The Lungs

The lung is a magnificent organ that performs a multitude of vital functions every second of our lives. Breathing is the most essential of these functions. With each breath, the lungs take in oxygen and remove carbon dioxide. The air (oxygen) we breathe enters the lungs via the main windpipe (trachea), which branches into two main tubes supplying the right and left lung, respectively. These tubes progressively branch 22 additional times to form more than 100,000 smaller tubes (bronchi, bronchioles) and more than 300 million air sacs (alveoli), which are only about 0.3 mm in diameter. Thus, the surface area of the lungs is huge - larger than the surface of a person's skin. In fact, if all the airways and air sacs of a person's lungs were laid flat on the ground, they would cover more than 100 square yards, which is larger than the size of a tennis court. Because the walls of these air sacs are 1/50th the thickness of tissue paper and are bathed with millions of tiny blood vessels called capillaries, there is an easy and efficient exchange of oxygen and carbon dioxide between the body and the environment. The lungs are also important in the body's defense against infection and other harmful environmental factors. While the nose is the first line of defense against inhaled harmful materials, the lungs provide the second line of defense. Inhaled particles (smoke, pollution) or infectious agents (bacteria, viruses) pass through the mouth or nose and lodge in the lungs. Mucus, a sticky fluid produced in the lungs, can trap these inhaled agents and aid the lungs' protective white blood cells (macrophages, neutrophils) in the engulfment and destruction of bacteria and other harmful materials. Coughing is the best way to clear mucus and other materials from the lungs; however, the larger airways have tiny hairlike cells called cilia that aid in this process. The cilia beat with a rhythm fast enough, and a force sufficient enough, to propel mucus and cells up the airways to be coughed out or swallowed. When a person smokes, the cilia are inactivated or destroyed, allowing thick mucus to accumulate and compromise lung defense.

This article was contributed by Dr. Dennis Doherty, co-chairman of the National Lung Health Education Program and Chief of Pulmonary and Critical Care Medicine at the University of Kentucky Medical Center. It provides a basic overview of the lungs and how they function - information important to understanding the effects of COPD on this vital organ.

What is COPD?

Chronic obstructive pulmonary disease, or COPD, is an umbrella term for two respiratory illnesses - chronic bronchitis and/or emphysema. There are 16 million Americans who have been diagnosed with COPD, of whom 14 million have chronic bronchitis and 2 million have emphysema. COPD results primarily from smoking tobacco. Years of smoking cause damage to the airways in the lungs. This lung damage continues to progress with the use of tobacco. Average current and former smokers will likely not notice or acknowledge symptoms for several years. Typically, they will begin noticing the first symptoms of shortness of breath when they reach their 40s. However, earlier signs of COPD are often present. These include chronic cough and increased mucus production. Recognizing these early signs is important because lifestyle modifications, such as smoking cessation and avoiding respiratory irritants, can be made to prevent additional damage to the airways. In technical terms, COPD is a slowly progressive disease that is characterized by a decrease in the ability of the lungs to maintain the body's oxygen supply and remove carbon dioxide. As a result of this decrease in lung function, COPDpatients alter their lifestyles because they become short of breath after minimal exertion. For example, instead of climbing a flight of stairs COPD patients take the elevator. Physical activities also take longer to complete. Lawn mowing that a COPD patient might have finished in 40 minutes only a year ago may now take an hour to do.

Current COPD Treatments

Compared with discussion of asthma therapy, the topic of COPD management has been relatively neglected in the past. That is changing, however. Major guidelines for treating COPD have been issued in recent years by the American Thoracic Society, British Thoracic Society, and European Respiratory Society. More recently, there has been a major statement on COPD from the scientific committee of the Global Initiative for Chronic Obstructive Lung Disease, a joint project of the National Heart, Lung, and Blood Institute and the World Health Organization. The treatment objectives for COPD include slowing the accelerated decline in lung function; relieving symptoms, such as shortness of breath and cough; improving daily lung function; decreasing exacerbations; and improving quality of life. The most important step in treating COPD is to encourage smoking cessation. There is a direct relationship between smoking and accelerated loss of lung function in susceptible persons. Smoking cessation has been shown to stop this accelerated loss, so that decline in lung function returns to the normal rate seen with aging. Most experts advocate early detection of COPD and active intervention to stop smoking. Smoking cessation has been shown to halt the accelerated loss of lung function associated with COPD. It also stops the loss of lung function in younger patients with relatively mild disease. However, any COPD patient can benefit from smoking cessation, no matter how advanced the disease.

Medications

Medications can be used to relieve symptoms of COPD, particularly shortness of breath, and to treat respiratory tract infections that can worsen COPD. Currently available medications that are helpful in treating COPD include bronchodilators and corticosteroids. Antibiotics are useful in treating exacerbations caused by bacterial infections. No medications have been found to cure the disease or reverse the loss of lung function caused by smoking. Medications of different classes have been found to be useful in treating COPD and can be used in combination. The overall approach to managing stable COPD involves a stepwise increase in treatment, depending on the severity of the disease.

Bronchodilators

Bronchodilators are a class of medications that relax the muscles around the bronchi to allow easier breathing. They are typically indicated for the relief of bronchospasm, which are contractions of the smooth muscle in the walls of the bronchi and bronchioles that cause the airways to constrict or narrow. Anticholinergic bronchodilators fall into this class of COPD medications, as do short-acting beta2-agonists, long-acting beta2-agonists, methylxanthines (e.g., theophylline), and a combination of an anticholinergic bronchodilator and a short-acting beta2-agonist. All major guidelines for COPD management recommend beginning treatment with aerosol bronchodilators, which are inhaled directly into the lungs and have few side effects.

Anticholinergic bronchodilators

In response to irritants such as cigarette smoke, the body produces a chemical "messenger" called acetylcholine that induces the airways to constrict. Anticholinergics are the only medications that act by blocking acetylcholine, thereby relaxing the muscle tissue and keeping the airways open. Anticholinergic medications work via part of the parasympathetic nervous system, which controls airway size. In addition to helping COPD patients take fuller breaths, maintenance use of anticholinergic medication may also help lower the incidence of acute exacerbations in COPD patients. The American Thoracic Society, a leading medical authority on respiratory illnesses, recommends anticholinergics as the first line of maintenance therapy for patients with daily COPD symptoms. The Global Initiative for Chronic Obstructive Lung Disease also recognizes anticholinergics as an important treatment for COPD. Anticholinergics are most often administered through metered-dose inhalers, or "puffers", as they are commonly called. The effects of the medication generally last from four to six hours, so physicians typically prescribe use four times a day. Inhaled anticholinergics are minimally absorbed, resulting in relatively few side effects. Some common side effects of ipratropium bromide, an inhaled anticholinergic therapy, include cough and nervousness. Anticholinergic bronchodilators, as a class, are the number one prescribed bronchodilator used in the treatment of COPD. Currently, the leading anticholinergic medication prescribed by physicians is ipratropium bromide. It is sold alone under the brand name ATROVENT, Inhalation Aerosol or in combination with albuterol sulfate under the brand name COMBIVENT, Inhalation Aerosol.

Beta2-agonists

Beta2-agonists work via part of the nervous system that controls muscle tissue around the airways. They work by stimulating receptors in the sympathetic nervous system, leading to dilation of air passages. Two types of beta2-agonists are available: short-acting beta-agonists and long-acting beta-agonists.

Short-acting beta2-agonists

These medications are recommended by the American Thoracic Society for patients with COPD who experience intermittent symptoms. They are also used as a "rescue" medication to fend off an impending attack of shortness of breath. Short-acting beta2-agonists are typically prescribed along with anticholinergics to open up the airways of COPD patients with continuing symptoms. The short-acting beta2-agonist most commonly prescribed by physicians is albuterol. In clinical studies, the most common side effects of albuterol included tremor, nausea, tachycardia, palpitations and nervousness.

Long-acting beta-agonists

These bronchodilators are taken twice a day and, like short-acting beta-agonists, work via part of the nervous system that controls muscle tissue around the airways. They are recognized as a treatment for COPD by the Global Initiative for Chronic Obstructive Lung Disease. Long-acting beta-agonists are often prescribed for nighttime breathing problems because they provide up to 12 hours of relief. Patients using long-acting beta-agonists need to be reminded to continue using their short-acting beta-agonist for "rescue" therapy, because long-acting beta-agonists do not work as quickly and are indicated for use only twice a day. The most common side effects seen with use of long-acting beta-agonists by patients with COPD include headache, upper respiratory tract infection, nasopharyngitis and cough.

Combination bronchodilators

The combination of an anticholinergic and short-acting beta2-agonist works via the part of the nervous system that controls airway size, as well as the part that controls muscle tissue around the airways. Increased efficacy is seen with this combination agent over the individual components, without an increase in side effects. The most common side effects include bronchitis, upper respiratory tract infection and headache.

Theophylline

Another bronchodilator used in the treatment of COPD is theophylline, which is taken orally. Theophylline affects many parts of the body, including muscle tissue and the heart. It works by opening up the airways, increasing muscle endurance, and decreasing muscle fatigue. At one time, theophylline was the most widely prescribed COPD medication, but it has lost favor because of side effects. However, theophylline may have benefits that go beyond bronchodilation, and it is still an important part of COPD management. Theophylline is taken orally once or twice a day, so it may be particularly valuable for noncompliant patients who cannot optimally use aerosol therapy. The dosage should be adjusted to reach a therapeutic serum level, so blood levels should be monitored. However, some patients experience side effects even at low serum levels. The most common side effects seen are nausea, vomiting, headache and insomnia.

Corticosteroids

Currently, inhaled corticosteroids are not indicated for the treatment of COPD. They are the cornerstone of asthma therapy, but have a limited role in the maintenance of lung function in patients with COPD. Only about 10 percent of patients with COPD show a significant improvement in lung function when treated with corticosteroids. The reason is that different mediators cause inflammation in asthma and COPD. The mediators that cause inflammation in COPD have only limited responsiveness to corticosteroids, while those mediators responsible for inflammation in asthma are dramatically affected by inhaled corticosteroids. Surveys of clinicians' prescribing habits, however, have shown little difference in the use of inhaled corticosteroids for asthma patients and for COPD patients. Guidelines for the treatment of COPD suggest that because inhaled corticosteroids play only a minor role in the maintenance treatment of COPD and may produce systemic side effects, they should be reserved for patients whose symptoms are not optimally controlled with bronchodilators. This subgroup of patients should receive inhaled or oral corticosteroids for a trial period. If a significant objective clinical response is not achieved, corticosteroids should be discontinued. When a benefit is observed with oral corticosteroids, the dose should be tapered to the lowest possible dose. At that point, a trial of an inhaled corticosteroid should be initiated. The most common side effects of inhaled corticosteroids include upper respiratory infection, headache and pharyngitis.

Antibiotics

Antibiotics may be given to patients with COPD for acute bacterial infections of the respiratory tract, including sinusitis, acute bronchitis and some types of pneumonia. Antibiotics are also used to treat exacerbations when symptoms of infection are present, such as fever, increased cough and sputum changes.

COPD Facts

COPD is the fourth leading cause of death in the United States. In 1998, approximately 107,000 Americans died of COPD. COPD's prevalence and death rate are rising. In 2025, COPD is projected to become the third leading cause of death in the United States. COPD has a higher mortality rate than asthma (5,438 deaths from asthma in 1998 versus 107,000 deaths from COPD in 1998). The highest increase in mortality has been in white women, as observed between 1960 and 1998. An estimated 30 million Americans have COPD. However, only 16 million adult Americans have been diagnosed with disease. In 2000, the annual cost to the nation for COPD was estimated to be approximately $30.4 billion. Health care expenditures accounted for $14.7 billion, and indirect costs (decreased income due to loss of work or premature death) were $15.7 billion.

Causes of COPD

Cigarette, Pipe, cigar and other types of tobacco smoking. Passive exposure to cigarette smoking. Occupational dusts and chemicals. Air pollution. Genetic factors (less than 5 percent of cases).

Diagnosing COPD

Physicians can determine whether a patient may have COPD based on the presence of three main symptoms: chronic cough, excess mucus production, or shortness of breath. Physicians can diagnose COPD with the assistance of a device known as a spirometer, especially in the early stages of the disease before the symptoms are debilitating or even before they are recognized and acknowledged by the patient. According to the National Lung Health Education Program, all persons aged 45 or older who currently smoke or have quit smoking should have spirometric testing.Spirometry can also be used to monitor progression of COPD. Testing with spirometry determines the presence and severity of the airway obstruction. The test is easy to administer, takes only a few minutes to complete, and is noninvasive. It can be conducted in primary care physicians' offices that are equipped with a spirometer. Patients take a deep breath and exhale into the spirometer as hard and fast as they can for a minimum of six seconds. The spirometer is connected to a computer that records the volume of air exhaled in one second (forced expiratory volume in one second, or FEV1) and the total amount of air exhaled (forced vital capacity, or FVC). The FEV1/FVC ratio is the primary measurement in identifying an obstructive impairment of the airways. Spirometry is simple, inexpensive and effective in testing for decreased lung function in past and current smokers. In fact, smokers and ex-smokers should have regular spirometric tests performed. Spirometry is also effective in detecting decreased lung function in other high-risk persons, such as those with occupational exposures to dusts or chemicals.

Symptoms of COPD

The symptoms of COPD are usually constant and can slowly progress over many years, unlike the episodic, variable symptoms of asthma.

The common symptoms of COPD include:

• breathlessness even after mild exertion
• chronic coughing, which may or may not produce mucus
• frequent clearing of the throat
• chest tightness and wheezing

Because COPD is a progressive disease, patients may attribute early symptoms to aging or being out of shape. They may also believe they only have a benign smoker's cough. Although symptoms of COPD may be present earlier, people are typically diagnosed with COPD when they are older than 45 and have at least a 20 pack-year smoking history. Pack-years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day ÷ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history). According to the National Lung Health Education Program, the symptoms of COPD develop because of airway obstruction, resulting in the lungs' inability to effectively use oxygen and remove carbon dioxide. Recognizing a persistent cough with or without mucus production as an early indicator of COPD can help prevent extensive damage to the airways.

COPD Exacerbations

Typically brought on by respiratory tract infections, exacerbations of COPD are characterized by increased coughing and mucus production; change in mucus color; and shortness of breath, possibly with wheezing. Patients may also show a decrease in FEV1 during an exacerbation. On average, COPD patients experience an acute exacerbation once or twice a year. However, as a patient's FEV1 falls, the frequency and severity of exacerbations increase. Emergency room visits and hospitalization may be required for patients experiencing exacerbations. In 1997, there were approximately 13.4 million physician office visits and more than 600,000 hospitalizations for COPD.

How Does COPD Differ from Asthma?

Although COPD and asthma have similar characteristics such as the signs of coughing and wheezing, they are two distinct conditions in terms of disease onset, frequency of symptoms and reversibility of airway obstruction.

1. The onset of asthma typically occurs during childhood or adolescence. COPD most often develops in smokers and former smokers who are in their mid-40s.

2. Exacerbations of asthma - characterized by recurrent wheezing, shortness of breath, chest tightness and cough - often have identifiable triggers such as allergens, cold air or exercise. However, exacerbations in COPD patients are commonly caused by respiratory tract infections.

3. With treatment, asthma patients have near-normal lung function and are symptom-free between exacerbations. COPD patients rarely experience a day without symptoms. Airflow obstruction in COPD sufferers is only partially reversible with smoking cessation and bronchodilator use.

Despite these distinctions, COPD is often misdiagnosed, and persons with COPD are treated instead for asthma. In fact, a survey of 75 primary care physicians revealed that they prescribe similar medications for COPD and asthma even though the appropriate treatments differ. The first-line maintenance therapy for most patients with asthma is an inhaled corticosteroid, with the addition of a bronchodilator if needed to control symptoms. However, the reverse is true for the treatment of COPD. Bronchodilators are the first-line maintenance treatment for COPD. Treatment with inhaled corticosteroids is reserved only for selected patients whose COPD is not adequately managed with bronchodilators. Survey findings also showed that primary care physicians had a low basis of suspicion for COPD.