Prevalence, Incidence, and Lifetime Risk for the Development of COPD in the Elderly : The Rotterdam Study

Yannick M. T. A. van Durme, Katia M. C. Verhamme, Theo Stijnen, Frank J. A. van Rooij, Geert R. Van Pottelberge, Albert Hofman, Guy F. Joos, Bruno H. Ch. Stricker and Guy G. Brusselle Chest 2009;135;368-377 DOI 10.1378/chest.08-0684 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/135/2/368.full.html

Chest is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright2009by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

Original Research
COPD

Prevalence, Incidence, and Lifetime Risk for the Development of COPD in the Elderly*
The Rotterdam Study
Yannick M. T. A. van Durme, MD; Katia M. C. Verhamme, MD, PhD; Theo Stijnen, MD, PhD; Frank J. A. van Rooij, DSc; Geert R. Van Pottelberge, MD; Albert Hofman, MD, PhD; Guy F. Joos, MD, PhD, FCCP; Bruno H. Ch. Stricker, MB, PhD; and Guy G. Brusselle, MD, PhD

Background: COPD is a major cause of chronic morbidity and mortality throughout the world. Although the prevalence of COPD is already well documented, there are only few studies regarding the incidence of COPD. Methods: In a prospective population-based cohort study among subjects aged > 55 years, COPD was diagnosed with an algorithm based on the validation of hospital discharge letters, files from the general practitioner, and spirometry reports. Results: In this study cohort of 7,983 participants, 648 cases were identified with incident COPD after a median follow-up time of 11 years (interquartile range, 7.8 years). This resulted in an overall incidence rate (IR) of 9.2/1,000 person-years (PY) [95% confidence interval (CI), 8.5 to 10.0]. The IR of COPD was higher among men (14.4/1,000 PY; 95% CI, 13.0 to 16.0) than among women (6.2/1,000 PY; 95% CI, 5.5 to 7.0), and higher in smokers than in never-smokers (12.8/1,000 PY; 95% CI, 11.7 to 13.9 and 3.9/1,000 PY; 95% CI, 3.2 to 4.7, respectively). Remarkable was the high incidence in the youngest female age category of 55 to 59 years (7.4/1,000 PY; 95% CI, 4.1 to 12.6). For a 55-year-old man and woman still free of COPD at cohort entry, the risk for the development of COPD over the coming 40 years was 24% and 16%, respectively. Conclusion: The overall incidence of COPD in an elderly population is 9.2/1,000 PY, with a remarkably high incidence in the youngest women, suggesting a further shift toward the female sex in the gender distribution of COPD. During their further lives, one of four men and one of six women free of COPD at the age of 55 years will have COPD develop. (CHEST 2009; 135:368 377)
Key words: COPD; epidemiology (pulmonary); incidence; lifetime risk; prevalence Abbreviations: CI confidence interval; GOLD Global Initiative for Chronic Obstructive Lung Disease; HR hazard ratio; IR incidence rate; PY person-years

OPD is defined as disease state characterized C by airflow limitationa 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 like tobacco smoke.13 COPD is a worldwide leading and stillincreasing cause of chronic morbidity and mortality. Chapman and colleagues4 and Mannino et al5 pro368

jected that from 1990 to 2020, COPD will move from the sixth- to the third-most-common cause of death worldwide, while rising from fourth to third in terms of morbidity. In the Netherlands, a study6 suggests that by 2015, there will be a 76% increase in the prevalence of COPD compared with 1994. In contrast to numerous reports710 on the prevalence of COPD, there have only been a few popuOriginal Research

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

lation-based studies1116 on the incidence of COPD. Tobacco smoking is by far the major environmental risk factor for the development of COPD in industrialized countries, but there seems to be a high variation in susceptibility to the disease among smoking individuals. Previous studies17 suggest that at least 15 to 20% of the smoking adults 50 years old have COPD. Interaction with other risk factors (eg, occupational dusts, air pollution, respiratory infections, or genetic factors) could determine the susceptibility of an individual smoker to the disease.2 Currently, no tests can predict which smoker will have COPD develop, but cessation of smoking should be strongly encouraged because this is the only therapeutic action that can slow down the disease. In this context, incidence studies can be important to elucidate new risk factors for COPD and to identify the susceptible smokers for the development of the disease. This may lead to the discovery of new pathophysiologic mechanisms and guide further clinical research. The objective of this study was to investigate the prevalence, incidence, risk factors, and lifetime risk of COPD as a function of age, gender, and smoking behavior in the participants of a large ongoing prospective population-based cohort study with 15 years of follow-up time.

Materials and Methods

Study Population and Baseline Data Collection The present study is part of the Rotterdam Study, an ongoing population-based cohort study aimed at assessing the occurrence of and risk factors for chronic diseases in the elderly. Objectives and methods of the Rotterdam Study have been described elsewhere.18,19 In short, the Rotterdam Study cohort includes 7,983 participants (78% of the eligible population) aged 55 years living in Ommoord, a well-defined suburb of the city of Rotterdam, the Netherlands. Almost all (99.8%) are of white descent. Baseline data were collected from 1989 until 1993. Participants were visited at home at the start of the study for a standardized interview on their health status. Since the start of the Rotterdam Study, cross-sectional surveys have been performed out every 2 to 3 years. Trained research assistants collected information from medical records of the general practitioners, hospitals, and nursing homes. The medical ethics committee of Erasmus Medical Center, Rotterdam, approved the study. Participants gave written informed consent and permission to retrieve information from treating physicians. Spirometry Spirometry was performed using a portable spirometer (SpiroPro; Erich Jaeger GmbH; Hoechberg, Germany) according to the American Thoracic Society/European Respiratory Society guidelines by trained paramedical personnel.1,20 FEV1, FVC, and FEV1/FVC were measured; the spirogram (volume-time curve) and maximal expiratory flow-volume curve were also recorded. Spirometries that yielded results that did not meet American Thoracic Society/European Respiratory criteria for acceptability and reproducibility were classified as not interpretable (9.6% of spirometries). Because of practical reasons, no reversibility tests were conducted. The interpretation of spirometry results was performed independently by two research physicians (Y. vD. and G. vP.); in case of discordance between both physicians (6.1% of spirometries), the final protocol was made by a senior respiratory physician (G.B.). Patient Identification and Validation For the validation of the COPD cases, we had access to hospital discharge letters, files from the general practitioners, spirometry reports, and pharmacy dispensing data for patients participating in the Rotterdam Study. Spirometry was performed in the context of he Rotterdam cohort study in 3,550 participants. In addition, throughout the entire study period, spirometries were also performed on clinical indication by respiratory specialists and internists with subspecialty in respiratory medicine. In the absence of spirometry, all medical information of subjects that used respiratory medication for at least 6 months (Anatomical Therapeutic Chemical classification codes: R03AC, R03AK, R03BA, R03BB, R03CC, R03DA),21 and all hospital discharge letters or mortality reports with a coded diagnosis of COPD (International Classification of Diseases, Tenth Revision: J40J44)22 were reviewed. The diagnosis of COPD was classified as definite or probable. Definite COPD was defined by a moderate-to-severe obstructive spirometry results (FEV1/FVC 0.7 and FEV1 80% of predicted), and/or as COPD diagnosed by a specialist in internal medicine (mainly respiratory physicians or internists with subspecialty in respiratory medicine) based on the combination of clinical history, physical examination, and spirometry. Probable COPD was defined by a mild obstructive spirometry (FEV1/FVC
CHEST / 135 / 2 / FEBRUARY, 2009

*From the Department of Respiratory Diseases (Drs. van Durme, Van Pottelberge, Joos, and Bruselle), Ghent University Hospital, Ghent, Belgium; Department of Epidemiology and Biostatistics (Drs. Verhamme, van Rooij, Hofman, and Stricker), Erasmus University Medical Center, Rotterdam, the Netherlands; and Department of Medical Statistics and Bioinformatics (Dr. Stijnen), Leiden University Medical Center, Leiden, the Netherlands. The Rotterdam Study is supported by Erasmus Medical Center Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; and the Ministry of Health, Welfare and Sports. This study was supported by the Netherlands Organization for Scientific Research grants 904-61-093 and 918-46-615. Dr. van Durme received a travel grant by the Belgian Thoracic Society and is a doctoral research fellow of the Fund for Scientific Research Flanders (Vlaanderen). The authors have no conflicts of interest to disclose. Manuscript received March 12, 2008; revision accepted August 19, 2008. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Bruno H. Ch. Stricker, MB, PhD, Department of Epidemiology and Biostatistics, Erasmus University Medical Center, PO Box 2040, 3000 DR Rotterdam, the Netherlands; e-mail: b.stricker@erasmusmc.nl DOI: 10.1378/chest.08-0684
www.chestjournal.org

369

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

10275 eligible subjects 2292 eligible subjects refused to participate 7983 participants 280 participants with prevalent COPD 7703 participants without prevalent COPD

648 participants with incident COPD

7055 participants without incident COPD

376 definite COPD

272 probable COPD

Figure 1. The Rotterdam Study.

0.7 and FEV1 80% of predicted), and/or as COPD diagnosed by a physician in another medical specialty (eg, a general practitioner). The index date was defined as the date of diagnosis of COPD found in the medical reports, or the date of a first prescription of COPD medication, or the date of the obstructive lung function examination, whichever came first. Follow-up time was defined as the time period between the start of the study (January 1, 1990) and the diagnosis of COPD, death, loss to follow-up, or the end of the study period (December 31, 2004). Smoking status was dichotomized into never-smokers and smokers. The category smokers included both current and former smokers. Statistical Analysis To compare the baseline characteristics of the COPD cases and the other participants, we used a Mann-Whitney U test for the continuous variables and 2 test for the categorical variables. Age- and gender-specific (in 5-year age categories) incidence rates (IRs) per 1,000 person-years (PY) were obtained by dividing the number of incident cases by the total number of PY accumulated by the study population (excluding patients with
370

COPD at baseline). The 95% confidence intervals (CIs) were calculated using a Poisson distribution. Cumulative prevalence of COPD per age was calculated by dividing the number of persons with prevalent COPD by the number of subjects present in the study with that specific age. All subjects of the total cohort were used for the analysis; 95% CIs were calculated with the Wilson score method for a binomial proportion. The cumulative incidence and the lifetime risk of COPD were calculated based on a Cox regression model with adjustment for competing risk of death, as described by Rosthoj et al23; 95% CIs were calculated based on a log transformation. The risk of COPD according to gender, differences in smoking behavior, and total number of pack-years smoked were analyzed using Cox regression models, adjusted for confounders. Cigarette pack-years were computed as duration of smoking (years) multiplied by the number of smoked cigarettes, divided by 20. Missing pack-year values were imputed by predicted values, based on a logistic regression analysis adjusted for age and gender. Statistical analysis was performed using statistical software (SPSS for Windows, version 15; SPSS; Chicago, IL; and SAS version 9.1; SAS Institute; Cary, NC); p 0.05 was accepted as significant.
Original Research

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

Table 1Baseline Characteristics of the Study Population (n 7,983)*

Characteristics Age, yr Gender Male Female Smoking status Current Former Never Missing Pack-yr 0 110 1120 2130 3140 4150 50 Cardiovascular comorbidity Yes No Missing Data 69.5 14.9

Incidence Six hundred forty-eight new cases of COPD were diagnosed during follow-up. This resulted in an overall incidence rate of 9.2/1,000 PY (95% CI, 8.5 to 10.0) [Table 2]. The incidence of COPD was higher in men (14.4/1,000 PY; 95% CI, 13.0 to 16.0) than in women (6.2/1,000 PY; 95% CI, 5.5 to 7.0) [Fig 3, top, A]. The incidence increased significantly from 6.9/ 1,000 PY (95% CI, 4.3 to 10.5) at the age of 55 to 59 years, to 12.8/1,000 PY (95% CI, 10.9 to 15.0) at the age of 75 to 79 years. This increase with age was no longer observed for the higher age categories (Fig 3, top, A), probably due to a healthy survivor effect. The incidence of COPD in the youngest female age categories (55 to 59 years) was remarkably high, namely 7.4/1,000 PY (95% CI, 4.1 to 12.6) [Fig 3, bottom panels, B]. Overall, the incidence was higher in smokers (9.4/1,000 PY; 95% CI, 8.1 to 10.8 for women, and 15.6/1,000 PY; 95% CI, 14.1 to 17.3 for men) than in never-smokers (3.8/1,000 PY; 95% CI, 3.1 to 4.6 for women, and 4.2/1,000 PY; 95% CI, 2.3 to 7.2 for men) [Fig 3, bottom panels, B]. The overall and age-specific incidence of COPD, broken down by gender and smoking, are shown in Table 2. Risk Factors for the Occurrence of COPD Cox regression analysis showed that male participants had a hazard ratio (HR) of 1.6 (95% CI, 1.4 to 2.2) for the development of COPD, in comparison with female participants, adjusted for age and smoking behavior (Table 3). The risk for COPD developing was 3.8-fold higher for smokers than neversmokers (95% CI, 2.7 to 5.3). The risk was highest for current smokers and for subjects who had smoked 50 pack-years (Table 3). Cumulative Incidence and Lifetime Risk The cumulative incidence of COPD over the 15.5 years of follow-up time of the cohort was 6.7% (95% CI, 5.5 to 8.0). Figure 4 shows the 10-, 20-, 30-, and 40-year risks for COPD to develop in men and women who are still free of the disease at a certain age, adjusted for the competing risk of dying. For a man free of COPD at 55 years of age, the risk for COPD over the coming 10, 20, 30, and 40 years was 4%, 10%, 18%, and 24%, respectively. For a woman, the risk was 3%, 8%, 13%, and 16%, respectively (Fig 4).

3,105 (38.9) 4,878 (61.1) 1,725 (21.6) 3,107 (38.9) 2,794 (35.0) 357 (4.5) 2,916 (36.5) 1,414 (17.7) 806 (10.1) 1,058 (13.3) 774 (9.7) 378 (4.7) 637 (8.0) 2,294 (28.7) 5,381 (67.4) 308 (3.9)

*Data are presented as median (interquartile range) or No. (%).

Results Baseline Characteristics Overall, 928 well-defined COPD cases were identified in the Rotterdam Study (536 men and 392 women). A total of 280 patients had prevalent COPD at baseline. In the remaining study population (n 7,703), COPD developed in 648 participants (8.4%), of whom 376 were classified as definite, and 272 as probable cases (Fig 1). The median follow-up time was 11 years (interquartile range, 7.8 years), and there were 70,209 years of observation; 3,669 participants (46%) were deceased, and 371 participants (4.7%) were unavailable for follow-up before the end of the study period on December 31, 2004. Table 1 shows the baseline characteristics of the total study population (n 7,983), including COPD cases (n 928) and non-COPD cases (n 7,055). Prevalence The overall baseline prevalence of COPD in the cohort was 11.6% (95% CI, 10.9 to 12.3). When considering the age-specific prevalence, a progressive rise of prevalence with age until the age of 79 years in men and 77 years in women was observed. Once above this age category, the prevalence estimates gradually declined. The prevalence was higher in men than in women (Fig 2).
www.chestjournal.org

Discussion In this large ongoing prospective cohort study of elderly people, the overall incidence rate of COPD was 9.2/1,000 PY. The incidence increased with age
CHEST / 135 / 2 / FEBRUARY, 2009

371

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

Age-specific prevalence in men

18 16 14 Prevalence (%) 12 10 8 6 4 2 0 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 Age (years)

Age-specific prevalence in women

18 16 14 Prevalence (%) 12 10 8 6 4 2 0 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 Age (years)

Figure 2. Age-specific cumulative prevalence of COPD in men (top) and women (bottom).

and was higher in men than in women, as well as higher in smokers than in never-smokers. This is the first study calculating the age- and sex-adjusted lifetime risk for the development of COPD, cor-

rected for the competing risk of dying. For a 55-yearold individual without COPD, the risk for the disease over the coming 40 years was 24% for men and 16% for women, respectively.

Table 2Incidence of COPD, Overall and Age Specific, Broken Down by Gender and Smoking Status*
Overall Age Groups, COPD IR yr 5559 6064 6569 7074 7579 80 All age categories 6.9 4.8 10.2 12.5 12.8 6.0 9.2 95% CI 4.310.5 3.56.4 8.712.0 10.714.4 10.915.0 4.97.2 8.510.0 Men COPD IR 95% CI 6.1 6.9 13.9 16.1 20.5 15.1 14.4 2.712.0 4.610.0 11.217.2 13.119.6 16.625.0 11.818.9 13.016.0 Smoking Men COPD IR 7.1 7.8 14.7 17.5 21.9 16.8 15.6 95% CI 3.214.0 5.211.2 11.718.2 14.221.4 17.626.8 13.121.3 14.117.3 Never-Smoking Men Women Smoking Women Never-Smoking Women

COPD COPD COPD COPD IR 95% CI IR 95% CI IR 95% CI IR 95% CI 0.0 0.0 3.8 2.2 5.4 4.3 4.2 0.015.6 0.06.2 0.712.0 0.210.2 1.117.2 0.913.8 2.37.2 7.4 3.3 7.4 10.0 8.4 2.9 6.2 4.112.6 2.05.1 5.79.5 8.012.3 6.510.6 2.13.9 5.57.0 11.1 5.719.7 5.1 3.08.2 10.4 7.713.7 13.4 10.317.2 12.5 9.116.9 3.5 2.05.9 9.4 8.110.8 2.9 0.9 4.0 6.6 5.7 2.9 3.8 0.69.2 0.22.9 2.36.5 4.59.5 3.78.3 1.94.1 3.14.6

*IRs are expressed as No./1,000 person-yr. Men and women, both smoking and never smoking. 372
Original Research

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

Age-specific incidence of COPD

A
Incidence/1000 PY

24 20 16 12 8 4 0 55-59 60-64 65-69 70-74 75-79 >=80 Age categories

Overall incidence Incidence in w omen Incidence in men

Age-specific incidence of COPD in men

24

20 Incidence/1000 person-years

16

12

0 55-59 60-64 65-69 Age categories Incidence in men Incidence in male non-smokers Incidence in male smokers 70-74 75-79 >=80

Age-specific incidence of COPD in women

24

20 Incidence/1000 person-years

16

12

0 55-59 60-64 65-69 Age categories Incidence in w omen Incidence in female non-smokers Incidence in female smokers 70-74 75-79 >=80

Figure 3. Top, A: Age- and gender-specific incidence rates of COPD (/1,000 PY). Bottom panels, B: Age- and gender-specific incidence rates of COPD (/1,000 PY) in smokers and never-smokers.

www.chestjournal.org

CHEST / 135 / 2 / FEBRUARY, 2009

373

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

Table 3Risk Factors for the Occurrence of COPD

Definite and Probable COPD COPD Risk Factors Gender Female Male Not adjusted Adjusted for age and Smoking status Never-smoker Smoker (in general) Not adjusted Adjusted for age and Current smoker Not adjusted Adjusted for age and Former smoker Not adjusted Adjusted for age and Pack-yr, No. 0 110 Not adjusted Adjusted for age and 1120 Not adjusted Adjusted for age and 2130 Not adjusted Adjusted for age and 3140 Not adjusted Adjusted for age and 4150 Not adjusted Adjusted for age and 50 Not adjusted Adjusted for age and Patients/Cohort, No. 276/4,573 372/2,821 372/2,821 101/2,645 541/4,409 541/4,409 268/1,725 268/1,725 273/3,107 273/3,107 105/2,916 61/1,414 61/1,414 86/806 86/806 127/1,058 127/1,058 95/774 95/774 53/378 53/378 121/637 121/637 HR 1.0 2.3 1.6 1.0 3.3 2.6 4.8 4.0 2.5 1.9 1.0 1.3 1.2 2.9 2.6 3.9 3.4 3.4 3.0 4.3 3.9 6.7 5.7 95% CI Reference 1.992.72 1.381.93 Reference 2.654.05 0.063.28 3.836.07 3.115.09 1.983.12 1.502.47 Reference 0.951.79 0.901.70 2.163.81 1.933.51 3.015.04 2.544.46 2.614.55 2.204.05 3.116.03 2.735.46 5.148.66 4.287.62 Definite COPD Patients/Cohort, No. 147/4,573 229/2,821 229/2,821 42/2,645 330/4,409 330/4,409 176/1,725 176/1,725 154/3,107 154/3,107 43/2,916 36/1,414 36/1,414 52/806 52/806 84/1,058 84/1,058 55/714 55/714 30/378 30/378 76/637 76/637 HR 1.0 2.7 1.8 1.0 4.9 3.8 7.8 6.3 3.4 2.6 1.0 1.9 1.8 4.3 3.9 6.3 5.3 5.0 4.3 6.1 5.4 10.5 8.8 95% CI Reference 2.223.36 1.412.19 Reference 3.526.70 2.665.30 5.5410.86 4.388.95 2.424.79 1.773.67 Reference 1.202.92 1.132.76 2.866.43 2.545.88 4.369.10 3.587.89 3.357.43 2.766.57 3.829.71 3.308.74 7.2515.32 5.8813.29

smoking

gender

gender

gender

gender

gender

gender

gender

gender

gender

Reviewing the literature, only six previous reports1116 on the incidence of COPD in a general population were found. The first two are earlier studies: a Finnish report11 and a Polish report.12 The annual IR of COPD in these studies was 2/1,000 and 5/1,000 persons per year, respectively. Two more recent Swedish studies,14,15 which found no gender difference, were based on the Obstructive Lung Disease in Northern Sweden cohort and included persons from 35 to 65 years old at study entry. The measured incidence of COPD was 7/1,000 PY according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) II criteria, and 16/1,000 PY according to GOLD criteria. Another report13 came from the Copenhagen City Heart Study in Denmark, which included subjects 20 years of age. COPD developed in 9.7% and 13.2% of the subjects after 5 years and 15 years of follow-up time, respectively. A more recent study16 was
374

published with data from an international cohort of young adults (age 20 to 44 years). The incidence of COPD in this study was 2.8/1,000 PY. The differences in incidence rates among these studies can be explained by the difference in study population and COPD definitions that have been used. It has been reported that the prevalence of COPD is higher in men than in women.24,25 We found that the same is true for the incidence of COPD, but our findings seem to be in contrast with other incidence studies,1315 which found no gender difference. This finding can be explained by the fact that smoking among female subjects in the Netherlands increased later in comparison to North-European countries,4 and that we had a cohort with on average older members, with traditionally more smoking men than women. Interestingly, we found a surprisingly high incidence in the youngest female age categories.
Original Research

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

Cumulative incidence of COPD in men

30%
Probability of C O PD

25% 20% 15% 10% 5% 0% 55 60 65 70 75 80

Age at cohort entry

Cumulative incidence of COPD in women 30%

Probability of C O PD

25% 20% 15% 10% 5% 0% 55 60 65 70 75 80

Age at cohort entry 10 year Cum Inc COPD 20 year Cum Inc COPD 30 year Cum Inc COPD 40 year Cum Inc COPD

Figure 4. Age-related risk for COPD to develop over the coming 10, 20, 30, and 40 years in men (top) and women (bottom). Cum Inc cumulative incidence.

This might be explained by the fact that women of this age started smoking in increasing numbers since 1940. Evidence for this hypothesis comes from epidemiologic reports25,26 from the United States showing that already in 2000, there were more deaths from COPD among female subjects of this age category than among male subjects. Incident COPD cases were also detected among male and especially female never-smokers, indicating that besides active smoking other environmental exposures such as passive smoking,
www.chestjournal.org

occupational exposures, and (outdoor and indoor) air pollution might contribute to the development of COPD. The strength of the Rotterdam Study is its prospective, population-based design, with similar data collection procedures for every participant and a virtually complete follow-up. More than 600 cases of incident COPD were identified over a total follow-up time of 15.5 years. The large cohort size and the use of PY instead of persons enabled us to estimate the incidence rate more accurately.
CHEST / 135 / 2 / FEBRUARY, 2009

375

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

A potential limitation to our study is that we did not have spirometric results for all cohort participants because of the large number of subjects that deceased during follow-up. Therefore, we also used information that came from hospital discharge letters and files from general practitioners. The reliance in the absence of spirometry on a history of respiratory medication use to examine the medical records for evidence of a COPD diagnosis probably resulted in an underestimate of the incidence of clinically silent but spirometrically identifiable COPD. Furthermore, we used prebronchodilator spirometric values for defining COPD instead of postbronchodilator values as suggested by the GOLD guidelines.1,2 In order to adjust for this, we excluded all subjects with asthma from our analysis. However, we cannot exclude the possibility of misclassification of COPD as asthma in some participants, especially among women, that also might have led to an underestimation of the true incidence of COPD. Interestingly, Johannessen et al27 found that the assessment of prognostic risk factors for COPD was not influenced by the type of lung function assessment (before or after bronchodilation), even if the prevalence of COPD defined without bronchodilation may be overestimated. In our study, we used a fixed value (0.7) of the FEV1/FVC to define airflow obstruction, rather than the fifth percentile of the predicted value.28 Literature29 has shown that the lower limit of the normal range of the FEV1/FVC decreases with age, meaning that we would overestimate the number of patients with COPD if we would only use this criterion. To correct for this misclassification bias in our elderly cohort, we only defined those subjects with a FEV1 80% of predicted as definite COPD cases because Lindberg et al14,15 found that this cut-off seemed to be more reliable than the GOLD criteria in identifying incident COPD among elderly subjects. Also, a recent study30 showed that subjects classified as normal using the lower limit of normal, but as abnormal using the fixed ratio of 0.7, were more likely to die and have COPD-related hospitalizations during further follow-up than healthy subjects. This effect was even more pronounced among those subjects with a FEV1 80% of predicted. In conclusion, we found that the overall incidence of COPD in a population-based elderly cohort in the Netherlands was 9.2/1,000 PY and that the lifetime risk for COPD to develop over the coming 40 years for a 55 year-old man and woman, still free of COPD, was 24% and 16%, respectively. The incidence increased with age, smoking, and was higher in men than in women. Remarkable was the high incidence in the youngest female age categories,
376

suggesting a future shift toward the female sex in the gender distribution of COPD.
ACKNOWLEDGMENT: The authors thank Mrs. Jolande Verkroost for preparing the data set for the validation of the COPD cases. We also thank Prof. Dr. Jan Heeringa, the research assistants, and all our other colleagues in the Ommoord Research Center for their efforts in the data collection.

References
1 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at: http://www.goldcopd.com/. Accessed March 5, 2008 2 Pauwels RA, Rabe KF. Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet 2004; 364:613 620 3 Rabe KF, Beghe B, Luppi F, et al. Update in chronic obstructive pulmonary disease 2006. Am J Respir Crit Care Med 2007; 175:12221232 4 Chapman KR, Mannino DM, Soriano JB, et al. Epidemiology and costs of chronic obstructive pulmonary disease. Eur Respir J 2006; 27:188 207 5 Mannino DM, Gagnon RC, Petty TL, et al. Obstructive lung disease and low lung function in adults in the United States: data from the National Health and Nutrition Examination Survey, 1988 1994. Arch Intern Med 2000; 160:16831689 6 Rutten van-Molken MP, Feenstra TL. The burden of asthma and chronic obstructive pulmonary disease: data from the Netherlands. Pharmacoeconomics 2001; 2(19 suppl):1 6 7 Anto JM, Vermeire P, Vestbo J, et al. Epidemiology of chronic obstructive pulmonary disease. Eur Respir J 2001; 17:982994 8 Buist AS, Vollmer WM, Sullivan SD, et al. The Burden of Obstructive Lung Disease Initiative (BOLD): rationale and design. COPD 2005; 2:277283 9 Groenewald P, Vos T, Norman R, et al. Estimating the burden of disease attributable to smoking in South Africa in 2000. S Afr Med J 2007; 97(8 pt 2):674 681 10 Zhong N, Wang C, Yao W, et al. Prevalence of chronic obstructive pulmonary disease in China: a large, populationbased survey. Am J Respir Crit Care Med 2007; 176:753760 11 Huhti E, Ikkala J. A 10-year follow-up study of respiratory symptoms and ventilatory function in a middle-aged ruralpopulation. Eur J Respir Dis 1980; 61:33 45 12 Krzyzanowski M, Jedrychowski W, Wysocki M. Factors associated with the change in ventilatory function and the development of chronic obstructive pulmonary disease in a 13-year follow-up of the Cracow Study: risk of chronic obstructive pulmonary disease. Am Rev Respir Dis 1986; 134:10111019 13 Vestbo J, Lange P. Can GOLD Stage 0 provide information of prognostic value in chronic obstructive pulmonary disease? Am J Respir Crit Care Med 2002; 166:329 332 14 Lindberg A, Jonsson AC, Ronmark E, et al. Ten-year cumulative incidence of COPD and risk factors for incident disease in a symptomatic cohort. Chest 2005; 127:1544 1552 15 Lindberg A, Eriksson B, Larsson LG, et al. Seven-year cumulative incidence of COPD in an age-stratified general population sample. Chest 2006; 129:879 885 16 De Marco R, Accordini S, Cerveri I, et al. Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm. Am J Respir Crit Care Med 2007; 175:3239 17 Yawn BP, Keenan JM. COPD: the primary care perspective; addressing epidemiology, pathology, diagnosis, treatment of
Original Research

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

18 19 20 21 22 23

24

smokings multiple morbidities and the patients perspective. COPD 2007; 4:67 83 Hofman A, Grobbee DE, de Jong PT, et al. Determinants of disease and disability in the elderly: the Rotterdam Elderly Study. Eur J Epidemiol 1991; 7:403 422 Hofman A, Breteler MM, van Duijn CM, et al. The Rotterdam Study: objectives and design update. Eur J Epidemiol 2007; 22:819 829 Celli BR, Macnee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004; 23:932946 World Health Organization. Anatomical therapeutic chemical classification system. Geneva, Switzerland: World Health Organization, 1996 World Health Organization. International statistical classification of diseases and related health problems: 10th revision. Geneva, Switzerland: World Health Organization 1992 Rosthoj S, Andersen PK, Abildstrom SZ. SAS macros for estimation of the cumulative incidence functions based on a Cox regression model for competing risks survival data. Comput Methods Programs Biomed 2004; 74:69 75 Langhammer A, Johnsen R, Gulsvik A, et al. Sex differences

25

26

27

28

29

30

in lung vulnerability to tobacco smoking. Eur Respir J 2003; 21:10171023 Han MK, Postma D, Mannino DM, et al. Gender and chronic obstructive pulmonary disease: why it matters. Am J Respir Crit Care Med 2007; 176:1179 1184 Mannino DM, Homa DM, Akinbami LJ, et al. Chronic obstructive pulmonary disease surveillance-United States, 19712000. Respir Care 2002; 47:1184 1199 Johannessen A, Omenaas ER, Bakke PS, et al. Implications of reversibility testing on prevalence and risk factors for chronic obstructive pulmonary disease: a community study. Thorax 2005; 60:842 847 Pellegrino R, Viegi G, Brusasco V, et al. Interpretative strategies for lung function tests. Eur Respir J 2005; 26:948 968 Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med 1999; 159:179 187 Mannino DM, Sonia BA, Vollmer WM. Chronic obstructive pulmonary disease in the older adult: what defines abnormal lung function? Thorax 2007; 62:237241

www.chestjournal.org

CHEST / 135 / 2 / FEBRUARY, 2009

377

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians

Prevalence, Incidence, and Lifetime Risk for the Development of COPD in the Elderly : The Rotterdam Study Yannick M. T. A. van Durme, Katia M. C. Verhamme, Theo Stijnen, Frank J. A. van Rooij, Geert R. Van Pottelberge, Albert Hofman, Guy F. Joos, Bruno H. Ch. Stricker and Guy G. Brusselle Chest 2009;135; 368-377 DOI 10.1378/chest.08-0684 This information is current as of December 26, 2011
Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/135/2/368.full.html References This article cites 27 articles, 16 of which can be accessed free at: http://chestjournal.chestpubs.org/content/135/2/368.full.html#ref-list-1 Cited Bys This article has been cited by 7 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/135/2/368.full.html#related-urls Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.

Downloaded from chestjournal.chestpubs.org by guest on December 26, 2011 2009 American College of Chest Physicians