Upon successful completion of this course, you will be able to:

• Define what is meant by Chronic Obstructive Pulmonary Disease (COPD)
• Discuss the scope and prevalence of COPD internationally
• Identify and explain the epidemiology and etiology of the disease
• Explain the techniques for diagnosing the disease
• List and discuss the key treatment/management/prevention strategies currently recommended
• Identify the key medications currently in recommended for COPD patients.

Chronic obstructive pulmonary disease (COPD) is a term referring to two lung diseases, chronic bronchitis and emphysema, that are characterized by obstruction to airflow that interferes with normal breathing. Both of these conditions frequently co-exist, hence physicians prefer the term COPD. The quality of life for a person suffering from COPD diminishes as the disease progresses. At the onset, there is minimal shortness of breath. People with COPD may eventually require supplemental oxygen and may have to rely on mechanical respiratory assistance.

Chronic Obstructive Pulmonary Disease (COPD) is a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States1 and is projected to rank fifth in 2020 as a worldwide burden of disease according to a study published by the World Bank/World Health Organization2. Yet, COPD fails to receive adequate attention from the health care community and government officials. With these concerns in mind, a committed group of scientists encouraged the US National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among GOLD’s important objectives are to increase awareness of COPD and to help the thousands of people who suffer from this disease and die prematurely from COPD or its complications.

The first step in the GOLD program was to prepare a consensus Workshop Report, Global Strategy for the Diagnosis, Management, and Prevention of COPD. The GOLD Expert Panel, a distinguished group of health professionals from the fields of respiratory medicine, epidemiology, socio-economics, public health, and health education, reviewed existing COPD guidelines, as well as new information on pathogenic mechanisms of COPD as they developed a consensus document. Many recommendations will require additional study and evaluation as the GOLD program is implemented.

A major problem is the incomplete information about the causes and prevalence of COPD, especially in developing countries. While cigarette smoking is a major known risk factor, much remains to be learned about other causes of this disease. The GOLD Initiative will bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary to control this major public health problem.

I would like to acknowledge the dedicated individuals who prepared the Workshop Report and the effective leadership of the Workshop Chair, Professor Romain Pauwels. It is a privilege for the National Heart, Lung, and Blood Institute to serve as one of the cosponsors. We look forward to working with the World Health Organization, and all other interested organizations and individuals, to meet the goals of the GOLD Initiative.

Development of the Workshop Report was supported through educational grants to the Department of Respiratory Diseases of the Ghent University Hospital, Belgium (WHO Collaborating Center for the Management of Asthma and COPD) from ASTA Medica, AstraZeneca, Aventis, Bayer, Boehringer-Ingelheim, Byk Gulden, Chiesi, GlaxoSmithKline, Merck, Sharp & Dohme, Mitsubishi-Tokyo, Nikken Chemicals, Novartis, Schering-Plough, Yamanouchi, and Zambon.

Claude Lenfant, MD
Director
National Heart, Lung, and Blood Institute

REFERENCES

1. National Heart, Lung, and Blood Institute. Morbidity & mortality: Chartbook on cardiovascular, lung, and blood diseases. Bethesda, MD: US Department of Health and Human Services, Public Health Service, National Institutes of Health; 1998. Available from: URL: www.nhlbi.nih.gov/nhlbi/seiin//other/cht-book/htm
2. Murray CJL, Lopez AD. Evidence-based health policy-lessons from the Global Burden of Disease Study, Science 1996; 274:740-3.

Human Respiratory System

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of chronic morbidity and mortality throughout the world. Many people suffer from this disease for years and die prematurely from it or its complications. COPD is currently the fourth leading cause of death in the world1, and further increases in its prevalence and mortality can be predicted in the coming decades2. A unified international effort is needed to reverse these trends.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) is conducted in collaboration with the US National Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO). Its goals are to increase awareness of COPD and decrease morbidity and mortality from the disease. GOLD aims to improve prevention and management of COPD through a concerted worldwide effort of people involved in all facets of health care and health care policy, and to encourage a renewed research interest in this highly prevalent disease.

A nihilistic attitude toward COPD has arisen among some health care providers, due to the relatively limited success of primary and secondary prevention (i.e., avoidance of factors that cause COPD or its progression), the prevailing notion that COPD is largely a self-inflicted disease, and disappointment with available treatment options. The GOLD project will work toward combating this nihilistic attitude by disseminating information about available treatments, both pharmacologic and non-pharmacologic.

Tobacco smoking is a major cause of COPD, as well as of many other diseases. A decline in tobacco smoking would result in substantial health benefits and a decrease in the prevalence of COPD and other smoking-related diseases. There is an urgent need for improved strategies to decrease tobacco consumption. However, tobacco smoking is not the only cause of COPD and may not even be the major cause in some parts of the world. Furthermore, not all smokers develop clinically significant COPD, which suggests that additional factors are involved in determining each individual's susceptibility. Thus, investigation of COPD risk factors and ways to reduce exposure to these factors is also an important area for future research. New research tools have recently revealed that inflammation plays a prominent role in COPD pathogenesis, but this inflammation is different than that involved in asthma. Further study of the molecular and cellular mechanisms involved in COPD pathogenesis should lead to effective treatments that slow or halt the course of the disease.

GOLD WORKSHOP REPORT: GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF COPD

One strategy to help achieve GOLD's objectives is to provide health care workers, health care authorities, and the general public with state-of-the-art information about COPD and specific recommendations on the most appropriate management and prevention strategies. The GOLD Workshop Report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, is based on the best-validated current concepts of COPD pathogenesis and the available evidence on the most appropriate management and prevention strategies. The Report has been developed by individuals with expertise in COPD research and patient care and extensively reviewed by many experts and scientific societies. It provides state-of-the-art information about COPD for pulmonary specialists and other interested physicians. The document will also serve as a source for the production of various communications during the implementation of the GOLD program, including a practical guide for primary care physicians and a document for use in developing countries.

The GOLD Report is not intended to be a comprehensive textbook on COPD, but rather to summarize the current state of the field. Each chapter starts with Key Points that crystallize current knowledge. The chapters on the Burden of COPD and Risk Factors demonstrate the global importance of COPD and the various causal factors involved. The chapter on Pathogenesis, Pathology, and Pathophysiology documents the current understanding of, and remaining questions about, the mechanism(s) that lead to COPD, as well as the structural and functional abnormalities of the lungs characteristic of the disease.

A major part of the GOLD Workshop Report is devoted to the clinical Management of COPD and presents a management plan with four components:

1. Assess and Monitor Disease;
2. Reduce Risk Factors;
3. Manage Stable COPD;
4. Manage Acute Exacerbations.

Management recommendations are largely symptom driven and are presented according to the severity of the disease, using a simple classification of severity to facilitate the practical implementation of the available management options. Where appropriate, information about health education for patients is included.

The final chapter identifies critical gaps in knowledge requiring Further Research and provides a summary of proposed directions for the development of new therapeutic approaches.

METHODS USED TO DEVELOP THIS REPORT

In January, 1997, COPD experts from several countries met in Brussels, Belgium to explore the development of a Global Initiative for Chronic Obstructive Lung Disease. Dr. Romain Pauwels served as Chair; representatives of the NHLBI and WHO attended. Participants agreed that the project was timely and important, and recommended the establishment of a panel with expertise on a wide variety of COPD-related topics to prepare an evidence-based document on diagnosis, management, and prevention of COPD. NHLBI and WHO staff, in concert with Dr. Pauwels, identified individuals from many regions of the world to serve on the Expert Panel, which included health professionals in the areas of respiratory medicine, epidemiology, pathology, socio-economics, public health, and health education. The first step toward developing the Workshop Report was to review the multiple COPD guidelines already published. The NHLBI collected these guidelines and prepared a summary table of similarities and differences between the documents. Where agreement existed, the Expert Panel drew on these existing documents for use in the Workshop Report. Where major differences existed, the Expert Panel agreed to carefully examine the scientific evidence to reach an independent conclusion.

In September, 1997, several members of the Expert Panel met with a consultant to develop a comprehensive set of terms to build a database of COPD literature. The database and a computer program to search the world literature on COPD have been developed, and they will be placed on the Internet and cross-referenced with the Workshop Report to help keep the Report current as new literature is published.

In April, 1998, the NHLBI and WHO cosponsored a workshop to begin the development of the Report. Workshop participants were divided into three groups: definition and natural history, chaired by Dr. Sonia Buist; pathophysiology, risk factors, diagnosis, and classification of severity, chaired by Dr. Leonardo Fabbri; and management, chaired by Dr. Romain Pauwels. A table of contents was developed and writing assignments were made. The Panel agreed that clinical recommendations would require scientific evidence, or would be clearly labeled as "expert opinion." Each chapter would contain a set of the most current and representative references.

In September, 1998, the Panel met to evaluate its progress. Members reviewed a variety of evidence tables and chose to assign levels of evidence to statements using the system developed by the NHLBI (Figure A). Levels of evidence are assigned to management recommendations where appropriate in Chapter 5, Management of COPD, and are indicated in boldface type enclosed in parentheses after the relevant statement - e.g., (Evidence A). The methodological issues concerning the use of evidence from meta-analyses were carefully considered (e.g., a meta-analysis of a number of smaller studies was considered to be evidence level B)2. The panel met in May, 1999, September, 1999, and May, 2000 in conjunction with meetings of the American Thoracic Society (ATS) and the European Respiratory Society (ERS). Symposia were held at these meetings to present the developing program and to solicit opinion and comments. The meeting in May, 2000 was the final consensus workshop.

After this workshop, the document was submitted for review to individuals and medical societies interested in the management of COPD. The reviewers' comments were incorporated, as appropriate, into the final document by the Chair in cooperation with members of the Expert Panel. Prior to its release for publication, the Report was reviewed by the NHLBI and the WHO. A workshop was held in September, 2000 to begin implementation of the GOLD program.

REFERENCES

1. World Health Organization. World health report. Geneva: World Health Organization; 2000. Available from: URL: http://www.who.int/whr/2000/en/statistics.htm
2. Murray CJL, Lopez AD. Evidence-based health policy - lessons from the Global Burden of Disease Study. Science 1996; 274:740-

KEY POINTS:

• COPD is 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 lungs to noxious particles or gases.
• The four-stage classification of COPD severity used throughout this report provides an educational tool and a general indication of the approach to management. This conceptual framework also emphasizes that COPD is usually progressive if exposure to the noxious agent is continued.
• The characteristic symptoms of COPD are cough, sputum production, and dyspnea upon exertion.
• Chronic cough and sputum production often precede the development of airflow limitation by many years and these symptoms identify individuals at risk of developing COPD.
• The focus of this Workshop Report is primarily on COPD caused by inhaled particles and gases, the most common of which worldwide is tobacco smoke.
• COPD can coexist with asthma, the other major chronic obstructive airway disease characterized by an underlying airway inflammation. However, the inflammation characteristic of COPD is distinct from that of asthma.
• Pulmonary tuberculosis may affect lung function and symptomatology and, in areas where tuberculosis is prevalent, can lead to confusion in the diagnosis of COPD.

DEFINITION

For years, clinicians, physiologists, pathologists, and epidemiologists have struggled with the definitions of disorders associated with chronic airflow limitation, including chronic bronchitis, emphysema, chronic obstructive pulmonary disease (COPD), and asthma. The definitions of these terms variably emphasize structure and function and are often based on whether the term is used for clinical or research purposes. For example, epidemiologists have created terminology and criteria, based on functional status, that can be monitored in population-based studies or studies of physicians' diagnoses1,2.

Based on current knowledge, a working definition of COPD is:
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 lungs to noxious particles or gases. Symptoms, functional abnormalities, and complications of COPD can all be explained on the basis on this underlying inflammation and the resulting pathology.

The chronic airflow limitation characteristic of COPD is caused by a mixture of small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), the relative contributions of which vary from person to person. Chronic inflammation causes remodeling and narrowing of the small airways. Destruction of the lung parenchyma, also by inflammatory processes, leads to the loss of alveolar attachments to the small airways and decreases lung elastic recoil; in turn, these changes diminish the ability of the airways to remain open during expiration. Airflow limitation is measured by spirometry, as this is the most widely available, reproducible test of lung function.

Many previous definitions of COPD have emphasized the terms "emphysema" and "chronic bronchitis," which are no longer included in the definition of COPD used in this report. Emphysema, or destruction of the gas-exchanging surfaces of the lung (alveoli), is a pathological term that is often (but incorrectly) used clinically and describes only one of several structural abnormalities present in patients with COPD. Chronic bronchitis, or the presence of cough and sputum production for at least 3 months in each of two consecutive years, remains a clinically and epidemiologically useful term. However, it does not reflect the major impact of airflow limitation on morbidity and mortality in COPD patients. It is also important to recognize that cough and sputum production may precede the development of airflow limitation; conversely, some patients develop significant airflow limitation without chronic cough and sputum production.

NATURAL HISTORY

COPD has a variable natural history and not all individuals follow the same course. However, COPD is generally a progressive disease, especially if a patient's exposure to noxious agents continues. If exposure is stopped, the disease may still progress due to the decline in lung function that normally occurs with aging. Nevertheless, stopping exposure to noxious agents, even after significant airflow limitation is present, can result in some improvement in function and will certainly slow or even halt the progression of the disease.

Classification of Severity: Stages of COPD

For educational reasons, a simple classification of disease severity into four stages is recommended (Figure 1-2). The staging is based on airflow limitation as measured by spirometry, which is essential for diagnosis and provides a useful description of the severity of pathological changes in COPD. Specific FEV1 cut-points (e.g.,< 80% predicted) are used for purposes of simplicity: these cut-points have not been clinically validated.

The impact of COPD on an individual patient depends not just on the degree of airflow limitation, but also on the severity of symptoms (especially breathlessness and decreased exercise capacity) and complications of the disease. A wide range of FEV1 values are included in Stage II: Moderate COPD, reflecting the major contribution of these additional factors to the disability caused by COPD. For the purposes of management, this category is subdivided into two segments (IIA and IIB), as discussed in Chapter 5.3, Manage Stable COPD, and Figure 5-3-8. The management of COPD is largely symptom driven, and there is only an imperfect relationship between the degree of airflow limitation and the presence of symptoms. The staging, therefore, is a pragmatic approach aimed at practical implementation and should only be regarded as an educational tool, and a very general indication of the approach to management. "All FEV1 values refer to post-bronchodilator FEV1."

Although COPD is defined on the basis of airflow limitation, in practice the decision to seek medical help (and so permit the diagnosis to be made) is normally determined by the impact of a particular symptom on a patient's lifestyle. Thus, COPD may be diagnosed at any stage of the illness.

The characteristic symptoms of COPD are cough, sputum production, and dyspnea upon exertion. Chronic cough and sputum production often precede the development of airflow limitation by many years, although not all individuals with cough and sputum production go on to develop COPD. This pattern offers a unique opportunity to identify those at risk for COPD and intervene when the disease is not yet a health problem. A major objective of GOLD is to increase awareness among health care providers and the general public of the significance of these symptoms.

Stage 0: At Risk— Characterized by chronic cough and sputum production. Lung function, as measured by spirometry, is still normal.

Stage I: Mild COPD—Characterized by mild airflow limitation (FEV1/FVC < 70% but FEV1 > 80% predicted) and usually, but not always, by chronic cough and sputum production. At this stage, the individual may not even be aware that his or her lung function is abnormal. This underscores the importance of health care providers doing spirometry in all smokers so that their lung function can be observed and recorded over time.

Stage II—Moderate COPD: Characterized by worsening airflow limitation (30% < FEV1 < 80% predicted), and usually the progression of symptoms with shortness of breath typically developing on exertion. This is the stage at which patients typically seek medical attention because of dyspnea or an exacerbation of their disease. The division into stages IIA and IIB is based on the fact that exacerbations are especially seen in patients with an FEV1 below 50% predicted. The presence of repeated exacerbations has an impact on patients’ quality of life and requires appropriate management.

Stage III—Severe COPD: Characterized by severe airflow limitation (FEV1 < 30% predicted) or the presence of respiratory failure or clinical signs of right heart failure. Respiratory failure is defined as an arterial partial pressure of oxygen (PaO2) less than 8.0 kPa (60 mm Hg) with or without arterial partial pressure of CO2 (PaCO2) greater than 6.7 kPa (50 mm Hg) while breathing air at sea level. Respiratory failure may also lead to effects on the heart such as cor pulmonale (right heart failure). Clinical signs of cor pulmonale include elevation of the jugular venous pressure and pitting ankle edema. "Patients may have severe (Stage III) COPD even if the FEV1 is > 30% predicted, whenever these complications are present." At this stage, quality of life is very appreciably impaired and exacerbations may be life threatening.

Variable Course of COPD
The common statement that only 15-20% of smokers develop clinically significant COPD is misleading. A much higher proportion develops abnormal lung function at some point if they continue to smoke. Not all individuals with COPD follow the classical linear course as outlined in the Fletcher and Peto diagram, which is actually the mean of many individual courses3.

Figure 1-3 shows four examples of the various courses that individual COPD patients may follow. Panel A illustrates an individual who has cough and sputum production, but never develops abnormal lung function (as defined in this Report). Panel B illustrates an individual who develops abnormal lung function but who may never come to diagnosis. Panel C illustrates a person who develops abnormal lung function around age 50, then progressively deteriorates over about 15 years and dies of respiratory failure at age 65. Panel D illustrates an individual who develops abnormal lung function in mid-adult life and continues to deteriorate gradually but never develops respiratory failure and does not die as a result of COPD.

SCOPE OF THE REPORT

The focus of this Report is primarily on COPD caused by inhaled particles and gases, the most common of which worldwide is tobacco smoke. Poorly reversible airflow limitation associated with bronchiectasis, cystic fibrosis, tuberculosis, or asthma is not included except insofar as these conditions overlap with COPD.

Asthma and COPD

COPD can coexist with asthma, the other major chronic obstructive airway disease characterized by an underlying airway inflammation. Asthma and COPD have their major symptoms in common, but these are generally more variable in asthma than in COPD. The underlying chronic airway inflammation is also very different (Figure 1-4): that in asthma is mainly eosinophilic and driven by CD4+ T lymphocytes, while that in COPD is neutrophilic and characterized by the presence of increased numbers of macrophages and CD8+ T lymphocytes. In addition, airflow limitation in asthma is often completely reversible, either spontaneously or with treatment, while in COPD it is never fully reversible and is usually progressive if exposure to noxious agents continues. Finally, the responses to treatment of asthma and COPD are dramatically different, in terms of both the overall magnitude of the achievable response and the qualitative effects of specific treatments such as anticholinergics and glucocorticosteroids. However, there is undoubtedly an overlap between asthma and COPD. Individuals with asthma who are exposed to noxious agents that cause COPD may develop a mixture of "asthma-like" inflammation and "COPD-like" inflammation. There is also evidence that longstanding asthma on its own can lead to airway remodeling and partly irreversible airflow limitation. Asthma can usually be distinguished from COPD, but until the causal mechanisms and pathognomonic markers of these diseases are better understood it will remain difficult to differentiate the two diseases in some individual patients. Given the current state of medical and scientific knowledge, an attempt to determine an absolutely rigid definition of COPD or asthma is bound to end up in semantics.

Pulmonary Tuberculosis and COPD

In many developing countries both pulmonary tuberculosis and COPD are common. In countries where tuberculosis is very common, respiratory abnormalities may be too readily attributed to this disease. Conversely, where the rate of tuberculosis is greatly diminished, the possible diagnosis of this disease is sometimes overlooked.

Chronic bronchitis/bronchiolitis and emphysema often occur as complications of pulmonary tuberculosis and are important contributors to the mixed lung function changes characteristic of tuberculosis4. The degree of obstructive airway changes5 in treated patients with pulmonary tuberculosis increases with age, the amount of cigarettes smoked, and the extent of the initial tuberculosis disease. In patients with both diseases, COPD adds to the disability of pulmonary tuberculosis, and vice versa.

Therefore, in all subjects with symptoms of COPD, a possible diagnosis of tuberculosis should be considered, especially in areas where this disease is known to be prevalent. Investigations to exclude tuberculosis should be a routine part of COPD diagnosis, the intensity of the diagnostic procedures depending on the degree of suspicion. Chest radiograph and sputum culture are helpful in making the differential diagnosis.

REFERENCES

1. Samet JM. Definitions and methodology in COPD research. In: Hensley M, Saunders N, eds. Clinical epidemiology of chronic obstructive pulmonary disease. New York: Marcel Dekker; 1989. p. 1-22.
2. Vermeire PA, Pride NB. A "splitting" look at chronic non-specific lung disease (CNSLD): common features but diverse pathogenesis. Eur Respir J 1991; 4:490-6.
3. Fletcher C, Peto R. The natural history of chronic airflow obstruction. BMJ 1977; 1:1645-8.
4. Leitch AG. Pulmonary tuberculosis: clinical features. In: Crofton J, Douglas A, eds. Respiratory diseases. Oxford: Blackwell Science; 2000. p. 507-27.
5. Birath G, Caro J, Malmberg R, Simonsson BG. Airway obstruction in pulmonary tuberculosis. Scand J Resp Dis 1966; 47:27-36.
6. Snider GL, Doctor L, Demas TA, Shaw AR. Obstructive airway disease in patients with treated pulmonary tuberculosis. Am Rev Respir Dis 1971; 103:625-40.

KEY POINTS:

• COPD prevalence and morbidity data that are available probably greatly underestimate the total burden of the disease because it is not usually recognized and diagnosed until it is clinically apparent and moderately advanced.
• Prevalence, morbidity, and mortality vary appreciably across countries, but in all countries where data are available COPD is a significant health problem in both men and women.
• The substantial increase in the global burden of COPD projected over the next twenty years reflects, in large part, the increasing use of tobacco worldwide, and the changing age structure of populations in developing countries.
• Medical expenditures for treating COPD and the indirect costs of morbidity can represent a substantial economic and social burden for societies and public and private payers worldwide. Nevertheless, very little economic information concerning COPD is available.

INTRODUCTION
COPD is a leading cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. COPD prevalence, morbidity, and mortality vary appreciably across countries and across different groups within countries, but in general are directly related to the prevalence of tobacco smoking. Most epidemiological studies have found that COPD prevalence, morbidity, and mortality have increased over time and are greater in men than in women. Very few studies have quantified the economic and social burden of COPD. In developed countries, the direct medical costs of COPD are substantial because the disease is both chronic and highly prevalent. In developing countries, the indirect cost of COPD from loss of work and productivity may be more important than the direct costs of medical care.

EPIDEMIOLOGY

Most of the information available on COPD prevalence, morbidity, and mortality comes from developed countries. Even in these countries, accurate epidemiological data on COPD are difficult and expensive to collect. Prevalence and morbidity data greatly underestimate the total burden of COPD because the disease is usually not diagnosed until it is clinically apparent and moderately advanced. The imprecise and variable definitions of COPD have made it hard to quantify the morbidity and mortality of this disease in developed1 and developing countries. Mortality data also underestimate COPD as a cause of death because the disease is more likely to be cited as a contributory than as an underlying cause of death, or may not be cited at all.

Prevalence
Available estimates of COPD prevalence have been developed by determining either the proportion of the population that reports having respiratory symptoms and/or airflow limitation, or the proportion that reports having been diagnosed with COPD, chronic bronchitis, or emphysema by a physician. Each of these approaches will yield a different estimate, and may be useful for different purposes. For example, studies that ask about the full range of COPD symptoms from early to advanced disease are useful to estimate the total societal burden of the disease. Data on doctor diagnoses of COPD are useful to estimate the prevalence of clinically significant disease that is of sufficient severity to require health services, and therefore is likely to incur significant costs.

The population surveys necessary to develop accurate estimates of COPD prevalence are costly to do and therefore have not been conducted in many countries. Obtaining reliable prevalence data for COPD in each country should be a priority in order to alert those responsible for planning prevention services and health care delivery to the high prevalence and cost of the disease. The prevalence of COPD is likely to vary appreciably depending on the prevalence of risk factor exposure, age distribution, and prevalence of susceptibility genes in different countries.

Until recently, virtually all population-based studies in developed countries showed a markedly greater prevalence and mortality of COPD among men compared to women3-6. Gender-related differences in exposure to risk factors, mostly cigarette smoking, probably explain this pattern. In developing countries, some studies report a slightly higher prevalence of COPD in women than men. This likely reflects exposure to indoor air pollution from cooking and heating fuels (greater among women) as well as exposure to tobacco smoke (greater among men)7-15. Recent large population-based studies in the US show a different pattern emerging, with the prevalence of COPD almost equal in men and women16,17. This likely reflects the changing pattern of exposure to the most important risk factor, tobacco smoke.
Estimates based on self-report of respiratory symptoms. COPD prevalence data based on self-report of respiratory symptoms (chronic cough, sputum production, wheezing, and shortness of breath) include people at risk for COPD (Stage 0) as well as those with airflow limitation, and thus yield maximum prevalence estimates. These studies reveal sizable variations in the prevalence of respiratory symptoms depending on smoking status, age, occupational and environmental exposures, country or region, and, to a lesser extent, gender and race. The data also reveal appreciable variations over time, reflecting important temporal changes in populations' exposure to risk factors such as smoking, outdoor air pollution, and occupational exposures.

The third National Health and Nutrition Examination Survey (NHANES 3)16, a large national survey conducted in the US between 1988 and 1994, included self-report questions about respiratory symptoms. The prevalence of respiratory symptoms varied markedly by smoking status (current>ex>never). Among white males, chronic cough was reported by 24% of smokers, 4.7% of ex-smokers, and 4.0% of never smokers. The prevalence of chronic cough among white women was 20.6% in smokers, 6.5% in ex-smokers, and 5.0% in never smokers. There was a smaller gradient in the prevalence of chronic cough by race (white>black). The prevalence of sputum production was similar to that of chronic cough in these groups.

Estimates based on the presence of airflow limitation. People may have respiratory symptoms such as cough and sputum production for many years before developing airflow limitation. Thus, COPD prevalence data based on the presence of airflow limitation provide a more accurate estimate of the burden of COPD that is, or probably soon will be, clinically significant. However, the use of different cut points to define airflow limitation makes comparing the results of different studies difficult.

In the NHANES study, airflow limitation was defined as an FEV1/FVC < 70%. The prevalence of airflow limitation was lower than the prevalence of respiratory symptoms found in the same study, but both sets of data reinforce the view that smoking is the most important determinant of COPD prevalence in developed countries. Among white males, airflow limitation was present in 14.2% of current smokers, 6.9% of ex-smokers, and 3.3% of never smokers. Among white females, the prevalence of airflow limitation was 13.6% in smokers, 6.8% in ex-smokers, and 3.1% in never smokers. Airflow limitation was more common among white smokers than among black smokers.

Estimates based on physician diagnosis of COPD. COPD prevalence data based on physician diagnosis provide information about the prevalence of clinically significant COPD that is of sufficient severity to prompt a visit to a physician. Few population-based prevalence surveys have been published to provide this information, and available data are often confusing because asthma and COPD diagnoses are not separated, all age groups are considered together, or chronic bronchitis and emphysema are considered separately.

In the UK the General Practice Research Database18, which is based on 525 practices serving 3.4 million patients (6.4% of the total population of England and Wales), provides population-based data on physician-diagnosed COPD (Figure 2-1). In 1997, the prevalence of COPD was 1.7% among men and 1.4% among women. Between 1990 and 1997, the prevalence increased by 25% in men and 69% in women. The prevalence of COPD among men plateaued in the mid-1990s, but continued to increase among women, reaching in 1997 the level observed in men in 1990. The General Practice Research Database includes all ages and thus underestimates the true impact of COPD on older adults.

The Global Burden of Disease Study. The WHO/World Bank Global Burden of Disease Study19,20 used data from both published and unpublished studies to estimate the prevalence of various diseases in different countries and regions around the world (Figure 2-2). Where few data for a region were available, experts made informed estimates. Where no information was available, preliminary estimates were derived from data from other regions that were believed to have similar epidemiological patterns. Using this approach, the worldwide prevalence of COPD in 1990 was estimated at 9.34/1,000 in men and 7.33/1,000 in women. However, these estimates include all ages and underestimate the true prevalence of COPD in older adults.

Figure 2.2 COPD Around the World (All Ages)

Given the striking dearth of population-based data on COPD prevalence in many countries of the world, the values listed in Figure 2-2 should not be viewed as very precise. Nevertheless, some general patterns emerge. The prevalence of COPD is highest in countries where cigarette smoking has been, or still is, very common, while the prevalence is lowest in countries where smoking is less common, or total tobacco consumption per capita is still low. The lowest COPD prevalence among men (2.69/1,000) was found in the Middle Eastern Crescent (a group of 36 countries in North Africa and the Middle East) and the lowest prevalence among women (1.79/1,000) was found in the region referred to as "Other Asia and Islands" (a group of 49 countries and islands, the largest of which is Indonesia and which includes Papua New Guinea, Nepal, Vietnam, Korea, Hong Kong, and many small island countries). Except in the Middle Eastern Crescent, the prevalence of COPD is higher among men than among women.

The Global Burden of Disease study reported a significantly higher prevalence of COPD in China than in most of the other regions (26.20/1,000 among men and 23.70/1,000 among women). A more recent survey conducted in three regions of China (Northern: Beijing; Northeast: Liao-Ning; and South-Mid: HuBei) in persons older than 15 years estimated the prevalence of COPD at 4.21/1,000 among men and 1.84/1,000 among women

Morbidity

Morbidity includes physician visits, emergency department visits, and hospitalizations. COPD databases for these outcome parameters are less readily available and usually less reliable than mortality databases. The limited data available indicate that morbidity due to COPD increases with age and is greater in men than women17,22,23.

In the UK, general practice consultations for COPD during one year ranged from 4.17/1,000 in 45- to 64-year-olds to 8.86/1,000 in 65- to 74-year-olds to 10.32/1,000 in 75- to 84-year-olds. These rates are 2 to 4 times the equivalent rates for chest pain due to ischemic heart disease.

In 1994, according to statistics from the UK Office of National Statistics25, there were 203,193 hospital admissions in Northern Ireland, Scotland, Wales, and England for COPD; the average length of hospital stay among those admitted for a COPD diagnosis was 9.9 days.

US data indicate that in 1997 there were 16.365 million (60.6/1,000) ambulatory care visits for COPD and 448,000 (1.66/1,000) hospitalizations for which COPD was the first-listed discharge diagnosis23. Hospitalization rates for COPD increased with age and were higher among men than among women. These data should be interpreted cautiously, however, because the ICD-9 codes for COPD that were in use in 1997, 490-492 and 494-496, include "bronchitis not specified as acute or chronic." Therefore, the data for ambulatory care visits are likely to have been inflated by inclusion of visits for acute bronchitis.

Mortality

Of all of the descriptive epidemiological data for COPD, mortality data are the most readily available, and probably the most reliable. (The World Health Organization publishes mortality statistics for selected causes of death annually for all WHO regions26; additional information is available from the WHO Evidence for Health Policy Department27.) However, inconsistent use of terminology for COPD causes problems that do not arise for many other diseases. For example, prior to about 1968 and the Eighth Revision of the ICD, the terms "chronic bronchitis" and "emphysema" were used extensively. During the 1970s, the term "COPD" increasingly replaced those terms in the US and some but not all other countries, making comparisons of COPD mortality in different countries very difficult. However, the situation has improved with the Ninth and Tenth Revisions of the ICD, in which deaths from COPD or chronic airways obstruction are included in the broad category of "COPD and allied conditions" (ICD-9 codes 490-496 and ICD-10 codes J42-46).

The age-adjusted death rates for COPD by race and sex in the US from 1960 to 1996 by ICD code are shown in Figure 2-317. COPD death rates are very low among people under age 45 in the US, but then increase with age, and COPD becomes the fourth or fifth leading cause of death among those over 4517, a pattern that reflects the cumulative effect of cigarette smoking28. Although appreciable variations in mortality across developed countries for both genders have been reported29, these differences should be interpreted cautiously. Differences between countries in death certification, diagnostic practices, the structure of health care systems, and life expectancy have an appreciable impact on reported mortality rates.

Figure 2.3 Age-Adjusted Death Rates for
COPD by Race and Sex, US 1960-96

Rate 100,000 Population

ECONOMIC AND SOCIAL BURDEN OF COPD

Because COPD is highly prevalent and can be severely disabling, direct medical expenditures and the indirect costs of morbidity and premature mortality from COPD can represent a substantial economic and social burden for societies and public and private insurance payers worldwide. Nevertheless, very little quantitative information concerning the economic and social burden of COPD is available in the literature today.

Economic Burden

Cost of illness studies provide insight into the economic impact of a disease. Some countries attempt to separate economic burden into disease-attributable direct and indirect costs. The direct cost is the value of health care resources devoted to diagnosis and medical management of the disease. Indirect costs reflect the monetary consequences of disability, missed work and school, premature mortality, and caregiver or family costs resulting from the illness. Data on these topics from developing countries are not available, but data from the US and some European countries provide an understanding of the economic burden of COPD in developed countries.

United States. Figure 2-4 compares the estimated costs of various lung disorders in the US in 1993. In 1993, the annual economic burden of COPD in the US was estimated at $23.9 billion17, including $14.7 billion in direct expenditures for medical care services, $4.7 billion in indirect morbidity costs, and $4.5 billion in indirect costs related to premature mortality. With an estimated 15.7 million cases of COPD in the US30, the estimated direct cost of COPD is $1,522 per COPD patient per year.

Figure 2.4
Direct and Indirect Costs of Lung Diseases, 1993 (US$ Billions)