Chapter 41 Chronic Obstructive Pulmonary Disease
Epidemiology, Pathophysiology, and Clinical Evaluation
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung condition characterized by airflow limitation that is not fully reversible. COPD is increasingly recognized as a major global problem that places a burden on both patients who suffer from this disabling condition and health care resources. Despite significant advances in our understanding of the pathogenesis, physiology, clinical features, and management of COPD in recent years, much remains to be discovered about this condition.
Although hidden by the generic term “chronic obstructive pulmonary disease,” COPD is a heterogeneous collection of syndromes with overlapping manifestations, which has led to major difficulties in obtaining an acceptable definition of the condition. In addition, as with many chronic inflammatory conditions, COPD is associated with extrapulmonary effects and comorbidities that affect both morbidity and mortality.
The acceptance that symptoms of breathlessness, cough, and sputum production are part of aging or an inevitable consequence of cigarette smoking, and not related to a disease, results in underdiagnosis despite the diagnosis of COPD being easily made. This underdiagnosis is exacerbated by the belief, reinforced by many definitions, that COPD is an “irreversible” condition and that there is nothing “to reverse” with treatment. This leads not only to underdiagnosis but also to undermanagement.
It is now well recognized that significant responses to treatment do occur, which has led to a much more positive approach to the diagnosis and treatment of COPD. Whereas previous treatments largely focused on patients at the severe end of the disease spectrum, recent guidelines recognize that diagnosis and treatment at an earlier stage can offer significant benefits for patients. Although unable to cure COPD, current treatments can reduce symptoms, improve function, and reduce exacerbations in patients as well as decrease the enormous health care costs associated with COPD.
In defining COPD, several problems must be considered. First, COPD is not just one disease but a group of diseases. Second, it is difficult to differentiate COPD from asthma; the persistent airways obstruction in older patients with chronic asthma is often difficult or even impossible to distinguish from that of COPD patients, who may demonstrate partial reversibility of their airflow limitation. Indeed, some patients with asthma may develop COPD, or these two common conditions may coexist in the same individual. Therefore the problem often is not whether the patient has asthma or COPD, but rather whether either asthma or COPD is present.
Chronic bronchitis is defined clinically by the American Thoracic Society (ATS) and the United Kingdom (UK) Medical Research Council as “the production of sputum on most days for at least three months in at least two consecutive years when a patient with another cause of chronic cough has been excluded.” This definition does not require the presence of airflow limitation. Chronic bronchitis results from inflammation in the larger airways, with bronchial gland hypertrophy and mucus cell hyperplasia.
Emphysema is defined pathologically as “abnormal, permanent enlargement of the distal air spaces, distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis.” As with chronic bronchitis the definition of emphysema does not require the presence of airflow limitation. As emphysema progresses, the consequent loss of lung elastic recoil contributes to the airflow limitation in COPD.
Bronchiolitis or small airways disease also occurs in COPD, where chronic inflammation in the smaller bronchi and bronchioles less than 2 mm in diameter leads to airway remodeling, resulting in airflow limitation. Although relatively little is known of the natural history, bronchiolitis may contribute increasingly, as it progresses, to the airflow limitation in COPD.
The relative contributions made by large or small airways abnormalities or emphysema to the airflow limitation, in individual patients with COPD, is difficult to determine. Thus the term “chronic obstructive pulmonary disease” was introduced in the 1960s to describe patients with incompletely reversible airflow limitation caused by a combination of airways disease and emphysema, without defining the contribution of these conditions to the airflow limitation.
In the statement on the standards for diagnosis and care of patients with COPD by ATS and European Respiratory Society (ERS), COPD is defined as “a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response in the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.” This is similar to the definition produced by the World Health Organization (WHO) Global Initiative on Obstructive Lung Disease (GOLD), which first introduced the concept of COPD as an inflammatory disease into its definition.
The diagnosis requires objective evidence of airflow limitation assessed by spirometry. A postbronchodilator forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) ratio of less than 0.7 confirms the presence of airflow limitation that is not fully reversible.
A number of specific causes of airflow limitation, such as cystic fibrosis, bronchiectasis, and bronchiolitis obliterans, are not included in the definition of COPD, but these should be considered in its differential diagnosis. COPD is considered primarily as a lung disease. However, the extrapulmonary effects and comorbidities should also be considered in patients with COPD.
Inflammation initiated by exposure to particles or gases underlies most of the pathologic lesions associated with COPD and represents the innate and adaptive immune responses to a lifetime exposure to noxious particles, fumes, and gases, particularly cigarette smoke. Enhanced inflammation also contributes to disease exacerbations, in which acute inflammation is superimposed on the chronic disease. There is good evidence that all smokers have inflammation in their lungs. However, there is individual susceptibility in the inflammatory response to tobacco smoking, and those who develop COPD show an enhanced or abnormal inflammatory response to inhaled toxic agents.
Although the clinical and physiologic presentation of chronic asthma may be indistinguishable from COPD, the pathologic changes are distinct from those in most cases of COPD, largely because of cigarette smoking. The histologic features of COPD in the 15% to 20% of COPD patients who are nonsmokers have not yet been studied in detail. Although complex, the pathology of COPD can be simplified by considering separate disease sites in which pathologic changes occur in smokers to produce a clinical pattern of largely fixed airflow limitation (Box 41-1). The clinicopathologic picture is complicated because chronic bronchitis, bronchiolitis, and emphysema may exist in an individual patient, resulting in the clinical and pathophysiologic heterogeneity seen in patients with COPD.
Box 41-1 Chronic Obstructive Pulmonary Disease (COPD)
Mucus is produced by mucous glands present in the larger airways and by goblet cells in the airway epithelium. Chronic bronchitis is characterized by hypertrophy of the mucous glands (Figure 41-1). Goblet cells that occur predominantly in the surface epithelium of the larger airways increase in number and change in distribution, extending more peripherally. Bronchial biopsy studies confirm findings in resected lungs and show bronchial wall inflammation in chronic bronchitis. Activated T lymphocytes are prominent in the proximal airway walls, with a predominance of the CD8 suppressor T lymphocyte subset, rather than the CD4 subset, as seen in asthma. Macrophages are also prominent. Sputum volume correlates with the degree of inflammation in the airway wall. Neutrophils are present, particularly in the bronchial mucus-secreting glands (Figure 41-1), and become more prominent as the disease progresses. In stable chronic bronchitis, the high percentage of intraluminal neutrophils is associated with the presence of neutrophil chemotactic factors, including interleukin-8 (IL-8) and leukotriene B4 (LTB4). Elastase released from these cells is a potent stimulant for the secretion of mucus. Macrophages and CD8+ T cells also accumulate in the mucous glands.
Figure 41-1 A, Central bronchus from lung of cigarette smoker with normal lung function. Only small amounts of muscle are present, and epithelial glands are small. This contrasts sharply with B, bronchus from patient with chronic bronchitis, where the muscle appears as a thick bundle and the glands are enlarged. C, Enlarged glands at higher magnification, showing evidence of chronic inflammation in glands involving polymorphonuclear leukocytes (arrowhead) and mononuclear cells, including plasma cells (arrow).
(Courtesy Dr. J. C. Hogg.)
Evidence indicates that the airway inflammation in patients with chronic bronchitis persists after smoking cessation, particularly if the production of sputum persists, although cough and sputum improve in most smokers who quit. Airway wall changes include squamous metaplasia of the airway epithelium, loss of cilia and ciliary function, and increased smooth muscle and connective tissue.
The smaller bronchioles (<2 mm in internal diameter) normally contribute relatively little to the total airway resistance, because there are so many airways of this size in parallel. Considerable narrowing of these airways can occur before pulmonary function becomes impaired and symptoms develop. Small airways inflammation is one of the earliest changes in asymptomatic cigarette smokers. The inflammatory cell profiles in the small airways are similar to those in larger airways, including the predominance of CD8+ lymphocytes, increase in CD8/CD4 ratio, and increased macrophages. Mucosal ulceration, goblet cell hyperplasia, and squamous cell metaplasia may be present, as well as mesenchymal cell accumulation and fibrosis. With progression of the condition, structural remodeling may occur, characterized by increased collagen content and scar tissue formation that narrows the airways and produces fixed airway obstruction (Figure 41-2).
Figure 41-2 Histologic sections of peripheral airways. A, Section from cigarette smoker with normal lung function, showing near-normal airway. B, Section from patient with small airways disease, showing inflammation in wall and inflammatory exudate in airway lumen. C, More advanced case of small airways disease, with reduced lumen, structural reorganization of airway wall, increased smooth muscle, and deposition of peribronchiolar connective tissue.
(Courtesy Dr. J. C. Hogg.)
Pulmonary emphysema is defined as abnormal permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by destruction of bronchiolar walls. The major types of emphysema are recognized according to the distribution of enlarged air spaces within the acinar unit, the part of lung parenchyma supplied by a single terminal bronchiole, as follows:
Figure 41-3 Diagrammatic representation and CT scans of distribution of abnormal air spaces within acinar unit in two major types of emphysema. A, Acinar unit in normal lung (left top) and in centrilobular emphysema, showing focal enlargement of air spaces around respiratory bronchiole. CT scans show patchy centrilobular emphysema. B, Panlobular (panacinar) emphysema, showing confluent, even involvement of acinar unit. CT scans show diffuse, low-attenuation areas of panlobular emphysema.
Centrilobular and panlobular emphysema can occur alone or in combination. The association with cigarette smoking is clearer for centrilobular than panlobular emphysema, although smokers can develop both types. Those with centrilobular emphysema appear to have more abnormalities in the small airways than those with panlobular emphysema. Panacinar emphysema appears more severe in the lower lobes, in contrast to centriacinar emphysema, which usually concentrates in the upper lobes. Panlobular emphysema is associated with α1-antitrypsin deficiency, but can also be found in patients with no identified genetic abnormality.
Other types include paraseptal (periacinar or distal acinar) emphysema, in which enlarged air spaces occur along the edge of the acinar unit, but only where it abuts against a fixed structure such as the pleura or a vessel. Mixed types of emphysema occur in COPD patients.
The bronchioles and small bronchi are supported by attachment to the outer aspect of adjacent alveolar walls. This arrangement maintains the tubular integrity of the airways. Loss of these attachments and consequent loss of lung elastic recoil may lead to distortion or irregularities of the airways, which contributes to the airflow limitation. The inflammatory cell profile in the alveolar walls is similar to that described in the airways and persists throughout the disease.
Changes in the pulmonary vasculature occur early in the course of COPD; thickening of the intima is followed by increase in smooth muscle and infiltration of the vessel wall with inflammatory cells, including macrophages and CD8+ T lymphocytes. As the disease progresses, greater amounts of smooth muscle, proteoglycans, and collagen accumulate, thickening the arterial wall. The development of chronic alveolar hypoxia in patients with COPD results in hypoxic vasoconstriction and subsequently leads to structural changes in the pulmonary vasculature, pulmonary hypertension, and right ventricular hypertrophy and dilation (cor pulmonale).
Cigarette smoking is the single most important identifiable etiologic factor in COPD. The cause-and-effect relationship between cigarette smoking and COPD derives from several well-controlled population studies over the last four decades.
Maternal smoking is associated with low birth weight and decreased lung function at birth, which may lead to decreased level of function in early adulthood, increasing the risk of developing COPD depending on lifestyle, particularly smoking history. Further, smoking by either parent is associated with an increase in respiratory illness in the first 3 years of life, which may contribute to airflow limitation in later life.
Mild airflow limitation and a reduced increase in lung function occur in smoking adolescents. In addition, the plateau FEV1 in the third decade of life is also shortened considerably by cigarette smoking, which results in the initiation of FEV1 decline years earlier than in those who do not smoke.
In adulthood the effect of smoking on FEV1 decline is well known. In general there is a significant dose-response effect, with smokers having lower lung function the more and the longer they smoke. There is, however, considerable variation. Most longitudinal studies indicate that the decline in FEV1 in smokers ranges from 45 to 90 mL per year, in contrast to the normal 30 mL/yr (Figure 41-4). However, values vary considerably among individuals, and some experience significantly greater decline, at least temporarily, which may explain why COPD may seem to surface over a short period in the fifth and sixth decades of life. Some nonsmokers have impaired lung function, and 15% to 20% of COPD patients are lifelong nonsmokers. Conversely, some heavy smokers are able to maintain normal lung function, although the frequently quoted “15% to 20%” of smokers who are thought to develop clinically significant COPD is probably an underestimate. About 35% of smokers with normal lung function initially developed COPD during a 25-year follow-up in the Copenhagen City Heart Study.
Figure 41-4 Decline in forced expiratory volume in 1 second (FEV1) in smokers and nonsmokers. Horizontal dashed lines represent level of FEV1 consistent with disability or death; curved dashed lines represent change in FEV1 decline with smoking cessation.
Pipe and cigar smokers have significantly greater morbidity and mortality from COPD than nonsmokers, although the risk is less than that from cigarettes. There is a trend to an increased relative risk of chronic airflow limitation from passive smoking, but the effect is not powerful enough to demonstrate clinical significance. Epidemiologic studies have associated cessation of smoking with a decrease in the prevalence of respiratory symptoms and improvement in the subsequent decline in FEV1 (Figure 41-4). The first effect on lung function after smoking cessation is a small increase of 50 to 100 mL in FEV1. There is some debate on whether decline in FEV1 after smoking cessation completely normalizes, although in general those who quit smoking continue to have an FEV1 decline slightly larger than in those who never smoked.
Air pollution has been recognized as a risk factor in chronic respiratory disease in association with various air pollution episodes in the past. The introduction of air quality standards in the 1950s and 1960s led to a decrease in smoke and sulfur dioxide levels, which produced less discernible peaks of pollution related to morbidity and mortality. However, more recent studies show an association between respiratory symptoms, general practitioner consultations and hospital admissions in patients with airways disease, including COPD, at levels of particulate air pollution below 100 µg/m3, levels currently experienced in many urban areas in Western countries.
The role of long-term exposure to outdoor air pollution as a risk factor for the development of COPD is still debated. Air pollution does appear to be a risk factor for mucus hypersecretion, although the association with airflow limitation and accelerated decline in FEV1 is less clear. Air pollution may affect the development of lung function in childhood, which may influence the risk of COPD in adulthood. It is also recognized that indoor air pollution, derived from the combustion of biomass fuel in fires and stoves, is an important etiologic factor in COPD and is a particular problem among women in developing countries. Exposure to biomass smoke is thought to increase the risk of COPD two-fold to three-fold.
There is a causal link between occupational dust exposure and the development of mucus hypersecretion. In addition, longitudinal studies in workforces exposed to dust show an association between dust exposure and a more rapid decline in FEV1. Selection bias must be considered in these associations, resulting from the “healthy worker effect,” with those having respiratory symptoms or lower lung function excluded before entering the occupation. An estimated 15% to 20% of COPD cases are caused by occupational dusts, which increases to 30% in never-smokers. A study of male workers in the Paris area exposed to occupational dusts showed a 5 to 15 mL/yr successive decline in FEV1 from dust exposure. Exposure to welding fumes is also associated with a small but significant risk of developing COPD, from a study in shipyard workers. Workers exposed to cadmium have an increased risk of emphysema.
Population studies of respiratory symptoms indicate a higher prevalence of cough and sputum among smokers than nonsmokers. Cessation of smoking is associated with cessation of sputum production in most cases. Earlier studies of working men in London showed that smoking accelerated the decline in FEV1, but failed to show a correlation between the degree of mucus hypersecretion and an accelerated decline in FEV1 or mortality. By contrast, mortality was strongly related to the development of a low FEV1. Data from a more general population study in Copenhagen between 1976 and 1994 suggested that mucus hypersecretion was associated with increased risk of hospital admission and excessive decline in FEV1 of 10 to 15 mL. Moreover, as FEV1 decreases, the association between mucus hypersecretion and mortality becomes stronger.
The “British hypothesis” suggested that chronic sputum production (chronic bronchitis) predisposed patients to recurrent bronchopulmonary infections, which subsequently resulted in biologic changes in the airways and alveoli, causing the progression of chronic airflow limitation. In the 1960s and 1970s, Fletcher and Peto refuted this hypothesis, showing no relationship between recurrent infective exacerbations of bronchitis and the decline in lung function in men with chronic bronchitis. This has been challenged more recently in the Lung Health Study, which showed an association in continued smokers between lower respiratory tract infection and a faster rate of decline in lung function. This is supported by more recent studies of patients with COPD.
Cough and sputum production in adulthood is more often reported in those with a history of chest illness in childhood. The association between childhood respiratory illness and ventilatory impairment in adulthood is probably multifactorial. Low economic status, greater exposure to passive smoking, poor diet and housing, and residence in areas of high pollution may all contribute to this finding.
Several studies indicate that mortality from chronic respiratory diseases and adult ventilatory function correlate inversely with birth weight and weight at 1 year of age. Thus, impaired growth in utero may be a risk factor for the development of chronic respiratory diseases, including COPD. Any factor that affects lung growth during gestation or in childhood, and thus subsequent attainment of maximum lung function, has the potential to increase the risk of developing COPD.
Diet may influence the development of COPD. Because oxidative stress is thought to have a role in the pathogenesis of COPD, dietary antioxidants such as vitamins A, C, and E should have a protective effect in smokers. The Seven Countries Study found an inverse relationship between baseline intake of fruit and fish and subsequent COPD mortality. In the U.S. Third National Health and Nutrition Examination Survey (NHANES-III), dietary factors, particularly a low intake of vitamin C and low plasma levels of ascorbic acid, were related to a diagnosis of bronchitis. Two British studies also showed that dietary intake of vitamins C and E influences lung function in adults. Studies further suggest a decreased risk of COPD in subjects with a high intake of omega-3 fatty acids.
The “Dutch hypothesis” proposed that smokers with chronic, largely irreversible airflow limitation and subjects with asthma shared a common constitutional predisposition to allergy, airway hyperresponsiveness, and eosinophilia. Smokers tend to have higher levels of immunoglobulin E (IgE) and higher eosinophil counts than nonsmokers, but not as high a level as in asthmatic patients. Studies in middle-aged smokers with a degree of airflow limitation found a positive correlation between accelerated decline in FEV1 and increased airway responsiveness to either methacholine or histamine. Over a range of studies, the presence of airway hyperresponsiveness adds approximately 10 mL/yr to decline in FEV1.
Bronchodilator reversibility has been suggested as a proxy for airway hyperresponsiveness, and some studies suggest reversibility as a predictor of FEV1 decline. However, these studies have not been adjusted for the actual value of the postbronchodilator FEV1; when this is done, minimal association appears to exist between reversibility and FEV1 decline.
Whether airway hyperresponsiveness is a cause or consequence of COPD remains a subject of debate. Although asthma has been considered confusingly as a risk factor for COPD, good evidence supports that asthmatic patients have a more rapid decline in FEV1 than nonasthmatic patients, as well as an increased mortality, primarily from COPD. Poorly controlled asthma will likely lead to airway remodeling and fixed airflow obstruction, fulfilling the definition of COPD.
Chronic obstructive pulmonary disease is a prime example of a condition of gene-environment interaction. The observation of a familial association for an increased risk of airflow limitation in smoking siblings of subjects with severe COPD suggests a genetic component to this disease. Genetic linkage analysis has identified several sites in the genome that may contain susceptibility genes, such as chromosome 2q. Genetic association studies show that a number of candidate genes are associated with the development of COPD or with rapid decline in FEV1. However, the associations are not consistent in different populations (Box 41-2).
Candidate Genes in Chronic Obstructive Pulmonary Disease
Because COPD is a complex and heterogeneous condition, COPD-related phenotypes may differ between different genetic subtypes of COPD. Several studies suggest polymorphisms in various genes related to emphysema severity or distribution of emphysema. A genetic predisposition to the development of COPD exacerbations has also been suggested.
Many genes with unknown functions likely contribute to the pathogenesis of COPD, and until recently, it has not been practical to interrogate the entire genome. Genome-wide association studies may provide a better alternative to candidate gene approaches. Recent genome-wide association studies have identified a single nucleotide polymorphism (SNP) on chromosome 15 that has a significant association with COPD. Multiple genes of interest are present near the most likely associated SNP, including subunits of the nicotinic acetylcholine receptor (CHRNA3 and CHRNA5) and an iron-binding protein (IREB2). A further genome-wide association study identified four SNPs on chromosome 4q, which is strongly associated with FEV1/FVC. Thus, although genome-wide association studies are at an early stage, chromosome 4 and 15 genetic associations appear to be most significant in COPD.
The most consistent association with COPD is alpha1-antitrypsin (α1-proteinase inhibitor) deficiency. Alpha1-antitrypsin is a glycoprotein that is the major inhibitor of serine proteases, including neutrophil elastase. More than 75 biochemical variants of α1-antitrypsin have been described relating to their electrophoretic properties, giving rise to the phase inhibitor (Pi) nomenclature (Table 41-1). The most common allele in all populations is PiM, and the most common genotype is PiMM, which occurs in 93% of the alleles in subjects of Northern European descent. PiMZ and PiMS are the next two most common genotypes and are associated with α1-proteinase inhibitor levels of 15% to 75% of the mean levels of PiMM subjects. Similar levels occur in the much less common PiSS type. The most important other type is PiSZ, in which basal levels are 35% to 50% of normal values. The threshold point for increased risk of emphysema is a level of about 80 mg/dL, which is about 30% of normal.
The homozygous PiZZ type, in which serum levels are 10% to 20% of the average normal value, is the strongest genetic risk factor for the development of emphysema. This recessive trait is most frequently seen in individuals of Northern European descent. Such individuals, particularly if they smoke, are likely to develop COPD, usually panlobular emphysema, at an early age. The onset of disease occurs at a median age of 50 in nonsmokers and 40 years in smokers.
The defect resulting in α1-antitrypsin deficiency is related to a single point mutation at position 342, where the nucleotide sequence for this codon is changed from GAG to AAG, resulting in an amino acid change from glutamic acid to lysine. In the PiZZ subject, α1-antitrypsin protein accumulates in the endoplasmic reticulum of the liver. The structure of the protein reveals that the defect results in the development of abnormal protein polymers, which prevents the α1-antitrypsin passing through the endoplasmic reticulum and thus prevents the secretion of the protein. These polymers may also be chemotactic for inflammatory cells and may thus contribute to the increased elastase burden. It is postulated that a deficiency in α1-proteinase inhibitor results in excess activity of neutrophil elastase and therefore tissue destruction and emphysema.
Studies of U.S. blood donors identify a 1 : 2700 prevalence of PiZZ subjects, the majority of whom had normal spirometry. An estimated 1 : 5000 UK children are born with the homozygous deficiency (PiZZ). However, the number of subjects identified with disease is much lower than predicted from the known prevalence of the deficiency. It is therefore by no means inevitable that all individuals with homozygous deficiency will develop respiratory disease.
An association between COPD patients’ economic status, education, and lung function and COPD hospitalization has been shown in a Danish study, despite relatively small differences among social classes. However, social risk factors are likely multifactorial and may relate to intrauterine exposure, childhood infections, childhood environment, diet, housing conditions, and occupational factors.
The role of gender as a risk factor for COPD remains unclear. Previous studies typically showed greater COPD mortality in men than women, but more recent studies show that COPD now has almost equal prevalence in men and women, probably reflecting the change in tobacco smoking. Women may be more susceptible to the effects of tobacco smoke than men, but this is still debated.
Although COPD is a leading cause of morbidity and mortality worldwide, its prevalence varies across countries. The imprecise, variable definitions of COPD and the lack of spirometry to confirm the diagnosis make it difficult to quantify morbidity and mortality. In addition, prevalence data underestimate the total disease burden because COPD typically is not diagnosed until it is clinically recognized, usually at a moderately advanced stage. Mortality from COPD is also likely to be underestimated because it is often cited as a “contributory factor” rather than a cause of death.
In the past, imprecise definitions of COPD and underdiagnosis have resulted in underreporting of the condition. Prevalence studies of COPD vary depending on the survey method employed, including self-report of physician diagnosis of COPD, prebronchodilator or postbronchodilator spirometry, and respiratory symptom questionnaires. The lowest prevalence figures come from physician self-reporting; most national surveys indicate that about 6% of the general population has been diagnosed with COPD. This figure probably reflects the underrecognition of COPD, particularly in the early stages, when symptoms are not recognized as representing a disease.
Studies based on standardized spirometry suggest that 25% of subjects over age 40 have airflow limitation (FEV1/FVC <0.7). However, prevalence data vary depending on the spirometric criteria used to define COPD. The use of a postbronchodilator, fixed FEV1/FVC (<0.7) leads to potential underdiagnosis in younger adults and overdiagnosis in older adults (>50). Other prevalence studies are based on percent predicted FEV1. In a UK population survey, 10% of men and 11% of women age 18 to 64 years had an FEV1 greater than 2 standard deviations (SD) below their predicted values; the numbers increased with age, particularly in smokers. In current smokers 40 to 65 years old, 18% of men and 14% of women had an FEV1 greater than 2 SD below normal, compared with 7% and 6% of male and female nonsmokers, respectively.
Approximately 14 million people in the United States have COPD, increasing by 42% since 1982. The best data available come from the 1988-1994 NHANES-III study. Prevalence of mild COPD (defined as FEV1/FVC <0.7 and FEV1 >80% predicted) was 6.9% and prevalence of moderate COPD (defined as FEV1/FVC <0.7 and FEV1 ≤80% predicted) was 6% for those age 25 to 75. The prevalence of both mild and moderate COPD was higher in males than females, in whites than in blacks, and increased steeply with age. Airflow limitation affected an estimated 14.2% of current white male smokers, 6.9% of ex-smokers, and 3.3% of never-smokers. Airflow limitation occurred in 13.6% of white female smokers, 6.8% of ex-smokers, and 3.1% of never-smokers. Less than 50% of COPD patients, based on the presence of airflow limitation, had a physician diagnosis of COPD.
Data from five Latin American cities in five different countries showed the presence of COPD (FEV1/FEC ratio <0.7) increased sharply with age. The highest prevalence was in the over-60 age-group and ranged from 18.4% in Mexico City to 31.1% in Montevideo, Uruguay. In 12 Asian-Pacific countries, prevalence of moderate to severe COPD in those over age 30 was 6.3%. However, prevalence rates ranged from 3.5% to 6.7% across the Asia-Pacific region.
The UK national study reported abnormally low FEV1 in 10% of males and 11% of females age 60 to 65 years. In England and Wales, an estimated 900,000 people have a diagnosis of COPD, although because of underdiagnosis, the true number is likely closer to 1.5 million. The mean age at diagnosis in the UK was 67 years, and prevalence increased with age. COPD was more common in men than in women and was associated with socioeconomic deprivation. The prevalence of diagnosed COPD has increased in the UK in women from 0.8% in 1990 to 1.4% in 1997, but did not change over the same period in men. Similar trends are found in the United States, again probably reflecting differences in smoking habits. National surveys of consultations in British general practices found a modest decline in the number of middle-aged men with symptoms of COPD and a slight increase in middle-aged women. These trends are confounded by changes over the years in the application of the diagnostic labels for this condition, particularly the overlap between COPD and asthma.