Ricardo Abreu, M.D.Pulmonary and Sleep Center of the Mid-Valley

Knapp Medical Plaza. 1330 E. 6th Street, Suite 303Weslaco, TX 78596

Tel. (956) 447-5557, Fax (956) 447-5747

Chronic Obstructive Lung Disease

What Is Chronic Obstructive Lung Disease?

The Lungs

The lungs are two spongy organs surrounded by a thin, moist membrane called the pleura. They are the largest organs in our body. Each lung is composed of smooth, shiny lobes; the right lung has three lobes and the left has two. Approximately 90% of the lung is filled with air and only 10% is solid tissue. When a person inhales, the air is carried from the trachea (the windpipe) into the lungs through flexible airways called bronchi. Like the branches of a tree, bronchi divide successively into over a million smaller airways called bronchioles. The bronchioles lead to grape-like clusters of microscopic sacs called alveoli. In each lung of the adult there are about 300 million of these tiny sacs, which are composed of a thin membrane through which oxygen and carbon dioxide pass to and from capillaries. Capillaries, the smallest of our blood vessels, carry blood throughout the body. Red blood cells contain factors that fight pollutants and white blood cells are the critical infection fighters in our body. The lungs are the only organs to receive all the blood from the heart with each heartbeat.

Chronic Obstructive Lung Disease

Chronic obstructive lung disease (COLD), also known as chronic obstructive pulmonary disease (COPD), refers to a set of breathing-related symptoms: chronic cough, spitting or coughing mucus (expectoration), breathlessness upon exertion, and progressive reduction in the ability to exhale. The two major diseases in this category are emphysema and chronic bronchitis and are 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 Asthma, Comprehensive Versions. ] Because smoking is overwhelmingly the cause of both diseases, they often develop together and frequently require similar treatments and approaches.

Emphysema. In emphysema, the walls of the alveoli that join the very small airways (bronchioles) are damaged and lose elasticity. (In a rare, inherited form of emphysema known as alpha-1-antitrypsin deficiency, both the walls of the bronchioles and alveoli to which they connect, usually in the lower lungs, are diseased.) Pockets of dead air form in the injured areas, impeding the ability to exhale and so reduce normal respiratory function (the working of the lungs). Inhalation, however, is not impaired, and until the late stages of the disease, oxygen and carbon dioxide levels are normal. The process leading to emphysema is primarily due to an imbalance in chemicals that, under ordinary circumstances, protect the lungs from infection and damage. Important chemicals in this process are enzymes called proteases, particularly those known as elastase and trypsin. These enzymes are produced by the immune system to fight infection and injury. However, if they are overproduced, they actually attack normal lung cell tissues and impair the structural integrity of elastin, the material that is essential for the "springy" quality of lung tissue. Ordinarily, these enzymes are neutralized by a protective protein called alpha 1-antitrypsin

(AAT), another critical chemical. (This is sometimes referred to as alpha 1-antiprotease.) Any condition that causes an imbalance in any of these substances may trigger emphysema.

Chronic Bronchitis. Chronic bronchitis is characterized by structural changes in the airways of the lungs and enlargement of the mucous glands, which causes coughing and production of sputum. As chronic bronchitis often coincides with emphysema, it is frequently difficult for a physician to distinguish between the two.

What Causes Chronic Obstructive Lung Disease?

Smoking

Cigarette smoke is the cause of 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. Emphysema most often develops when the damage caused by smoke incites the body's immune system to overproduce the damaging enzymes known as proteases, particularly elastase and tripsin. The protective alpha 1-antitrypsin (AAT) protein ordinarily neutralizes these enzymes, but smoke generates oxygen-free radical particles that deactivate AAT and make it ineffective, even in smokers who have sufficient and even high amounts of AAT.

Cigarette smoke also causes chronic bronchitis through inflammation and damage to the airways. It also damages the cilia, hair-like waving projections that move bacteria and foreign particles out of the lungs, increasing the risk for infections that can lead to chronic bronchitis.

Genetic Factors

Genetic factors that cause lungs to be hyper-reactive to stimulants and allergens may also increase the risk for COLD.

Alpha 1-Antitrypsin Deficiency (A1AD). An inherited condition that causes a deficiency in the protective enzyme AAT can trigger early-onset emphysema, even in nonsmokers. Known as alpha 1-antitrypsin deficiency (A1AD)-related emphysema, it accounts for only about 3% of all emphysema cases. The AAT protein is produced in the liver and neutralizes the effects of the protease enzymes, most importantly neutrophil elastase, which attacks the cell linings in the lungs. Without adequate amounts of AAT, the enzyme's destructive action is even more pronounced, causing early progressive damage to the lungs. In such cases, both the walls of the alveoli and the airways leading to them are damaged. There is also some evidence that in such patients the immune system over-responds to toxins or microorganisms, such as bacteria, and produces excess amounts of damaging inflammatory substances. Because smoke is a major toxin and also deactivates any residual amounts of AAT that these patients are able to produce, patients with A1AD who smoke have no chance at all for escaping emphysema.

Other Genetic Disorders. Researchers recently identified a group of patients who might have an inherited form of COLD that is unrelated to A1AD. In such patients, a genetic susceptibility may increase the effects of smoking so that severe COLD develops at an earlier age than usual. Some evidence suggests that some genetic factors may involve microsomal epoxide hydrolase, an important enzyme which is responsible for the breakdown of harmful oxidants found in cigarette smoke. Two variants of the gene regulating the enzyme cause it to act either rapidly or slowly. A 1997 study showed that, compared to healthy people, those with COLD are four to five times more likely to have the genetic variant that slows the action of this enzyme, possibly making such people more vulnerable to lung damage.

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, their role or the role of 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 symptomatic attacks.

What Are The Symptoms Of Chronic Obstructive Lung Disease?

Symptoms of Emphysema

Emphysema patients have typically lost between 50% and 70% of their lung tissue by the time symptoms begin to appear. Shortness of breath is the predominant early symptom. Coughing is usually minor and there is little sputum. Typically, a heavy smoker in his or her mid-50s who develops emphysema has shortness of breath with light exertion, and by age 60 may be breathless during rest or after minimal exertion. Late, severe symptoms include rapid, labored breathing and persistent air hunger even without physical exercise. Physicians sometimes refer to patients with severe emphysema as "pink puffers" because they tend to have pinkish skin and barrel-shaped chests due to overinflated lungs. The symptoms of A1AD-related emphysema tend to appear in adults between the ages of 30 and 40. As with standard emphysema, they include shortness of breath after exertion, wheezing, and exercise intolerance.

Symptoms of Chronic Bronchitis

Chronic bronchitis also causes shortness of breath and is often accompanied by infection, mucus production, and coughing. A diagnosis of chronic bronchitis is suggested when a patient experiences coughing with excessive sputum on most days for at least three months of a year over a period of at least two years. Lying down at night worsens the condition, so patients with advanced disease must sleep sitting up. In late, severe stages, some patients, who often have emphysema as well, are called "blue bloaters" because lack of oxygen causes the skin to have a blue cast (cyanosis) and because the body is swollen from fluid accumulation caused by congestive heart failure.

What Other Diseases Resemble Chronic Obstructive Lung Disease?

Acute Bronchitis

Acute bronchitis is usually caused by a virus and in most cases is self-limiting. The cough it causes typically lasts for about a week to ten days, but in about half of patients, coughing can last for up to three weeks, and 25% of patients continue to cough for over month. Although it 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 virtually always present during an attack. Usually 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, in fact, 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 well established. Frequent bouts of pneumonia or lung infection that does not clear up in a seemingly healthy adult normally 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 adults it may be associated with rare genetic diseases, including cystic fibrosis and Kartagener's syndrome.

How Serious Is Chronic Obstructive Lung Disease?

Chronic obstructive lung disease is responsible for more than 100,000 deaths in the US each year, making it the fourth leading cause of death. It is the only major disease that is rising in both prevalence and mortality. Nearly half of those with COLD report that daily activities are limited. They have trouble walking upstairs or carrying even small packages. Breathing becomes hard work. Chronic obstructive lung disease is progressive, although when patients stop smoking the disease often levels off. If emphysema is detected before it causes 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.

Chronic bronchitis does not cause as much lung damage as emphysema, although the airways become blocked from mucous plugs and narrowing due to inflammation. This poor ventilation causes reduced levels of oxygen and high carbon dioxide levels. Eventually, both varieties of COLD cause low oxygen levels (hypoxia) and high levels of carbon dioxide (hypercapnia), which can lead to very severe and life-threatening conditions. In order to boost oxygen delivery, the body compensates in a number of ways: the rate of breathing is increased, more red blood cells are produced to increase the blood's oxygen-carrying capacity, the heart rate increases to pump more blood, and vessels in the lung constrict to force blood and oxygen through the circulatory system.

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 pressure in the lungs (pulmonary hypertension) can cause a complication called cor pulmonale, in which the right ventricle of the heart enlarges, eventually leading to heart failure. Low oxygen levels can also impair mental functioning and short-term memory.

Any disease that affects the lungs is dangerous for COLD patients. Pneumonia can cause acute attacks of chronic bronchitis, which in turn 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. The smoking that causes COLD is also associated with high risks for pneumonia, lung cancer, stroke, and heart attacks. Chronic bronchitis itself appears to increase the risk of death from coronary artery disease by 50%, even after considering the effects of smoking.

Who Gets Chronic Obstructive Lung Disease?

Risk Factors for Chronic Obstructive Lung Disease

General Risk Factors. As of 1993, about two million Americans had emphysema and 13.8 million had chronic bronchitis. Some experts believe this figure was underestimated then, and the incidence, in any case, has increased since. Of those who have this condition, 55% are men and 45% are women, although the prevalence in women increased by 24% between 1982 and 1993 and has leveled off in men. The lungs of female smokers, in fact, appear to be more susceptible to the effects of smoking and pollution than men's. Lung function gets worse as people get older. Older Caucasians are more susceptible to emphysema than their African Americans peers, but younger African men are at higher risk than younger white men. Thinness is associated with emphysema; obesity is linked to chronic bronchitis.

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

Air Pollutants. People exposed to toxic fumes for a long time, industrial smoke or dust, such as from grain or in mines, and other air pollutants are also at increased risk for COLD. The effects of air pollutants are far less significant for COLD, however, than smoking.

Allergens. Allergens, such as fungi, molds, and house dust, can also cause changes in the lungs in some people that lead to COLD.

Dietary Factors. Some evidence indicates that having low dietary intake of antioxidant nutrients (vitamins A, C, and E and other food chemicals) could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables.

Risk Factors for A1AD-Related Emphysema

Between 75,000 and 100,000 people in the US have the genetic deficiency of the protein alpha 1-antitrypsin, which increases the risk for A1AD-related, or early-onset, emphysema. Only 20,000 to 40,000 of these people actually develop emphysema, however; in order to acquire the disease, both parents must carry the defective gene. Smoking, of course, increases the risk significantly. The disease 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 can lead to alpha 1-antitrypsin deficiency-related emphysema. 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. If the condition is present in the family, testing the children is important.

What Are The Diagnostic Tests For Chronic Obstructive Lung Disease?

Physical Examination and Medical History

The physician will request a history that includes information on past and present smoking, exercise capacity (eg, whether the patient has trouble climbing stairs, the distance he or she can walk), and exposure to any industrial pollutants. The physician will next perform a simple examination of the chest area. Using a stethoscope, the physician will listen to the patient's breathing for signs of emphysema, such as diminished or distant breath sounds. Tapping the chest will usually produce a hollow, drum-like sound. In patients with chronic bronchitis, the physician is likely to hear wheezing or gurgling sounds.

Pulmonary Function Tests

The best tests for determining the presence and severity of chronic obstructive lung disease are pulmonary function tests. Using a spirometer, an instrument that measures the air taken into and exhaled from the lungs, the physician will determine two important values. The forced vital capacity (FVC) is the maximum volume of air that can be exhaled with force and is an indicator of the lung size, elasticity, and how well the air passages open and close. The forced expiratory volume (FEV1) measures the maximum volume of air expired in one second. Calculating a ratio of FEV1 to FVC is the best method for determining the presence and severity of COLD, but simply observing a reduction in FEV1 is useful. For example, a FEV1 of less than 1 liter/second is an indicator of a poor outlook for people with advanced emphysema.

Chest X-Ray and Other 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 a flattened diaphragm, exaggerated lung inflation in upper areas, abnormally large amounts of air spaces in the lung, and 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. X-rays are rarely useful for diagnosing chronic bronchitis, although they sometimes show a so-called dirty chest (mild scarring and thickened airway walls).

Computed Tomography. Computed tomography (CT) scans may be used to determine the size of the air pocked (bullae) in the lungs.

Laboratory Tests

Physicians will typically test for the protective enzyme, alpha 1-antiprotease (or antitrypsin), which is often deficient in COLD patients (although asthma patients may also have low levels). The physician may request an arterial blood gas test to determine the amount of oxygen and carbon dioxide in the blood (its saturation). This procedure draws blood from an artery, which can be quite painful. A less painful test is called a pulse ox, which involves placing a probe on the finger or ear lobe; this only measures oxygen in the blood. When blood is fully saturated with oxygen, it forms a compound called oxyhemoglobin, which gives blood its bright red color. When blood has insufficient oxygen, it turns a bluish color (called cyanosis). 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 (measured as PO2) is useful for determining which patients would benefit from oxygen therapy. 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.

What Are The Drug And Non-Surgical Treatments For Chronic Obstructive Lung Disease?

Bronchodilators

Bronchodilators are drugs that open the airways in the lungs and offer significant symptomatic relief for many, but not all, people with chronic obstructive lung disease. Patients whose FEV1 is between 1.5 and 2 liters per second should be given a week's trial of these drugs to determine their benefit. If the bronchodilator brings relief, then the patient is a good candidate for this therapy. The bronchodilators usually described are the beta2 agonists, the anticholinergic drug ipratropium, and theophylline. Some experts believe that ipratropium should be the first choice for many patients, although a number of studies indicate that the beta2 agonists and ipratropium are equally effective, so patients can choose one most suited to their individual conditions and needs. If patients do not respond to one bronchodilator, combinations may be tested. Unfortunately, less than half of patients continue to comply with this therapy after a year. It should be noted that no treatment, except for oxygen therapy, prolongs survival, but drug treatments can improve the quality of life.

Anticholinergic Agents. Anticholinergic agents relax the bronchial muscles. Some experts recommend ipratropium (Atrovent) as the first choice in treating COLD. It is an inhaled anticholinergic that acts as a bronchodilator over time. It has a very slow onset, so is not useful for people with acute asthma attacks, but it has been beneficial for people with emphysema and chronic bronchitis, particularly since it can be used as maintenance therapy with few severe side effects. Some common side effects 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 being sprayed in the eye with the drug, which could worsen the condition. A patient should not take more than 12 inhalations per day. A single inhaler containing ipratropium and the common beta2 agonist albuterol (Combivent) may be a good alternative for patients who do not respond to single drugs.

Beta2 Agonists. Beta2 agonists are the most widely prescribed bronchodilators. These drugs are generally inhaled using a metered-dose inhaler or nebulized. They are also available orally. One study indicated that compliance may be better with the nebulizer than with the inhaler, although the inhaler is most often prescribed; survival rates are similar. Oral forms should be used only when patients cannot use inhalers. They have more side effects than inhaled beta2 agonists and have a slower onset of action. The most popular beta2 agonist available is albuterol (Proventil, Ventolin). Other similar forms are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), and bitolterol (Tornalate). These are short-acting drugs with effects lasting from three to six hours. Long-acting drugs, salmeterol (Serevent) or formoterol (Foradil), are also now available. Beta2 agonists are less effective when taken regularly for a prolonged period than when given only as needed to control symptoms. This loss of effectiveness may increase the danger of overuse and possible overdose. Side effects of beta2 agonists include anxiety, tremor, restlessness, and headaches. Patients may experience fast and irregular heartbeats, which could indicate an overdose; a physician should be notified immediately. Individuals with heart disease, diabetes, high blood pressure, hyperthyroidism, benign prostatic hypertrophy, narrow-angle glaucoma, or a history of seizures should take beta2 agonists with caution. They can interact with other drugs, and patients should tell the physician about any other medications they are taking. It should also be noted that one study of COLD and asthmatic patients reported that 90% made errors in their use of metered-dose or dry powder inhalers. The most common errors were not inhaling slowly

enough after releasing the medication and not exhaling fully before making the inhalation. Older patients had particular problems with the devices.

Theophylline. Theophylline (Theodur, Slo-bid, Uniphyl, Theo-24) relaxes the muscles around the bronchioles and stimulates the process of breathing. Although some experts question its value for COLD, patients have reported improvement with its use. If theophylline is taken as prescribed no major problems should arise. If theophylline is not taken exactly as prescribed an overdose can easily occur. Toxicity causes nausea, vomiting, headache, and insomnia. Cardiac arrhythmias and convulsions are possible. A physician should be contacted immediately if any of these side effects occur. Theophylline is available in oral and rectal forms, but absorption is inconsistent using the rectal form, which increases the risk for overdose, so the oral form is preferred. It should be noted that, like the bronchodilators, oral and nebulizer forms of theophylline increase the risk for cardiac death in people with existing heart disease. Also, chronic smokers metabolize theophylline much more quickly and require higher doses of the drug than nonsmokers; prolonged-release versions are helpful for such people. Patients taking theophylline should keep their daily caffeine intake to the equivalent of six cups of coffee or less, as too much caffeine can increase the concentration of this drug and prolong the time it stays in the body. Theophylline also interacts with many common drugs, including barbiturates, anticonvulsants, anti-hypertensives, certain antidepressants, thyroid horrmone, regampin, certain antibiotics, oral contraceptives, histamine H2-receptor blocking agents, and others. In some cases it enhances them and in some it reduces their potency. A patient should report any drugs, even over the counter, that they are taking to their physicians. Theophylline should not be taken by anyone with active peptic ulcer disease, and it should be taken with caution by the elderly and by individuals with heart disease, liver disease, hypertension, seizure disorders, or congestive heart failure. People with heart conditions who take theophylline face an increased risk for sudden death from heart-related causes. A pharmacist or physician should always be consulted if there are any questions about theophylline.

Anti-Inflammatory Agents

Corticosteroids. Corticosteroids, commonly called steroids, are powerful anti-inflammatory drugs. They inhibit substances known as prostaglandins that cause narrowing of the airways. Steroids are commonly administered using a metered-dose inhaler (MDI), which provides effective local anti-inflammatory activity in the lungs with minimal systemic effects. Standard corticosteroids are beclomethasone (Beclovent, Vancenase, Beconase, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). Newer, more powerful inhaled or intranasal steroids include triamcinolone (Azmacort and others), flunisolide (Aerobid), budesonide (Rhinocort), and fluticasone (Flovent). Common side effects are throat irritation, hoarseness, and dry mouth. Rashes, wheezing, and facial swelling (edema) are also possible. Inhaled steroids increase the risk for infections, including fungal infection in the mouth, throat, and even esophagus. If a sore mouth, sore throat, or other side effects develop, the patient should consult a physician. People using oral or inhaled steroids in any form, particularly if they need high doses for prolonged periods, should be checked for glaucoma. More than 20 puffs a day can cause adrenal suppression, a condition in which the adrenal gland loses its capacity to secrete natural stress hormones. Women who use inhaled corticosteroids for long periods may be at greater risk for osteoporosis. Intermittent administration of the bisphosphonate drug etidronate (Didronel) may help prevent bone loss and may even increase bone density in patients on high-dose corticosteroid therapy. Inhalers have no benefit for patients with advanced COLD who have not responded to the oral steroids. No one should stop taking these medications without consulting a physician first, and if steroids are withdrawn, regular follow-up monitoring is necessary.

In general, the drugs are most useful for patients with chronic bronchitis with or without emphysema, and they may also enhance the benefits of bronchodilators. Steroids are generally not useful in patients who have emphysema alone. In some patients, oral corticosteroids have been found to improve FEV1 by 30% in short-term studies, but long-term use of this form has

significant side effects, including fluid retention, weight gain, high blood pressure, high blood sugar, adrenal gland suppression, mental changes, increased susceptibility to infection, osteoporosis, and cataracts. Oral steroids are recommended only for severe flare-ups or for those who do not respond to bronchodilators.

Leukotriene Antagonists. Leukotriene antagonists and inhibitors, including zafirlukast (Accolate) and zileuton (Zyflo), are anti-inflammatory agents now used for asthma. They may prove to be useful for COLD patients as well.

Oxygen-Replacement Therapy

Eventually, patients may need to rely on supplemental oxygen provided through portable or stationary tanks.

Continuous Therapy. Continuous (24-hour) oxygen therapy is the only treatment for emphysema that has been proven to prolong survival. It also improves alertness, motor speed, and hand strength. Usually continuous oxygen therapy is recommended if the lung oxygen level (measured as arterial blood gas PO2) is below 55 mm/Hg while the patient is resting, or less than 60 mm/Hg if the patient has right heart failure or an abnormal increase in red blood cells (polycythemia). The patient should receive enough oxygen to keep the PO2 ideally at 65 but no less than 60 mm/Hg, or as blood tests show an oxygen saturation of at least 90%. An additional liter per minute of oxygen flow may be needed during sleep or exertion. About 40% of patients improve enough in one 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 may prove to offer additional benefits.

Noncontinuous Oxygen. Patients with less severe COLD who are not on permanent oxygen maintenance may need supplemental oxygen during specific circumstances. Patients whose PO2 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 PO2 drops below 55 mm/Hg during sleep. Such patients usually experience fitful, poor-quality sleep.

Oxygen during Travel. For those on continuous oxygen therapy who are traveling by plane, oxygen should be increased during the trip by one to two liters per minute. Supplemental oxygen may be required during air travel for those with COLD who are on intermittent oxygen therapy if the trip is longer than two hours and they develop symptoms or experience a drop in PO2 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 range from $64 to $1500.

Delivery Systems. Unless they are bed bound, patients usually use a combination of stationary and mobile oxygen 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. Compressed gas or liquid oxygen can be administered in large stationary tanks or small portable ones. Portable units containing electronic oxygen-conserving devices weigh only a few pounds and can provide up to 8 hours of oxygen. Portable units of liquid oxygen are available that weigh 6.5 lb with oxygen supplies lasting four hours, or 9.5 lb with oxygen lasting eight hours when used at a flow rate of two liters per minute. 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 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.

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.

Administration Devices. Oxygen is usually administered in one of three ways: using a nasal canula, a transtracheal catheter, or an electronic demand device. 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 is delivered directly into the wind-pipe (trachea) through a catheter tube implanted by a surgeon. The device is inconspicuous, and compliance is excellent. The cost is high, however, and 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 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.

Oxygen Delivery in Respiratory Failure. In emergency situations, if the patient is able to breathe naturally, oxygen may be delivered through a tube using a tightly-fitted oxygen mask, such as a continuous positive airway pressure (CPAP) mask, to maintain airway pressure during breathing. 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. 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. Mechanical ventilation may cause discomfort, requiring pain killers, sedatives, or even muscle relaxants. There are also a number of complications. A study found that patients may be able to go off the ventilator more quickly if they are screened daily and encouraged to breath spontaneously as soon as possible. Unfortunately, patients have a low tolerance of intubation and the tubes are often removed prematurely (in nearly 30% of patients in one study). Reasons include ejection after coughing, mucus plugging, bleeding, and other causes. Removing them too early produces adverse events in nearly all such patients. Possible solutions are devices called noninvasive positive-pressure ventilators, which are attached to nasal or face masks for oxygen administration. They are proving to be very useful for patients who need the tubes removed early; they may even preempt the need for intubation in many patients. These devices 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 have a tight seal.

Antibiotics

The most common organisms causing pneumonia in chronic obstructive lung disease patients include Streptococcus pneumoniae , Chlamydia pneumoniae , Haemophilus influenzae , and Legionella pneumphila. Of some concern, is the increase in more unusual and difficult-to-treat organisms known as gram-negative bacteria. Detecting the specific organism causing pneumonia

is often difficult. Since any pneumonia is dangerous in COLD patients, aggressive therapy using powerful antibiotics is usually called for when pneumonia occurs. 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 are now prescribed only for patients with chronic bronchitis who show signs of potential infection (increasing shortness of breath and mucus production with indications of pus), deficient immune systems, or bronchiectasis (another lung disorder). The most common oral antibiotics used are: the penicillins (eg, penicillin V, ampicillin, amoxicillin, and many more); augmented penicillins, such as amoxicillin-clavulanate (Augmentin); cephalosporins, often classed as first generation (cephalexin, cefadroxil), second generation (cefaclor), or third generation (cefixime); macrolides (erythromycin, azithromycin, clarithromycin); tetracycline; fluoroquinolones (eg, ciprofloxacin); and trimethoprin-sulfamethoxazole (Bactrim, Septra). [ For more information, see Pneumonia, Comprehensive Version. ]

Replacement Treatment for A1AD Deficiency

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. Therapy is life long. Patients with inheritied A1AD deficiency, regardless of their smoking history, are eligible for this therapy. Other COLD patients who are also current smokers are not candidates. Gene therapy is currently under investigation.

Mucolytics

Mycolytics contain ingredients such as guafenesin or acetylcysteine that make sputum more watery and so easier to cough up. Although there is some controversy over their value, an analysis of many studies indicated that oral mucolytics reduce the number of severe symptoms in patients with chronic bronchitis and have a small but significant effect on breathing function. Other mucolytic agents being tested include surfacant, pancreatic dornase, and detergents.

Experimental Therapies

All-Trans-Retinoic Acid. In an animal study, retinoic acid, a vitamin A derivative, reversed airway abnormalities in emphysemic rats. Human trials are now underway.

Selective Phosphodiesterase 4 Inhibitors. Studies using a drug called a selective phosphodiesterase 4 (PDE4) inhibitor (Ariflo) is showing promise. The drug acts on cells that trigger the inflammatory process leading to lung damage. Results from a small 1999 study were promising.

Aerosolized Hyaluronic Acid. Aerosolized hyaluronic acid may protect lungs from injury by elastase, the enzyme that causes lung tissue to lose elasticity.

Anabolic Steroids. In one study, elderly malnourished men with COLD who took anabolic steroids (testosterone and stanozolol) gained about five pounds after 27 weeks. Muscles that affected respiration increased, although there was no positive impact on exercise capacity.

Treatment for Complications of Advanced COLD

Analgesics (pain killers) may be beneficial for patients with severe shortness of breath. However, long-term effects on breathing function are unknown. (Opiates are known to depress respiratory function.) Antidepressants or antianxiety medications may be helpful. When patients are in advanced stages of COLD, they may need treatment for fluid accumulation and congestive heart

failure. The physician may prescribe one or more different drugs to help, including vasodilators (drugs that dilate blood vessels), inotropics (drugs that increase the heart's ability to contract), and diuretics (drugs to reduce fluid). [ See also Congestive Heart Failure, Comprehensive Version. ] Phlebotomy, the withdrawal of blood in order to remove excess red blood cells, has been commonly performed in the past; oxygen replacement therapy has reduced the need for this treatment.

How Is Chronic Obstructive Lung Disease Managed Day To Day?

Quitting Smoking and Avoiding Other Irritants

Quitting smoking is the first and most essential step in treating chronic obstructive lung disease. Once a patient stops smoking, lung function may stabilize and even improve slightly, eventually declining at only about the same rate as nonsmokers in the same age group. No one should smoke; smokers who live or work around the patient should make every effort to quit. [ For more information, see Smoking, Comprehensive Version.]

Preventing Upper Respiratory Infections

Washing hands thoroughly and often is a simple way to avoid some communicable infections. [ For more information see Upper Respiratory Tract Infections (Colds, Flu, Sore Throat, and Acute Bronchitis). ]

Vaccines. People with emphysema should be vaccinated against influenza each year at least six weeks before flu season. The other important vaccination is the pneumococcal vaccine, which 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.

Influenza Agents. Four antiviral drugs are now available for preventing and treating influenza: amantadine, rimantadine, zanamivir, and oseltamivir. The first two are effective against influenza A while the last two can be used for both A and B influenza strains. All offer some protection but none are substitutes for vaccinations.

Breathing Exercises

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 the 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.

The use of an incentive spirometer for 15 minutes twice a day may also be helpful in strengthening breathing muscles and loosening 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.

Controlling Secretions

Patients who experience congestion and heavy sputum can benefit from maintaining good fluid intake and keeping their homes humidified. If a nebulizer is used, the reservoirs, tubes, and mouthpieces mabe be kept clean to avoid bacterial contamination in the lungs. Although unproven, many patients report benefits from using expectorant drugs that thin mucus available in many over-the-counter brands. The use of incentive spirometry [ see Breathing Exercises, above], rhythmic inhalation and coughing, and chest tapping may also help in loosening and raising sputum. In rhythmic breathing and coughing, the patient should inhale deeply three or four times and then cough to produce sputum. 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. When coughing to produce mucous one effective method is to lean forward and "huff" repeatedly, take relaxed breaths, and huff again. If possible, forceful coughing should be avoided.

Exercise

Although exercise does not change lung function, it does help some patients with chronic lung disease by strengthening their limb muscles and thus improving their endurance and reducing breathlessness. In studies of pulmonary 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. Yoga or martial arts exercises, such as tai chi, may be useful.

Diet

Studies have indicated that diets rich in antioxidants, including vitamins E and C, selenium, and beta carotene, improve lung function and may provide some protection against lung damage from chronic obstructive pulmonary disease among smokers. However, in one study, the protection appeared to be effective for smokers only if such foods were eaten throughout the smoking years. Another study found protection from diets rich in vitamin C, but other antioxidants, including vitamins E, A, and beta carotene, had no effect. Beta carotene supplements, in any case, are not recommended because of studies suggesting an increased risk of lung cancer in smokers. Foods rich in such antioxidants include dark colored fruits and vegetables (vitamin C and beta carotene), whole grains, nuts (selenium), and vegetable oils and wheat germ (vitamin E). The trace elements zinc and selenium may have some effect in reducing the severity of upper respiratory tract infections.

Other Measures

Patients should not take tranquilizers, sedatives, or other drugs that suppress respiration. As much as possible, a patient should avoid exposure to airborne irritants, including hair sprays and any aerosol products, paint sprayers, and insecticides. To minimize the amount of contaminants in the home, the following may be helpful measures:

Ventilate by keeping windows open (weather permitting), by using exhaust fans for stoves and vents for furnaces, and by keeping fireplace flues open.

Make sure wood-burning stoves or fireplaces are well ventilated and meet the Environmental Protection Agency's safety standards and 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 stemming 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 Asthma in Adults, Comprehensive Version. ]

What Are The Surgical Procedures For Chronic Obstructive Lung Disease?

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

Emphysema is responsible for over half of the lung transplants performed, and according to one analyst, they can reduce the risk of dying in emphysema patients by 77% compared to those who do not receive transplants. Lung transplants were first performed in 1985, and in 1988 the waiting time for a transplant was four months; as of 1998 it was two years. The increasingly long waiting time is a growing problem. The best candidates are under 65 and have good general health aside from lung disease. Techniques have been developed so that both lungs may be replaced in sequence. A lung or liver transplantation may be the only hope for some patients with the inherited disease alpha 1-antitrypsin (AAT) deficiency-related emphysema. AAT is produced in the liver, so a healthy transplanted liver may produce adequate supplies of the protein. Drugs that suppress the immune system must be taken lifelong after a transplantation 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 8%. One major transplant center reported survival rates of 83% at one year, 70% at three years, and 54% at five years.

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 appears to be due to an improvements in the lung and chest wall's elastic recoil (its ability to spring back during breathing), a reduction in lung hyperinflation, and an increase in small airway opening. When the operation is successful, patients report significant improvement in symptoms, weight, and quality of life. Many patients can engage in active daily events, such as golf or climbing stairs, without oxygen. Recent data indicate that at six months breathing function improves by over 50%, and newer advances in techniques are reporting improvement of up to nearly 70%. It is unknown how long the benefits last. One study reported that in the first year after the procedure 78% of patients were not dependent on oxygen but by the fourth year only 22% were off oxygen. In general, about 30% of patients derive no benefit from the procedure. According to a 1999 study, the long-term study survival rates after the procedure are 83% at one year and 76% at two years. (There was no comparative group, however, to determine if these survival rates were any better than without the operation.)

Although the procedure is new, according to one study, mortality rates are about 5% within 30 days of the operation. However, as the procedure is modified and surgeons gain more experience, it is becoming safer. Candidates are usually those under 75 years old with severe obstruction (FEV1 less than 40% of expected value) and hyperinflated lungs (total lung capacity greater than 120% of the predicted value). Patients with very reduced lung elasticity but who retain good airway structure are good prospects for the procedure. Studies have suggested that success is greater when emphysema is localized in the upper lobes of the lungs than when the damage is more diffusely spread throughout the lung (although both groups improve). (Patients with deficiency of alpha 1-antitrypsin and disease in the lower lobe, however, may also do well.) Patients are usually excluded if they have any of the following: severe heart disease or other conditions that limit the predicted life span to less than five years, severe psychologic problems, recent drug or alcohol dependence, chest wall deformity, corticosteroid dependence, any tobacco

use within the past three months, or scarring around the membrane of the lung, pulmonary hypertension, hypercapnia (difficulty expelling CO2), or other indicators of severe lung complications. As experience with the procedure grows, however the list of potential candidates may also increase, including older candidates and those with other severe medical conditions. Some research even suggests that LVRS may facilitate surgery for early lung cancer in some patients who would ordinarily by inoperable.

At this time, the best technique for most patients appears to be one called bilateral lung volume reduction. To accomplish it, surgeons are using either an open approach, which uses a large incision in the chest area, or video-assisted thoracoscopy (VATS), which is less invasive. So far, results are similar. An alternative procedure is called unilateral LVRS, but it does not appear to be as effective for most patients. In one study, 68% of patients with bilateral technique were off oxygen six months after the procedure, compared to 36% in the unilateral group. The use of lasers does not appear to offer any advantage.

Bullectomy

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

Where Else Can Help For Chronic Obstructive Lung Disease Be Found?

The American Lung Association and American Thoracic Society, 1740 Broadway, New York, New York 10019-4374. Call (800-LUNG-USA) Internet sites connected with the American Lung Association are as follows:

American Thoracic Society (http://www.thoracic.org/ )

American Lung Association (http://www.lungusa.org/ )

Society of Thoracic Surgeons (http://www.sts.org/ )

National Heart, Lung, and Blood Institute, P.O. Box 30105, Bethesda, MD 20824-0105.

Write for information or on the Internet (http://www.nhlbi.nih.gov/ ) They offer information, including treatment centers, on the National Emphysema Treatment Trial (NETT) designed to determine the role, safety, and effectiveness of bilateral lung volume

reduction surgery. (http://www.nhlbi.nih.gov/health/prof/lung/nett/lvrsweb.htm )

National Jewish Center for Immunology and Respiratory Medicine, 1400 Jackson Street, Denver, CO 80206. This excellent organization publishes a number of booklets for the public. For their information line staffed by trained nurses call (800-222-LUNG or 303-355-LUNG). For recorded messages on

specific problems call (800-552-LUNG) or on the Internet (http://www.njc.org/ )

Alpha1 National Association, 4220 Old Shakopee Road, Minneapolis, MN 55437-2974. Call (612-703-9979) and for recorded message (800-425-7421) or on the Internet (http://www.alpha1.org/

) This is an excellent organization that offers support and information for people with A1AD.

American Association for Respiratory Care, 11030 Ables Lane, Dallas, TX 75229-4593. Call (972-

243-2272 ) or on the Internet (http://www.aarc.org/ )

The National Emphysema Foundation

http://emphysemafoundation.org/

Useful Internet Site

Links for respiratory problems (http://www.xmission.com/~gastown/herpmed/respi.htm )

Good sites for information on oxygen, including contacts for obtaining it during travel: American

Society for Respiratory Care (http://oxygen4travel.com/ ), Transtracheal Systems

(www.transtracheal.com ), and Amtrak (www.amtrak.com )

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