

Bronchiectasis is an irreversible lung disease in which the airways in the lung are chronically dilated. The patient may have chronic sinusitis, a chronic cough, and heavy sputum, often containing blood. The condition is usually preceded by serious, frequent respiratory infections, often starting in childhood. In one study nearly 30% of COLD patients had signs of bronchiectasis. It is also associated with rare genetic diseases, including cystic fibrosis and Kartagener's syndrome, a disorder that affects that cilia's ability to move.

Complications

In 2002, chronic obstructive lung disease was responsible for 120,000 deaths. COLD costs in the U.S. in 2004 reached $37.2 billion. It is the fourth leading cause of death in the U.S., and its death rates are increasing. Some evidence suggests that these death rates may be higher than current estimates, because COLD patients are at greater risk for life-threatening conditions, notably heart attack and pulmonary embolism.

Chronic obstructive lung disease is progressive; however, when patients stop smoking the disease often levels off.

• Outlook for Patients with Emphysema. If emphysema is detected before causing symptoms, there may be some chance of reversing it, although permanent changes in the alveoli usually occur, even in young smokers. Patients with the inherited form of early-onset emphysema are at risk for early death unless the disease is treated and its progression halted or slowed. Emphysema patients who experience severe involuntary weight loss (which indicates muscle wasting) have a poorer outlook, regardless of lung function.
• Outlook for Patients with Chronic Bronchitis. Chronic bronchitis does not cause as much lung damage as emphysema, although the airways become blocked by mucous plugs, and narrow due to inflammation. Thus poor air exchange causes reduced levels of oxygen, and high carbon dioxide levels. This state of poor gas exchange can lead to serious, life-threatening conditions that include severe breathing difficulty and heart failure.

Acute Exacerbations

Acute exacerbations are episodes that occur with both types of COLD. The airways suddenly become obstructed, and symptoms worsen. Such events are associated with inflammation in the airways and are triggered by infections about 80% of the time. They are not due to other complications of COLD, including pneumonia, heart failure, or a collapsed lung.

A new study found that 25% (one quarter) of people with COLD, who have an acute exacerbation with no known cause, actually suffer from pulmonary embolism (a blood clot in the lung). The risk for pulmonary embolism was higher in patients who had blood clot problems in the past and patients with cancer. The risk was also increased in patients whose carbon dioxide pressure in the alveoli was significantly reduced, compared to their usual levels.

Acute exacerbations include the following symptoms:

• Worsened shortness of breath. This is the most common and distressing acute symptom.
• Increased volume of sputum, which is also typically thicker and greenish in color.
• Wheezing.

Acute exacerbations occur, on average, between two and three times a year in patients with moderate to severe COLD. In about 80% of the cases, they are triggered by infections. Smokers have more episodes than nonsmokers do. Acute exacerbations resolve on their own, but they are still the most common cause of hospitalization in these patients. Patients with frequent acute exacerbations of COLD are at higher risk for disease deterioration, including reduced quality of life and increasing rates of hospitalizations. Furthermore, in patients who are hospitalized, the morality rates are 11%. Survivors of a first hospitalization have a 50% change of rehospitalization within 6 months.

A new study looked at physical activity levels of patients recovering from an acute exacerbation of COLD. The study found that such patients have very low levels of physical activity while in the hospital and after being discharged. The study found that patients with lower physical activity 1 month after discharge were more likely to be hospitalized within a year, for another episode of acute exacerbation. The researchers recommend adding appropriate amounts of exercise to the treatment of such patients.

Effect on Quality of Life and Mood

Nearly half of patients with COLD report that daily activities are limited. They have trouble walking up stairs or carrying even small packages. Breathing becomes hard work. More than half of patients with COLD often suffer from insomnia. Such impairment in quality of life can greatly impair mood. If patients with COLD become anxious or depressed, they may have a poorer outlook than those without these emotional problems. Even low-level depression can impair health. Of some concern was a 2003 study reporting a higher rate of suicidal thoughts in patients with COLD or asthma than in those with any other major chronic illness, including arthritis, diabetes, heart disease, and cancer. More research is needed on this subject. Certainly, however, psychological interventions may be particularly helpful for people with COLD.

Medical Complications from Oxygen Deprivation

Over time, both varieties of COLD cause low oxygen levels (hypoxia) and high levels of carbon dioxide (hypercapnia) in the body. In order to boost oxygen delivery, the body compensates in a number of ways:

• The rate of breathing increases.
• More red blood cells are produced to increase the blood's oxygen-carrying capacity.
• The heart rate increases to pump more blood.
• Blood vessels in the lung constrict to force blood and oxygen through the circulatory system. This leads to high blood pressure in the lungs (pulmonary hypertension).

Eventually these activities can lead to very serious and even life-threatening conditions:

• Patients with prolonged and severe hypoxia and hypercapnia are at risk for acute respiratory failure, which can cause heart rhythm abnormalities or other life-threatening conditions if not treated immediately.
• Abnormally high blood pressure in the lungs can cause a complication called cor pulmonale, in which the right ventricle of the heart enlarges, eventually leading to heart failure.
• The effects of COLD can threaten the heart. Chronic bronchitis itself is associated with a 50% higher risk of death from coronary artery disease, even after considering the effects of smoking.
• Low oxygen levels can also impair mental functioning and short-term memory.

Chronically low blood levels of oxygen may lead to pulmonary hypertension (high blood pressure in the lungs), and possibly to cor pulmonale. Cor pulmonale is also called right-sided heart failure, and is characterized by enlargement of the right ventricle. Treatment targets the underlying illness and may include supplemental oxygen, a low-salt diet, or calcium channel blockers.

Effects of Respiratory Infections

Any disease that affects the lungs is dangerous for COLD patients. Pneumonia can cause acute attacks of chronic bronchitis. This may precipitate acute respiratory failure, which is life threatening for COLD patients. Viral or bacterial infections in the lungs, seasonal changes, certain medications, and exposure to irritants in the air may also trigger serious lung events.

Other Serious Medical Problems Associated with COLD

The smoking that causes COLD is also associated with high risks of pneumonia, lung cancer, stroke, and heart attacks.

Lung Cancer. Patients with a 30-year history of smoking, who have indications of airflow limitation (in other words, most patients with COLD), are at high risk for lung cancer. In such patients, the incidence of this cancer is 2%. Computed tomography (CT) screening is making it easier to detect this deadly cancer in earlier stages, and such patients should consider having this test.

Sleep Apnea. About half of those with severe COLD experience obstructive sleep apnea, a condition in which breathing stops and starts many times each night. This condition is more serious than previously thought. It has been associated with an elevated risk for hypertension (high blood pressure), stroke, dementia, and pulmonary hypertension.

Osteoporosis. Osteoporosis is a significant problem in patients with COLD. Many conditions associated with COLD (smoking, vitamin D deficiencies, a sedentary lifestyle, the use of corticosteroids) put people at risk for bone density loss and osteoporosis.

Risk Factors

As of 2003, 10.7 million adults were diagnosed with chronic obstructive lung disease, 2.1 million of them people with emphysema. Because emphysema and chronic bronchitis so often occur together, it is difficult to determine the number of emphysema patients versus those with chronic bronchitis. Experts estimate, however, that more than half of Americans with impaired lung function go undiagnosed. Many patients, even if their symptoms are severe, regard their condition as a natural part of aging, or blame lack of fitness, and fail to seek medical evaluation.

General Risk Factors for Chronic Obstructive Lung Disease

The typical COLD patient is a smoker or ex-smoker, with a pack-a-day habit of more than 20 years, who is over 50. Lung function gets worse as people get older.

According to a major 2002 government report, since 1987 more women than men have reported symptoms of COLD. Furthermore, the death rate from COLD has increased dramatically in women since the early 1970s. In 2000, the number of women who died from these lung diseases surpassed the number of men who died of the same causes. The lungs of female smokers, moreover, appear to be more susceptible to the effects of smoking and pollution than those of men. Studies suggest that COLD is underdiagnosed in both genders, but especially in women. Caucasians are more susceptible to emphysema than African Americans.

On the positive side, the proportion of adults under 55 who are diagnosed with mild to moderate COLD has been declining, indicating that the high death rate will level out, especially as more people stop smoking. In particular, the rate of COLD in young African Americans is declining significantly. The rate in younger Caucasians is not decreasing as dramatically.

Smoking

Over 80% of people who die from COLD are or were smokers. The longer a person smokes, the higher the risk for emphysema. Once a smoker quits, the rate of lung function loss becomes the same as in a nonsmoker; however, much of the lung damage incurred during smoking may be irreversible. About 10% to 20% of people who smoke more than one pack a day develop significant airway obstruction, so other factors must be present.

Occupational Risk Factors

Workers exposed for a long time to toxic chemicals (such as silica or cadmium), industrial smoke, dust, or other air pollutants are at increased risk for COLD. Such workers include miners, furnace workers, grain farmers, cooks, and other food producers who work in small spaces.

Allergies and Asthma

Allergens are allergy-causing particles and organisms such as fungi, molds, and house dust. Allergens can cause changes in the lungs that lead to COLD in some people. Some experts believe that a susceptibility to allergens or asthma puts smokers at higher risk for COLD.

Dietary Factors

Some evidence indicates that poor nutrition, particularly low levels or lack of certain nutrients (e.g., vitamins A, C, and E), could increase the risk for impaired lung function. Fresh fruits and vegetables, nuts, and whole grains are a good source of such nutrients.

Low Birth Weight

Low birth weight is associated with increased risk for COLD in later life, perhaps because poor nutrition during a fetus's development may lead to smaller, ill-functioning lungs.

Periodontal Disease

In a 2001 study, patients with periodontal (gum) disease had one and a half times the risk for COLD as those without gum disease. Experts speculate that the bacteria causing periodontal disease could theoretically travel through saliva or breath into the lungs. The bacteria in periodontal disease also cause inflammation, which may also affect the linings of the airway.

Diagnostic Tests

In spite of the widespread incidence and seriousness of chronic obstructive lung disease, studies strongly suggest that it is underdiagnosed, especially in women. Some experts recommend that any adult smoker who complains of a daily cough should be screened for COLD. In one 2002 study, nearly half of patients over 60 who regularly smoked had COLD.

Medical and Personal History

The doctor will request a history that evaluates the patient's risk factors. Risk factors include past and present smoking, low exercise capacity (e.g., whether the patient has trouble climbing stairs, the distance he or she can walk), and exposure to any industrial pollutants.

Physical Examination

Appearance. The appearance of the patients may be a clue to the condition. Bluish skin tone and swelling in the legs suggest chronic bronchitis. Healthy skin tone, but having an inflated chest, suggests emphysema.

The patient will also be asked to cough and produce sputum, if possible.

Chest Examination. The physician will next perform a simple examination of the chest area. Using a stethoscope, the physician will listen to the patient's breathing:

• Diminished or distant breath sounds are signs of emphysema. Tapping the chest will usually produce a hollow, drum-like sound.
• In chronic bronchitis, the physician is likely to hear wheezing or gurgling sounds.

Pulmonary Function Tests (Spirometry)

The best tests for determining the presence of COLD, and managing its response to treatment, are pulmonary function tests. The most common test is spirometry. Spirometry measures the volume and force of air as it is exhaled from the lungs. The patient is asked to breathe in and to exhale forcefully into an instrument several times. The force of the air is then monitored and measured.

Using the results, the physician determines two important values:

• The forced vital capacity (FVC). FVC is the maximum volume of air that can be exhaled (breathed out) with force, and is an indicator of lung size, elasticity, and how well the air passages open and close.
• The forced expiratory volume in one second (FEV1). FEV1 is the maximum volume of air exhaled in 1 second. Airflow is considered to be limited if the outflow of forced exhalation stays low over the course of one second. Steady but faster than normal decline in FEV1 over time characterizes COLD.
• Calculating a ratio of FEV1 to FVC is the best method for determining the presence and severity of COLD.

Severe COLD is an FEV1/FVC ratio of 34 - 49%, whereas very severe COLD is an FEV1/FVC ratio of less than 34%.

Spirometry is a painless study of air volume and flow rate within the lungs. Spirometry is frequently used to evaluate lung function in people with obstructive or restrictive lung diseases such as asthma or cystic fibrosis.

Tests for Measuring the Ability of the Lung to Exchange Gases

Arterial Blood Gas. The physician may request an arterial blood gas test to determine the amount of oxygen and carbon dioxide in the blood (its saturation). Low oxygen (hypoxia) and high carbon dioxide (hypercapnia) levels are often indicative of chronic bronchitis, but not always of emphysema. A blood gas analysis that shows very low oxygen levels is useful for determining which patients would benefit from oxygen therapy (see below). This procedure typically involves drawing blood from an artery in the wrist, which can be painful.

Click the icon to see a depiction of arterial blood gas sampling.

Pulse Oximetry Test. A safe and painless test for measuring oxygen in the blood is called a pulse oximetry, which involves placing a probe on the finger or ear lobe. The probe emits two different lights, and the amount of each light the blood absorbs is related to how much oxygen the red blood cells carry. This test measures only oxygen in the blood, however, and not carbon dioxide. Results should be taken together with other tests to determine the need for medication or oxygen therapy.

Carbon Monoxide Diffusing Capacity. The lung carbon monoxide diffusing capacity (DLCO) test determines how effectively gases are exchanged between the blood and airways in the lungs. Patients should not eat or exercise before the test, and they should not have smoked for 24 hours. The patient inhales a mixture of carbon monoxide, helium, and oxygen and holds his or her breath for about 10 seconds. The gas levels are then analyzed from the exhaled breath. Results can help physicians differentiate emphysema from chronic bronchitis and asthma. Patients with emphysema have lower DLCO results, indicated by a reduced ability to take up oxygen. Such results are also important in helping to determine appropriate candidates for lung reduction surgery. Carbon monoxide levels that are 20% or less than predicted values pose a very high risk for poor survival.

Click the icon to see an image of lung diffusion testing.

Imaging Tests

Chest X-Rays. Chest x-rays are often performed, but they are not very useful for detecting early COLD. By the time an x-ray reveals the disease, the patient is well aware of the condition.

Clear signs of emphysema include the following:

• A flattened diaphragm
• Exaggerated lung inflation in upper areas
• Abnormally large amounts of air spaces in the lung
• A smaller heart; if heart failure is present, however, the heart size becomes normal and signs of overinflated lungs are not present.
• A1AD-related emphysema patients show larger amounts of air in the lower lungs

Chest x-rays are rarely useful for diagnosing chronic bronchitis, although they sometimes show mild scarring and thickened airway walls.

Computed Tomography. Computed tomography (CT) scans can accurately assess the severity of COLD and may be used to determine the size of the air pockets (bullae) in the lungs. This imaging technique may even be useful for assessing mild COLD.

Other Tests for Chronic Obstructive Lung Disease

Noninvasive Methods for Determining Severity. Questionnaires and short exercise tests are very useful for determining the severity of COLD.

Test for ATT. Physicians will typically test for the protective enzyme, alpha 1-antiprotease (ATT or antitrypsin), which is often deficient in COLD patients (although asthma patients may also have low levels).

Additional Blood and Sputum Tests. Additional tests may be required if the physician suspects other medical problems. If pneumonia is present, for instance, blood and sputum tests and cultures may be performed to determine the cause of infection.

Medications

Anticholinergic Agents

Anticholinergic agents relax the bronchial muscles. They are generally inhaled and act as a bronchodilator over time.

Brands and Benefits. Anticholinergics used for COLD include ipratropium (Atrovent) and tiotropium (Spiriva). Ipratropium is the older agent, and experts recommend it as the first choice in treating COLD. It has a very slow onset and can be used as maintenance therapy for people with emphysema and chronic bronchitis. Anticholinergic agents have few severe side effects. They are less likely to impair sleep than the other standard inhaled medications.

A patient should not take more than 12 inhalations per day. Tiotropium (Spiriva) requires only one daily inhalation, and evidence suggests it may be particularly effective for COLD patients. A single inhaler containing both ipratropium and the common beta2-agonist albuterol (Combivent) may prove to be better than either medicine alone. Anticholinergics target the central airways, and beta agonists target the smaller airways, thus explaining, according to current theory, the additive benefits of the combination.

Side Effects. Some common side effects of anticholinergic agents include blurred vision and urinary obstruction. Patients with allergies to soy or peanut products should not use these drugs. Those with glaucoma should be very careful to prevent spraying the medication in the eye, as this could worsen their glaucoma.

Beta2-Agonists

Beta2-agonists are the most widely prescribed bronchodilators, most often for asthma. These drugs are generally inhaled using a metered-dose inhaler (MDI) or nebulizer. A nebulizer delivers a larger dose of the drug and is more expensive than the MDI. Experts recommend the inhaler for most patients and suggest reserving the nebulizer for patients with severe disease who are unable to use the MDI. Survival rates are similar. Beta2-agonists are also available in oral forms, although oral forms have more side effects than the inhaled beta2-agonists, and they take longer to start working. Oral beta2-agonists should be reserved only for patients who cannot use inhaled forms.

Short-Acting Beta2-agonists. Short-acting bronchodilators are the primary agents for most COLD patients. Albuterol (Proventil, Ventolin) is the standard short-acting beta2-agonist. Others include isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), bitolterol (Tornalate), and isoetharine (Bronkometer, Bronkosol), which is available in nebulizers. Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the standard agents. Most are administered through inhalation and are effective for 3 to 6 hours.

Long-Acting Beta2-Agonists. Long-acting forms, salmeterol (Serevent) or formoterol (Foradil), are proving to be particularly effective for COLD. Major analyses suggest they reduce exacerbations by 20% to 25%. They may help inhibit bacteria from building up on the airways and may offer real improvements in lung function. Unlike short-acting forms, these beta2-agonists may even have anti-inflammatory properties.

Inhalers that combine a long-acting beta2-agonist and a corticosteroid (Advair, Seretide, Symbicort) are even more effective than either agent -- reducing exacerbations by 30%. A new study found that Advair significantly cuts inflammation of the bronchi in smokers and ex-smokers with COLD. This drug combination also improved lung function.

Side Effects. Side effects of both long-and short-acting beta2-agonists include anxiety, tremor, restlessness, and headaches. Patients may experience fast and irregular heartbeats. A physician should be notified immediately if such side effects occur, particularly in people with existing heart conditions. Such patients face an increased risk for sudden death from cardiac related causes. This risk is higher with oral or nebulized agents, but there have also been reports of heart attacks and angina in some patients using inhaled beta2-agonists.

Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists become less effective when taken regularly over time, increasing the risk for overuse. The degree to which this affects the airways is uncertain. In some studies, the duration of action has declined, but the peak effect appears to be preserved, making these drugs still useful for acute attacks. Regular use of long-acting beta2-agonists may reduce the effect of short-acting forms.

It's a major concern that patients who perceive beta2-agonists as being less effective may over-use them. Overdose can be serious and in rare cases even life-threatening, particularly in patients with heart disease.

Theophylline and Other Methylxanthines

Methylxanthines a number of actions in the lungs that should help COLD patients. They include opening airways, improving exchange of gases, reducing shortness of breath, improving mucus clearance, and stimulating the process of breathing. These agents are recommended by expert groups for patients with severe exacerbations or incomplete responses to bronchodilators.

Unfortunately, a major 2003 analysis indicated these agents do not produce any significant improvement in lung functions, symptoms, or overall outcomes after treatment for acute exacerbations. Some experts, then, believe that these modest benefits do not outweigh the risk for the toxic effects commonly associated with these agents.

Nausea and vomiting occur in a third of patients, and can be serious side effects in COLD patients. Headache and insomnia are common. Cardiac arrhythmias and convulsions are possible. A physician should be contacted immediately if any of these side effects occur. Certain conditions (e.g., liver disease) and medications increase the risk for toxicity. Such medications include some antibiotics, calcium channels blockers, and H2 blockers such as famotidine (Pepcid AC), cimetidine (Tagamet HB), or ranitidine (Zantac 75).

Theophylline. Theophylline (Theodur, Slo-bid, Uniphyl, Theo-24) is the standard methylxanthine and is available in oral and rectal forms. The oral form is preferred. Absorption is inconsistent using the rectal form, therefore posing a higher risk for overdose. Chronic smokers metabolize theophylline much more quickly and require higher doses of the drug than nonsmokers. Prolonged-release versions are helpful for such people. If theophylline is taken as prescribed, no major problems should arise. If theophylline is not taken exactly as prescribed, an overdose and toxicity can easily occur.

Doxofylline. Doxofylline is a unique xanthine that may prove to be an effective bronchodilator without the adverse effects on the heart that theophylline and beta2-agonists have. More research is needed.

Corticosteroids

Corticosteroids, commonly called steroids, are powerful anti-inflammatory drugs.

Oral Corticosteroids. Oral corticosteroids are used to treat acute exacerbations of COLD. A major study also indicated patients who take them for 10 days after an exacerbation (along with antibiotics and bronchodilators) significantly reduce their risk for a relapse.

They are also often prescribed for patients with stable COLD in order to prevent acute exacerbations and reduce symptoms. It is not clear, however, if these benefits outweigh the potential side effects of steroids. In one analysis, patients given steroids were only 10% more likely to improve than those on placebo. Patients should be monitored regularly and should take the lowest dose possible for improvement.

Common oral corticosteroids include prednisone, prednisolone, methylprednisolone, and hydrocortisone. Adverse effects of long-term use can be very serious. They include cataracts, glaucoma, osteoporosis, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and psychosis.

Long-term use of steroid medications also suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists. It can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. Uncommonly, switching from oral to inhaled steroids has caused severe adrenal insufficiency and, in rare cases, has resulted in death. The risk increases during times of stress. Patients should discuss with their physician measures for preventing adrenal insufficiency, particularly during stressful times. No one should stop taking any steroids without consulting a physician first, and if steroids are withdrawn, regular follow-up monitoring is necessary.

Inhaled Corticosteroids. Inhaled corticosteroids are often used for treating chronic COLD. The most recent generation of inhaled steroids include (in order of potency) fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer agents, possibly with the exception of flunisolide, are more powerful than the older generation agents when used with standard inhalers.

The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhaler systems, such as QVAR, however, may prove to be as effective as the newer, more potent steroids. QVAR uses extra fine formulations of beclomethasone to allow deep delivery into the lungs.

The widespread use of inhaled corticosteroids for COLD patients is under debate, particularly since other agents are equally -- or more -- effective. Studies are mixed on whether long-term use improves lung function. They also can have some significant adverse effects over time, particularly in reducing bone density, which weakens bones. Combination inhalers that contain both a corticosteroid and a long-acting beta2-agonist may prove to be a good option.

Common side effects of inhaled steroids are throat irritation, hoarseness, and dry mouth. Other possible but less common adverse effects include rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising.

Inhaled steroids are generally considered safe and effective. They rarely cause any of the more serious side effects reported with prolonged use of oral steroids. There are some risks with long-term use, however. A 2001 study reported a higher risk for cataracts in patients over age 40. Others are reporting a higher risk for bone loss in patients who take inhaled steroids regularly. Several bone-preserving medications are now available that might safely offset this effect. There is also some concern that the more potent agents, particularly fluticasone, may suppress the adrenal system (which secretes natural steroids) to a greater degree than other steroid inhalants. This is a serious side effect of oral steroids.

Antibiotics

Treating Acute Bronchitis or Pneumonia in COLD Patients. People with COLD are at heightened risk for pneumonia, but any lung infection can worsen symptoms and is dangerous in COLD patients. Aggressive therapy using powerful antibiotics is usually called for when acute bronchitis or pneumonia occurs. The most common organisms causing pneumonia in people with chronic obstructive lung disease include Streptococcus pneumoniae, Chlamydia pneumoniae, Haemophilus influenzae, and Legionella pneumophila. Of some concern is the increase in infection rates by more unusual and difficult-to-treat organisms known as gram-negative bacteria.

The primary choice of medicine still includes the less expensive antibiotics, such as amoxicillin/clavulanate, doxycycline, and trimethoprim-sulfamethoxazole. Antibiotic classes known as macrolides and quinolones appear to be beneficial as well. Detecting the specific organism causing the lung infection is often difficult. [For more information, see In-DepthReport #64: Pneumonia.]

Preventive (Prophylactic) Antibiotics in COLD Patients. In the past, antibiotics were given daily for patients with even mild COLD until studies found that they did not alter progression of either the disorder or the disabilities associated with it. Preventive antibiotics may be given for 1 week per month, alternating the medications that are used. They are now prescribed only for COLD patients with one or more of the following conditions:

• Four or more episodes a year of acute infection with intensified COLD symptoms, including worsened shortness of breath and mucus production
• Deficient immune systems
• Bronchiectasis, an irreversible lung disease in which the airways in the lung are always dilated

Treatment for AAT Deficiency

Replacement Treatment. Augmentation or replacement therapy supplements the existing alpha 1-antitrypsin (AAT) levels in the blood. The replacement AAT is derived from human blood, which has been screened for viruses and is injected weekly or bimonthly. One study reported that patients taking this supplement had a mortality rate that was two thirds of those not on this therapy. Replacement therapy may also reduce the severity and frequency of lung infections. Therapy is life-long. Patients with inherited AAT deficiency, regardless of their smoking history, are eligible for this therapy. Unfortunately, this therapy is in short supply.

An inhaled AAT replacement treatment produced from the milk of genetically bred sheep is under investigation. An oral form is also under investigation.

Other Investigative Treatments for AAT Deficiency. Aerosolized hyaluronic acid may protect lungs from injury by elastase. Elastase is the enzyme that causes lung tissue to lose elasticity. A clinical trial is underway.

Medicines That Loosen Lung Secretions

Patients with persistent coughing and sputum often use agents that loosen secretions and help move them out of the lungs. However, it is not clear if these agents offer any important benefits.

Expectorants. Expectorants, such as guaifenesin (found in common cough remedies), stimulate the flow of fluid in the airways and help move secretions using cilia motion (the hair-like structures in the lung) and coughing.

Mucolytics. Mucolytics contain ingredients that make sputum more watery and easier to cough up. One of these ingredients, acetylcysteine, also acts as an antioxidant, which could provide additional benefit to people with COLD. Although there is some controversy over their value, an analysis of many studies indicated that oral mucolytics reduce the number of symptoms in patients with severe chronic bronchitis, and have a small but significant effect on breathing function. They should not be used, however, during an acute attack, since they may worsen lung function. They also do not appear to be very helpful for patients with mild COLD.

Experimental Therapies

Selective Phosphodiesterase 4 Inhibitors. Cilomilast (Ariflo) and roflumilast (Daxas) are selective phosphodiesterase 4 (PDE4) inhibitors. They block PDE4, an enzyme that is overproduced in COLD and asthma and causes inflammation in the airways. Studies are very promising. A 2003 report on reflumilast, for example, found significant improvement in lung function and quality of life compared to placebo. The drugs can cause diarrhea and nausea, which may limit their tolerability.

Leukotriene-Antagonists. Leukotriene-antagonists (also called anti-leukotrienes) are oral medications that block leukotrienes. These are powerful chemicals in the immune system that, in excess, produce inflammation and spasms in the airways. Agents include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). They are currently used for preventing asthma attacks. Studies indicate that they also have benefits for people with COLD, although it is not clear if they have advantages over standard COLD agents.

Retinoic Acid. All-trans retinoic acid (ATRA), a derivative of vitamin A, may reverse some of the damage that occurs in emphysema. One such agent is being developed; researchers hope it will grow new air sacs in the lungs.

Sildenafil. In 2005, the FDA approved sildenafil citrate (the active ingredient in Viagra) to treat pulmonary hypertension, a serious complication of chronic obstructive lung disease (COLD).

Testosterone Replacement. People with COLD tend to have low levels of testosterone. Researchers are investigating testosterone replacement in both men and women with COLD for increasing muscle strength and function.

P2Y(2) Receptor Agonists. P2Y(2) receptor agonists are experimental agents that increase the action of the cilia (hair-like structures) in the lung and clear out mucus. The most promising agent to date is currently referred to as INS37217.

Other Investigative Agents. A number of agents are in very early stages of investigation. They include drugs called antiproteases (e.g., sivelestat ONO-6818. batimastat), new antioxidants, and many others.

Treatment

Stopping Smoking and Healthy Lifestyle. Stopping smoking is the first and primary step to treating COLD and slowing its progression. In addition, all patients should maintain a healthy diet rich in fruits and vegetables. An exercise program may be useful, particularly if it is tailored to improve lung function.

Pulmonary Rehabilitation Programs. Patients with COLD need to be very active in managing their condition. Patients might check with their physicians to determine whether a pulmonary rehabilitation program would be appropriate, if one were available in their area. Such programs are conducted by a team of health professionals to improve lung function. It involves medical treatments, exercise, breathing retraining, and psychological interventions, when needed. If available and affordable, it can be extremely effective, particularly after acute exacerbations. The benefits of pulmonary rehabilitation include improvements in symptoms, exercise capacity, quality of life, and mood. Patients with severe COPD may benefit from programs that last at least 6 months.

Medications for Managing Chronic COLD. A major goal with the use of medications for COLD is to prevent acute exacerbations, which can hasten deterioration of lung function. The main treatment strategy employs a stepped approach with the use of increasingly stronger medications depending on the patient's response:

• Beta2-agonists and anticholinergics, classes of drugs known as bronchodilators, open the airways in the lungs and are the cornerstone of COLD drug therapy. In a major analysis, long-acting beta2-agonists and anticholinergics were most effective and reduced exacerbation rates by 20% to 25%.
• Inhaled corticosteroids also reduce exacerbations by up to 25%. Studies are mixed on whether long-term use improves lung function, and these agents may also have some adverse effects with long-term use. Inhalers that combine a long-acting beta2-agonists and a corticosteroid (Advair, Seretide, Symbicort) are even more effective than either agent alone -- reducing exacerbations by 30%. Some studies suggest they may offer significant improvements in lung function and even improve survival rates, but more research is needed to confirm such findings.
• Antibiotics are sometimes used preventively, but they seem to have only a small effect in reducing illness days. Experts do not recommend them routinely.

An inhaler is a quick way of administering medicine directly into the bronchial passageways to promote clearer breathing.

Oxygen Replacement. Oxygen replacement is an important component in most COLD treatments. It is the only treatment known to improve survival in COLD patients. The patient is assessed for specific timing and needs.

Surgery. If the patient no longer responds to medications, then surgery may be an option for some patients. Choices may include bullectomy, lung reduction, or lung transplantation.

General Guidelines for Treating Acute Exacerbations

Doctors recommend the following treatments for patients who need to be hospitalized:

• Supplemental oxygen, either mechanical or through noninvasive positive pressure ventilation, should be given.
• Bronchodilators; an inhaled or nebulized (see Administering Inhaled Drugs, below) beta2-agonist, with an anticholinergic agent added if the patient does not respond. Theophylline is not recommended, because it provides very little benefit, and carries a risk of serious side effects.
• Antibiotics if there are signs of infections, particularly if the acute exacerbation is very severe. Courses are usually 5 to 10 days.
• Corticosteroids are usually given for up to 2 weeks (oral corticosteroids in most cases, intravenous in severe cases). An important 2003 study indicated that relapse rates were significantly reduced when the patient also took oral corticosteroids in combination with antibiotics and bronchodilators for 10 days after the episode.
• Chest therapy may be helpful in some patients.

It is not always clear what triggers acute exacerbation episodes, so treatment can be controversial. Bacteria are obvious suspects, but because COLD patients commonly harbor bacteria, it has been difficult to determine which or even whether organisms are responsible. One 2002 study suggested that some episodes may be caused by changes in the strains of bacteria that are commonly present rather than an introduction of a new bacteria. In other cases, viruses and atypical bacteria may be responsible. In some acute exacerbations, however, no sign of infection is present. As with asthma, an inflammatory response in the airways unrelated to infection may suddenly cause changes that bring on an attack (although it is likely to be different from this response in asthma patients). In any case, even minor obstruction in the airways may be able to produce an acute exacerbation.

Treating Complications of Advanced COLD

COLD is associated with a number of complications as lung function worsens. Various treatments may be required.

Opioids. Opioids, such as morphine, are generally not used for patients with COLD because of a concern that they may reduce respiratory function. Nonetheless, some studies are reporting that low doses of oral morphine can improve severe breathlessness in patients who cannot find relief from other methods. Such agents can cause nausea, vomiting, and constipation.

Antidepressants and Antianxiety Agents. Antidepressants or antianxiety medications may be helpful in reducing anxiety that complicates symptoms.

Improving Sleep. More than half of patients with COLD often suffer from insomnia. Most of the standard sleep agents may impair lung function. Newer ones, such as zolpidem (Ambien), zaleplon (Sonata), and zopiclone (Imovane), may be less hazardous than older agents. Tricyclic antidepressants may also be helpful without significant effects on breathing. Behavioral methods are the best approach to this problem, however. [See In-Depth Report# 27: Insomnia.]

Treating Heart Failure. When patients are in advanced stages of COLD, they may need treatment for fluid accumulation and congestive heart failure. [See In-Depth Report #13: Congestive heart failure.]

Oxygen-Replacement Therapy

Eventually, lung function may worsen to the point that patients may need to rely on supplemental oxygen provided through portable or stationary tanks.

Continuous Therapy. Continuous oxygen therapy (more than 15 hours a day) is the only treatment for emphysema that has been proven to prolong survival in certain patients. It also improves alertness, motor speed, and hand strength. Usually continuous oxygen therapy is recommended for patients under the following circumstances:

• Lung oxygen level is below 55 mm/Hg while the patient is resting.
• Resting oxygen level is less than 60 mm/Hg, and the patient has right heart failure or an abnormal increase in red blood cells.

The patient should receive enough oxygen to keep the oxygen level at 65 mm/Hg ideally, but at no less than 60 mm/Hg, or at an oxygen saturation level of at least 90%. Additional oxygen flow may be needed during sleep or exertion (physical activity).

About 40% of patients improve enough in 1 month to stop continuous treatment, although such patients should be observed closely. COLD frequently deteriorates, requiring reinstitution of oxygen therapy. Some patients worsen in spite of treatment, although at this point it is not possible to predict who is at risk for oxygen therapy failure. The addition of nitric oxide, a gas that dilates blood vessels, may offer additional benefits.

Intermittent Oxygen. Patients with less severe COLD who are not on permanent oxygen maintenance may need supplemental oxygen during specific circumstances:

• Patients whose oxygen level drops below 55 mm/Hg only while exercising may benefit from supplemental oxygen during physical activity. Supplemental oxygen does not necessarily improve exercise performance, but it does enhance delivery of oxygen to the muscles while they are working.
• Oxygen may be needed at night for patients whose oxygen level drops below 55 mm/Hg during sleep. Such patients usually experience fitful, poor-quality sleep. This type of oxygen therapy does not appear to affect survival or to delay prescription of continuous oxygen therapy.

Oxygen During Travel. People on continuous oxygen therapy who are traveling by plane should increase their oxygen by one to two liters per minute during the trip. Supplemental oxygen may be required during air travel for those with COLD who are on intermittent oxygen therapy. This happens if the trip is longer than 2 hours and they develop symptoms, or if they experience a drop in oxygen levels before travel. People are not allowed to bring their own tanks on board an airplane; many airlines (unfortunately, not all) will provide oxygen if notified between 48 and 72 hours in advance. A 1999 study reported that costs for in-flight oxygen ranged from $64 to $1,500. It should be noted, however, that aircraft cabins are actually pressurized to the equivalent of 8,000 feet above sea level. (Most people believe they are pressurized to sea level.) Such pressures could be potentially dangerous for people with severe COLD.

Oxygen Storage and Delivery Systems

Unless they are bed bound, patients usually use a combination of stationary and mobile oxygen systems.

Stationary Systems. The most common stationary oxygen system is the concentrator, an electrical device that extracts oxygen from the air. It weighs about 35 pounds and cannot be battery operated, so a patient can use it only at home.

Portable Units. Portable units containing electronic oxygen-conserving devices weigh only a few pounds and can provide up to 8 hours of oxygen. As examples, some portable units weigh 6.5 lb with liquid oxygen supplies lasting 4 hours. Some weigh 9.5 lb with oxygen supply lasting 8 hours, when used at a flow rate of two liters per minute.

Compressed or Liquid Oxygen. Oxygen can be administered in large stationary tanks or small portable ones, either as compressed gas or liquid oxygen. A container of liquid oxygen lasts four times longer than compressed gas of the same weight and is easier to fill. Liquid oxygen is very beneficial for patients who want to maintain an active life, although the tanks require occasional venting to release pressure, thereby wasting oxygen. They are also more expensive. For example, in some areas a stationary liquid oxygen system costs $3,500 compared to a compressed oxygen tank at $350.

Precautions. Supplemental oxygen is a fire hazard, and some hotels and residences do not allow its use. No one should smoke near an oxygen tank, and tanks should be stored safely, secured to a wall and away from heaters and furnaces.

Devices for Administering Oxygen

Oxygen is usually administered in one of three ways: using a nasal canula, a transtracheal catheter, or an electronic demand device.

Nasal Canula. Using a nasal canula, oxygen is delivered through a long, slender plastic tube that runs from the oxygen tank to small plastic prongs that fit in the nostrils. The tube can be very long when attached to a stationary tank in order to accommodate walking throughout a house, or relatively short when attached to a portable unit.

A reservoir pouch is a recent innovation added to this device that provides an extra rush of oxygen as a patient starts to inhale. This method is inexpensive and easy to use, but some patients are embarrassed by its appearance under their noses.

Transtracheal Oxygen. Transtracheal oxygen is delivered directly into the windpipe (trachea) through a catheter tube implanted by a surgeon. The device is inconspicuous, and compliance is excellent. The initial cost is high, but over time expenses are reduced because of more efficient oxygen usage. Long-term complications may include infection, dislodgment, and blockage by mucus, which can be very serious. Complications of the procedure itself occur in 3% to 5% of cases and include lung spasms and uncontrollable coughing.

Electronic Demand Devices. Electronic devices that sense the beginning of a breath and deliver a pulse of oxygen are also available, although they are complicated, expensive, and have a risk for mechanical failure. Newer units have a continuous flow bypass switch that allows delivery of oxygen if the battery has run down.

Continuous Positive Airflow Pressure (CPAP)

Continuous positive airflow pressure (CPAP) supplies a steady stream of air through a tube that connects to a small bedside machine. The patient wears a plastic mask, and the machine applies sufficient air pressure to prevent the tissues from collapsing during sleep. It is not an oxygen-delivery system, but is intended to improve airflow into the lungs. The device is sometimes uncomfortable, and noncompliance rates are high. Studies are mixed on its benefits, suggesting that certain patients, but not others, may be helped by it. More studies are needed. [For detailed information on this device, see In-DepthReport #65: Sleep Apnea.]

Oxygen Delivery in Emergency Situations

In emergency situations, oxygen may be delivered to the patient in various ways:

Intubation. When standard oxygen therapy does not meet the needs of the patient, endotracheal intubation may be required to deliver high concentrations of oxygen. With intubation, a tube is inserted down through either the nose or the mouth through which oxygen is administered.

Noninvasive Positive Pressure Ventilation (NPPV). If the patient is able to breathe naturally, oxygen is delivered through a tube using a tightly fitted oxygen mask to maintain airway pressure during breathing. Experts now believe such devices should be first-line treatments (in addition to medications) for managing respiratory failure after an acute exacerbation. They allow the patient to communicate and drink fluids and are much better tolerated than nose or throat tubes. They cannot be used on patients with rapidly deteriorating disease, who are uncooperative, or who have facial structures that do not allow the mask to make a tight seal.

Mechanical Ventilation. In very serious cases, such as acute respiratory failure, a mechanical ventilator takes over the function of breathing. The primary goal of ventilation is to eliminate carbon dioxide and restore a balanced exchange of gases with oxygen administration.

A variety of mechanical ventilators are currently in use. A 1999 study reported that mechanical ventilators that use small breaths of air reduced mortality rates by 25% compared to those that required larger breaths.

Unfortunately, most patients have a low tolerance for intubation, and the tubes are often removed prematurely because of discomfort. Painkillers, sedatives, or even muscle relaxants may be needed.

There are also several complications that cause removal of breathing tubes:

• Ejection of the tube after coughing
• Mucus plugging
• Bleeding

Removing ventilation tubes too early produces adverse events in nearly all such patients. A study found that patients may be able to go off the ventilator more quickly and safely if they are screened daily and encouraged to breathe spontaneously as soon as possible.

Lifestyle Changes

Quitting Smoking and Avoiding Other Irritants

Quitting smoking is the first and most essential step in treating chronic obstructive lung disease and slowing its progress. In many people who quit, lung function stabilizes and eventually declines at about the rate of nonsmokers in the same age group. In some people, lung function may even improve slightly after quitting. A number of effective aids, including nicotine replacement devices and antidepressants, such as bupropion (Zyban), are available to help people quit.

Preventing Upper Respiratory Infections

Good Hygiene. Everyone should wash his or her hands before eating and after going outside. Ordinary soap is sufficient. Antibacterial soaps add little protection, particularly against viruses. One study suggests that common liquid dish washing soaps are up to 100 times more effective than antibacterial soaps in killing respiratory syncytial virus (RSV), which is known to cause pneumonia.

Vaccines. Two important vaccinations help protect against respiratory infection.

• Influenza vaccination. People with emphysema should be vaccinated against influenza each year at least 6 weeks before flu season. Severely ill patients may experience mild initial adverse side effects. In general, however, the vaccination is very safe and appears to help reduce the severity of COPD during flu season.
• Pneumococcal vaccine. The pneumococcal vaccine protects against the major bacterium that causes pneumonia. The vaccine remains effective for years. Flu and pneumococcal vaccines can be administered at the same time without increasing any adverse effects.

[For more information, see In-DepthReport #94: Colds and Flus.]

Breathing Exercises

Pursed-Lip Breathing. A technique called pursed-lip breathing can help improve lung function before starting activities. It takes about 10 minutes. When first learning the technique, the patient should lie flat on a bed with his or her head on a pillow. Later, the technique can be performed while walking or enduring any activity requiring extra air.

• First, the patient inhales through the nose, moving the abdominal muscles outward so that the diaphragm lowers and the lungs fill with air.
• The patient then exhales through the mouth with the lips pursed, making a hissing sound.
• The exhalation should be twice as long as the inhalation, so that pressure is experienced in the windpipe, and chest and trapped air is forced out.

Breath Holding and Coughing. A simple technique is to inhale deeply and slowly, holding the breath for five to 10 seconds. Then the patient coughs on exhalation.

Controlling Secretions

Fluids and Humidity. Patients who experience congestion and heavy sputum can benefit from maintaining good fluid intake and keeping their homes humidified.

Expectorants. Although unproven, many patients report benefits from using over-the-counter expectorant drugs that thin mucus. These drugs should not be used during an acute exacerbation of COLD, however.

Chest Therapy. Chest therapy involves rhythmic inhalation for three or four deep breaths followed by coughing to produce sputum. Tapping the chest may also help in loosening and raising sputum. This should be avoided during an acute exacerbation of COLD.

Postural Drainage. The patients should also practice postural drainage. This involves leaning over the side of the bed, head down with elbows on a pillow placed on the floor. A family member or caregiver thumps gently on the back while the patient coughs.

Mucus-Producing Coughs. When coughing to produce mucus, one effective method is to lean forward and "huff" repeatedly, take relaxed breaths, and huff again. If possible, forceful coughing should be avoided.

Devices for Improving Lung Function

Flutter Valve. The flutter valve is a small hand-held device that looks like a pipe. It contains a steel ball that sits in a small plastic cone. The patient inhales deeply, holding the breath for two to three seconds. As the patient exhales (keeping the cheeks in), the ball is pushed up toward the top of the device and then falls back down. About 10 to 50 vibrations per second are generated and transmitted to the lungs to help loosen secretions. This is repeated for up to 15 breath cycles. The patient coughs at the end.

Chest Compression Devices. Devices are available that allow the patient to be passive and still expel air. One called the Vest (formerly the ThAIRapy Vest) consists of an inflatable vest attached by hoses to a generator that triggers pulses of air into the vest. The rapid pressure and release of the air around the chest acts like tiny hugs to create small coughs. It is very expensive (about $16,000), but may be covered by insurance for specific patients.

Neuromuscular Electrical Stimulation (NMES). An investigative device uses electrical pulses to stimulate muscles in the legs. In an early study, patients were treated for 16 minutes per leg during the first week and 30 minutes per leg thereafter for a total of 30 sessions. At the end of 6 weeks, endurance capacity increased significantly, and patients reported less muscle fatigue and shortness of breath.

Physical Exercise

Certain physical exercise may be very helpful.

Strengthening Exercises for the Limbs. Exercising and strengthening the limb muscles helps some patients improve their endurance and reduce breathlessness.

Walking. In studies of lung rehabilitation, regular exercise increases walking distance and improves breathing. Walking is the best exercise for people with emphysema. Patients should try to walk three to four times daily for five to 15 minutes each time. Devices that assist ventilation may reduce breathlessness that occurs during exercise.

Yoga and Eastern Practices. Yoga or tai chi practices, which use deep breathing and medication techniques, may be particularly beneficial for COPD patients. A clinical trial is underway to determine if yoga is helpful for COPD patients.

Click the icon to see an image depicting yoga practice.

Breath Training

Inspiratory Muscle Training and Incentive Spirometer. Inspiratory muscle training involves exercises and devices that make inhaling more difficult in order to strengthen breathing muscles. In a 2001 study, patients who took part in a training group improved their breathing, walking capacity, and quality of life. The use of an incentive spirometer for 15 minutes twice a day may also be helpful as part of a training program. It also helps loosen sputum. This is a small hand-held device that contains a breathing gauge. The patient exhales and then inhales forcefully through the tube, using the pressure of the inhalation to raise the gauge to the highest level possible. A device called a peak inspiratory flow (PIF) meter measures the patient's ability to draw air into the lungs and assesses the fitness of the breathing muscles.

Dietary Factors

Protein and Fats. Many COLD patients are deficient in protein. Although most healthy diets emphasize proteins from fish, poultry, and lean meat, people with COLD may benefit from foods with a higher fat content than average. (People should still prefer healthy fats, however, such as those found in olive oil and oily fish.) Some evidence suggests that high-carbohydrate meals may reduce exercise capacity.

Fruits, Vegetables, and Whole Grains. Healthy foods are as important for lung function as they are for health in general. Specific foods that may be important for healthy lungs are those that contain antioxidants (best obtained from fresh, deep green and yellow-orange fruits and vegetables), selenium (fish, red meat, grains, eggs, chicken, liver, garlic), plant chemicals called flavonoids (apples, onions), and magnesium (green leafy vegetables, nuts, whole grains, milk, and meats).

Fish Oil. Omega-3 fatty acids, found in cold-water oily fish and in supplements (preferably DHA-EPA, the important compounds in fish oil), have anti-inflammatory effects. A new study showed a significant benefit for COPD patients who received omega-3 fatty acid supplements. Inflammatory chemicals in the sputum decreased in this group, and oxygen saturation and breathing during exertion improved.

Alcohol and Red Wine. Some evidence suggests that resveratrol (a chemical found in red wine, grapes, and olive oil) may have various health benefits, including possible protection of the lungs. In people who are not at risk for abuse, moderate intake of wine may be healthful, although no evidence suggests that wine itself improves lung function, and high amounts can impair the immune system. Women who are pregnant or at high risk for breast cancer, people who can't drink moderately, and people with liver disease should avoid alcohol.

Dietary Supplements. Some studies report benefits for COLD patients who took supplements of N-acetyl-cysteine, a powerful antioxidant that is a form of cysteine-a common amino acid in the body. Other antioxidants being studied include L-carnitine and coenzyme Q10. Evidence of benefit is weak, however, for all these chemicals.

No vitamin or mineral supplements have been shown to improve lung function. The trace elements zinc and selenium may have some effect in reducing the severity of upper respiratory tract infections, but they should be obtained in food. One study found protection from diets rich in vitamin C, but other specific antioxidants, including vitamins E, A, and beta carotene, had no effect. Furthermore, evidence suggests that high doses of antioxidant vitamin supplements can be harmful. A surprising study in 2002 reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Beta carotene supplements, in any case, are not recommended for smokers, because studies suggest an increased risk of lung cancer in this group.

Psychological Support

Patients with COLD have a high risk for depression and anxiety, which can impair outlook. Psychological and social supports are important for improving emotional states, for coping with daily stresses, and for maintaining independence and social relationships. Patients who have emotional difficulties should consider group support or individual counseling.

Minimizing Airborne Contaminants

As much as possible, a patient should avoid exposure to airborne irritants, including hair sprays, aerosol products, paint sprayers, and insecticides.

To minimize the amount of contaminants in the home, the following may be helpful:

• Ventilate by keeping windows open (weather permitting), using exhaust fans for stoves and vents for furnaces, and keeping fireplace flues open.
• Make sure wood-burning stoves or fireplaces are well ventilated and meet the Environmental Protection Agency's safety standards. Burn pressed wood products labeled "exterior grade" since they contain the least amount of pollutants from resins.
• Have furnaces and chimneys inspected and cleaned periodically.
• Eliminate molds and mildews that result from household water damage.
• People who are sensitive to allergens -- such as pollen, pet dander, house dust, and mold -- should avoid exposure to them. [See In-Depth Repor t#04: Asthma in Adults.]

Surgical Procedures

Surgical procedures for emphysema are still investigative. They are all very expensive and often not covered by insurance. The great majority of patients cannot be helped by surgery, and no single procedure is ideal for those that can be helped.

Lung and Liver Transplantation

Advanced emphysema is responsible for over half of the lung transplants performed. Three-year survival rates after lung transplantation are about 60% for patients with either emphysema or AAT deficiencies. Techniques have been developed so that both lungs may be replaced in sequence. The increasingly long waiting time and the extraordinary expense are both significant problems.

Candidates. The best candidates are under 65 and have good general health aside from lung disease. A lung or liver transplantation may be the only hope for some patients with the alpha 1-antitrypsin (AAT) deficiency-related emphysema. AAT is produced in the liver, so a healthy transplanted liver may produce adequate supplies of this enzyme.

Waiting Time. Unfortunately, up to a third of patients awaiting lung transplantation die before a suitable donor is available. There were 1,042 lung transplantation operations in 2002, and as of this nearly 4,000 people are waiting for the operation. Not all lung transplant centers, even in major cities like New York, accept Medicare. Starting in 2005, the United Network for Organ Sharing (UNOS) is assigning lungs for transplants based on an allocation score, rather than time spent on the waiting list. The allocation score takes into account the length of time a patient is likely to survive before and after transplant. This policy applies to transplant candidates aged 12 or older.

Complications. Transplant patients must take drugs that suppress the immune system to prevent the body from rejecting the transplanted organ. Nevertheless, rejection is the primary cause of late complications and death. The mortality rate from the procedure itself is about 10%.

Lung Volume-Reduction Surgery

Lung volume-reduction surgeries (LVRS) remove over 30% of severely diseased lung tissue, and the remaining parts of the lung are joined together. Improvement in breathing after surgery appears to be largely due to the following factors:

• An improvement in the lung and chest wall's ability to spring back during breathing
• Improvement in function of the muscles, such as the diaphragm, involved with breathing

Prognosis. Two-year results of the largest study to date, called the National Emphysema Treatment Trial (NETT), indicate that patients who are good candidates for LVRS achieve better lung function with surgery, and have no higher risk of death, than those on medical therapy. Mortality rates within 90 days of surgery are almost 8% compared to about 1% in patients on medical therapy. However, in spite of the early spike in deaths after surgery, there are no overall differences in long-term survival rates.

When the operation is successful, patients report significant improvement in walking distance, weight, and quality of life. Many patients can engage in active daily events, such as golf or stair-climbing, without oxygen. Even in carefully selected candidates, however, about 15% of patients derive little or no benefit from the procedure, and about 4% get worse. Furthermore, even in successful cases, the improvement is most notable within the first 6 months, after which the condition progresses again. Beyond 2 years, lung function deteriorates to the same level as it was before the procedure. It is not clear yet if surgery is cost effective over time, compared to medical therapy.

Possible Candidates. For now, the procedure is used only in people who have severe emphysema and not chronic bronchitis. And it is applicable only to a minority of these patients. Appropriate candidates are those with the following characteristics:

• Under 75 years old
• Having severe obstruction (FEV1 less than 40% but higher than 20% of expected value)
• Carbon monoxide diffusing capacity of more than 20% of expected value
• Hyperinflated lungs (total lung capacity greater than 120% of the expected value)
• Appropriate candidates who have deficiency of alpha 1-antitrypsin, even if they have disease in the lower lobe, may do well

The most recent NETT results indicate that surgical patients who had emphysema in the upper lungs, and a low exercise capacity, may have better survival rates and outcome than the same patient group who is given medical therapy.

Poor Candidates for Surgery. Early results from NETT suggest that the following patients have a high risk of a poor prognosis, and are generally not good candidates for LVRS:

• Those with a very low FEV1 (less than 20% of expected value), plus
• Those with carbon monoxide diffusing capacity of less than 20% of expected value, or
• Those with even distribution of emphysema in the lungs

In the study, patients with these characteristics had a 16% mortality rate at 30 days after surgery compared to no deaths in similar patients who were treated with medications only. Such high-risk patients accounted for about 12.5% of the patient population in the study.

Patients may also be excluded if they have severe medical conditions that limit their life span; severe psychological problems; recent tobacco, drug, or alcohol dependence; chest wall deformity; corticosteroid dependence; or scarring around the membrane of the lung. Other indicators for a poor outlook include severe lung complications and isolated bullae (air pockets in diseased area of the lungs).

Specific Techniques. At this time, the preferred technique is bilateral lung volume reduction (surgery is done on both lungs). Surgeons use either an open approach, making a large cut in the chest area, or video-assisted thoracoscopy (VATS), which is less invasive and involves several small cuts. Either method is effective and has similar complication rates. Lines of staples are typically used to reduce lung volume.

The alternative technique is unilateral lung volume reduction. Unilateral means one-sided -- surgery is done on only one lung. Some centers believe this approach may cause fewer complications and slower decline in benefits, although not all evidence supports its use over the bilateral method.

Bullectomy

Another option for COLD is bullectomy, in which giant air pockets and surrounding lung tissue are removed. It is generally limited to younger patients, particularly those with alpha 1-antitrypsin deficiency.

Lots More Information

Resources

• www.lungusa.org  -- American Lung Association
• www.nhlbi.nih.gov  -- National Heart, Lung, and Blood Institute
• www.aarc.org  -- American Association for Respiratory Care
• www.njc.org  -- National Jewish Medical and Research Center
• www.alpha1.org  -- Alpha1 National Association
• www.emphysemafoundation.org  -- The National Emphysema Foundation
• www.nlhep.org  -- National Lung Health Education Program
• www.thoracic.org  -- American Thoracic Society
• www.sts.org  -- Society of Thoracic Surgeons
• www.unos.org  -- United Network for Organ Sharing
• www.copd-international.com  -- COPD International (patient support site)

References

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Review Date: 4/28/2006
Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital