Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD)
[Search Terms: COPD, Emphysema, Chronic Bronchitis, Smokers Cough]

INTRODUCTION

Chronic obstructive pulmonary disease, or COPD, is the name given to a group of disorders characterized by narrowing of the breathing tubes that limits (obstructs) the movement of air in and out of the lungs. Specific diseases in this group include chronic bronchitis and emphysema. In most cases, COPD is associated with cigarette smoking. In the older literature and in certain parts of the world, COPD has been called chronic obstructive lung disease (COLD) or chronic obstructive airway disease (COAD), but the term COPD is now preferred.

COPD is often confused with asthma, because some of the symptoms and physical signs are similar. The major difference is that in asthma, most (or in many cases all) of the obstruction to airflow in the bronchial tubes is reversible. In other words, when asthmatic patients are examined or tested in between attacks of their asthma, their lung function is often normal. In contrast, once COPD is established, the lung function is never normal. When patients have flares or “exacerbations” of COPD, they typically get better with administration of medication, but their lung function never normalizes, although it may return to their pre-exacerbation baseline.

Chronic Bronchitis is a clinical diagnosis, based on a history of cough and sputum production on most days, for 3 months of the year, for 2 consecutive years. In contrast, a diagnosis of Emphysema cannot be made on clinical grounds alone. Because emphysema involves destruction of lung tissue, evidence of that destruction is required to confirm the diagnosis. In the past a definitive diagnosis could not be made without pathologic examination of lung tissue (e.g., at autopsy or in surgically resected lung), although a reduction in diffusing capacity (a lung function measurement that reflects the number and integrity of small blood vessels involved in oxygen exchange in the lung) has been used to infer the presence of emphysema. Today, computed tomography (CT) scans of the chest can visualize emphysema.

The number of cases of COPD is increasing worldwide, and data suggest that the true number of cases is far greater than appreciated, because COPD often goes undiagnosed. Even more concerning is the fact that deaths from COPD are increasing at a time when deaths from most other major diseases are unchanged or decreasing. COPD is not “curable,” but there are several interventions that can positively impact the natural history of the disease. In addition, there are a number of approaches, including medications and non-pharmacologic interventions, which can significantly improve function and quality of life in patients with COPD.

HOW DOES COPD DEVELOP?

In 2001, a panel convened jointly by the US National Heart, Lung & Blood Institute and the World Health Organization released a report of their Global Initiative for Chronic Obstructive Lung Disease, commonly referred to as the “GOLD Guidelines” (1). In this report, COPD is defined as “a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.”

Most COPD is associated with smoking, and 80-90% of patients with COPD have a smoking history of at least 10-20 “pack years.” (“Pack years” is a convenient term that permits quantification of an individual’s smoking history. To calculate pack years, the average number of packs smoked per day is multiplied by the number of years: e.g., 1 pack per day x 20 years = 20 pack years.) Although cigarette smoking is the most important risk factor for COPD in the United States and most of the developed world, exposure to fumes from biomass fuels is a major factor in the developing world. The World Health Organization (WHO) estimates that there are 400,000 COPD deaths per year related to exposure to biomass fuels.

In the right setting, these noxious or environmental exposures initiate an inflammatory response in the lungs and airways that results in damage to the lung tissue. The inflammatory response is characterized by increased numbers of specific inflammatory cells that migrate from the bloodstream into the lung and airways. Most investigators believe that the cell that contributes most to the lung damage in COPD is the neutrophil. Neutrophils are one type of white blood cell that plays an important role in the body’s response to infection. However, when present in large numbers, especially in the absence of infection, the potent chemicals they release can damage the tissues. Neutrophil products, especially proteases, have many effects in the lungs and airways. They may result in:
        • Increased mucus (phlegm) production
        • Damage to the thin walls of lung air spaces (alveoli)
        • Loss of elasticity of the lung tissue
        • Scarring and narrowing of the small bronchial tubes

All of these contribute to the breathing difficulties experienced by patients with COPD. Inflammation around the airways leads to swelling and sometimes scarring that results in a reduction in the size of the bronchial tubes themselves. Obviously, it is harder to move air in and out of the lungs if the tubes are smaller than normal. Loss of elasticity of the lung tissue, caused by specific proteases that degrade elastic fibers (e.g., neutrophil elastase), results in collapse of airways during exhalation, which makes it much harder to breathe. Increased mucus stimulates coughing, but the patient with COPD often has difficulty coughing up this mucus through narrowed bronchial tubes. In addition, mucus can sometimes plug up small airways far out in the lungs, thereby interfering with the ability of fresh air (and oxygen) to reach the site in the lung where it is absorbed into the bloodstream.

Genetics may be important. Although 80-90% of patients with COPD have a history of smoking, only about 20% of smokers develop COPD. This suggests an interaction between exposure to smoke and another risk factor. It seems likely that genetic factors predispose individuals to the damage produced by smoke – what is often referred to as a “gene-by-environment interaction.”  The best understood genetic factor is alpha1-antitrypsin deficiency. This is a recessive trait, found mainly in individuals of Northern European ancestry. It is estimated that approximately 100,000 Americans have this gene mutation that results in the reduced ability to inhibit the activity of some of the proteases that cause lung damage. A number of other genes have been studied, but to date, no mutations other than alpha 1-antitrypsin have been convincingly linked to the development of COPD.

HOW COMMON IS COPD?

Studies from the US Centers for Disease Control report that approximately 12 million adults had a diagnosis of COPD in 2001. However, COPD is clearly underdiagnosed, and the National Health and Nutrition Examination Survey (NHANES III) http://www.cdc.gov/nchs/products/elec_prods/subject/nhanes3.htm of 20,050 adults in the United States suggests that as many as 24 million Americans are affected. The WHO estimates that as of 2007, there were 210 million people throughout the world with COPD. In addition, the WHO estimates 1.1 billion smokers worldwide, increasing to 1.6 billion by 2025. As public sentiment and policy make smoking less acceptable in Europe and North America, tobacco companies have focused their marketing efforts on low- and middle-income countries where the rates of smoking are increasing at an alarming rate.

THE CONSEQUENCES OF COPD

The burden of COPD is enormous. In the United States it is a leading cause of death, illness, and disability. In 2004 there were 121,987 deaths from COPD in the United States, making this the 4th leading cause of death. Projections suggest that COPD will be the 3rd highest cause of death in the US by the year 2020. According to the WHO, COPD is tied with HIV/AIDS as the 4th/5th leading causes of death worldwide, after coronary heart disease, cerebrovascular disease, and acute respiratory infection.Perhaps more importantly, deaths from COPD are rising at a time when deaths from other major diseases are not

 

 

 

http://www.cdc.gov/nchs/fastats/copd.htm. From 1965 to 1998, the US death rates fell for coronary heart disease (-59%), stroke (-64%), other cardiovascular disease (-35%), and mortality from all other causes (-7%). During this same period, deaths from COPD increased by 163%.  Ironically, as the role and value of women in US society has grown, so has marketing of tobacco products to women (the “Virginia Slims” phenomenon), and the prevalence of smoking by women has increased significantly since the 1940s. Unfortunately, so has the prevalence of COPD. From 1980 to 2000 the COPD death rate for women grew much faster than the rate for men, and in 2000, for the first time, more women (59,936) than men (59,118) died from COPD.

In addition to causing death, COPD has a significant impact on individuals and on society. In 1990, the World Bank and WHO identified COPD as the 12th leading cause of disease burden worldwide; estimates suggest that by the year 2020 COPD will be 5th. COPD accounted for approximately 1.5 million emergency department visits and 726,000 hospitalizations per year in the US in 2000. The total estimated cost of COPD in the US in 2002 was $32.1 billion ($18 billion in direct costs and $14.1 billion in indirect costs, such as lost wages).

WHEN SHOULD I BE CONCERNED THAT I HAVE COPD?  

            Answer: "Cough and spit are not normal!"

Although the diagnosis of COPD is not difficult to make, many patients (perhaps the majority) remain undiagnosed. This reflects, in part, the insidious onset of symptoms. The most common symptoms are:

        • Shortness of breath
        • Cough
        • Sputum (phlegm or mucus) production

Chronic cough and sputum production may occur years before lung function becomes abnormal and are often attributed to smoking – the “smokers cough.” It is important to understand that this is not normal, and any cough that persists more than a few weeks beyond a respiratory illness should probably be investigated. In an analysis of the NHANES III data of 20,050 adults in the US, approximately 26% of symptomatic smokers above the age of 45 had abnormal lung function tests consistent with COPD (2).

Shortness of breath may occur some time after the onset of cough and sputum, or it may occur in the complete absence of these symptoms. Shortness of breath does typically not occur until there has been a significant loss of lung function. Because healthy individuals all have more lung function than is needed for most activities of daily living in modern society, it is possible for lung function to deteriorate significantly before an individual becomes symptomatic. The difference between the lung function required for strenuous exercise and that utilized at rest is “reserve.” Unless the system is tested (i.e., exercise), a disease process can eat into this reserve without producing shortness of breath. In early COPD, shortness of breath typically occurs only with exercise, and individuals often attribute it to aging or to being “out of shape.” While both age and conditioning may be contributing factors, shortness of breath or decreased exercise tolerance in an individual who is at risk for development of COPD warrants evaluation.

Other symptoms experienced by some patients with COPD include wheezing, chest tightness or chest pressure, inability to take a deep breath or to breathe out, and difficult doing activities that were previously routine.

 

DO I NEED A DOCTOR TO DIAGNOSE COPD?

Not only do you need a doctor for this, but your doctor may need some tests. In the evaluation of a patient with possible COPD the following tests may be useful – although it is unlikely that they will all be ordered at once:
        • Medical History
        • Physical Examination
        • Chest X-ray
        • Routine blood tests
        • Spirometry
        • Oxygen Saturation Measurement (using a probe that clips on to your finger)
        • Arterial Blood Gas (blood drawn from an artery, usually in your wrist)
        • Chest CT scan
        • Alpha 1-antitrypsin level (blood test)

Although a history and physical examination can suggest a diagnosis of COPD, there is no way that COPD can be distinguished from asthma or certain other conditions on this basis alone. Similarly, a chest X-ray can suggest COPD or emphysema, but this is really no more sensitive than the history and physical. A CT scan of the chest can reveal emphysema, which appears as “swiss cheese”-like holes in the lung, but it will not diagnose the non-emphysema forms of COPD or asthma. 

Blood tests and measurement of oxygen by finger probe or arterial blood draw provide information about how severe your breathing problems are, but they are not specific for diagnosing COPD. The alpha 1-antitrypsin blood test does identify those individuals with this rare condition that leads to COPD – but it does not provide information about whether lung involvement has occurred.

The definitive test for COPD is a breathing test, sometimes called a Pulmonary Function Test, a Lung Function Test, or Spirometry. This tests measures how much air you can blow out of your lungs, and how fast you can do it. No matter how hard you try, it takes longer to blow air out through narrowed bronchial tubes than it does through normal-sized tubes. Predicted values for your lung function are available based on your age, size, gender, and race, and your performance on the test is compared to these predicted values. The diagnosis of COPD is based on these results, and the severity of your COPD can be graded depending on how close or far your values are from predicted.

HOW SPIROMETRY WORKS

Spirometry is the most commonly used screening test of lung function. Although it has been built into many large and sophisticated machines that measure all aspects of lung function, most modern spirometers are small, stand-alone machines, very often small enough to hold in your hand. The concept is simple: you fill your lungs up with air, then blow it out through a tube that goes into the machine. The spirometer then measures the amount of air you blew out, and how fast you did so. In practice, this test is sometimes difficult for people with advanced COPD. Because these people have trouble just breathing, breathing hard into the machine is sometimes uncomfortable. It can make you short of breath, and it may make you cough.

The spirometer has a computer that calculates the values from your test, compares them to your predicted values, and displays these values on a report. Although most physicians look at a graphic depiction of the entire maneuver, called the flow-volume curve, there are 2 values that are of special interest: the FEV1 and the FVC. The FEV1 (Forced Expiratory Volume in 1 second) is a measure of the amount of air you can blow out in 1 second, and reflects the size of your airways (i.e., it takes longer to blow air out through a small tube than through a larger one). The FVC (Forced Vital Capacity) measures the total amount of air exhaled, and is a general measure of the size of your lungs.

In healthy individuals, at least 70% of the vital capacity should be exhaled in the first second. Thus the FEV1/FVC ratio should be greater than 70%. By convention, an FEV1 to FVC ratio of less than 70% following the administration of a bronchodilator (medication that relaxes the bronchial tubes) is required to confirm the diagnosis of COPD. Based on the GOLD Guidelines, updated in 2007 (3), the severity of COPD is classified as follows:

Classification of COPD Severity
        Stage I Mild FEV1/FVC < 0.70; FEV1 ≥ 80% predicted
        Stage II Moderate FEV1/FVC < 0.70; FEV1 50 – 80% of predicted
        Stage III Severe FEV1/FVC < 0.70; FEV1 30 – 50% of predicted
        Stage IV Very Severe FEV1/FVC < 0.70; FEV1 ≤ 30% predicted
                            http://www.goldcopd.org

THE NATURAL HISTORY OF COPD

COPD is usually a progressive disease, and once established tends to progress inexorably. Although there are many pharmacologic and non-pharmacologic interventions that can improve symptoms, performance, and quality of life, only 3 things have been convincingly shown to change the natural history of the disease:
        1) Smoking Cessation
        2) Long-term Oxygen Therapy (LTOT), in patients whose oxygen levels are too low
        3) Lung volume reduction surgery in a very small, select group of patients

 

Smoking Cessation

Interestingly, in healthy individuals, lung function improves through childhood and early adulthood, and then begins to deteriorate slowly. Much as the elasticity of the skin decreases with time, lung elastic recoil decreases and FEV1 decreases slowly as a result. In a healthy, 40-year-old, 5’10” male, the normal FEV1 is approximately 4-5 Liters (4000-5000 ml). In healthy individuals over the age of 40, FEV1 decreases approximately 20-25 ml/year. In smokers with COPD the decrease in FEV1 is approximately 60 ml/year (4). In smokers with COPD who stop smoking, the rate of loss returns to approximately that of never-smokers, but the loss experienced prior to smoking cessation is not recovered. Thus, smoking cessation is the single most important intervention for individuals with COPD, and the earlier this is accomplished, the greater the beneficial impact on lung function over time (5).

Use of Oxygen

In most patients with COPD, oxygen levels at rest are normal, and the use of supplementary oxygen is neither necessary nor beneficial. In very severe COPD (e.g., Stage IV) patients may develop chronic respiratory failure, and oxygen levels may decrease to levels that can negatively impact the function of vital organs. When oxygen levels in blood are too low for too long, patients can develop pulmonary hypertension (increased pressure in the artery delivering blood to the lungs), and right-sided heart failure (because the right ventricle of the heart has to pump against this elevated pulmonary artery pressure). The administration of oxygen for at least 15 hours per day (Long-Term Oxygen Therapy, LTOT) to patients with chronic respiratory failure has been shown convincingly to increase survival (6) (7).

Most clinicians will recommend, and most insurance companies will approve LTOT under the following conditions:
        • PaO2 (the oxygen in the arterial blood, measured by needle stick) is less than 55 mmHg
        • SaO2 (the oxygen saturation, measured by finger probe) is less than 88%
        • PaO2 is 55-60 mmHg and there is pulmonary hypertension, peripheral edema suggesting congestive heart                 failure or polycythemia (too many red blood cells - the body's compensation for too little oxygen)

The goal of oxygen therapy is to increase the baseline PaO2 to at least 60 mmHg and/or to raise the SaO2 to at least 90%. In certain cases, too much oxygen can be dangerous and can lead to respiratory failure. For this reason, physicians usually assess the oxygen and carbon dioxide levels in the blood (an arterial blood gas test) after a patient has been started on supplementary oxygen. Sometimes this is done as part of an “oxygen prescription test.”

THE FOUR COMPONENTS OF COPD MANAGEMENT

The GOLD Guidelines (3) describe four components of COPD management:
        1) Assess and monitor disease
        2) Reduce risk factors
        3) Manage stable disease
        4) Manage exacerbations

Assess and Monitor Disease

Because there is no “cure” for COPD, prevention and early detection are especially important. Any patient who is at risk and/or who has chronic cough or sputum production or shortness of breath should be evaluated for COPD. In addition to a detailed medical history and physical examination, this evaluation should include spirometry, with determination of post-bronchodilator FEV1 and FVC. Measurement of arterial blood gas tensions should not be performed routinely, but should be considered in all patients with FEV1 <50% of predicted or with clinical signs suggestive of respiratory failure or right heart failure. Symptoms and objective measures of lung function should be monitored periodically to assess for the progressive decline in lung function that occurs over time and to aid in decisions about therapy.

Reduce Risk Factors

    Smoking Cessation

Smoking cessation is the single most effective and cost effective intervention – both to reduce the risk of developing COPD and to stop its progression (3). Strong evidence exists that smoking cessation slows the loss of lung function in patients with established COPD.

“If your doctor doesn’t ask you about quitting, ask your doctor.” 

 

The US Public Health Service has published guidelines for smoking cessation (8), and recommends a five-step program that physicians should use to help patients quit.

 

 

 

 

Cigarette smoking is a powerful addiction, and smoking cessation is not easy, even for the highly motivated individual. There are a number of medications that have been shown to be effective as aids to smoking cessation, and many patients will require the simultaneous use of more than one medication in order to succeed. Some medications may not be appropriate for patients with certain other conditions. Medications should be combined with counseling or behavior modification therapy for optimum efficacy.

Pharmacologic agents shown to be effective include nicotine replacement therapy (available as gum, inhaler, nasal spray, transdermal patch, sublingual tablet, lozenge), bupropion, nortriptyline, and varenicline.

Decrease Environmental Exposures

In some individuals, the irritant stimulus for the development of COPD is not cigarettes. Air pollution, occupational exposures, or those in the home, as from use of biomass fuels, may be responsible for 10-20% of COPD cases. Even in smokers, it is likely that other exposures may be additive or synergistic to the effects of cigarette smoke. It is feasible to reduce these exposures, but it will require changes in public policy in the form of air quality and workplace standards, and reduction in the use of biomass fuels.

For patients with established disease, counseling on these issues is important. Patients should make every effort to reduce potentially dangerous exposures to second-hand cigarette smoke, wood fires, air pollution, occupational irritants. If ambient levels of pollutants/irritants cannot be reduced, patients should be cautioned to avoid exposure. For many, this may mean remaining indoors during periods of high air pollution.

Manage Stable COPD

There is no cure for COPD, and none of the medications approved for treatment of COPD have been shown to modify the progressive loss of lung function that characterizes this disease. Medical therapy can, however, prevent and control symptoms, increase the capacity to exercise, reduce the frequency and severity of exacerbations, and improve quality of life. Education should play an important role. Understanding the risk factors for the development of disease and factors that lead to exacerbations makes avoidance and early treatment feasible. Furthermore, exercise, and physical and psychological coping skills can improve exercise tolerance and quality of life in patients with limited lung function.

Medications 

The use of medications for COPD is based on a step-wise approach, with escalation of therapy based on severity of disease (3). 

Bronchodilators

Treatment usually starts with bronchodilators, medications that dilate or “open” the bronchial tubes, making it easier to breathe. In patients with very mild disease these are usually prescribed on an “as needed” basis, for relief of symptoms. As the disease progresses, they may be prescribed on a regular basis to prevent or reduce symptoms. Commonly used short-acting bronchodilators include albuterol, levalbuterol, terbutaline, and ipratropium; commonly used long-acting agents include salmeterol, formoterol, tiotropium, and theophylline.

All of the bronchodilator drugs have been shown to reduce symptoms and to increase exercise capacity in COPD. All of these agents except theophylline are administered by inhalation, which is associated with far fewer side effects than when similar medications are given orally. There is much debate amongst experts as to which medications are preferred and in which sequence additional medications are added. In general, the decision may be based on personal preference, individual patient response, and availability. The latter may depend on cost, formulary decisions, geographic preference, and the decisions of national regulatory agencies.

Data suggest that combining certain bronchodilators results in improved efficacy (e.g., greater effect and/or greater duration of action), and a reduced risk of side effects.

Theophylline

For much of the 20th century, theophylline and theophylline-like remedies (e.g., caffeine) were the mainstay of therapy for obstructive lung diseases. Theophylline is a phosphodiesterase inhibitor, and acts as a bronchodilator by a mechanism completely different from most of the bronchodilators described above. Prior to the availability of metered dose inhalers, aminophylline suppositories were the most common form of “quick relief” medication. As oral preparations of theophylline with high bioavailability became available, their use for COPD and asthma became common. Unfortunately, this drug has a narrow “therapeutic index” – the ratio of the amount of drug that causes a beneficial effect to the amount that causes toxicity.  

For this reason, side effects were common, and sometimes serious side effects occurred without previous warning. With the development of highly effective, safe, inhaled bronchodilators, theophylline fell out of favor. However, in recent years an additional effect of theophylline has been discovered that makes it potentially more interesting for treatment of COPD. Although its bronchodilator effect is generally less than that of other classes of drugs, it appears to have an effect on inflammatory gene transcription that may be important in COPD, and in enhancing the response to corticosteroids (9) (10). Further studies are necessary to identify its place in the treatment algorithm. 

 

Corticosteroids 

Although systemic (i.e., oral or intravenous) corticosteroids are used for treatment of exacerbations of COPD, their routine use for management of stable disease is not recommended. Inhaled corticosteroids offer the advantage of targeted delivery to the lung, with minimal systemic absorption. In recent years, several multinational, multicenter studies have examined whether the regular long-term use of inhaled corticosteroids alters the natural history of established COPD. Unfortunately, these studies of nearly 5000 patients demonstrated no effect of inhaled corticosteroids on the progressive loss of lung function that occurs in patients with COPD (11), (12) (13). However, they showed convincingly that regular treatment with inhaled corticosteroids reduced the frequency of COPD exacerbations and improved the overall health status of these patients. Treatment with inhaled corticosteroids does not reduce mortality, and is associated with an increased risk of pneumonia.

Combination Therapy

Various combinations have been used, in an attempt to minimize drug side effects and maximize benefit. A beta2-agonist (e.g., albuterol) combined with an anti-muscarinic (e.g., ipratropium) generally results in a larger and longer lasting improvement in lung function than standard doses of either drug alone. Similarly, the combination of an inhaled corticosteroid and a long-acting beta2-agonist is more effective at improving lung function and reducing exacerbations than either agent alone.

 

 Antibiotics

Antibiotics are generally reserved for the treatment of acute exacerbations of COPD in which there is a strong suspicion for a bacterial infection. However, there are data to suggest that in some patients, chronic bacterial colonization or a change in the strain of bacteria found in the lower airway may be the initiating factor in COPD exacerbations. In addition, certain antibiotics (e.g., azithromycin, clarithromycin) appear to have anti-inflammatory effects that are independent of their anti-microbial effects. For this reason, the National Heart, Lung, & Blood Institute’s COPD Clinical Research Network (NHLBI-CCRN) is currently conducting a study (http://www.copdcrn.org/study.htm) to see if chronic treatment with low-dose azithromycin can prevent exacerbations, or mitigate their severity.

Leukotriene Modifiers

Medications such as montelukast, zafirlukast, and zileuton that interfere with the production of inflammatory mediators known as leukotrienes have been used in patients with COPD. Although there is some rationale, based on the increase in leukotrienes found in some smokers, these agents have not been proven in clinical trials to be effective for the management of chronic COPD. These agents may be useful in the treatment of acute exacerbations, and a NHLBI-CCRN study of this is also underway (http://www.copdcrn.org/leukostudy.htm).

Mucolytics

A number of products are reported to thin mucus and/or to promote the clearance of mucus from the lungs. These include ambroxol, erdosteine, carbocysteine, acetylcysteine, and iodinated glycerol. The evidence for a benefit in COPD is limited, and the GOLD guidelines oppose the widespread use of these agents (3).

Antioxidants

Studies on the pathogenesis of COPD suggest an important role for oxidative stress, initiated by active smoking, air pollutants, or as part of the inflammatory cascade in the lungs and airways that is initiated by these exposures. As a result, there has been great interest in the possibility that antioxidants can protect against the development of exacerbations of COPD and reduce the annual decline in FEV1. Investigators in Europe examined this hypothesis in 523 patients in a recent clinical trial and found no difference between the yearly rate of decline in lung function in patients treated with the antioxidant N-acetylcysteine for 3 years and those treated with placebo. The number of exacerbations also did not differ significantly between groups (14). Based on these data, the routine use of antioxidants is not warranted.

Manage Exacerbations (flare-ups) of COPD

On average, patients with COPD experience 1-3 exacerbations per year.  These are usually characterized by an increase in shortness of breath, cough, and/or sputum production that lasts for more than 2 days and that warrants a change in medication.  Most are due to respiratory infections (viral or bacterial) or to environmental exposures.  Early treatment is often effective in limiting the severity of an exacerbation, and patients should be taught how to recognize an exacerbation, and when to seek help.  In addition, much of our therapy and research in COPD is focused on trying to prevent exacerbations.

EVERYONE WITH COPD SHOULD BE VACCINATED

There is convincing evidence that yearly vaccination against influenza can dramatically reduce serious illness and death in patients with COPD. In addition, patients with COPD are at higher risk for bacterial infections, including those by the bacterium, Streptococcus pneumonia, which can cause pneumonia, bronchitis, and other life-threatening infections. Vaccination against Streptococcus pneumonia (the “pneumonia vaccine”) has been shown to reduce the incidence of this pneumonia, and patients with COPD should receive the vaccination approximately every 5 years. A study is underway to compare the two FDA-approved pneumonia vaccines in patients with COPD (http://www.copdcrn.org/prevstudy.htm).

EAT WELL AND GET LOTS OF EXERCISE

Often overlooked are the non-pharmacologic treatments of COPD. Nutritional status is important. Patients with COPD often lose weight because they consume far more energy to perform the work of breathing than do people without COPD. Poor nutrition and weight loss can result in weakness of the respiratory muscles, which makes breathing and exercise even more difficult. Nutritional counseling and supplements may be helpful. In addition, people with COPD often feel particularly uncomfortable after eating a large meal. This is because their lungs are overexpanded or “hyperinflated,” which pushes down on the diaphragm. When the stomach is full it makes it more difficult for the diaphragm to move, creating the sensation of shortness of breath. Eating smaller meals and avoiding meals that produce gas may help.

Exercise and Pulmonary Rehabilitation

The ability to perform exercise, even the activities of daily living, depends on the interaction between the muscles, the lungs, and the heart. Even in healthy individuals, strenuous exercise results in an increase in the respiratory rate, and often ends with shortness of breath. In people with COPD, it takes less exercise to reach the point at which shortness of breath becomes uncomfortable. This often leads to a “vicious cycle” in which an individual limits his or her activity because it produces shortness of breath. The less they do, they less they are subsequently able to do. The situation is complicated further by the “fear factor”: shortness of breath can be scary, and many people are afraid that they are doing themselves harm by exercising to the point of shortness of breath. While this may be true in some cases, especially if the oxygen level in the blood decreases with exertion, for most people exercise is both safe and beneficial. For a given level of lung function, an individual can do more exercise if the muscles and the heart are performing more efficiently. Regular exercise helps to accomplish this.

Pulmonary rehabilitation is a formal program to improve the overall physical conditioning of people with COPD. Most programs include education about COPD, nutritional counseling, and a monitored, graded, individualized exercise program. Because the program is staffed by doctors, nurses, and other healthcare and exercise specialists, and patients are monitored while they exercise, safety is ensured, and patients can comfortably determine how much they are able to do. Studies have shown that participation in a pulmonary rehabilitation program reduces symptoms, increases exercise tolerance, and improves quality of life. In many cases, pulmonary rehabilitation is paid for by insurance. Some programs will pay for an initial course, but require patients to pay for the ongoing “maintenance” program. Exercise need not be limited to formal rehabilitation programs, and a regular program of exercise at home or in the gym, including walking, can be highly beneficial.

IS THERE A ROLE FOR SURGERY?

Lung Volume Reduction Surgery

Individuals with severe COPD usually have overexpanded or hyperinflated lungs. This occurs because they have difficulty exhaling completely and air becomes “trapped” in the lung. Because the lung is so full, even at the end of an exhalation, there is very little space for inhalation – and this is perceived as shortness of breath. In addition, because the diaphragms are flattened by the overinflated lung, they are at a mechanical disadvantage and do not work efficiently. Investigators postulated that if they removed parts of the lungs (especially the hyperinflated parts) they might correct some of these abnormalities and improve lung function – and surgeons began to perform this procedure, called “Lung Volume Reduction Surgery” (LRVS). After years of controversy over whether or not it worked, the National Heart, Lung, and Blood Institute (NHLBI), the Center for Medicare & Medicaid Service (CMS), and the Agency for Healthcare Research and Quality (AHRQ), jointly sponsored a large, multicenter study of 1,200 patients, comparing LVRS with medical treatment (15), (16). The study showed that in a very select group of patients (those with emphysema involving predominantly the upper lobes of the lungs, and with a low exercise capacity), those who received surgery had a greater survival rate, better improvement in exercise capacity, and better quality of life than those who received medical therapy. However, this is expensive and risky surgery, and is recommended only for a very small minority of patients. Several companies have developed one-way valves that can be inserted into the airways without surgery in an attempt to accomplish volume reduction without the risk of surgery. Studies are underway to test this approach.

Lung Transplantation

Lung transplantation has been performed for COPD, and has been shown to improve lung function, exercise capacity, and quality of life. However, this also is major surgery, and requires life-long treatment with potent immunosuppressive drugs, to prevent rejection. Although the outcomes can be quite dramatic, individuals who have undergone lung transplantation are at risk for complications of their therapy. The one-year survival after lung transplantation is 80-90%; the five-year survival is approximately 50%.

FLARE-UPS OR EXACERBATIONS

An exacerbation of COPD is defined as an increase in shortness of breath, cough, and/or sputum that lasts for more than 2 days and that warrants a change in medication. Most patients with COPD average 1-3 exacerbations per year. Some patients seem to have more and are sometimes referred to as “frequent exacerbators.”

The most common causes of exacerbations are respiratory infection (viral or bacterial) and air pollution.

Lung function often deteriorates during an exacerbation, and it does not always return to baseline after the exacerbation is over. Thus, there is a suggestion that frequent or severe exacerbations lead to an accelerated loss of lung function over time. As a result, there is now great interest in therapy that can prevent exacerbations, or minimize their severity. Inhaled corticosteroids, long-acting bronchodilators, anti-muscarinics, and combinations of these agents have all been shown to reduce exacerbations. Although these agents do not always improve symptoms, there appears to be some rationale for using them nonetheless, because of their effect on exacerbations.  Studies are underway to examine the role of antibiotics and even statins in preventing exacerbations of COPD (http://www.copdcrn.org/study.htm).

KEY WORDS:

COPD, Emphysema, Chronic Bronchitis, Smoker's Cough, COPD Exacerbation, Smoking Cessation, Oxygen therapy, Pulmonary Rehabilitation

MORE INFORMATION

Web Resources

Global Initiative for COPD (GOLD): http://www.goldcopd.org

NHLBI COPD Clinical Research Network: http://www.copdcrn.org/aboutcopd.htm

Centers for Disease Control & Prevention (CDC) - Facts About COPD: http://www.cdc.gov/nceh/airpollution/copd/copdfaq.htm

National Center for Health Statistics: http://www.cdc.gov/nchs/fastats/copd.htm.

National Lung Health Education Program: http://www.nlhep.org

National Heart Lung & Blood Institute Diseases and Conditions Index: http://www.nhlbi.nih.gov/health/dci/Diseases/Copd/Copd_WhatIs.html

American Lung Association COPD Fact Sheet: http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35020

UCSF Airway Clinical Research Center: http://acrc.ucsf.edu/index.html

 

REFERENCES

1. Global Strategy for Diagnosis, Management and Prevention of COPD. Available from http://www.goldcopd.org, 2001.
2. Ferguson GT, Enright PL, Buist AS, and Higgins MW. Office spirometry for lung health assessment in adults: a consensus statement for the National Lung Health Education Program. CHEST; 117:1146-1161, 2000.
3. Buist AS. Global Strategy for Diagnosis, Management and Prevention of COPD - Updated 2007. Available from http://www.goldcopd.org.
4. Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, Conway WA, Jr., Enright PL, Kanner RE, O'Hara P, et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA; 272(19):1497-1505, 1994.
5. Fletcher C, and Peto R. The natural history of chronic airflow obstruction. Br Med J; 1:1645-1648, 1977.
6. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Ann Intern Med; 93:391-398, 1980.
7. Report of the Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Lancet; 1:681-686, 1981.
8. The Tobacco Use and Dependence Clinical Practice Guideline Panel, staff, and consortium representatives. A clinical practice guideline for treating tobacco use and dependence. JAMA; 28:3244-3254, 2000.
9. Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Huyashi S, Adcock IM, Hogg JC, et al. Decreased histone deacetylase activity in COPD. N Engl J Med; (352):1967-1976, 2005.
10. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, and Barnes PJ. A molecular mechanism of action of theophylline: induction of HDAC activity to decrease inflammatory gene expression. PNAS; 99:8921-8926, 2002.
11. Pauwels RA, Lofdahl CG, Laitinen LA, Schouten JP, Postma DS, Pride NB, and Ohlsson SV. Long-term Treatment with Inhaled Budesonide in Persons with Mild Chronic Obstructive Pulmonary Disease Who Continue Smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease. N Engl J Med; 340:1948-1953, 1999.
12. Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, and Maslen TK. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial. BMJ; 320(7245):1297-1303, 2000.
13. The Lung Health Study Research Group. Effect of Inhaled Triamcinolone on the Decline in Pulmonary Function in Chronic Obstructive Pulmonary Disease. N Engl J Med; 343:1902-1909, 2000.
14. Decramer M, Rutten-van Molken M, Dekhuijzen PN, Troosters T, van Herwaarden C, and Pellegrino R. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet; 365:1552-1560, 2005.
15. Naunheim KS, Wood DE, Mohsenifar Z, Sternberg AL, Criner GJ, and DeCamp MM. Long term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group. Ann Thorac Surg; 82:431-443, 2006.
16. Fishman A, Martinez F, Naunheim K, Piantadosi S, Wise R, Ries A, Weinmann G, Wood DE, National Emphysema Tretment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med;  348:2059-73, 2003.