COPD: THE GOLD REPORT

TABLE OF CONTENTS
(click on the links below to view more details)

   Learning Objectives
   Global Initiative for Chronic Obstructive Lung Disease (GOLD)
   Preface
   Introduction: The Gold Report
   Ch. 1: Definition of COPD-Classification of Severity
   Ch. 2: The Burden of COPD
   Ch. 3: Risk Factors
   Ch. 4: Pathogenesis, Pathology, and Pathophysiology
   Ch. 5: Management of COPD
                Component 1: Assess and Monitor Disease
                Component 2: Reduce Risk Factors
                Component 3: Manage Stable COPD
                Component 4: Manage Exacerbations
   Ch. 6: Future Research
   Post-Test

   Learning Objectives

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

• Explain what the Gold Report is, and discuss its importance to health care professionals treating COPD.
  
  
• Identify the “working” definition of COPD as provided by the Gold Report.
  
  
• Explain the prevalence COPD and the impact it is having on worldwide health.
  
  
• Discuss the etiology and epidemiology of COPD, and explain how it is diagnosed.
  
  
• Describe the latest international standards presented by the Gold Report regarding prevention, management, and treatment protocols for COPD.
  
  
• Identify and discuss the usefulness and side effects of medications currently in use for COPD patients.

   Global Initiative for Chronic Obstructive Lung Disease (GOLD)

The condition known as COPD has been associated with considerable confusion and disagreement among health care professionals. Even defining the term has been somewhat controversial—much less determining how to diagnose and manage the condition. Given the relative confusion and disagreement among health care professionals regarding the topic of “COPD,” it was an historic breakthrough that on April 4, 2001, the medical world was greeted with the following important news release:

International Guidelines Released on Chronic Obstructive Lung Disease (COPD)
Fourth Leading Cause of Death in US and Worldwide

The first international guidelines for the diagnosis, management, and prevention of Chronic Obstructive Lung Disease (COPD) — currently the fourth leading cause of death in the US and worldwide — were released today by an international team of scientists from the Global Initiative for Chronic Obstructive Lung Disease (GOLD). The GOLD Workshop Report, which provides evidence-based recommendations for the clinical management of COPD, is the first step in an international effort to boost awareness of COPD and improve the way it is treated. GOLD was created by the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health and the World Health Organization.

According to NHLBI Director Dr. Claude Lenfant, "COPD has become a major public health problem worldwide. That's why we, with the WHO, initiated this program. We hope that this report will increase worldwide awareness of COPD and help the millions of people who suffer from this disease."

COPD, a term used to describe chronic bronchitis and emphysema, is a slowly progressive airways disease characterized by a gradual loss of lung function. In the US, it is caused primarily by cigarette smoking. There is no known cure, but smoking cessation can slow disease progression.

COPD has been on the increase in the US, and in 1996, an estimated 16 million Americans had COPD. The number of deaths attributed to COPD has also increased substantially in the past 40 years to approximately 100,000 men and women per year in the US alone. The highest rate of increase in deaths has been seen in white women.

It is expected that by 2020, COPD will rank as the third leading cause of death, surpassing stroke. The annual cost of COPD to the US economy is estimated at nearly $30.4 billion.
The GOLD Report, which was reviewed extensively by medical societies in more than 100 countries throughout both the developed and developing world, emphasizes the need for clinicians and patients to recognize cough and sputum production as early signs of possible COPD and calls for the use of spirometry, a simple test of lung function, to confirm the diagnosis. It also provides a general scheme for classifying COPD by severity to help clinicians determine how best to manage the condition. Practical recommendations for reducing risk factors and for managing both stable COPD and exacerbations are also provided.

Said Lenfant, "A concerted effort by government officials, health care workers, biomedical researchers, industry, and patients throughout the world is required to improve the way COPD is diagnosed and managed and to increase research into improved treatments and ultimately a cure. This effort has begun with the launch of the GOLD Initiative today."

Subsequent to the issuance of this press release, the report itself was made available, and we present the most relevant sections of that report here:

   Preface

The Report

Preface

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.

   Introduction

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-

   Chapter 1: Definition

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 tuberculous 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.

   Chapter 2: The Burden of COPD

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 all2.

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 3 study16, airflow limitation was defined as an FEV1/FVC < 70%. The prevalence of airflow li