COPD Prevalence in Salzburg, Austria* Results From the Burden of Obstructive Lung Disease (BOLD) Study

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1 Original Research COPD COPD Prevalence in Salzburg, Austria* Results From the Burden of Obstructive Lung Disease (BOLD) Study Lea Schirnhofer, MD; Bernd Lamprecht, MD; William M. Vollmer, PhD; Michael J. Allison, BS; Michael Studnicka, MD, FCCP; Robert L. Jensen, PhD; and A. Sonia Buist, MD Background: COPD is projected to be the third leading cause of death worldwide by The Burden of Obstructive Lung Disease initiative was started to measure the prevalence of COPD in a standardized way and to provide estimates of the social and economic burden of disease. Methods: We surveyed a gender-stratified, population-based sample of 2,200 adults > 40 years of age. The findings of prebronchodilator and postbronchodilator spirometry, as well as information on smoking and reported respiratory disease was recorded. Irreversible airflow obstruction was defined as a postbronchodilator FEV 1 /FVC ratio of < Results: For 1,258 participants with good-quality postbronchodilator spirometry findings, the overall prevalence of COPD at stage I or higher was 26.1%, and was equal in men and women. The prevalence of COPD stage II or higher (FEV 1 /FVC ratio, < 0.7; FEV 1, < 80% predicted) was 10.7%. The prevalence of COPD stage I, and COPD stage II, increased with age and cigarette smoking. A doctor diagnosis of COPD was reported by only 5.6% of participants. Conclusion: One quarter of residents of Salzburg County (Austria) who were > 40 years of age had at least mild irreversible airflow obstruction. The high prevalence of COPD highlights the impending health-care crisis that will affect many countries as a result of this greatly underappreciated condition. (CHEST 2007; 131:29 36) Key words: airway obstruction; Burden of Obstructive Lung Disease; COPD prevalence; smoking prevalence Abbreviations: ATS American Thoracic Society; BOLD Burden of Obstructive Lung Disease; GOLD Global Initiative for Obstructive Lung Disease; NHANES National Health and Nutrition Examination Study In 1990, COPD ranked sixth among all causes of death worldwide, and is projected to rank third in This increase in mortality will be largely due to the cumulative exposure of the present population to cigarette smoke and the expected aging of the world population. US mortality data for from 1970 to 2002 support this projection. While mortality for major diseases such as cancer, heart disease, and *From the Department of Pneumology (Drs. Schirnhofer, Lamprecht, and Studnicka), Paracelsus Private Medical School, Salzburg, Austria; the Center for Health Research (Dr. Vollmer and Mr. Allison), Kaiser Permanente Northwest, Portland, OR; the University of Utah School of Medicine (Dr. Jensen), Salt Lake City, UT; and the Oregon Health & Science University (Dr. Buist), Portland, OR. The BOLD project in Salzburg, Austria, was funded by unrestricted grants from Altana; Astra-Zeneca; Boehringer-Ingelheim; GlaxoSmithKline; Merck, Sharpe & Dohme; Pfizer; and Novartis. GlaxoSmithKline also provided in-kind contributions. The study was supported by the Salzburger Gebietskrankenkasse (local public health insurance) and the local government of Salzburg. The BOLD Initiative is funded by unrestricted educational grants from ALTANA, AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Merck, Novartis, and Pfizer to the Operations Center located at the Center for Health Research in Portland, OR ( The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Manuscript received February 10, 2006; revision accepted July 30, Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( org/misc/reprints.shtml). Correspondence to: Michael Studnicka, MD, MSc, FCCP, Müllner Hauptstrasse 48, Department of Pneumology, 5020 Salzburg, Austria; m.studnicka@salk.at DOI: /chest CHEST / 131 / 1/ JANUARY,

2 stroke decreased by 3%, 52%, and 63% respectively, mortality for COPD increased by 103%, an increase that is unparalleled by any other major disease. 2 Given this dramatic increase in COPD mortality, prevalence data indicating the full burden of the disease have surprisingly not been available. In the past, COPD prevalence estimates were not comparable because of the nonuniformity of definitions across international scientific societies. 3 In 2001, the Global Initiative for Obstructive Lung Disease (GOLD) 4 defined COPD as a disease state characterized by airflow limitation that is not fully reversible. Chronic symptoms may or may not coexist. Reversibility is usually measured by spirometry conducted before and after therapy with an inhaled bronchodilator. This definition of COPD and the staging by spirometry were subsequently also adopted by the American Thoracic Society (ATS), the European Respiratory Society, as well as many other national scientific societies. 5 While in the GOLD guidelines 4 COPD was described as a usually progressive disease, the ATS- European Respiratory Society document modified this definition; for the first time COPD was described as a preventable disease. Population-based surveys in the United States, 6 Japan, 7 Korea, 8 Spain, 9 Sweden, 10 and South America 11 that have used spirometry have highlighted the underdiagnosis of COPD and the huge gap between national estimates of COPD prevalence, which are usually based on self-reported diagnosis. 10 For example, the 10.9% prevalence of COPD reported by a 2004 population-based prevalence survey in Japan 7 contrasts sharply with the Japanese Ministry of Health estimate of 0.3%. In that study, only 9.4% of those with documented airflow obstruction reported a physician diagnosis of COPD. Similar rates of underdiagnosis have been reported, and underdiagnosis was consistently related to severity of COPD, with milder disease being missed more often than severe disease. On the other hand, longitudinal data indicate that even COPD in GOLD stage I is associated with an increased mortality risk, 12 and early and aggressive smoking cessation is warranted. Strategies to prevent the loss of pulmonary function and disease progression might be most rewarding in patients with mild disease. 13 The Burden of Lung Disease (BOLD) initiative began in order to develop and use standardized methods to measure the prevalence of COPD and its risk factors in various areas around the world. BOLD seeks further to provide data to estimate the burden of COPD in terms of its impact on quality of life, activity limitation, respiratory symptoms, and use of health-care resources. 14 This report of a populationbased COPD prevalence survey carried out in Salzburg, Austria, is the first from a country participating in the BOLD initiative. Materials and Methods We followed the BOLD protocol as has been reported elsewhere. 14 All staff participated in training, supervised by the BOLD operations center. Study Population We surveyed a gender-stratified random sample of the inhabitants of Salzburg County, who were 40 of age. Participants were selected using a commercially available database that contained information on 63% of residents. The age, sex, and socioeconomic status of individuals in this database are known to correspond closely to those of Salzburg County as a whole. Following an initial recruitment letter, participants were contacted by phone to schedule a clinic visit; where necessary, testing was conducted in the participant s home. For all subjects contacted, answers to a minimal data questionnaire were obtained. Of the 2,200 individuals (1,100 men and 1,100 women) whom we attempted to contact, 118 were age-ineligible, untraceable, had permanently moved from the area, or were deceased. Of the remaining 2,082 eligible participants, 1,258 (60%) completed the full protocol and had spirometry findings that met ATS quality control criteria (see below); these individuals constitute the primary sample for this analysis (Fig 1). Ninety-one individuals (4%) completed the protocol but had unusable spirometry data; 529 (25%) completed only a minimum data questionnaire, with information on smoking history, respiratory symptoms, and comorbidities; 130 individuals (6%) formally declined any participation in the study; and 74 individuals (4%) did not respond to repeated attempts to contact them. The study was approved by the local Ethics Committee of Salzburg County, and all participants gave written informed consent. Study Measures Spirometry was performed according to ATS criteria 15 by trained and certified technicians (EasyOne spirometer; ndd Medizintechnik; Zurich, Switzerland) with participants in a seated position. Separate measurements were made before and at least 15 min after two puffs of salbutamol (400 g) administered via metered-dose inhaler with a spacer (Volumatic; GlaxoSmith- Kline; Research Triangle Park, NC). Spirometry data were sent electronically to the Pulmonary Function Quality Control Centre in Salt Lake City, UT, where each spirogram was reviewed and graded using ATS guidelines. 15 To be deemed usable for analysis, spirometry had to meet ATS acceptability and reproducibility criteria, which included the following: at least three trials; two acceptable (ie, free from artifact, sudden stops, and backextrapolated volumes of 5.0% of FVC) and reproducible (ie, difference between largest and second largest values was 200 ml) tests for both FEV 1 and FVC. Study technicians were continuously monitored. When technicians quality scores dropped below a preset level, they had to stop conducting testing and be retrained and recertified. Questionnaire Data The complete BOLD questionnaire included information on respiratory symptoms, risk factors for COPD, health status, 30 Original Research

3 Figure 1. Flow diagram of the study population. medication use, health-care utilization, comorbidities, respiratory diagnoses, and limitation of activity. 14 The questionnaire was translated from English into German, and then back-translated to assure accuracy. The staff that administered the questionnaire were trained and certified. For participants who did not complete the full spirometry protocol minimal data questionnaire on smoking, history and comorbidities were obtained. Definitions In accordance with the GOLD guidelines, irreversible airflow obstruction was defined as a postbronchodilator FEV 1 /FVC ratio of 0.70, which corresponds to GOLD stage I or higher COPD. We also report data for GOLD stage II or higher COPD, and GOLD stage III or higher COPD, which corresponds to an FEV 1 /FVC ratio of 0.70 and an FEV 1 of 80% predicted; and FEV 1 /FVC ratio of 0.70 and an FEV 1 of 50% predicted, respectively. The National Health and Nutrition Examination Study (NHANES) III reference equations for white men and women 16 were used to calculate the percent predicted values for the primary analysis. A secondary analysis was performed using prediction equations derived from healthy, never-smoking men and women in the study population. Doctor-diagnosed COPD was defined as self-reported physician s diagnosis of chronic bronchitis, emphysema, or COPD. The number of pack-years of cigarette smoking was defined as the average number of cigarettes smoked per day divided by 20 (ie, packs per day) times the duration of smoking in years. Statistical Analysis Prevalence estimates were calculated for the overall Salzburg County population, as well as for subgroups defined by gender and either age or pack-years of cigarette smoking. These calculations were made (PROC SURVEYMEANS in SAS, version 9.1; SAS Institute; Cary, NC) to assure that the estimated prevalences and SEs properly reflect the sampling design. Because the gender distribution of participants 40 years of age in the commercial database (50.1% male) differed slightly from that for Salzburg County as a whole (45.9% male), the data for men and women were weighted so that the resulting prevalence estimates would better match those of Salzburg County as a whole. Additional weighting class adjustments 17 were made to adjust for differential response rates for the eight categories defined by gender and age (ie, 40 to 49, 50 to 59, 60 to 69, and 70 years). Role of Funding Source The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication. Results Table 1 summarizes the main characteristics of the 1,258 individuals included in this analysis. Former smoking was more prevalent in men (p 0.001), while current smoking was slightly higher in women (p 0.067). Not surprisingly, workplace dust exposure was reported by 35.3% of men, but by only 18.2% of women (p 0.001). Compared with these participants, the 824 eligible individuals who were excluded from the analysis CHEST / 131 / 1/ JANUARY,

4 Table 1 Characteristics of the Study Sample Characteristics Men Women Total p Value Sex* 685 (54.5) 573 (45.5) 1,258 (100) Age,* yr (28.3) 168 (29.3) 362 (28.8) (28.3) 170 (29.7) 364 (28.9) (25.6) 153 (26.7) 328 (26.1) (17.8) 82 (14.3) 204 (16.2) Smoking status* Current smoker 119 (17.4) 123 (21.5) 242 (19.2) Former smoker 291 (42.5) 130 (22.7) 421 (33.5) Never-smoker 275 (40.1) 320 (55.8) 595 (47.3) Pulmonary function FEV 1 L 3.38 (0.797) 2.53 (0.610) 2.99 (0.833) % predicted 0.95 (0.168) 0.96 (0.166) 0.95 (0.167) FVC 4.54 (0.892) 3.39 (0.707) 4.02 (0.996) FEV 1 /FVC ratio (8.504) (8.609) (8.551) Exposure to dust at the workplace* Never 443 (64.7) 469 (81.8) 912 (72.5) yr 103 (15.0) 37 (6.5) 140 (11.1) yr 139 (20.3) 67 (11.7) 206 (16.4) Education,* yr 4 58 (8.5) 80 (14.0) 138 (11.0) (65.3) 364 (63.5) 811 (64.5) (9.6) 56 (9.8) 122 (9.7) (16.6) 73 (12.7) 187 (14.9) *Values are given as No. (%). Values are given as the mean (SD). (nonrespondents and those with poor quality spirometry results) were more likely to be women (response rate: women, 54.8%; men, 66.1%; p ) and more likely to be older (response rate: 40-year, 64.7%; 50-year, 69.5%; 60-year, 64.2%; 70-year, 46%; 80-year, 29.0%; p ). Based on minimal data questionnaire information from 620 of those persons who were excluded, the response rates were as follows: never-smokers, 61.6%; current smokers, 69.6%; and former smokers, 74.7% (p 0.001). With regard to reported comorbidities, the response was more frequent in those without reported comorbidities (response rate, 69.9%) compared with those reporting comorbidities (response rate, 61.3%). Table 2 shows the estimated prevalence of smoking in Salzburg County by age and gender. Overall, 18.2% of individuals 40 years of age were smokers at the time of the study, and an additional 31.5% were former smokers. These percentages were generally similar for both sexes, although for subjects aged 40 to 59 years, smoking was more prevalent in women than in men. The overall prevalence of GOLD stage I or higher COPD was 26.1%, and was similar for women (25.7%) and men (26.6%; difference not significant) [see Table 4]. The prevalence of GOLD stage II or higher COPD was 10.7% and was also similar for men and women (difference not significant). Only 1% of the population met the criteria for GOLD stage III or IV COPD. The prevalence of airways obstruction increased quite steeply with age (Fig 2). With regard to age and gender, younger women (40 to 59 years of age) demonstrated a greater prevalence of GOLD stage II COPD or higher degree of airflow obstruction than men. The prevalence of airflow obstruction of GOLD stage I or higher COPD increased from 20.4% in subjects who had never smoked to 36.7% in those Table 2 Smoking Distribution in Salzburg, Austria, by Age and Gender* Variables yr yr yr 70 yr All Male gender Never-smoker Current smoker Former smoker Female gender Never-smoker Current smoker Former smoker Total Never-smoker Current smoker Former smoker *All values are %. 32 Original Research

5 Figure 2. Prevalence of COPD (GOLD I and higher COPD) by gender and age groups. with a smoking history of 20 pack-years. Similarly, the prevalence of GOLD stage II or higher COPD increased from 7.1% in subjects who had never smoked to 18.7% in those with the most pack-years of smoking. Data by gender and smoking status (see Table 4, Fig 2) also show the expected rise in prevalence of airflow obstruction with increasing numbers of pack-years in both men and women (p ). The prevalence of doctor-diagnosed chronic bronchitis, emphysema, or COPD was 5.6%, in both men and women. This was about half the prevalence of GOLD stage II or higher COPD (10.7%). As seen in Tables 3 and 4, the prevalence of doctor-diagnosed airflow obstruction increased with age, but no clear trend was seen with increasing pack-years of smoking. Similar GOLD stage II and higher COPD prevalences were seen when we used local prediction equations in place of the US NHANES III equations (data not shown). Discussion The key findings of this population-based prevalence survey are that one quarter of residents of Salzburg County, Austria, 40 years of age had at least mild airflow obstruction, and that this was as common in women as in men. This finding illustrates the magnitude of the burden that COPD will pose in the near future, as the proportion of the population living into the chronic disease age range continues to increase. 1 To set this study in perspective, the sparse literature on COPD prevalence includes studies that have used a variety of diagnostic approaches to estimate prevalence, including self-report, clinical examination, symptoms, and spirometry. Hardly any of these published reports estimate prevalences of the magnitude that we report, and particularly not in women. 10 Risk for COPD increases with increasing age and cumulative exposure to inhaled particles and gases. 4,18 Indeed, the projected increase in the prevalence of COPD worldwide is being driven more by the projected aging of the world population than by estimated changes in the prevalence of smoking. 19 Demonstrating this point, our data show a steep gradient in COPD prevalence with increasing age, with the highest prevalence seen in men and women 70 years of age. Table 3 Prevalence of COPD According to GOLD Stage I and Higher COPD, GOLD Stage II and Higher COPD, and Doctor-Diagnosed COPD by Age and Gender* GOLD Stage yr, % yr, % yr, % 70 yr, % All, % p Value I 26.1 (1.3) Male 8.2 (2.0) 21.9 (3.0) 28.4 (3.4) 54.5 (4.5) 26.6 (1.7) Female 12.3 (2.5) 20.4 (3.1) 23.2 (3.4) 47.6 (5.5) 25.7 (2.0) GOLD II 10.7 (1.0) Male 1.5 (0.9) 8.3 (2.0) 11.9 (2.4) 22.3 (3.8) 10.3 (1.2) Female 3.5 (1.4) 9.0 (2.2) 6.6 (2.0) 25.0 (4.7) 11.0 (1.5) Doctor-diagnosed 5.6 (0.7) Male 1.9 (0.9) 4.9 (1.5) 5.3 (1.6) 11.5 (2.8) 5.6 (0.9) Female 4.3 (1.5) 5.8 (1.8) 5.0 (1.7) 7.2 (2.6) 5.6 (1.0) *Values are given as the mean (SE), unless otherwise indicated. p Values correspond to age categories. CHEST / 131 / 1/ JANUARY,

6 This finding does not minimize the fact that smoking is, by far, the single most important risk factor for COPD. 4,18 Consistent with the present understanding of the role of smoking, 4,18 we found a strong dose-response relationship with pack-years of smoking. Nevertheless, surprisingly high prevalence of COPD was also found in never-smokers. Whether this finding is related to background exposure that is relevant only to our study site (eg, air pollution) or other yet unknown risk factors deserves further study. Occupational exposures 20,21 and exposure to indoor air pollution from unvented heating and cooking, especially in developing countries and in women, 22 are also important, and often underappreciated, risk factors for COPD. 4,18 In most of the countries surveyed, COPD prevalence in women is usually lower than that seen in men because traditionally women have not been as likely to smoke as men. 7,8,23,24 This situation has changed in some developed countries, where the prevalence of smoking in women is now often as high as that in men. 25 There has been considerable controversy as to whether women are at equal or perhaps at greater risk than men given an equal exposure. This controversy has not been resolved, although there is increasing evidence that women may be more vulnerable. 26 If our results can be extrapolated, the increase in smoking among women, that is likely to occur, especially in developing countries, will lead to a tidal wave of COPD as women both have more exposure and live longer. Women are also more likely than men to be exposed to high indoor air pollution levels in developing countries. In order to obtain accurate estimates of COPD prevalence, we used standardized methods developed by the BOLD initiative 14 that incorporate many quality control measures, including careful population-based sampling with high response rate, standardized spirometry equipment, central training, certification, and monitoring of technicians, and overreading of all spirograms to include only those meeting preset standards, strict protocol for the translation of questionnaires, the training and certification of data entry personnel, and the standard methods for data cleaning and analysis. Although we made any possible effort to obtain an accurate prevalence estimate, the use of a commercial database might have introduced some minute, yet immeasurable, bias. This database was recommended to us by the statistical bureau of the County of Salzburg to represent the target population with regard to sex, age, and socioeconomic status. Prevalence estimates depend on the diagnostic criteria and methods used. 3 In order to make our results comparable across many countries and readily comparable to similar surveys that will be performed in the future, we used the GOLD criteria and staging, which were originally published in 2001 and were revised in 2003, 4 since they have become the standard for COPD staging. As defined by GOLD and other national guidelines 27 and international guidelines, 5 the term COPD is most appropriately used to describe irreversible airflow obstruction in individuals who have a history of exposure to inhaled particles and gases. Such definitions do not necessarily translate into easily applied epidemiologic definitions, however, so BOLD has chosen to use the term chronic airflow obstruction, rather than COPD, when referring to outcomes based solely on lung function measurements. We do so recognizing that irreversible airflow obstruction in the absence of exposure to inhaled particles and gases may result from a number of factors, including 1 -antitrypsin deficiency, the long-term sequelae of asthma, and tuberculosis. This is a potential source of misclassification of our prevalence estimates. However, the extent of this misclassification is not likely to have been large, and the management approach to such individuals is similar to that for COPD patients. Table 4 Prevalence of COPD According to GOLD Stage I and higher COPD, GOLD Stage II and higher COPD, and Doctor-Diagnosed COPD by Pack-Years and Gender* GOLD Stage Never-Smoker, % 0 10 pack-yr, % pack-yr, % 20 pack-yr, % Total, % p Value I 26.1 (1.3) Male 19.9 (2.5) 19.3 (4.5) 26.3 (4.8) 37.2 (3.2) 26.6 (1.7) Female 20.7 (2.5) 27.3 (5.0) 34.9 (6.6) 35.9 (5.2) 25.7 (2.0) II 10.7 (1.0) Male 4.6 (1.3) 7.8 (3.1) 8.2 (3.0) 18.6 (2.6) 10.3 (1.2) Female 8.6 (1.8) 9.3 (3.7) 14.1 (5.1) 18.9 (4.2) 11.0 (1.5) Doctor-diagnosed 5.6 (0.7) Male 4.6 (1.2) 7.2 (2.8) 5.5 (2.4) 6.2 (1.6) 5.6 (0.9) Female 4.5 (1.2) 8.1 (3.1) 1.5 (1.5) 9.5 (2.8) 5.6 (1.0) *Values are given as the mean (SE), unless otherwise indicated. p Values correspond to age categories. 34 Original Research

7 The use of a fixed ratio of FEV 1 /FVC of 0.70 to be the cut point for airflow obstruction, as recommended by the GOLD, has the potential to misclassify at older ages, since the ratio has a small but significant age-related regression. 28 The present controversy revolves around the question of whether using a fixed ratio of FEV 1 /FVC or a more statistically appropriate metric, such as the lower limit (eg, 95th percentile) of the population distribution is a better way to separate normal aging from abnormal aging (ie, disease). Similar controversies have arisen in relation to other reference values with significant age regressions, such as BP and bone mineral density. The present GOLD guidelines 4 endorse the use of the fixed ratio, while recognizing that there is potential for misclassification. Choice of the appropriate set of predicted equations is also a matter of debate and might influence prevalence estimates. However, using either the NHANES III predictions or predictions based on the study sample gave the same high COPD prevalence. Our data can be compared with those from a small number of reports on COPD prevalence using the same methods. 11,29,30 The PLATINO study as well as data from two other BOLD sites have so far been reported. For five Latin American cities, Menenzes et al 11 presented estimates between 7.8% and 19.7% for irreversible airway obstruction of GOLD stage I or higher COPD. The corresponding estimates from South Africa 29 and Turkey 30 are 23.2% (30.3% in men, 19% in women) and 19.1% (28% in men, 10.3% in women), respectively. However, these data are from countries with different ethnic, socioeconomic, and demographic backgrounds, while smoking rates are expectedly higher. The COPD prevalence found in our study most likely reflects the aging of our study population. An important finding of our study is that there was a huge gap between physician diagnosis of COPD and the presence of airflow obstruction defined by spirometry. Only 5.6% of both men and women reported a physician diagnosis of COPD. We conclude from this that awareness of COPD among health professionals needs to increase, which will require more use of objective measures of lung function to confirm the diagnosis. COPD is now considered a preventable and treatable disease, and avoidance of exposure to harmful particles and gases can prevent the vast majority of cases of the disease. In particular, early diagnosis and intervention (primarily smoking cessation) can prevent progression to a clinically significant stage. Even when detected at a more advanced stage, active management can improve health status and prolong life. 4,18 Health-care professionals have an opportunity and responsibility to do more active case finding, adopt a more active management approach, and above all take a more aggressive stance on the reduction of tobacco use. If these are done, the epidemic of COPD could be controlled. ACKNOWLEDGMENT: We thank Terry Kimes for her assistance with analyzing the data. We also thank the whole Austrian BOLD team involved with the study. References 1 Murray CJL, Lopez AD. Alternative projections of mortality and disability by cause : Global Burden of Disease Study. Lancet 1997; 349: Jemal A, Ward E, Hao Y, et al. Trends in the leading causes of death in the United States, JAMA 2005; 294: Celli BR, Halbert RJ, Isonaka S, et al. Population impact of different definitions of airway obstruction. Eur Respir J 2003; 22: Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at: Accessed July 21, Celli BR, MacNee W, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ ERS position paper. Eur Respir J 2004; 23: Mannino DM, Gagnon RC, Petty TL, et al. Obstructive lung disease and low lung function in adults in the United States. Arch Intern Med 2000; 160: Fukuchi Y, Nishimura M, Ichinose M, et al. COPD in Japan: the Nippon COPD Epidemiology study. Respirology 2004; 9: Kim DS, Kim YS, Chung KS, et al. Prevalence of chronic obstructive pulmonary disease in Korea: a population-based spirometry survey. Am J Respir Crit Care Med 2005; 172: Peña VS, Miravitlles, Gabriel R, et al. Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC Multicentre Epidemiological Study. Chest 2000; 118: Halbert RJ, Isonaka S, George D, et al. Interpreting COPD prevalence estimates: what is the true burden of disease? Chest 2003; 123: Menezes AM, Perez-Padilla R, Jardim JB, et al. Chronic obstructive pulmonary disease in five Latin American cities (the Platino study): a prevalence study. Lancet 2005; 366: Mannino DM, Doherty DE, Buist AS. Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study. Respir Med 2006; 100: Tashkin DP, Altose MD, Connett JE, et al. Methacholine reactivity predicts changes in lung function over time in smokers with early chronic obstructive pulmonary disease: the Lung Health Study Research Group. Am J Respir Crit Care Med 1996; 153: Buist AS, Vollmer WM, Sullivan SD, et al. The Burden of Obstructive Lung Disease Initiative (BOLD): rationale and design. COPD 2005; 2: American Thoracic Society Statement. Standardization of spirometry, 1994 update. Am J Respir Crit Care Med 1995; 152: Hankinson JL, Odencrantz JR, Fedan KB. Spirometric referwww.chestjournal.org CHEST / 131 / 1/ JANUARY,

8 ence values from a sample of the general US population. Am J Respir Crit Care Med 1999; 159: Lohr SL. Sampling: design and analysis. Pacific Grove, CA: Duxbury Press Publishing Company, 1999; Pauwels RA, Buist AS, Calverley PMA, et al. The GOLD Scientific Committee: global strategy for diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 163: Feenstra TL, van Gunugten ML, Hoogenveen RT, et al. The impact of aging and smoking on the future burden of chronic obstructive pulmonary disease: a model analysis in the Netherlands. Am J Respir Crit Care Med 2001; 164: Hnizdo E, Sullivan PA, Bang KM, et al. Association between chronic obstructive pulmonary disease and employment by industry and occupation in the US population: a study of data from the Third National Health and Nutrition Examination Survey. Am J Epidemiol 2002; 156: Trupin L, Earnest G, San Pedro M, et al. The occupational burden of chronic obstructive pulmonary disease. Eur Respir J 2003; 22: Perez-Padilla R, Regalado J, Vedal S, et al. Exposure to biomass smoke and chronic airway disease in Mexican women: a case control study. Am J Respir Crit Care Med 1996; 154: De Marco R, Accordini S, Cerveri I, et al. An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages. Thorax 2004; 59: Soriano JB, Maier WC, Egger P, et al. Recent trends in physician diagnosed COPD in women and men in the UK. Thorax 2005; 55: Lundbaeck B, Lindberg A, Lindstroem M, et al. Not 15 but 50% of smokers develop COPD? Report from the Obstructive Lung Disease in Northern Sweden Studies. Respir Med 2003; 97: Connett JE, Murray RP, Buist AS, et al. Lung Health Study Research Group: changes in smoking status affect women more than men; results of the Lung Health Study. Am J Epidemiol 2003; 157: National Collaborating Centre for Chronic Conditions. COPD: management of adults with chronic obstructive pulmonary disease in primary and secondary care; draft for second stakeholder consultation Available at: nice.org.uk/pdf/copd_fullguideline_2ndconsultation.pdf. Accessed July 20, Hardie J, Buist AS, Vollmer WM, et al. Risk of overdiagnosis of COPD in asymptomatic elderly never-smoker. Eur Respir J 2002; 20: Jithoo A, Bateman ED, Lombard CJ, et al. Prevalence of COPD in South Africa: results from the BOLD Study [abstract]. Proc Am Thorac Soc 2006; 3:A Kocabas A, Hancioglu A, Turkyilmaz S, et al. Prevalence of COPD in Adana, Turkey (BOLD-Turkey Study) [abstract]. Proc Am Thorac Soc 2006; 3:A Original Research