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COPD Prevalence in Salzburg, Austria^*

Results From the Burden of Obstructive Lung Disease (BOLD) Study

^* 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.

Correspondence to: Michael Studnicka, MD, MSc, FCCP, Müllner Hauptstrasse 48, Department of Pneumology, 5020 Salzburg, Austria; e-mail: m.studnicka{at}salk.at

Abstract

Background: COPD is projected to be the third leading cause of death worldwide by 2020. 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 FEV₁/FVC ratio of < 0.70.

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 (FEV₁/FVC ratio, < 0.7; FEV₁, < 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.

Key Words: airway obstruction • Burden of Obstructive Lung Disease • COPD prevalence • smoking prevalence

In 1990, COPD ranked sixth among all causes of death worldwide, and is projected to rank third in 2020.¹ 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 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 guidelines⁴ 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 America¹¹ 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 Japan⁷ 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 population-based 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.

View larger version (15K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Flow diagram of the study population.

Questionnaire Data
The complete BOLD questionnaire included information on respiratory symptoms, risk factors for COPD, health status, 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 FEV₁/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 FEV₁/FVC ratio of < 0.70 and an FEV₁ of < 80% predicted; and FEV₁/FVC ratio of < 0.70 and an FEV₁ of < 50% predicted, respectively. The National Health and Nutrition Examination Study (NHANES) III reference equations for white men and women¹⁶ 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 adjustments¹⁷ 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).

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.

View larger version (10K): [in this window] [in a new window] [Download PPT slide]   Figure 2. Prevalence of COPD (GOLD I and higher COPD) by gender and age groups.

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 3and 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).

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.⁴¹⁸ 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.

This finding does not minimize the fact that smoking is, by far, the single most important risk factor for COPD.⁴¹⁸ Consistent with the present understanding of the role of smoking,⁴¹⁸ 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 exposures²⁰²¹ 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.⁴¹⁸

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.⁷⁸²³²⁴ 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 initiative¹⁴ 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 guidelines²⁷ 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.

The use of a fixed ratio of FEV₁/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 FEV₁/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 guidelines⁴ 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.¹¹²⁹³⁰ The PLATINO study as well as data from two other BOLD sites have so far been reported. For five Latin American cities, Menenzes et al¹¹ presented estimates between 7.8% and 19.7% for irreversible airway obstruction of GOLD stage I or higher COPD. The corresponding estimates from South Africa²⁹ and Turkey³⁰ 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.⁴¹⁸ 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.

Acknowledgements

We thank Terry Kimes for her assistance with analyzing the data. We also thank the whole Austrian BOLD team involved with the study.

Footnotes

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

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 (www.boldcopd.org).

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.

Received for publication February 10, 2006. Accepted for publication July 30, 2006.

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