Chronic obstructive lung disease (COLD), also known as chronic obstructive pulmonary disease (COPD), is characterized by airflow limitation in the lung that develops over time and is not totally reversible. [For description of the lung, see box The Lungs.] COLD is associated with a set of breathing-related symptoms:

• Chronic cough.
  
  
• Spitting or coughing mucus (expectoration).
  
  
• Breathlessness upon exertion.
  
  
• Progressive reduction in the ability to exhale.
  

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. [ See Box The Lungs.]

It generally takes the following course:

• The walls of the alveoli become inflamed and damaged. Over time they lose elasticity and pockets of dead air (called bullae) form in the injured areas.
  
  
• These pockets impair the ability exhale and 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.
  
  
  

In chronic bronchitis, the disease process is generally marked by the following characteristics:

• Structural changes in the airways of the lungs that cause obstruction and impair air flow
  
  
• Coughing and overproduction of mucus for at least three months during each of the two consecutive years.
  
  
  

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.

Biologic Factors and Smoking in Emphysema. In emphysema, evidence suggests that smoking produces an imbalance in the following chemicals, which in turn leads to destruction in the alveoli, the grapelike clusters of sacs at the end of the airways:

• Proteases, particularly those known as elastase and trypsin. Proteases are enzymes released by white blood cells in the immune system called neutrophils. Under normal circumstances these immune factors are important for fighting infection and injury. However, smoking can incite the immune system to the extent that proteases become overproduced. In excess, these enzymes actually impair the structural integrity of material called elastin , which is essential for the "springy" quality of lung tissue.
  
  
• Alpha 1-antitrypsin (AAT). The protective alpha 1-antitrypsin (AAT) protein ordinarily neutralizes the proteases. Patients with emphysema, however, typically have reduced levels of AAT. Smoking, for example, generates oxygen-free radical particles that deactivate AAT and make it ineffective, even in smokers who have sufficient and even high amounts of AAT.

• Damage to the cilia, 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.
  
  
• Overgrowth in the smooth muscle cells in the airway.

Not all smokers develop COLD. Genetic factors may increase susceptibility to airway damage in smokers.

Inherited Susceptibility to Lung Abnormalities. Some people may have genetic factors that cause the lungs to be hyper-reactive to stimulants and allergens.

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 is estimated to affect about 100,000 people (although only about 6% have been diagnosed.) Without adequate amounts of AAT, early and progressive damage in both the walls of the alveoli and the airways leading to them occurs. 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 Factors. Other genetic factors are being investigated that might offer additional clues to the cause of COLD:

• Researchers 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 abnormalities in an important enzyme called microsomal epoxide hydrolase, 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.
  
  
• Researchers are also studying a variant of a gene responsible for producing tumor necrosis factor, an immune factor responsible for inflammatory damage in a number of diseases. In a group of Taiwanese who harbored the genetic variant, the risk for COLD was ten times the normal level. A group of Britons with the same variant, however, had no higher risk for COLD.

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.

The hallmark symptoms of either 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.

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

• The predominant early symptom is shortness of breath with light exertion. Coughing is usually minor and there is little sputum.
  
  
• Late, severe symptoms include rapid, labored breathing and persistent air hunger even without physical exercise, even during rest or after minimal exertion.
  
  
• 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.
  
  
• In some cases, involuntary weight loss.

Chronic bronchitis usually causes the following symptoms:

• Coughing with excessive sputum on most days for at least three months of the year over two successive years. (These symptoms in this time frame are the standard minimums for a diagnosis.)
  
  
• As with emphysema, shortness of breath occurs, but it may not be as severe during rest as in emphysema.
  
  
• Lying down at night worsens symptoms in advanced conditions, however, so patients 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.

A number of lung diseases have similar symptoms, and in fact, may accompany COLD.

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 one 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.

The classic sympt#ms 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.

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 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 Kartageners syndrome.

Impaired lung function reduces survival, even in nonsmokers. 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 cause of death that is rising in both prevalence and mortality.

Chronic obstructive lung disease is progressive, although when patients stop smoking the disease often levels off. Patients with frequent acute exacerbations of COLD are at higher risk for disease deterioration, including reduced quality of life and increasing rates of hospitalizations. Acute exacerbations can be defined as the following:

• Worsened shortness of breath
  
  
• Increased in thickness and color change in sputum
  
  
• Increased sputum volume
  
  
• can be triggered by respiratory infections, environmental conditions, or medical disorders (eg, heart failure, infections outside the lungs, pulmonary embolisms.)

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.

Over time, both varieties of COLD cause low oxygen levels ( hypoxia) and high levels of carbon dioxide ( hypercapnia). 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.
  
  
• 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 accounts for COLD is also associated with high risks for pneumonia, lung cancer, stroke, and heart attacks.

Lung Cancer. Patients with a 30- year history of smoking and 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 screening is making it easier to detect this deadly cancer in earlier stages, and such patients should consider having it done.

Heart Disease. Chronic bronchitis itself is associated with a 50% higher risk of death from coronary artery disease, even after considering the effects of smoking.

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 and has been associated with an elevated risk for hypertension, stroke, dementia, and pulmonary hypertension.

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. An estimated 15 million American have chronic obstructive lung disease. Because emphysema and chronic bronchitis so often occur together, it is difficult to determine the number of emphysema versus chronic bronchitis patients. Lung function gets worse as people get older. Some studies suggest that two thirds of adults have some evidence of emphysema by the time they die.

The incidence of COLD has increased over the past decades, particularly in women. The lungs of female smokers, in fact, appear to be more susceptible to the effects of smoking and pollution than men's. In spite of this, a 2001 study suggested that COLD is underdiagnosed in women.

Older Caucasians are more susceptible to emphysema than their African Americans peers, but younger African American men are at higher risk than younger white men.

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, however, so other factors must be present.

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, and cooks who work in small spaces.

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

Some evidence indicates that having poor nutrition, particularly 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.

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.

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.

In a 2001 study, patients with periodontal 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 inflamm#tion, which may also affect the linings of the airway.

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. 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.

The physician will request a history that assesses the patient's risk factors, which 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.

Appearance. The appearance of the patients may be a clue to the condition. Bluish skin tone and swelling in the legs ("the blue bloater") suggests chronic bronchitis. Healthy skin tone but having an inflated chest ("the pink puffer") 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:

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

The best tests for determining the presence and managing the response to treatment of chronic obstructive lung disease are pulmonary function tests, most often spirometry. Such tests employ a spirometer, an instrument that measures the air taken into and exhaled from the lungs. Using these measurements, the physician will determine two important values:

• The forced vital capacity (FVC). 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 in one second (FEV1). FEV1 is the maximum volume of air expired in one second.

• Mild is 70% or higher
  
  
• Moderate is 60% to 69#
  
  
• Moderately severe is 50% to 59%
  
  
• Severe is 34% to 49%
  
  
• Very severe is less than 34%.
  
  

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 (measured as PO2) is useful for determining which patients would benefit from oxygen therapy. This procedure typically draws blood from an artery in the wrist, which can be painful.


Pulse Ox Test. A less painful test form measuring oxygen in the blood is called a pulse ox, which involves placing a probe on the finger or ear lobe. 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). This test only measures oxygen in the blood, however, and not carbon dioxide, so it is not useful in determining candidates for long-term supplemental oxygen.

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.)

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.

Test for ATT. Physicians will typically test for the protective en#yme, 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.

A major treatment goal in COLD is to prevent acute exacerbations of COLD, which can hasten deterioration of lung function. The main treatment strategy employs a stepped approach with the use of increasingly potent medications depending on the patient's response. It should be noted, however, that no treatment, except for oxygen therapy, prolongs survival, but drug treatments can improve the quality of life. Some experts suggest the following steps in a medication program:

Step 1. Bronchodilators. Bronchodilators open the airways in the lungs and offer significant symptomatic relief for many, but not all, patients. Patients whose FEV1 is between 1.5 and 2 liters per second should be given a week's trial to determine their benefit. If the bronchodilator brings relief, then the patient is a good candidate for this therapy.

The main bronchodilators are beta2 agonists , certain anticholinergic drugs , and theophylline. 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.

• The initial agent of choice is ipratropium (Atrovent), which is known as an anticholinergic. These agents are usually inhaled with the use of metered-dose inhaler (MDI). [ See Box Administering Inhaled Drugs.]
  
  
• If the patients does not respond, a beta-2 agonist is added. This agent is also usually taken with an inhaler.
  
  
• The third agent added if the patient does not respond may be theophylline, an oral bronchodilator.
  
  

• If the patient experiences significant improvement, the dosage it reduced to as minimal as possible and the patient is switched to an inhaled corticosteroid.
  
  
• If the patient does not improve, the oral corticosteroid is withdrawn as rapidly as possible.

Other treatments are offered depending on the presence of other conditions:

Low Oxygen Levels. Oxygen replacement is an important component in most COLD treatments. In fact, it is the only treatment known to improve survival in COLD patients. The patient is assessed for specific timing and needs.

Coughing and Persis#ent Sputum. Patients may try expectorants, such as guaifenesin, or agents known as mucolytics, which thin mucus. They should not be used, however, when there are acute exacerbations of COLD. They may even reduce lung function.

Frequent Episodes of Acute Bronchitis. If a patient has four or more episodes of acute bronchitis, preventive antibiotics may be warranted.

In addition to medications, all smokers should actively attempt quitting and maintain a healthy diet, rich in fruits and vegetables. A number of techniques are available for improving breathing, loosening secretions, and help lung function.

Administering Inhaled Drugs Most COLD drugs are inhaled using special devices or nebulizers. The standard inhalers have used ozone-depleting chlorofluorocarbons as propellants, but alternative delivery methods and propellants are increasingly available that do not threaten the environment and may even be better in delivering the drugs. Metered-Dose Inhaler. The standard device has been the metered-dose inhaler (MDI), which allows precise doses to be delivered directly to the lungs. Until recently, MDIs have used chlorofluorocarbons (CFCs) as propellants, but a new propellant called hydrofluoroalkane is proving not only to be environmentally-safe but possibly more effective than CFCs. MDI-delivered drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Some patients hold the MDI too close to their mouths, or even inside them. Others may exhale too forcefully before inhalation. Often, the devices continue to deliver propellant after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered. Dry Powder Inhalers. A number of inhalers now deliver a powdered form of medications directly into the lungs and do not threaten the environment. Such devices are called dry powder inhalers (DPIs) and include Rotahaler, Spinhaler, Turbuhaler, Clickhaler, Easyhaler, QVAR, Diskhaler, Twisthaler, Spiros, and many others. DPIs are proving to be as effective as the older devices, and generally have a better taste and are easier to manage. They may differ among themselves, however, in their ability to deliver drugs into the airways. Comparative and long-term studies are needed. Humidity or extreme temperatures can also effect their performance, so they should not be stored in places that are humid (eg, bathroom cabinets) or subject to high temperatures (eg, glove compartments during summer months). Nebulizers. A nebulizer is a device that administers the drug in a fine spray that the patient breathes in. They are mostly used in hospital settings or when the patient cannot use an inhaler.

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

Brands and Benefits. Some experts recommend ipratropium (Atrovent) as the first choice in treating COLD. It has a very slow onset and can be used as maintenance therapy for people with emphy#ema and chronic bronchitis with few severe side effects. A patient should not take more than 12 inhalations per day. Tiotropium (Spiriva), an agent not yet available in the US, requires only one daily inhalation and may turn out to be more effective than ipratropium for persons with emphysema. A single inhaler containing both ipratropium and the common beta2 agonist albuterol (Combivent) may prove to be better than either agent alone. Anticholinergics target the central airways and beta agonists target peripheral airways, thus explaining, so some doctors hypothesize, the additive benefits of the combination.

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.

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 have more side effects than inhaled beta2 agonists and have a slower onset of action. Oral beta2 agonists should be reserved only for patients who cannot use other forms.

Short-Acting Beta2-Agonists. Short-acting bronchodilators are the primary agents for most COLD patients. Albuterol (Proventil, Ventolin), called salbutamol outside the US, is the standard short-acting beta2-agonist in America. Other short-acting beta2-agonists are 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. Most are administered through inhalation, however, and are effective for three to six hours.

Long-Acting Beta2-Agonists. Long-acting forms, salmeterol (Serevent) or formoterol (Foradil), are also available and may be particularly effective for COLD. They may help inhibit bacteria from building up on the airways, and a 2000 study suggested that salmeterol may offer real improvements in lung function. (Formoterol appears to be similar.) A combination agent (Advair), which contains salmeterol and fluticasone, a corticosteroid, may be even more effective. Salmeterol is also effective in combination with theophylline. In any case, with salmeterol alone or in combination it takes at least three months to achieve full benefits.

Side Effects. 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. Beta2 agonists can interact with other drugs, and patients should tell the physician about any other medications they are taking.

Errors in Administration . In one study 90% of COLD and asthmatic patients 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. [ See Box Administering Inhaled Drugs.]

Possible Loss of Effectiveness. 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. If symptoms become or continue to be severe or frequent at cu#rent dosages, the patient should consult a physician before increasing the use of the beta2-agonists.

Theophylline has many benefits for COLD patients, including opening airways, improving exchange of gases, reducing shortness of breath, improving mucus clearance, and stimulating the process of breathing. Nevertheless, it poses a high risk for toxicity, and some experts question its value for COLD patients. Nevertheless, it may help some patients who do not respond to less potent agents.

Brands. Theophylline (Theodur, Slo-bid, Uniphyl, Theo-24) is available in oral and rectal forms. The oral form is preferred. Absorption is inconsistent using the rectal form, which therefore poses 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.

Adverse Effects. 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. Certain conditions, such as liver disease, and medications increase the risk for toxicity. Such medications include certain antibiotics, calcium channels blockers, and H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet HB), or ranitidine (Zantac 75).

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

Oral Corticosteroids. Oral corticosteroids have helped about 10% of COLD patients. Common oral corticosteroids include prednisone, prednisolone, methylprednisolone, and hydrocortisone. Appropriate candidates for oral steroids are the following:

• Patients whose condition is not controlled by standard COLD medications.
  
  
• Patients whose FEV1 rates improve by over 20% with steroid use for two weeks.

• The most recent generation of inhaled steroids include (in order of potency) fluticasone (Floven#), 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.

• 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.

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 chronic obstructive lung disease patients include Streptococcus pneumoniae , Chlamydia pneumoniae , Haemophilus influenzae , and Legionella pneumophila. Of some concern is the increase in more unusual and difficult-to-treat organisms known as gram-negative bacteria.

The primary choice of agent still includes the less expensive antibiotics, such as amoxicillin/clavulanate, doxycycline and trimethoprim-sulfamethoxazole. Antibiotic classes known as the macrolides and quinolones appear to be beneficial as well. [ See Table , Some Antibiotics, below.] Detecting the specific organism causing the lung infection is often difficult. [For more information, see 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 give one week a month with alternative agents. They are now prescribed only for COLD patients with one or more of the following conditions:

• Having four or more episodes a year of acute infection with intensified COLD symptoms, including worsened shortness of breath and mucus production.
  
  
• Having deficient immune systems.
  
  
• Having bronchiectasis, an irreversible lung disease in which the airways in the lung are chronically dilated.

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. A 2000 survey of patients suggested that b#nefits of replacement therapy may include a reduction in severity and frequency of lung infections. Therapy is life long. Patients with inherited A1AD deficiency, regardless of their smoking history, are eligible for this therapy. Unfortunately, this therapy is in short supply.

An AAT protein that is produced from the milk of genetically bred sheep, which would increase availability of the treatment, is under investigation.

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 such as iodinated glycerol 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. They should not be used, however, during an acute attack, since they may worsen lung function.

Uridine 5'-Triphosphate (UTP). Inhaled uridine 5'-triphosphate (UTP) is an agent that helps clear mucus by enhancing actions of the cylia and increasing the fluidity of the airway secretions. Early studies suggest that it may be helpful for patients with mild chronic bronchitis.

Selective Phosphodiesterase 4 Inhibitors. Cilomast (Ariflo) is an agent called a selective phosphodiesterase 4 (PDE4) inhibitor. The drug acts on cells that trigger the inflammatory process leading to lung damage. Studies are very promising. A 2001 study reported that it significantly improved FEV1 with no serious adverse effects.

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.

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.

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 Well-Connected , Report #13, Congestive Heart Failure .] 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.

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 for patients under the following circumstances:

• If the lung oxygen level (measured as arterial blood gas PO2) is below 55 mm/Hg while the patient is resting.
  
  
• If the PO2 is less than 60 mm/Hg and the patient has right heart failure or an abnormal increase in red blood cells (polycythemia).

• 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 (nocturnal oxygen) for patients whose PO2 drops below 55 mm/Hg during sleep. Such patients usually experience fitful, poor-quality sleep. Such oxygen therapy does not appear to affect survival or to delay prescription of continuous oxygen therapy.

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 four hours. Some weigh 9.5 lb with oxygen lasting eight 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 tanks require occasional venting to release pressure, thereby wasting oxygen. They are also more expensive, however. 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.

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 wind-pipe (trachea) through a catheter tube implanted by a surgeon. The device is inconspicuous, and compliance is excellent. The initial cost is high, but overtime 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.

A system called continuous positive airflow pressure (CPAP) employs a machine weighing about five pounds that fits on a bedside table and supplies a steady stream of air through a tube that connects to a plastic mask. The machine applies sufficient air pressure to prevent the tissues from collapsing during sleep. It is not an oxygen-delivery system, but it improves air flow into the lungs and may help reduce hospitalization, particularly when combined by long-term oxygen. Long-term studies are needed to confirm its benefits. The device is sometimes uncomfortable, however, and noncompliance rates are high. [For detailed information on this device, see Well-Connected Report #65, Sleep Apnea.]

In emergency sit#ations, 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.

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, patients have a low tolerance of intubation and the tubes are often removed prematurely because of discomfort. Pain killers, sedatives, or even muscle relaxants may be needed. There are also a number of complications that cause early removal:

• Ejection after coughing.
  
  
• Mucus plugging.
  
  
• Bleeding, and other causes.

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 lung function may even improve slightly after quitting. A number of new aids, including nicotine replacement devices and antidepressants, such as bupropion (Zyban) are available that are proving to help people quit. [For more information, see Well-Connected, Report #41, Smoking.]

Good Hygiene. Everyone should always wash his or her hands before eating and after going outside. Ordinary soap is sufficient. Antibacterial soaps add little protection, particularly against viruses. In fact, 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. There are two important vaccinations to help protect against respiratory infection.

• Influenza vaccination. People with emphysema should be vaccinated against influenza each year at least six 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 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.

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 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.

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 expectorant drugs that thin mucus available in many over-the-counter brands. They should not be used during an acute acerbation 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.

Flutter Valve. The flutter valve is a small hand-held device that looks like 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 by this process that are transmitted to the lungs and 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 ThAIRapy Vest, which was developed for cystic fibrosis, 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, however (about $16,000).

Strengthening Exercises for the Limbs. Exercise helps some patients with chronic lung disease by strengthening their limb muscles and thus improving their endurance and reducing 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.

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 ability to air into the lungs and assesses the fitness of the breathing muscles.

Yoga and Eastern Practices. Yoga or tai chi practices, which use deep breathing and medication techniques may be particularly beneficial for COPD patients.

Protein. Many COLD patients are deficient in protein. Protein choices should emphasize fish, poultry, and lean meat.

Antioxidant-Rich Foods and Supplements. 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).

Trace Elements. The trace elements zinc and selenium may have some effect in reducing the severity of upper respiratory tract infections.

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 s#re 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 the Well-Connected report Asthma in Adults .]

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.

Advanced emphysema is responsible for over half of the lung transplants performed. According to one analyst, they can reduce the risk of dying in emphysema patients by 77% compared to those who do not receive transplants. 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 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.

Complications and Outlook. 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 10%. Survival rates of patients with transplants performed between 1987 and 1997 are 74% at one year and about 50% at five years.

Waiting Time. There were 956 lung transplantation operations in 2000 and as of this report there are nearly 3,800 people waiting for the operation. Not all lung transplant centers, even in major cities like New York, accept Medicare patients. The system is currently operated on a first-come first-served basis (rather than by urgency).

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 elastic recoil (its ability to spring back during breathing).
  
  
• Improvement in function of the muscles, such as the diaphragm, involved with breathing.

• 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 predicted value).
  
  
• Appropriate candidates who have deficiency of alpha 1-antitrypsin, even if they have disease in the lower lobe, may do well.

• Patients with very reduced lung elasticity but who retain good airway structure.
  
  
• When emphysema is localized to the upper lobes, rather than if the damage is more diffusely spread throughout the lung or if it occurs in lower lobes, although appropriate candidates with either condition improve).

• Having a very low FEV1 (less than 20% of expected value) plus
  
  
• Having a carbon monoxide diffusing capacity of less than 20% of expected value, or
  
  
• Having computed tomography (CT) scans showing a uniform distribution of emphysema in the lungs.

• 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.
  
  
• Scarring around the membrane of the lung.
  
  
• Indicators of severe lung complications, including pulmonary hypertension, hypercapnia (difficulty expelling CO2), or other conditions.
  
  
• Isolated bullae (air pockets in diseased area of the lungs), which may be more appropriately and effectively treated by bullectomy. [ See below. ]

An 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 1-antitripta#e deficiency.

The American Lung Association and American Thoracic Society, 1740 Broadway, New York, New York 10019-4374. Call (212) 315-8700. Internet sites connected with the American Lung Association are as follows:

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

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

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


National Heart, Lung, and Blood Institute. On the Internet (http://www.nhlbi.nih.gov/)
For all health related questions and requests for copies of publications, please contact a trained information specialist at (NHLBIinfo@rover.nhlbi.nih.gov).
Please include a valid E-mail address as well as a current postal address, since many resources are available only as printed publications.
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/lvrspr.htm)


National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. Call (800-222-LUNG or 303-388-7700)
For recorded messages on specific problems: Call (800-552-LUNG)or on the Internet (http://www.njc.org/)
This excellent organization publishes a number of booklets for the public.


Alpha1 National Association, 8120 Penn Avenue South, suite 549, Minneapolis, MN 55431-1326 Call (952) 703-9979 and for recorded message (800) 521-3025 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/)


On the Internet:

The National Emphysema Foundation (http://emphysemafoundation.org/)

National Lung Health Education Program: (http://www.NLHEP.org/)


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


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

Breathin' Easy Travel Guide, 225 Daisy Dr., Napa, CA 94558 Call (707) 252-9333or on the Internet (http://oxygen4travel.com/)

Transtracheal Systems 109 Inverness Drive East, Suite J, Englewood, Colorado 80112-5105 Call (303) 790-4766 or (800) 527-2667 or on the Internet (www.transtracheal.com)


F#r information on organ transplantation:

United Network for Organ Sharing (http://www.unos.org/).