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DOI 10.1378/chest.08-06842009;135;368-377Chest

Joos, Bruno H. Ch. Stricker and Guy G. BrusselleFrank J. A. van Rooij, Geert R. Van Pottelberge, Albert Hofman, Guy F.Yannick M. T. A. van Durme, Katia M. C. Verhamme, Theo Stijnen,The Rotterdam Studythe Development of COPD in the Elderly :Prevalence, Incidence, and Lifetime Risk for

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Prevalence, Incidence, and LifetimeRisk for the Development of COPD inthe 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 studiesregarding the incidence of COPD.Methods: In a prospective population-based cohort study among subjects aged> 55 years, COPDwas diagnosed with an algorithm based on the validation of hospital discharge letters, files fromthe general practitioner, and spirometry reports.Results: In this study cohort of 7,983 participants, 648 cases were identified with incident COPDafter a median follow-up time of 11 years (interquartile range, 7.8 years). This resulted in anoverall incidence rate (IR) of 9.2/1,000 person-years (PY) [95% confidence interval (CI), 8.5 to10.0]. 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 cohortentry, 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 aremarkably high incidence in the youngest women, suggesting a further shift toward the femalesex in the gender distribution of COPD. During their further lives, one of four men and one ofsix women free of COPD at the age of 55 years will have COPD develop.

(CHEST 2009; 135:368377)

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

COPD is defined as a disease state characterizedby airflow limitation that is not fully reversible.

The airflow limitation is usually both progressive andassociated with an abnormal inflammatory responseof the lungs to noxious particles or gases like tobaccosmoke.13 COPD is a worldwide leading and still-increasing cause of chronic morbidity and mortality.Chapman and colleagues4 and Mannino et al5 pro-

jected that from 1990 to 2020, COPD will movefrom the sixth- to the third-most-common cause ofdeath worldwide, while rising from fourth to third interms of morbidity. In the Netherlands, a study6

suggests that by 2015, there will be a 76% increase inthe prevalence of COPD compared with 1994.

In contrast to numerous reports710 on the preva-lence of COPD, there have only been a few popu-

Original ResearchCOPD

368 Original Research

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lation-based studies1116 on the incidence of COPD.Tobacco smoking is by far the major environmentalrisk factor for the development of COPD in indus-trialized countries, but there seems to be a highvariation in susceptibility to the disease among smok-ing individuals. Previous studies17 suggest that atleast 15 to 20% of the smoking adults 50 years oldhave COPD. Interaction with other risk factors(eg, occupational dusts, air pollution, respiratoryinfections, or genetic factors) could determine thesusceptibility of an individual smoker to the dis-ease.2 Currently, no tests can predict whichsmoker will have COPD develop, but cessation ofsmoking should be strongly encouraged becausethis is the only therapeutic action that can slowdown the disease. In this context, incidence stud-ies can be important to elucidate new risk factorsfor COPD and to identify the susceptible smok-ers for the development of the disease. This may

lead to the discovery of new pathophysiologicmechanisms and guide further clinical research.The objective of this study was to investigate theprevalence, incidence, risk factors, and lifetimerisk of COPD as a function of age, gender, andsmoking behavior in the participants of a largeongoing prospective population-based cohortstudy 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 ongoingpopulation-based cohort study aimed at assessing the occurrenceof and risk factors for chronic diseases in the elderly. Objectivesand methods of the Rotterdam Study have been describedelsewhere.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 ofRotterdam, the Netherlands. Almost all (99.8%) are of whitedescent. Baseline data were collected from 1989 until 1993.Participants were visited at home at the start of the study for astandardized interview on their health status. Since the start ofthe Rotterdam Study, cross-sectional surveys have been per-formed out every 2 to 3 years. Trained research assistantscollected information from medical records of the general prac-titioners, hospitals, and nursing homes. The medical ethicscommittee of Erasmus Medical Center, Rotterdam, approved thestudy. Participants gave written informed consent and permissionto retrieve information from treating physicians.

Spirometry

Spirometry was performed using a portable spirometer (Spiro-Pro; Erich Jaeger GmbH; Hoechberg, Germany) according tothe American Thoracic Society/European Respiratory Societyguidelines by trained paramedical personnel.1,20 FEV1, FVC, andFEV1 /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 AmericanThoracic Society/European Respiratory criteria for acceptabilityand reproducibility were classified as not interpretable (9.6% ofspirometries). Because of practical reasons, no reversibility tests

were conducted. The interpretation of spirometry results wasperformed independently by two research physicians (Y. vD. and

G. vP.); in case of discordance between both physicians (6.1% ofspirometries), the final protocol was made by a senior respiratoryphysician (G.B.).

Patient Identification and Validation

For the validation of the COPD cases, we had access tohospital discharge letters, files from the general practitioners,spirometry reports, and pharmacy dispensing data for patientsparticipating in the Rotterdam Study. Spirometry was performedin 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 special-ists and internists with subspecialty in respiratory medicine. In

the absence of spirometry, all medical information of subjectsthat used respiratory medication for at least 6 months (Anatom-ical Therapeutic Chemical classification codes: R03AC, R03AK,R03BA, R03BB, R03CC, R03DA),21 and all hospital dischargeletters or mortality reports with a coded diagnosis of COPD(International Classification of Diseases, Tenth Revision: J40-J44)22 were reviewed.

The diagnosis of COPD was classified as definite or probable.Definite COPD was defined by a moderate-to-severe obstructivespirometry results (FEV1/FVC 0.7 and FEV1 80% of pre-dicted), and/or as COPD diagnosed by a specialist in internalmedicine (mainly respiratory physicians or internists with sub-specialty in respiratory medicine) based on the combination ofclinical history, physical examination, and spirometry. ProbableCOPD was defined by a mild obstructive spirometry (FEV1/FVC

*From the Department of Respiratory Diseases (Drs. vanDurme, Van Pottelberge, Joos, and Bruselle), Ghent UniversityHospital, Ghent, Belgium; Department of Epidemiology andBiostatistics (Drs. Verhamme, van Rooij, Hofman, and Stricker),Erasmus University Medical Center, Rotterdam, the Nether-lands; and Department of Medical Statistics and Bioinformatics(Dr. Stijnen), Leiden University Medical Center, Leiden, theNetherlands.The Rotterdam Study is supported by Erasmus Medical CenterRotterdam; the Erasmus University Rotterdam; the NetherlandsOrganization for Scientific Research; the Netherlands Organiza-tion for Health Research and Development; the Research Insti-tute 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 Organiza-tion for Scientific Research grants 904-61-093 and 918-46-615.Dr. van Durme received a travel grant by the Belgian ThoracicSociety and is a doctoral research fellow of the Fund for ScientificResearch Flanders (Vlaanderen).The authors have no conflicts of interest to disclose.Manuscript received March 12, 2008; revision accepted August19, 2008.Reproduction of this article is prohibited without written permissionfrom the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).Correspondence to: Bruno H. Ch. Stricker, MB, PhD, Depart-

ment of Epidemiology and Biostatistics, Erasmus UniversityMedical Center, PO Box 2040, 3000 DR Rotterdam, the Nether-lands; e-mail: [email protected]: 10.1378/chest.08-0684

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0.7 and FEV1 80% of predicted), and/or as COPD diag-nosed by a physician in another medical specialty (eg, a generalpractitioner).

The index date was defined as the date of diagnosis of COPDfound in the medical reports, or the date of a first prescriptionof COPD medication, or the date of the obstructive lungfunction 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 tofollow-up, or the end of the study period (December 31,2004). Smoking status was dichotomized into never-smokersand smokers. The category smokers included both current andformer smokers.

Statistical Analysis

To compare the baseline characteristics of the COPD casesand the other participants, we used a Mann-WhitneyU test forthe continuous variables and 2 test for the categorical variables.Age- and gender-specific (in 5-year age categories) incidencerates (IRs) per 1,000 person-years (PY) were obtained by dividingthe number of incident cases by the total number of PYaccumulated by the study population (excluding patients with

COPD at baseline). The 95% confidence intervals (CIs) werecalculated using a Poisson distribution. Cumulative prevalence ofCOPD per age was calculated by dividing the number of persons

with prevalent COPD by the number of subjects present in thestudy with that specific age. All subjects of the total cohort wereused for the analysis; 95% CIs were calculated with the Wilsonscore method for a binomial proportion. The cumulative inci-dence and the lifetime risk of COPD were calculated based on a

Cox regression model with adjustment for competing risk ofdeath, as described by Rosthoj et al23; 95% CIs were calculatedbased on a log transformation.

The risk of COPD according to gender, differences insmoking behavior, and total number of pack-years smoked

were analyzed using Cox regression models, adjusted forconfounders. Cigarette pack-years were computed as durationof smoking (years) multiplied by the number of smokedcigarettes, divided by 20. Missing pack-year values wereimputed by predicted values, based on a logistic regressionanalysis adjusted for age and gender. Statistical analysis wasperformed using statistical software (SPSS for Windows, ver-sion 15; SPSS; Chicago, IL; and SAS version 9.1; SASInstitute; Cary, NC); p 0.05 was accepted as significant.

648 participants with

incident COPD

7703 participants without

prevalent COPD


incident COPD

10275 eligible subjects

7983 participants


prevalent COPD

2292 eligible subjects refused

to participate

376

definite COPD

272

probable COPD


incident COPD


prevalent COPD


incident COPD

10275 eligible subjects

7983 participants


prevalent COPD

2292 eligible subjects refused

to participate

376

definite COPD

272

probable COPD

Figure 1. The Rotterdam Study.




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Results

Baseline Characteristics

Overall, 928 well-defined COPD cases wereidentified in the Rotterdam Study (536 men and392 women). A total of 280 patients had prevalent

COPD at baseline. In the remaining study popu-lation (n 7,703), COPD developed in 648 par-ticipants (8.4%), of whom 376 were classified asdefinite, and 272 as probable cases (Fig 1). Themedian follow-up time was 11 years (interquartilerange, 7.8 years), and there were 70,209 years ofobservation; 3,669 participants (46%) were de-ceased, and 371 participants (4.7%) were unavail-able for follow-up before the end of the studyperiod on December 31, 2004. Table 1 shows thebaseline characteristics of the total study popula-tion (n 7,983), including COPD cases (n 928)and non-COPD cases (n 7,055).

Prevalence

The overall baseline prevalence of COPD in thecohort was 11.6% (95% CI, 10.9 to 12.3). Whenconsidering the age-specific prevalence, a progres-sive rise of prevalence with age until the age of 79years in men and 77 years in women was observed.Once above this age category, the prevalence esti-mates gradually declined. The prevalence was higherin men than in women (Fig 2).

Incidence

Six hundred forty-eight new cases of COPD werediagnosed during follow-up. This resulted in anoverall incidence rate of 9.2/1,000 PY (95% CI, 8.5 to10.0) [Table 2]. The incidence of COPD was higherin men (14.4/1,000 PY; 95% CI, 13.0 to 16.0) than inwomen (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 59years, to 12.8/1,000 PY (95% CI, 10.9 to 15.0) at theage of 75 to 79 years. This increase with age was nolonger 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 agecategories (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 higherin smokers (9.4/1,000 PY; 95% CI, 8.1 to 10.8 forwomen, 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, 2.3to 7.2 for men) [Fig 3, bottom panels, B]. The overalland age-specific incidence of COPD, broken downby gender and smoking, are shown in Table 2.

Risk Factors for the Occurrence of COPD

Cox regression analysis showed that male partici-pants had a hazard ratio (HR) of 1.6 (95% CI, 1.4 to2.2) for the development of COPD, in comparisonwith female participants, adjusted for age and smok-

ing behavior (Table 3). The risk for COPD develop-ing was 3.8-fold higher for smokers than never-smokers (95% CI, 2.7 to 5.3). The risk was highestfor current smokers and for subjects who hadsmoked 50 pack-years (Table 3).

Cumulative Incidence and Lifetime Risk

The cumulative incidence of COPD over the 15.5years of follow-up time of the cohort was 6.7% (95%CI, 5.5 to 8.0). Figure 4 shows the 10-, 20-, 30-, and40-year risks for COPD to develop in men andwomen who are still free of the disease at a certainage, adjusted for the competing risk of dying. For aman free of COPD at 55 years of age, the risk forCOPD over the coming 10, 20, 30, and 40 years was4%, 10%, 18%, and 24%, respectively. For a woman,the risk was 3%, 8%, 13%, and 16%, respectively (Fig 4).

Discussion

In this large ongoing prospective cohort study ofelderly people, the overall incidence rate of COPDwas 9.2/1,000 PY. The incidence increased with age

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

Characteristics Data

Age, yr 69.5 14.9Gender

Male 3,105 (38.9)Female 4,878 (61.1)

Smoking status

Current 1,725 (21.6)Former 3,107 (38.9)Never 2,794 (35.0)Missing 357 (4.5)

Pack-yr0 2,916 (36.5)110 1,414 (17.7)1120 806 (10.1)2130 1,058 (13.3)3140 774 (9.7)4150 378 (4.7) 50 637 (8.0)

Cardiovascular comorbidityYes 2,294 (28.7)

No 5,381 (67.4)Missing 308 (3.9)

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




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

rected for the competing risk of dying. For a 55-year-old individual without COPD, the risk for the diseaseover 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*

Age Groups,yr

Overall Men Smoking MenNever-Smoking

Men Women Smoking WomenNever-Smoking

Women

COPDIR 95% CI

COPDIR 95% CI

COPDIR 95% CI

COPDIR 95% CI

COPDIR 95% CI

COPDIR 95% CI

COPDIR 95% CI

5559 6.9 4.310.5 6.1 2.712.0 7.1 3.214.0 0.0 0.015.6 7.4 4.112.6 11.1 5.719.7 2.9 0.69.26064 4.8 3.56.4 6.9 4.610.0 7.8 5.211.2 0.0 0.06.2 3.3 2.05.1 5.1 3.08.2 0.9 0.22.96569 10.2 8.712.0 13.9 11.217.2 14.7 11.718.2 3.8 0.712.0 7.4 5.79.5 10.4 7.713.7 4.0 2.36.57074 12.5 10.714.4 16.1 13.119.6 17.5 14.221.4 2.2 0.210.2 10.0 8.012.3 13.4 10.317.2 6.6 4.59.57579 12.8 10.915.0 20.5 16.625.0 21.9 17.626.8 5.4 1.117.2 8.4 6.510.6 12.5 9.116.9 5.7 3.78.3 80 6.0 4.97.2 15.1 11.818.9 16.8 13.121.3 4.3 0.913.8 2.9 2 .13.9 3.5 2.05.9 2.9 1.94.1All age

categories9.2 8.510.0 14.4 13.016.0 15.6 14.117.3 4.2 2.37.2 6.2 5.57.0 9.4 8.110.8 3.8 3.14.6

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

Age-specific prevalence in men

0

2

4

6

8

10

12

14

16

18

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)

Prevalence(%)

Age-specific prevalence in women

0

2

4

6

8

10

12

14

16

18

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)

Prevalence(%)

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




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Age-specific incidence of COPD

0

4

8

12

16

20

24

55-59 60-64 65-69 70-74 75-79 >=80

Age categories

Incidence/1000

PY

Overall inc idence Incidence in w omen Incidence in men

Age-specific incidence of COPD in men

0

4

8

12

16

20

24

55-59 60-64 65-69 70-74 75-79 >=80

Age categories

Incidence/1000

person-years

Incidence in men Incidence in male non-smokers Incidence in male smokers

Age-specific incidence of COPD in women

0

4

8

12

16

20

24

55-59 60-64 65-69 70-74 75-79 >=80

Age categories

Inc

idence/1000

person-years

Incidence in w omen Incidence in female non-smokers Incidence in female smokers

A

B

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.




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Reviewing the literature, only six previous re-ports1116 on the incidence of COPD in a generalpopulation were found. The first two are earlierstudies: a Finnish report11 and a Polish report.12 Theannual IR of COPD in these studies was 2/1,000 and5/1,000 persons per year, respectively. Two morerecent Swedish studies,14,15 which found no gender

difference, were based on the Obstructive LungDisease in Northern Sweden cohort and includedpersons from 35 to 65 years old at study entry. Themeasured incidence of COPD was 7/1,000 PY ac-cording to the Global Initiative for Chronic Obstruc-tive Lung Disease (GOLD) II criteria, and 16/1,000PY according to GOLD criteria. Another report13

came from the Copenhagen City Heart Study inDenmark, which included subjects 20 years ofage. COPD developed in 9.7% and 13.2% of thesubjects after 5 years and 15 years of follow-uptime, respectively. A more recent study16 was

published with data from an international cohortof young adults (age 20 to 44 years). The incidenceof COPD in this study was 2.8/1,000 PY. Thedifferences in incidence rates among these studiescan be explained by the difference in study popu-lation 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 Wefound that the same is true for the incidence ofCOPD, but our findings seem to be in contrastwith other incidence studies,1315 which found nogender difference. This finding can be explainedby the fact that smoking among female subjects inthe Netherlands increased later in comparison toNorth-European countries,4 and that we had acohort with on average older members, with tra-ditionally more smoking men than women. Inter-estingly, we found a surprisingly high incidence inthe youngest female age categories.

Table 3Risk Factors for the Occurrence of COPD

COPD Risk Factors

Definite and Probable COPD Definite COPD

Patients/Cohort, No. HR 95% CI Patients/Cohort, No. HR 95% CI

GenderFemale 276/4,573 1.0 Reference 147/4,573 1.0 ReferenceMale

Not adjusted 372/2,821 2.3 1.992.72 229/2,821 2.7 2.223.36

Adjusted for age and smoking 372/2,821 1.6 1.381.93 229/2,821 1.8 1.412.19Smoking statusNever-smoker 101/2,645 1.0 Reference 42/2,645 1.0 ReferenceSmoker (in general)

Not adjusted 541/4,409 3.3 2.654.05 330/4,409 4.9 3.526.70Adjusted for age and gender 541/4,409 2.6 0.063.28 330/4,409 3.8 2.665.30

Current smokerNot adjusted 268/1,725 4.8 3.836.07 176/1,725 7.8 5.5410.86Adjusted for age and gender 268/1,725 4.0 3.115.09 176/1,725 6.3 4.388.95

Former smokerNot adjusted 273/3,107 2.5 1.983.12 154/3,107 3.4 2.424.79Adjusted for age and gender 273/3,107 1.9 1.502.47 154/3,107 2.6 1.773.67

Pack-yr, No.0 105/2,916 1.0 Reference 43/2,916 1.0 Reference110

Not adjusted 61/1,414 1.3 0.951.79 36/1,414 1.9 1.202.92Adjusted for age and gender 61/1,414 1.2 0.901.70 36/1,414 1.8 1.132.76

1120Not adjusted 86/806 2.9 2.163.81 52/806 4.3 2.866.43Adjusted for age and gender 86/806 2.6 1.933.51 52/806 3.9 2.545.88

2130Not adjusted 127/1,058 3.9 3.015.04 84/1,058 6.3 4.369.10Adjusted for age and gender 127/1,058 3.4 2.544.46 84/1,058 5.3 3.587.89







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This might be explained by the fact that womenof this age started smoking in increasing numberssince 1940. Evidence for this hypothesis comesfrom epidemiologic reports25,26 from the UnitedStates showing that already in 2000, there weremore deaths from COPD among female subjectsof this age category than among male subjects.Incident COPD cases were also detected amongmale and especially female never-smokers, indi-cating thatbesides active smokingother envi-ronmental exposures such as passive smoking,

occupational exposures, and (outdoor and indoor)air pollution might contribute to the developmentof COPD.

The strength of the Rotterdam Study is itsprospective, population-based design, with similardata collection procedures for every participantand a virtually complete follow-up. More than 600cases of incident COPD were identified over atotal follow-up time of 15.5 years. The large cohortsize and the use of PY instead of persons enabledus to estimate the incidence rate more accurately.

Cumulative incidence of COPD in men

0%

5%

10%

15%

20%

25%

30%

55 60 65 70 75 80

Age at cohort entry

Probability

ofCO

PD

Cumulative incidence of COPD in women

0%5%

10%

15%

20%

25%

30%

55 60 65 70 75 80

Age at cohort entry

Probability

ofCO

PD

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). CumInc cumulative incidence.




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A potential limitation to our study is that we didnot have spirometric results for all cohort partici-pants because of the large number of subjects thatdeceased during follow-up. Therefore, we also usedinformation that came from hospital discharge lettersand files from general practitioners. The reliance inthe absence of spirometry on a history of respiratorymedication use to examine the medical records for

evidence of a COPD diagnosis probably resulted inan underestimate of the incidence of clinically silentbut spirometrically identifiable COPD. Further-more, we used prebronchodilator spirometric valuesfor defining COPD instead of postbronchodilatorvalues as suggested by the GOLD guidelines.1,2 Inorder to adjust for this, we excluded all subjects withasthma from our analysis. However, we cannot ex-clude the possibility of misclassification of COPD asasthma in some participants, especially amongwomen, that also might have led to an underestima-tion of the true incidence of COPD. Interestingly,

Johannessen et al27 found that the assessment ofprognostic risk factors for COPD was not influencedby the type of lung function assessment (before orafter bronchodilation), even if the prevalence ofCOPD defined without bronchodilation may beoverestimated.

In our study, we used a fixed value (0.7) of theFEV1/FVC to define airflow obstruction, rather thanthe fifth percentile of the predicted value.28 Litera-ture29 has shown that the lower limit of the normalrange of the FEV1/FVC decreases with age, meaningthat we would overestimate the number of patients

with COPD if we would only use this criterion. Tocorrect for this misclassification bias in our elderlycohort, we only defined those subjects with a FEV1 80% of predicted as definite COPD cases be-cause Lindberg et al14,15 found that this cut-offseemed to be more reliable than the GOLD criteriain identifying incident COPD among elderly subjects. Also, a recent study30 showed that subjectsclassified as normal using the lower limit of nor-mal, but as abnormal using the fixed ratio of 0.7, were more likely to die and have COPD-relatedhospitalizations during further follow-up than

healthy subjects. This effect was even more pro-nounced among those subjects with a FEV1 80%of predicted.

In conclusion, we found that the overall incidenceof COPD in a population-based elderly cohort in theNetherlands was 9.2/1,000 PY and that the lifetimerisk for COPD to develop over the coming 40 yearsfor a 55 year-old man and woman, still free ofCOPD, was 24% and 16%, respectively. The inci-dence increased with age, smoking, and was higherin men than in women. Remarkable was the highincidence in the youngest female age categories,

suggesting a future shift toward the female sex in thegender distribution of COPD.

ACKNOWLEDGMENT: The authors thank Mrs. Jolande Verk-roost for preparing the data set for the validation of the COPDcases. We also thank Prof. Dr. Jan Heeringa, the researchassistants, and all our other colleagues in the Ommoord ResearchCenter for their efforts in the data collection.

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DOI 10.1378/chest.08-06842009;135; 368-377Chest

H. Ch. Stricker and Guy G. BrusselleA. van Rooij, Geert R. Van Pottelberge, Albert Hofman, Guy F. Joos, BrunoYannick M. T. A. van Durme, Katia M. C. Verhamme, Theo Stijnen, Frank J.

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

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