Chronic Obstructive Lung Disease
Chronic Obstructive Lung Disease
Chronic obstructive lung disease (COLD), also known as chronic obstructive pulmonary disease (COPD), is
characterized by a limitation of the airflow in the lung, which develops over time and is not totally reversible.
COLD is associated with a set of breathing?related symptoms:
Spitting or coughing mucus (expectoration).
Breathlessness upon exertion.
Progressive reduction in the ability to exhale.
The two major diseases in this category are emphysema and chronic bronchitis, which 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, seeWell?Connected Report #04,
Asthma in Adults.]
Because smoking is overwhelmingly the cause of both emphysema and chronic bronchitis, they often develop together
and frequently require similar treatments and approaches. As chronic bronchitis often coincides with emphysema, it is
frequently difficult for a physician to distinguish between the two.
Emphysema is a disease marked by destruction in the alveoli, grapelike clusters of air sacs at the end of the smallest
airways (the bronchioles) in the lung. It generally takes the following course:
The walls of the alveoli become inflamed and damaged. Over time they lose elasticity and pockets of dead air
(called bullae) form in the injured areas.
These pockets impair the ability to exhale and normal working of the lungs.
Inhalation, however, is not impaired and until the late stages of the disease, oxygen and carbon dioxide levels
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.
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, air travels through the following pathways into the lungs.
Air is carried from the trachea (the windpipe) into the lung through flexible airways called
Like the branches of a tree, bronchi divide successively into over a million smaller airways called
The bronchioles lead to grape?like clusters of microscopic sacs called
In each lung of an adult there are millions of these tiny alveoli, which are composed of a thin membrane
through which oxygen and carbon dioxide pass to and from capillaries.
During deep inhalation, the elastic alveoli unfold and unwind to allow this passage to occur.
Capillaries, the smallest of our blood vessels, carry blood throughout the body.
Red blood cells contain factors that fight pollutants; white blood cells are the critical infection fighters in our
Chronic Obstructive Lung Disease
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
Causes of Emphysema
Smoking is the major cause of emphysema. In some rare inherited disorders, emphysema can develop even in
The Disease Process Leading to Emphysema. The key process leading to emphysema is destruction of a protein in the
lung called elastin, which is essential for the "springy" quality of many tissues in the body. This protein is specifically
important in the lungs for maintaining flexibility in the alveoli??the tiny sacs at the end of the airways.
An imbalance in the following chemicals may be important in this process:
, particularly those known as elastase and trypsin. Proteases are enzymes released by white blood
cells called neutrophils in the immune system. Under normal circumstances, these enzymes are important for
fighting infection and injury. In excess, however, these enzymes can degrade or destroy elastin
(AAT). The AAT protein neutralizes proteases and so protects elastin from destruction.
An excess of protease coupled with impaired or deficient AAT can lead to emphysema. Eventually, the imbalance in
these factors produces the inelastic walls of the alveoli and the pockets of dead air characteristic of emphysema. Any
condition that causes an imbalance in any of these substances may trigger emphysema. Smoking is the major culprit,
but genetic factors can also cause this imbalance.
Smoking and Biologic Factors Leading to Emphysema. Emphysema caused by smoking most often occurs in the upper
lobes of the lungs. Some experts believe that smoking causes an imbalance between AAT and proteases in the
Heavy smoking can over?stimulate the immune system so that proteases are overproduced.
In addition, cigarette smoke triggers the release of damaging particles called oxygen?free radicals (or
oxidants) that deactivate AAT and make it ineffective. Emphysema, then, can develop in smokers who have
sufficient and even high amounts of AAT.
Only 15% to 20 all smokers develop emphysema, however. Other factors, such as genetic abnormalities, may need to
be present to increase susceptibility to airway damage. Some genetic factors being investigated are the following:
Researchers identified a group of patients who might have an inherited susceptibility to the effects of smoking,
so that severe COLD develops at an earlier age than usual.
Some people may have genetic factors that cause the lungs to be hyper?reactive to stimulants and allergens.
Some evidence points to genetic abnormalities in an important enzyme called microsomal epoxide hydrolase,
which is responsible for the breakdown of harmful oxidants found in cigarette smoke.
Researchers are also studying a variant of the gene for tumor necrosis factor, an immune factor responsible for
inflammatory damage in a number of diseases.
Alpha 1?Antitrypsin (AAT) Deficiency. An estimated 70,000 people Americans have inherited condition called alpha
1?antitrypsin deficiency (AAT) deficiency that caused emphysema in between 20,000 to 40,000 of them. This disorder
results in inadequate amounts of the protective enzyme AAT. Without adequate amounts of AAT, early and progressive
damage occurs in both the walls of the alveoli and the airways leading to them. Because smoke is a major toxin and
deactivates any residual amounts of AAT, smokers with AAT deficiency have almost no chance of escaping
emphysema. Nonsmokers also are at high risk, however. 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. 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.
Causes of Chronic Bronchitis
Biologic Factors and Smoking in Chronic Bronchitis. In chronic bronchitis, smoking triggers inflammation that causes
damage in the airways. The processes involved are less understood than in emphysema, but most likely include the
Chronic Obstructive Lung Disease
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
Enlargement of the mucus glands in the large airways of the lungs.
Overgrowth in the smooth muscle cells in the airway.
Bacteria and Viruses. Certain bacteria, particularly Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella
catarrhalis, are common in the lower airways of nearly half of chronic bronchitis patients. However, the role of
bacteria, viruses, and other organisms in causing chronic symptoms and inflammation is unclear. Some experts believe
that a low?level infection in the lungs may trigger an inflammatory reaction that continues to produce subsequent acute
The hallmark symptoms of chronic obstructive lung disease are progressive shortness of breath, frequently
accompanied by a phlegm?producing cough, with episodes of wheezing. Symptoms may vary, however, or others may
be present depending on which disease predominates.
Symptoms of Emphysema
Typically, first symptoms of emphysema occur in heavy smokers in their mid?50s. Emphysema patients have typically
lost between 50% 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.
Symptoms of A1AD?related emphysema tend to appear between the ages of 30 and 40. As with standard emphysema,
they include shortness of breath after exertion, wheezing, and exercise intolerance.
Symptoms of Chronic Bronchitis
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 are referred to as "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. (Such patients often have emphysema as well.)
Diseases with Similar Symptoms
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 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 symptoms of an asthma attack are coughing, wheezing, and shortness of breath (dyspnea). Wheezing when
breathing out is usually present during an attack. Typically, the attack begins with wheezing and rapid breathing, and as
it becomes more severe, all breathing muscles become visibly active. Irritation of the nose and throat, thirst, and the
need to urinate are common symptoms and may occur before an asthma attack begins. Some people first experience
chest tightness or pain or a nonproductive cough that is not associated with wheezing. Chest pain, 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.
Chronic Obstructive Lung Disease
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 Kartagener's
In 2000, chronic obstructive lung disease was responsible for 1.5 million visits to the emergency room, 726,000
hospitalizations, and 119,000 deaths. It is the fourth leading cause of death, and its death rate is increasing. Some
evidence also suggests that mortality rates from COLD may be even higher than current estimates, because such
patients are at greater risk for life?threatening conditions, notably heart attack and pulmonary embolism.
Chronic obstructive lung disease is progressive; although when patients stop smoking the disease often levels off.
Outlook for Patients with Emphysema.
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. Emphysema patients who experience severe involuntary weight
loss (which indicates muscle wasting) have a poorer outlook, regardless of lung function.
Outlook for Patients with Chronic Bronchitis.
Chronic bronchitis does not cause as much lung damage as
emphysema, although the airways become blocked from mucous plugs and narrowing due to inflammation.
This poor ventilation causes reduced levels of oxygen and high carbon dioxide levels.
Acute exacerbations are episodes that occur with both types of COLD, in which airways suddenly become obstructed
and symptoms worsen. Such events are associated with inflammation in the airways and are triggered by infections
about 80% of the time. They are not due to other complications of COLD, including pneumonia, heart failure, blood
clots, or a collapsed lung.
Acute exacerbations include the following symptoms:
Worsened shortness of breath. This is the most common and distressing acute symptom.
Increased volume of sputum, which is also typically thicker and greenish in color.
Acute exacerbations occur, on average, between two and three times a year in patients with moderate to severe COLD.
In about 80% of cases they are triggered by infections. Smokers have more episodes than nonsmokers. Acute
exacerbations are self?limited but they are still the most common cause of hospitalization in these patients. Patients
with frequent acute exacerbations of COLD are at higher risk for disease deterioration, including reduced quality of life
and increasing rates of hospitalizations. Furthermore, in patients who are hospitalized, the morality rates are 11%.
Survivors of a first hospitalization have a 50% change of rehospitalization within six months.
Effect on Quality of Life and Mood
Nearly half of patients with COLD report that daily activities are limited. They have trouble walking up stairs or
carrying even small packages. Breathing becomes hard work. More than half of patients with COLD often suffer from
insomnia. Such impairment in quality of life can greatly impair mood. If patients with COLD become anxious or
depressed, they may have a poorer outlook than those without these emotional problems. Even low?level depression
can impair health. Of some concern was a 2003 study reporting a higher rate of suicidal thoughts in patients with
COLD or asthma than in those with any other major chronic illness, including arthritis, diabetes, heart disease, and
cancer. It is not clear if these results are generally applicable. More research is needed. Certainly, however,
psychological interventions may be particularly helpful for these patients.
Medical Complications from Oxygen Deprivation
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:
Chronic Obstructive Lung Disease
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.
Eventually these activities can lead to very serious and even life?threatening conditions:
Patients with prolonged and severe hypoxia and hypercapnia are at risk for
acute respiratory failure, which
can cause heart rhythm abnormalities or other life?threatening conditions if not treated immediately.
Abnormally high 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.
The effects of COLD can threaten the heart. Chronic bronchitis itself is associated with a 50% higher risk of
death from coronary artery disease, even after considering the effects of smoking.
Low oxygen levels can also impair mental functioning and short?term memory.
Effects of Respiratory Infections
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.
Other Serious Medical Problems Associated with COLD
The smoking that accounts for COLD is also associated with high risks for pneumonia, lung cancer, stroke, and heart
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 (CT) screening is making it easier to detect this deadly cancer in earlier stages, and such
patients should consider having it done.
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.
Osteoporosis. Osteoporosis is a significant problem in patients with COLD. Many conditions associated with COLD
(smoking, vitamin D deficiencies, a sedentary lifestyle, the use of corticosteroids) put people at risk for bone density
loss and osteoporosis.
About 10 million adults are diagnosed with chronic obstructive lung disease each year, with about two million of them
having emphysema. (Because emphysema and chronic bronchitis so often occur together, it is difficult to determine the
number of emphysema patients versus those with chronic bronchitis.) Experts estimated, however, that more than half
of Americans with impaired lung function go undiagnosed. Many patients, even if their symptoms are severe, regard
their condition as a natural part of aging or due to lack of fitness and fail to seek medical evaluation.
General Risk Factors for Chronic Obstructive Lung Disease
The typical COLD patient is a smoker or ex?smoker with a pack?a?day habit of more than 20 years who is over 50.
Lung function gets worse as people get older.
According to a major 2002 government report, since 1987, more women than men have reported symptoms of COLD.
Furthermore, the death rate from COLD has increased dramatically in women since the early 1970s, and in 2000 the
number of women who died from these lung diseases surpassed deaths in men. The lungs of female smokers, in fact,
appear to be more susceptible to the effects of smoking and pollution than those of men. Studies suggest that COLD is
underdiagnosed in both genders, but especially in women. Caucasians are more susceptible to emphysema than their
African American peers.
On the positive side, the proportion of adults under 55 who are diagnosed with mild to moderate COLD has been
declining, indicating that the high death rate will level out, particularly as more people stop smoking.In particular, the
rate of COLD in young African Americans is declining significantly. (The rate in younger Caucasians is not decreasing
Chronic Obstructive Lung Disease
Over 80% of people who die from COLD are or were smokers. The longer a person smokes, the higher the risk for
emphysema. Once a smoker quits, the rate of lung function loss becomes the same as in a nonsmoker; however, much
of the lung damage incurred during smoking may be irreversible. About 10% to 20% of people who smoke more than
one pack a day develop significant airway obstruction, so other factors must be present.
Occupational Risk Factors
Workers exposed for a long time to toxic chemicals (such as silica or cadmium), industrial smoke, dust, or other air
pollutants are at increased risk for COLD. Such workers include miners, furnace workers, grain farmers, cooks, and
other food producers who work in small spaces.
Allergies and Asthma
Allergens, such as fungi, molds, and house dust, can cause changes in the lungs in some people that leads 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 deficiencies in certain nutrients (e.g., vitamins A, C,
and E, potassium, magnesium, and other food chemicals) could increase the risk for impaired lung function. Such
nutrients should be obtained from fresh fruits and vegetables, nuts, and whole grains ?? not from supplements.
Low Birth Weight
Low birth weight is associated with increased risk for COLD in later life, perhaps because poor nutrition during a
fetusâ€™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 inflammation, which may also affect the linings of
In spite of the widespread incidence and seriousness of chronic obstructive lung disease, studies strongly suggest that it
is underdiagnosed, especially in women. Some experts recommend that any adult smoker who complains of a daily
cough should be screened for COLD. In one 2002 study, nearly half of patients over 60 who regularly smoked had
Medical and Personal History
The physician will request a history that assesses the patient's risk factors. They include past and present smoking, low
exercise capacity (e.g., whether the patient has trouble climbing stairs, the distance he or she can walk), and exposure to
any industrial pollutants.
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")
The patient will also be asked to cough and produce sputum, if possible.
Chest Examination. The physician will next perform a simple examination of the chest area. Using a stethoscope, the
physician will listen to the patient's breathing:
Diminished or distant breath sounds are signs of emphysema. Tapping the chest will usually produce a hollow,
In chronic bronchitis, the physician is likely to hear wheezing or gurgling sounds.
Chronic Obstructive Lung Disease
Pulmonary Function Tests (Spirometry)
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. Spirometry measures the volume and force of air as it is exhaled
from the lungs. The patient is asked to breathe in and to exhale forcefully into an instrument several times. The force of
the air is then monitored and measured.
Using the results, the physician determines two important values:
The forced vital capacity (FVC). FVC is the
maximum volume of air that can be exhaled 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. Airflow is considered to be limited if the outflow of forced exhalation is persistently low over the
course of one second. Steady but faster than normal decline in FEV1 over time characterizes COLD.
Calculating a ratio of FEV1 to FVC is the best method for determining the presence and severity of COLD. The
severity of airway obstruction may be graded by the percentage of the patient's predicted FEV1:
Mild COLD is an FEV1/FVC ratio of 70% or higher, with a predicted FEV1 of less than 80%.
Moderate is an FEV1/FVC ratio of 60% to 69%, with a predicted FEV1 of less than 80%.
Moderately severe is an FEV1/FVC ratio of 50% to 59%
Severe is an FEV1/FVC ratio of 34% to 49%
Very severe is an FEV1/FVC ratio of less than 34%.
Tests for Measuring the Ability of the Lung to Exchange Gases
Arterial Blood Gas. The physician may request an arterial blood gas test to determine the amount of oxygen and carbon
dioxide in the blood (its saturation). Low oxygen (hypoxia) and high carbon dioxide (hypercapnia) levels are often
indicative of chronic bronchitis, but not always of emphysema. A blood gas analysis that shows very low oxygen levels
(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 for 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.
Chronic Obstructive Lung Disease
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 can accurately assess the severity of COLD and may be
used to determine the size of the air pockets (bullae) in the lungs. This imaging technique may even be useful for
assessing mild COLD.
Other Tests for Chronic Obstructive Lung Disease
Noninvasive Methods for Determining Severity. Questionnaires and short exercise tests are very useful for determining
the severity of COLD.
Test for ATT. Physicians will typically test for the protective enzyme, alpha 1?antiprotease (ATT or antitrypsin), which
is often deficient in COLD patients (although asthma patients may also have low levels).
Additional Blood and Sputum Tests. Additional tests may be required if the physician suspects other medical problems.
If pneumonia is present, for instance, blood and sputum tests and cultures may be performed to determine the cause of
Stopping Smoking and Healthy Lifestyle. Stopping smoking is the first and primary step to treating COLD and slowing
its progression. In addition, all patients should maintain a healthy diet rich in fruits and vegetables. An exercise
program may be useful, particularly if it is tailored to improve lung function.
Pulmonary Rehabilitation Programs. Patients with COLD need to be very active in managing their condition. Patients
might check with their physicians to determine whether a pulmonary rehabilitation program would be appropriate, if
one were available in their area. Such programs are conducted by a team of health professionals to improve lung
function. It involves medical treatments, exercise, breathing retraining, and psychological interventions, when needed.
If available and affordable, it can be extremely effective, particularly after acute exacerbations, for improving
symptoms, exercise capacity, quality of life, and mood. Patients with severe COPD may benefit from programs that last
at least six months.
Medications for Managing Chronic COLD. A major goal with the use of medications for COLD is to prevent acute
exacerbations, which can hasten deterioration of lung function. The main treatment strategy employs a stepped
approach with the use of increasingly potent medications depending on the patient's response:
Beta 2 agonists and anticholinergics, classes of drugs known as bronchodilators, open the airways in the lungs
and are the cornerstone of COLD drug therapy. In a major analysis, long?acting beta 2 agonists and
anticholinergics were most effective and reduced exacerbation rates by 20% to 25%.
Inhaled corticosteroids also reduce exacerbations by up to 25%. Studies are mixed on whether long?term use
improves lung function, and these agents may also have some adverse effects with long?term use. Inhalers that
combine a long?acting beta 2 agonists and a corticosteroid (Advair, Seretide, Symbicort) are even more
effective than either agent alone???reducing exacerbations by 30%. Some studies suggest they may offer
significant improvements in lung function and even improve survival rates, but more research is needed to
confirm such findings.
Antibiotics are sometimes used preventively, but they seem to have only a small effect in reducing illness
days. Experts do not recommend them routinely.
Oxygen Replacement. 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.
Surgery. If the patient no longer responds to medications, then surgery may be an option for some patients. Choices
may include bullectomy, lung reduction, or lung transplantation.
General Guidelines for Treating Acute Exacerbations
Acute exacerbations are episodes in which airways suddenly become obstructed and symptoms worsen. In general,
some expert groups recommend the following treatments for patients who need to be hospitalized:
Bronchodilators. An inhaled or nebulized beta2 agonist, with an anticholinergic agent added if the patient does
not respond. Consider oral or intravenous xanthines when the condition is very severe.
Antibiotics if there are signs of infections, particularly if the acute exacerbation is very severe. (Courses are
usually 5 to 10 days.)
Chronic Obstructive Lung Disease
Corticosteroids (short term use of oral corticosteroids in most cases; intravenous in severe cases). An
important 2003 study indicated that relapse rates were significantly reduced when the patient also took oral
corticosteroids in combination with antibiotics and bronchodilators for 10 days after the episode.
Noninvasive positive?pressure ventilation in patients at risk for respiratory failure.
Chest therapy may be helpful in some patients.
It is not always clear what triggers these episodes, so treatment can be controversial. Bacteria are obvious suspects, but
because COLD patients commonly harbor bacteria, it has been difficult to determine which or even whether organisms
are responsible. One 2002 study suggested that some episodes may be caused by changes in the strains of bacteria that
are commonly present rather than an introduction of a new bacteria. In other cases, viruses and atypical bacteria may be
responsible. In some acute exacerbations, however, no sign of infection is present. As with asthma, an inflammatory
response in the airways unrelated to infection may suddenly cause changes that bring on an attack (although it is likely
to be different from this response in asthma patients). In any case, even minor obstruction in the airways may be able to
produce an acute exacerbation.
Treating Complications of Advanced COLD
COLD is associated with a number of complications as lung function worsens. Various treatments may be required.
Opioids. Opioids, such as morphine, are generally not used for patients with COLD because of a concern that they may
reduce respiratory function. Nonetheless, some studies are reporting that low doses of oral morphine can improve
severe breathlessness in patients who cannot find relief from other methods. Such agents can cause nausea, vomiting,
Antidepressants and Antianxiety Agents. Antidepressants or antianxiety medications may be helpful.
Improving Sleep. More than half of patients with COLD often suffer from insomnia. Most of the standard sleep agents
may impair lung function. Newer ones, such as zolpidem (Ambien), zaleplon (Sonata), and zopiclone (Imovane), may
be less hazardous than older agents. Tricyclic antidepressants may also be helpful without significant effects on
breathing. Behavioral methods are the best approach to this problem, however. [SeeWell?Connected Report #27
Treating Heart Failure. When patients are in advanced stages of COLD, they may need treatment for fluid
accumulation and congestive heart failure. [See Well?Connected, Report #13, Congestive Heart Failure.]
Administering Inhaled Drugs
Most COLD drugs are inhaled using metered dose inhalers, dry powder inhalers, or nebulizers.
Metered?Dose Inhaler. The standard device has been the metered?dose inhaler (MDI). This device, particularly when
used with a holding chamber, allows precise doses to be delivered directly to the lungs. 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. The holding chamber, or spacer, allows the patient additional time to inhale the medication and so improves
delivery. They vary, however, in their ability to deliver medication. For example, in one study the AiroChamber?Plus
was more effective than the EasiVent in delivering an inhaled steroid. It should be noted that often MDIs 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.
Breath?Actuated Inhalers. Breath?actuated rotary inhalers (e.g., Easi?Breathe and Autohaler) deliver the drug directly
to the back of the throat as the user inhales. Their primary advantage over the MDI is their ease of use. They also do
not use CFCs as propellants. In comparison studies, patients have been very successful with the breath?actuated
Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2 agonists or corticosteroids directly
into the lungs. They also do not used CFCs. Such devices include Rotahaler, Spinhaler, Turbohaler, Clickhaler,
Easyhaler, Diskhaler, Discus, Twisthaler, Spiros, and others. DPIs are 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. In one study, for example, the Turbohaler was easier to use than the Diskhaler and so achieved
better delivery. The Discus is another effective DPI; it has a dose counter and protects against exhalation effects. More
research is needed.
Humidity or extreme temperatures can effect their performance, so they should not be stored in humid places (e.g.,
bathroom cabinets) or locations subject to high temperatures (e.g., glove compartments during summer months).
Other Hand?Held Inhalers. Respimat delivers a fine?mist spray that is created by forcing the liquid medication
through nozzles. It does not use any propellant.
Chronic Obstructive Lung Disease
Nebulizers. A nebulizer is a device that administers the drug in a fine spray that the patient breathes in. They are often
used in hospital settings or when the patient cannot use an inhaler. Nebulizers may be important for delivering newer
agents used in asthma treatment.
Anticholinergic agents relax the bronchial muscles. They are generally inhaled and act as a bronchodilator over time.
Brands and Benefits. Anticholinergics used for COLD include ipratropium (Atrovent) and tiotropium (Spiriva).
Ipratropium is the older agent and experts recommend it as the first choice in treating COLD. It has a very slow onset
and can be used as maintenance therapy for people with emphysema and chronic bronchitis. Anticholinergic agents
have few severe side effects.They are less likely to impair sleep than the other standard inhaled medications.
A patient should not take more than 12 inhalations per day. Tiotropium (Spiriva) requires only one daily inhalation and
evidence suggests it may be particularly effective for COLD patients. A single inhaler containing both ipratropium and
the common beta2 agonist albuterol (Combivent) may prove to be better than either 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. Others include
isoproterenol (Isuprel, Norisodrine, Medihaler?Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair),
terbutaline (Brethine, Brethaire, Bricanyl), bitolterol (Tornalate), and isoetharine (Bronkometer, Bronkosol), which is
available in nebulizers. Newer beta2 agonists, including levalbuterol (Xopenex), have more specific actions than the
standard agents. Most are administered through inhalation and are effective for three to six hours.
Long?Acting Beta2 Agonists. Long?acting forms, salmeterol (Serevent) or formoterol (Foradil), are proving to be
particularly effective for COLD. Major analyses suggest they reduce exacerbations by 20% to 25%. They may help
inhibit bacteria from building up on the airways and may offer real improvements in lung function. In fact, unlike
short?acting forms, these beta2 agonists may even have anti?inflammatory properties.
Inhalers that combine a long?acting beta 2 agonist and a corticosteroid (Advair, Seretide, Symbicort) are even more
effective than either agent???reducing exacerbations by 30%. Some studies suggest they may offer significant
improvements in lung function and even improve survival rates, but more research is needed to confirm such findings.
Side Effects. Side effects of both long?and short?acting beta2 agonists include anxiety, tremor, restlessness, and
headaches. Patients may experience fast and irregular heartbeats. A physician should be notified immediately if such
side effects occur, particularly in people with existing heart conditions. Such patients face an increased risk for sudden
death from cardiac related causes. This risk is higher with oral or nebulized agents, but there have also been reports of
heart attacks and angina in some patients using inhaled beta2 agonists.
Loss of Effectiveness and Overdose. There has been some concern that short?acting beta2 agonists become less
effective when taken regularly over time, increasing the risk for overuse. The degree to which this affects the airways is
uncertain. In some studies, the duration of action has declined but the peak effect appears to be preserved, making these
drugs still useful for acute attacks. Regular use of long?acting beta2 agonists may reduce the effect of short?acting
It's a major concern that patients who perceive beta2 agonists as being less effective may over?use them. Overdose can
be serious and in rare cases even life?threatening, particularly in patients with heart disease.