COPD prevalence in a random population survey: a matter of definition

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1 Eur Respir J 2007; 30: DOI: / CopyrightßERS Jouras Ltd 2007 COPD prevaece i a radom popuatio survey: a matter of defiitio P. Shirtciffe*, M. Weathera #, S. Marsh*, J. Travers*, A. Hase ", A. McNaughto*, S. Adigto*, H. Mueerova + ad R. Beasey*,1 ABSTRACT: A recet America Thoracic Society ad Europea Respiratory Society joit Task Force report recommeds usig a ower imit of orma (LLN) of forced expiratory voume i oe secod/forced vita capacity as opposed to a fixed ratio of,0.7 to diagose airfow obstructio, i order to reduce fase positive diagoses of chroic obstructive pumoary disease (COPD) as defied by the Goba Iitiative for Obstructive Lug Disease (GOLD). To date, there is o reiabe spirometry-based prevaece data for COPD i New Zeaad ad the effect of differet defiitios of airfow obstructio based o post-brochodiator spirometry is ot kow. Detaied writte questioaires, fu pumoary fuctio tests (icudig pre- ad postbrochodiator fow voume oops) ad atopy testig were competed i 749 subjects recruited from a radom popuatio sampe. The GOLD-defied, age-adjusted prevaece (95% cofidece iterva) for aduts aged o40 yrs was 14.2 ( )% compared with a LLN-defied, age-adjusted, post-brochodiator prevaece i the same group of 9.0 ( )%. The prevaece of chroic obstructive pumoary disease varied markedy depedig o the defiitio used. Further research usig ogitudia rather tha cross-sectioa data wi hep decide the preferred approach i chroic obstructive pumoary disease prevaece surveys. KEYWORDS: Chroic obstructive pumoary disease, ower imit of orma, prevaece The sigificace of chroic obstructive pumoary disease (COPD) as a cause of goba morbidity ad mortaity is udisputed. Withi the ext 20 yrs, COPD is projected to move from the sixth to the third most commo cause of death wordwide, whie risig from fourth to third i terms of morbidity withi the same time-frame [1]. For such a sigificat coditio, there is a reative dearth of accurate prevaece iformatio, a major difficuty beig a ack of cosesus about the defiitio of COPD [2]. A umber of differet approaches have bee used, icudig sefreportig, doctor diagosis, diagosis based o the presece of respiratory symptoms ad diagosis based o the presece of various defiitios of airfow imitatio (pre- or post-brochodiator). The Goba Iitiative for Chroic Obstructive Lug Disease (GOLD), first pubished i 2001 ad at preset updated yeary, has resuted i a agreemet o spirometry threshods for diagosis ad severity ad has become the god stadard, at east for epidemioogica purposes. GOLD defies COPD as a post-brochodiator For editoria commets see page 189. ratio of forced expiratory voume i oe secod (FEV1) to forced vita capacity (FVC) of,0.7 [3]. A very simiar defiitio (post-brochodiator FEV1/FVC f0.7) has bee agreed o by the America Thoracic Society (ATS) ad the Europea Respiratory Society (ERS) [4]. Whie it is geeray accepted that the FEV1/FVC ratio is the most importat guide whe idetifyig airfow obstructio, the practice of cassifyig vaues of FVC ad FEV1,80% predicted ad a fixed FEV1/FVC ratio of,0.7 as aborma has o statistica basis [5]. Sice FEV1/FVC ratios decrease with age, a fixed ratio resuts i a apparet icrease i the prevaece of impairmet associated with ageig or with age-cofouded factors, such as cigarette smokig [5]. However, oe statisticay acceptabe approach for estabishig ower imits for ay spirometric measure is to defie the owest 5% of the referece popuatio as beow the ower imit of orma (LLN) [5]. I cotrast to the ATS, ERS ad GOLD defiitios of COPD, a recet joit ATS/ ERS Task Force has proposed usig a cut-off vaue for the FEV1/FVC ratio set at the fifth percetie of the orma distributio, rather tha at a fixed vaue of 0.7, i a attempt to reduce the AFFILIATIONS *Medica Research Istitute of New Zeaad, ad # Weigto Schoo of Medicie ad Heath Scieces, Weigto, New Zeaad. " Imperia Coege, ad + GaxoSmithKie, Lodo, ad 1 Uiversity of Southampto, Southampto, UK. CORRESPONDENCE R. Beasey Medica Research Istitute of New Zeaad P.O. Box Weigto New Zeaad Fax: E-mai: Richard.Beasey@mriz.ac.z Received: December Accepted after revisio: March SUPPORT STATEMENT The preset study was supported by a research grat from GaxoSmithKie. A. Hase is a Wecome Trust Itermediate Ciica Feow supported by grat o STATEMENT OF INTEREST A statemet of iterest for H. Mueerova ca be foud at statemets.shtm Europea Respiratory Joura Prit ISSN Oie ISSN VOLUME 30 NUMBER 2 EUROPEAN RESPIRATORY JOURNAL

2 P. SHIRTCLIFFE ET AL. COPD PREVALENCE DEPENDS UPON DEFINITION umber of fase positive diagoses [6]. It was aso oted that a sow vita capacity (SVC) maoeuvre may be more accurate tha usig FVC to diagose airfow obstructio. However, the two studies o which the LLN recommedatio was made did ot icude post-brochodiator spirometry [7, 8], which is a prerequisite for the defiitio of airfow imitatio that is ot fuy reversibe [3, 4, 9]. I the preset study, the mai aim was to estabish the GOLDdefied prevaece of COPD i a adut urba New Zeaad popuatio for the first time. Additioay, the curret authors aimed to compare the GOLD-defied prevaece rate with that obtaied with the LLN defiitio of FEV1/SVC ad FEV1/FVC usig both pre- ad post-brochodiator vaues. METHODS Study subjects A tota popuatio of 3,500 idividuas, radomy seected ad equay divided amog five groups accordig to age at the time of seectio (25 34, 35 44, 45 54, ad yrs), were set a posta screeig questioaire (SQ). Subjects were idetified from the New Zeaad eectora register for five eectora wards i the Greater Weigto regio ad the separate Maori (the mai ethic miority) eectora register costraied for the same geographica area. Subjects who competed the SQ were ivited to atted the research cetre to compete a iterviewer-admiistered questioaire (referred to as the mai questioaire (MQ)), foowed by visits to udergo: detaied pumoary fuctio testig; exhaed itric oxide measuremets; peak fow recordigs over a 1-week period; ski-prick testig; bood tests (fu bood cout, carboxyhaemogobi eve, tota serum immuogobui E eve, a 1 -atitrypsi eve ad DNA extractio); uriary cotiie; ad a computed tomography sca of the chest. The Weigto Ethics Committee approved the study ad writte iformed coset was obtaied from each subject. Questioaire A participats competed a detaied writte questioaire compied from a series of vaidated questioaires [10] ad admiistered by a traied iterviewer i a stadardised maer. Data obtaied by the questioaire icuded: demographic iformatio; respiratory history ad symptoms; smokig history, icudig exposure to marijuaa ad evirometa tobacco smoke; aergy; famiy history; occupatio; medicatio; ad use of heath services. Smokig status was a cacuated fied based o smokig of tobacco cigarettes. The pack-yr fied was based oy o the tobacco cigarette history, with 1 pack-yr defied as equivaet to 20 cigarettes? day -1 for 1 yr. Pumoary fuctio tests These have bee described i detai esewhere [11, 12]. I brief, pumoary fuctio tests (PFTs) were carried out o oe site usig two Jaeger Master Scree body voume costat pethysmography uits with peumotachograph ad diffusio uit (Masterab 4.5 ad 4.6; Erich Jaeger, Wurzburg, Germay) by traied operators. A measuremets were carried out i accordace with ATS ad ERS guideies [13 15]. Measuremets of ug voumes ad spirometry were repeated 45 mi after the admiistratio of 400 mg of sabutamo (Vetoi TM ; GaxoSmithKie (NZ) Ltd, Auckad, New Zeaad) via a spacer (Space Chamber TM ; Medica Deveopmets Iteratioa Ltd, Sprigvae, Austraia). Resuts were corrected for body temperature, ambiet pressure, water vapour saturatio ad expressed as per cet of predicted based o oca formuae derived usig iear regressio techiques. The referece sampe was take from withi the subject group of the survey ad from a cocurret study ivestigatig the pumoary effects of marijuaa smokig. This represeted a coveiece sampe of aduts aged yrs recruited through ewspaper ad radio advertisemets ad iforma cotacts. Norma subjects from both studies were defied usig ATS guideies ad were required to sef-idetify as New Zeaad Europea ad be ever-smokers with o diagosis of respiratory disease, o recet respiratory symptoms ad o use of ihaed medicatio [12]. Ski-prick testig A subjects received testig to the foowig ie ocay reevat aerges: house dust mite (Dermatophagoides pteroyssius 30,000 aergy uits (AU)?mL -1 ); pie (odge poe ad Wester yeow pie 1:20); birch (1:20); grass mix (10,000 bioequivaet aergy uits (BAU)?mL -1 ); Aspergius fumigatus (1:10); dog hair (1:10); feather mix (chicke, duck, goose 1:10); cat pet (10,000 BAU?mL -1 ); ad cockroach mix, pus a positive (histamie dihydrochoride) ad a egative cotro (saie). The subject s arm was ceaed with soap ad water. Foowig this, 10 umbered poits were marked at 2-cm itervas o the aterior aspect of the forearm with a pe. A drop of each aerge extract was paced aogside the poit ad a sterie acet was used to make a prick through the cetre of the drop. A ew acet was used for each aerge. The forearm was botted with tissue paper ad the tests were read 15 mi ater. Reactios were assessed by the degree of erythema ad the size of the wea produced. A positive resut was defied as a wea o2 mm tha that of the egative cotro. Diagostic criteria for COPD I the preset aayses, the defiitio of COPD proposed by GOLD (a post-brochodiator ratio of FEV1/FVC,0.7) was used for primary outcome. Severity of disease was aso defied accordig to the GOLD guideies [3]. I the LLN defiitio, the cut-off vaue of the post-brochodiator ratio was set at the fifth percetie of the orma distributio [5]. The referece equatio for the LLN defied by the FEV1/SVC ratio was: (FEV1/SVC predicted) ( ) (1) where FEV1/SVC predicted (0.2716age) for maes ad FEV1/SVC predicted (0.2716age) for femaes, with age i years at time of PFTs [12]. The referece equatio for LLN defied by the FEV1/FVC ratio was: (FEV1/FVC predicted) ( ) (2) where FEV1/FVC predicted (0.246age) (10.66height), with age i years at time of PFTs ad height i metres [12]. Post-brochodiator vaues for SVC were used i the LLN equatios. A doctor s diagosis of COPD was based o positive aswers to the questios Did your doctor ever te you that you had chroic brochitis?, Did a doctor ever te you that you had c EUROPEAN RESPIRATORY JOURNAL VOLUME 30 NUMBER 2 233

3 COPD PREVALENCE DEPENDS UPON DEFINITION P. SHIRTCLIFFE ET AL. emphysema? ad Have you ever bee tod by a doctor that you had chroic obstructive respiratory disease? Idividuas with brochiectasis or sarcoidosis ad airfow obstructio were ot couted as havig COPD. Statistica aaysis Cofidece imits for proportios were cacuated by a exact method. The kappa coefficiet was used to describe agreemet betwee differet methods to defie COPD. The prevaece of COPD was adjusted to the age distributio of the Weigto popuatio usig the method cited i [16]. Where appropriate, upaired t-tests were used to compare cotiuous variabes betwee groups. Differeces betwee post- ad pre-brochodiator FEV1 vaues are expressed as the per cet chage from pre-brochodiator FEV1. The FEV1/FVC ratio is expressed as a percetage. Odds ratios (OR) i the uivariate ad mutivariate aaysis were cacuated by ogistic regressio. RESULTS A tota of 3,500 idividuas were ivited to compete a SQ betwee Apri 14, 2003 ad Jue 3, A tota of 2,319 out of 2,978 idividuas with vaid cotact detais retured the SQ, givig a respose rate of 77.9%. A tota of 1,017 idividuas of the group who competed the SQ (43.9% of the 2,319 subjects returig the SQ; 34.2% of the origia 2,978 subjects with vaid cotact detais) wet o to compete the MQ. A 1,017 subjects were ivited to udergo PFT, of whom 795 atteded. A fu set of competed pre- ad post-brochodiator fow voume oops were obtaied for the 749 idividuas whose resuts are aaysed i the preset paper (fig. 1). Tabe 1 compares respiratory symptoms ad seected risk factors for idividuas competig the SQ, the MQ ad for those who uderwet PFT. Geeray, differeces were sma, but respoders to the MQ were more ikey to compai of ever havig breathig troube (35 versus 25.3%), were more ikey to be ex-smokers (42 versus 36.1%), had a higher prevaece of doctor-diagosed asthma (23.9 versus 19.1%) ad had ess wheeze i the previous 12 moths (22.3 versus 26.0%) tha those subjects i the SQ group. There were oy sma differeces betwee the MQ group ad those idividuas with fu PFTs. Characteristics of the study popuatio by age, sex, ethicity, smokig status ad pack-yrs are detaied i tabe 2. More maes tha femaes participated i the study (54.2 versus 45.8%). The mea SD age of the study popuatio was yrs. Less tha haf of the participats (46.2%) had ever smoked tobacco cigarettes. Of the curret or ex-smokers, 28.4% had a pack-yr history for tobacco cigarette smokig of o20 yrs. A tota of 47.1% of the participats were atopic based o a positive resut to oe of ie ocay reevat aerges ad 9.2% had a diagosis of chidhood asthma. The overa raw ad age-adjusted prevaece rates of COPD are preseted i tabe 3 ad figure 2. The GOLD-defied ageadjusted (to the age distributio of the Weigto popuatio) prevaece (95% cofidece iterva (CI)) for aduts aged o40 yrs was 14.2 ( )%. The LLN-defied age-adjusted prevaece for aduts aged o40 yrs usig SVC ad FVC was 9.0 ( )% ad 9.5 ( )%, respectivey. A LLN Origia eectora ro sampe (=3500) Vaid cotact detais (=2979) Competed screeig questioaire (=2319) Competed mai questioaire (=1017) Competed pumoary fuctio tests (=758) Pre- ad postbrochodiator fow voume oops (=749) TABLE 1 Baseie characteristics of subjects competig the screeig questioaire (SQ), the mai questioaire (MQ) ad pumoary fuctio tests (PFTs) to iustrate possibe differeces i subject characteristics by various phases of the study programme SQ MQ PFTs Sex mae 1097 (47.3) 514 (50.5) 412 (54.4) Wheezig i previous 603 (26.0) 227 (22.3) 165 (21.8) 12 moths Cough without cod usuay 533 (23.0) 247 (24.3) 181 (23.9) Cough 3 moths each year 544 (23.5) 188 (18.5) 141 (18.6) Phegm 3 moths each year 223 (9.6) 125 (12.3) 95 (12.5) Breathig troube ever 587 (25.3) 356 (35.0) 261 (34.4) Doctor-diagosed chroic brochitis 198 (8.5) 102 (10.0) 75 (13.9) Doctor-diagosed emphysema 34 (1.5) 9 (0.9) 6 (0.8) Doctor-diagosed asthma 443 (19.1) 243 (23.9) 182 (24.0) Curret smoker 279 (12.0) 123 (12.1) 96 (12.7) Ex-smoker 837 (36.1) 427 (42.0) 332 (43.8) Respose rate o45 yrs 1613 (69.6) 741 (72.9) 557 (73.5) Tota Data are preseted as (%), uess otherwise stated. Subjects uabe to be cotacted e.g. retur to seder, moved away, died (=521) Norespoders or did ot wat to compete screeig questioaire (three attempts to cotact =660) Decied further ivovemet or uabe to cotact (=1302) Withdrew # (=222) Uabe to compete pumoary fuctio tests (=37) Missig pre-/post- or pread post-brochodiator fow voume oop data (=9) FIGURE 1. Fow-chart of participatig subjects. # : due to a chage of mid (5130), movig away (551), beig pregat or presetig other medica coditios (529), beig deceased (55), beig obese (54; idividuas of.125 kg were excuded due to scaer weight imit) or eedig a iterpreter (53). 234 VOLUME 30 NUMBER 2 EUROPEAN RESPIRATORY JOURNAL

4 P. SHIRTCLIFFE ET AL. COPD PREVALENCE DEPENDS UPON DEFINITION TABLE 2 Characteristics of the study popuatio by age, sex, ethicity, smokig status ad pack-yrs (%) Mea SD Media (IQR) Age yrs Overa ( ) (2.0) (14.7) (17.8) (26.6) (25.1) o (13.9) Sex Mae 406 (54.2) Femae 343 (45.8) Ethicity New Zeaad Europea 654 (87.3) Maori # 26 (3.5) Other " 68 (9.1) Not stated 1 Smokig status Never-smoker Curret smoker pack-yrs 17.8 ( ) Ex-smoker pack-yrs 8.0 ( ) Overa smokers pack-yrs 10.0 ( ) Pack-yrs (49.6) (22.0) o (28.4) Atopy e 350/743 (47.1) Prematurity ## 22/749 (2.9) Eary hospitaisatio 11/749 (1.6) Chid asthma "" 69/749 (9.2) Tota 749 IQR: iterquartie rage. # : mai idigeous ethic miority i New Zeaad; " : maiy Asia ad Pacific isaders; + : refers to osmokers of tobacco cigarettes, sice there were 30 smokers of tobacco who did ot smoke cigarettes; 1 : refers to tobacco cigarette smokers; e : based o a positive skiprick test to oe of the test substaces (excudig the positive cotro); ## : based o the aswer to the questio Were you bor prematurey (o1 moth before the date expected for your birth)? ; "" : based o the respose to two questios Did a doctor ever te you that you had asthma? ad How od were you whe you had your first attack of asthma? (,18 yrs). defiitio usig pre-brochodiator vaues of FVC gave a prevaece of 15.2 ( )%. The estimate for COPD prevaece based o a doctor diagosis i the same o40 yrs age group was 10.5 ( )%. Tabe 4 shows the moderate degree of agreemet betwee GOLD ad the other defiitios except for doctor diagosis. The GOLD criteria cassified more subjects as havig COPD tha the post-brochodiator LLN for either FEV1/FVC or FEV1/SVC. The OR (95% CI) per decade oder for a diagosis of COPD by GOLD compared with the LLN (defied by postbrochodiator FEV1/SVC) was 2.5 ( ; p,0.0001). For the pre-brochodiator LLN for FEV1/FVC there was a substatia proportio of subjects miscassified i both directios. For the post-brochodiator LLN for FEV1/FVC, fewer subjects were cassified as havig COPD tha by the pre-brochodiator LLN for FEV1/FVC. With regards to doctor s diagosis, oy 17 (15%) out of 116 of those idividuas who met the GOLD criteria had a doctor s diagosis of COPD. I tota, 99 (85%) out of 116 subjects met the GOLD criteria but did ot report a doctor s diagosis of COPD. Of those subjects with GOLDdefied COPD ad who were i the severe categories (511), four (36%) had a doctor s diagosis of COPD. The prevaece of GOLD-defied COPD is preseted by age, sex, ethicity, smokig status ad pack-yrs i tabe 5. The prevaece was higher i maes tha i femaes ad icreased with icreasig age. COPD was more frequet i curret ad ex-smokers ad icreased with icreasig pack-yrs. I the group of 749 idividuas, the prevaece of COPD accordig to GOLD severity stages was as foows: 1) mid (FEV1 o80% pred), 53 (7.1%); 2) moderate (50%fFEV1,80% pred), 52 (6.9%); 3) severe (30%fFEV1,50% pred), 8 (1.1%); 4) very severe (FEV1,30% pred), 3 (0.4%). Thus, 105 (14.0%) out of 749 subjects had GOLD-defied COPD i the mid or moderate categories. Amogst the subjects with GOLD-defied COPD, the mea SD percetage chage i FEV1 from baseie after brochodiator was %. There were 35 (30.2%) out of 116 COPD subjects who met the criteria for a positive brochodiator respose [6]. This compares to a mea SD chage of % i the group without COPD, of whom oy 23 (3.6%) out of 633 met the criteria for a positive brochodiator respose. DISCUSSION The preset study foud that the prevaece of GOLD-defied COPD i aduts aged o40 yrs was 14.2%. To date, there is o reiabe data for COPD from New Zeaad popuatio surveys COPD rate per 1000 popuatio ³70 Age yrs FIGURE 2. Prevaece of chroic obstructive pumoary disease (COPD) by diagostic defiitio ad age group. &: Goba Iitiative for Chroic Obstructive Lug Disease; h: ower imit of orma (LLN) post-brochodiator; #: LLN prebrochodiator; $: doctor s diagosis. Age group yrs excuded due to sma umbers (515). c EUROPEAN RESPIRATORY JOURNAL VOLUME 30 NUMBER 2 235

5 COPD PREVALENCE DEPENDS UPON DEFINITION P. SHIRTCLIFFE ET AL. TABLE 3 Overa raw ad age-adjusted prevaece of chroic obstructive respiratory disease (COPD) by differet criteria Method of diagosis Subjects with COPD/tota Raw prevaece (95% CI) Age-adjusted prevaece # (95% CI) GOLD " A ages 116/ ( ) 9.3 ( ) o40 yrs 109/ ( ) 14.2 ( ) LLN FEV1/SVC + A ages 73/ ( ) 7.0 ( ) o40 yrs 66/ ( ) 9.0 ( ) LLN FEV1/FVC Post-brochodiator A ages 78/ ( ) 7.7 ( ) o40 yrs 69/ ( ) 9.5 ( ) Pre-brochodiator A ages 120/ ( ) 14.5 ( ) o40 yrs 100/ ( ) 15.2 ( ) Doctor diagosis 1 A ages 79/ ( ) 9.8 ( ) o40 yrs 67/ ( ) 10.5 ( ) CI: cofidece iterva; GOLD: Goba Iitiative for Chroic Obstructive Lug Disease; LLN: ower imit of orma; FEV1: forced expiratory voume i oe secod; SVC: sow vita capacity; FVC: forced vita capacity. # : adjusted to the age distributio of the Weigto popuatio at the 2001 cesus [12]; " : diagostic criteria as per the GOLD guideies; + : defiitio of a obstructive pumoary defect based o FEV1/FVC ratio (the cut-off vaue of this ratio is set at the fifth percetie of the orma distributio rather tha at a fixed vaue of 0.7). This ratio ca be used with either pre- or post-brochodiator vaues. Three subjects had missig data for SVC. 1 : based o the questios Did your doctor ever te you that you had chroic brochitis?, Did a doctor ever te you that you had emphysema? ad Have you ever bee tod by a doctor that you had chroic obstructive respiratory disease? based o either pre- or post-brochodiator ug fuctio criteria with which to compare this figure [17]. Previous prevaece studies i other coutries have bee summarised i two recet reviews of the iterature [18, 19]. I the first review [18], 32 studies were idetified i the period , oy 11 of which were based o spirometry, with just three ceary statig that post-brochodiator vaues were measured. I the most recet review ad meta-aaysis of 37 prevaece studies i the period , a pooed prevaece estimate i aduts aged o40 yrs was 9.0% [19]. Oy ie studies icuded post-brochodiator ug fuctio ad oy six were from the Wester Pacific regio [19]. Sice 2004, there have bee two geera popuatio-based studies wordwide that have appied post-brochodiator vaues. The Proyecto Latioamericao de Ivestigació e Obstrucció Pumoar (PLATINO) study [20] idetified crude rates i aduts aged o40 yrs of 7.8 ad 19.7% i Mexico City (Mexico) ad Motevideo (Uruguay), respectivey, ad a Scadiavia study reported a prevaece of 7% i idividuas aged yrs [21]. The ogoig Burde of Lug Disease (BOLD) iitiative is desiged primariy as a COPD prevaece survey amog oistitutioaised aduts aged o40 yrs, ad shoud faciitate direct compariso of GOLD-defied COPD prevaece rates betwee coutries [22]. The prevaece of COPD was aso estimated by referece to the LLN for the FEV1/VC ratio as proposed by the ATS/ERS Task Force to reduce the umber of fase positive diagoses that occurs as FEV1/FVC ratios decrease with age. I the same group of aduts aged o40 yrs (usig post-brochodiator vaues), the estimate was oy 9.0%, givig a discordat rate of 5.2%. Aocatio by GOLD to COPD was more ikey for maes ad oder aduts tha by the LLN defiitio. Lookig at this aother way, the LLN for the FEV1/FVC i the preset study was 0.65 ad 0.63 for a 70 ad a 75 yr-od, respectivey. The preset authors are ot aware of ay studies which specificay cosider the differece betwee a fixed ratio of 0.7 ad the LLN usig post-brochodiator vaues. MARGOLIS et a. [23] performed a retrospective review of PFTs (o postbrochodiator vaues) at a Vetera s Admiistratio hospita comparig a fixed ratio of 0.7 with 95th percetie-based umeric criteria ad foud discordat readigs i 7.2% of the 664 idividua tests. ROBERTS et a. [24] foud simiar discordat rates of % depedig o the referece rage used, but agai did ot icude post-brochodiator vaues. I cotrast to the preset fidigs, a study deveopig referece rages for post-brochodiator ug fuctio by JOHANNESSEN et a. [25] foud that the LLN FEV1/FVC for both maes ad femaes after reversibiity testig exceeded 0.7 across a ages. This might suggest that the LLN woud diagose more peope with COPD, but this fidig is more ikey to be a cosequece of the sma umber of observatios i edery maes. The fidigs coud aso suggest that the GOLD cut-off poit is usefu as og as post-brochodiator vaues are used. I terms of the ciica impact of the differece betwee the two defiitios, MANNINO et a. [26] oted that edery subjects cassified as orma usig the LLN but aborma usig the fixed ratio, died at a simiar rate to the cohort cassified as aborma usig the LLN criteria. It was 236 VOLUME 30 NUMBER 2 EUROPEAN RESPIRATORY JOURNAL

6 P. SHIRTCLIFFE ET AL. COPD PREVALENCE DEPENDS UPON DEFINITION TABLE 4 Agreemet betwee various defiitios of chroic obstructive pumoary disease (COPD) Post-brochodiator LLN FEV1/FVC Pre-brochodiator LLN FEV1/SVC postbrochodiator # Doctor diagosis Yes No Yes No Yes No Yes No GOLD Yes No Kappa (95% CI) 0.74 ( ) 0.70 ( ) 0.71 ( ) 0.06 ( ) LLN FEV1/FVC postbrochodiator Yes No Kappa (95% CI) 0.69 ( ) 0.89 ( ) 0.09 ( ) LLN FEV1/FVC prebrochodiator Yes No Kappa (95% CI) 0.66 ( ) 0.09 ( ) LLN FEV1/SVC postbrochodiator Yes No Kappa (95% CI) 0.09 ( ) LLN: ower imit of orma; FEV1: forced expiratory voume i oe secod; FVC: forced vita capacity; SVC: sow vita capacity; GOLD: Goba Iitiative for Chroic Obstructive Lug Disease; CI: cofidece iterva. # : three subjects had missig data for SVC. cocuded that the fixed ratio may idetify at-risk patiets. This aaysis was, however, imited by the uavaiabiity of post-brochodiator vaues. It is ot surprisig that the use of pre-brochodiator vaues for the LLN defiitio gave a higher COPD prevaece of 15.2%. The preset 31% reductio i the prevaece estimate usig post-brochodiator vaues is simiar to the 27% differece oted by JOHANNESSEN et a. [21]. The issue of whether FVC or SVC is used appears to make itte differece, as the vaues for these variabes were very simiar for most subjects, athough this differece may be greater i a popuatio group with a higher proportio of subjects with more severe COPD. The rage of prevaece estimates depedig o defiitio has bee cosidered by other groups. A reported a wide rage depedig o defiitio, but oe of these icuded postbrochodiator testig [27 29]. The importace of usig postbrochodiator ug fuctio is debated ad comes dow to a attempt to distiguish betwee asthma ad COPD. Both disease compexes share simiar symptoms ad demostrate airfow obstructio. However, the variabiity of symptoms ad chages i airfow imitatio that occur spotaeousy or i respose to treatmet has traditioay bee ascribed to asthma. The degree of reversibiity i FEV1 that idicates a diagosis of asthma is geeray accepted as o12% (or o200 ml) from the pre-brochodiator vaue [30]. However, the 1995 ATS officia statemet o COPD metios that a sigificat icrease i FEV1 after a ihaed b-adreergic agoist has bee observed i up to oe third of COPD patiets durig sige-testig sessios [31]. The recet ERS/ATS Task Force did ot achieve a cosesus o the iterpretatio of brochodiator resposiveess i subjects with airfow obstructio, athough it was commeted that vaues o12% ad 200 ml are sigificat. It aso states that eve though asthmatics ted to show arger resposes to brochodiators, this respose has ever bee show to be capabe of ceary separatig the two casses of patiets [6]. The prevaece estimates i the preset study were based oy o the resuts of spirometry. It is ackowedged that a ciica diagosis of COPD requires a history of chroic progressive symptoms, possibe abormaities o physica examiatio ad a cosideratio of risk factors; however, objective evidece of airfow obstructio determied by forced expiratory spirometry is the stadard for demostratig ad quatifyig airfow obstructio [3, 26, 32]. It is we recogised that COPD is uder-diagosed i the commuity, at east i part because it is ciicay siet uti the disease process is we advaced. I the third Natioa Heath ad Nutritio Examiatio Survey, 44% of idividuas with a FEV1,50% pred did ot have a curret diagosis of COPD [33]. The mai stregth of the preset study was the wide rage of objective measures performed i idividuas from a radom popuatio survey. The major probem with the preset study was the arge drop-out betwee those idividuas seected from the eectora ro to those with fu competio of tests. c EUROPEAN RESPIRATORY JOURNAL VOLUME 30 NUMBER 2 237

7 COPD PREVALENCE DEPENDS UPON DEFINITION P. SHIRTCLIFFE ET AL. TABLE 5 Prevaece of chroic obstructive pumoary disease (COPD) # by age, sex, ethicity, smokig status ad pack-yrs Subjects with COPD/tota (%) 95% CI simiary report post-brochodiator vaues. A rage of prevaece rates from % for the same popuatio group depedig o defiitio has bee show. Logitudia studies usig post-brochodiator spirometry are required to determie whether a ower-imit-of-orma approach woud better estimate the true chroic obstructive pumoary disease prevaece, abeit at the cost of simpicity. Age yrs Overa 116/ /125 (5.6) /133 (4.5) /199 (11.6) /188 (25.0) o70 33/104 (31.7) Sex Mae 80/406 (19.7) Femae 36/343 (10.5) Ethicity New Zeaad Europea 98/654 (15.0) Maori 6/26 (23.1) Other " 12/56 (17.7) Smokig status + Nosmoker 45/376 (12.0) Curret smoker 20/76 (26.3) Ex-smoker 51/297 (17.2) Pack-yrs /185 (9.2) /82 (19.5) o20 38/106 (35.9) CI: cofidece iterva. # : defied accordig to Goba Iitiative for Chroic Obstructive Lug Disease criteria, i.e. post-brochodiator forced expiratory voume i oe secod/forced vita capacity,0.7; " : maiy Asia ad Pacific isaders; + : a further 30 subjects were tobacco smokers but ot smokers of cigarettes. However, subjects competig the ivestigative modues were broady simiar to those competig the SQ. More detaied aaysis by age bad (resuts ot show) idicated a differece betwee the eectora ro sampig frame ad the SQ, where respose rate icreased by age ad this was accouted for by adjustig the prevaece rates to the age distributio of the Weigto popuatio. However, there was itte differece by age bad i the proportios participatig i the SQ versus MQ versus idividuas competig PFT. The reativey sma sampe size ad sma umber of subjects with COPD by ay defiitio ed to the wide CI for prevaece as iustrated i tabe 5. It is ackowedged that the ogoig discussio aroud the topic of a fixed ratio versus a LLN defiitio is focused o the edery patiet with mid disease. The preset sampe has few idividuas i this group. A imitatio of performig such a study i New Zeaad is that it is a coutry with a reativey youg popuatio, imitig the umber of oder aduts accessibe through the eectora ro. I cocusio, the preset study has provided a first estimate of the Goba Iitiative for Obstructive Lug Disease-defied prevaece of chroic obstructive pumoary disease i a urba New Zeaad popuatio. This prevaece is broady comparabe with the few other studies wordwide that ACKNOWLEDGEMENTS The preset authors woud ike to thak J. Soriao (Fudació Caubet-CIMERA Ies Baears, Buyoa, Spai) ad H. Coxso (Uiversity of British Coumbia, Vacouver, Caada) for their hepfu commets i the desig of the Weigto Respiratory Heath Survey (WRHS) ad iterpretatio of the resuts; D. Fabia ad A. Pritchard for their hep with the WRHS ad i producig the mauscript; A. Hot, P. Heuser ad E. Chambers for their hep i coductig the questioaires; M. Wiiams for his hep i coductig the pumoary fuctio tests (a from Medica Research Istitute of New Zeaad, Weigto, Austraia); ad M. Nowitz, A. Kigzett-Tayor ad the radiography ad admiistrative staff of Pacific Radioogy (Weigto, New Zeaad). REFERENCES 1 Chapma KR, Maio DM, Soriao JB, et a. Epidemioogy ad costs of chroic obstructive pumoary disease. Eur Respir J 2006; 27: Lopez AD, Shibuya K, Rao C, et a. Chroic obstructive pumoary disease: curret burde ad future projectios. Eur Respir J 2006; 27: Goba Iitiative for Chroic Obstructive Lug Disease. Goba Strategy for the Diagosis, Maagemet ad Prevetio of COPD, Date ast accessed: Jauary 30, Cei BR, MacNee W, Augusti A, et a. Stadards for the diagosis ad treatmet of patiets with COPD: a summary of the ATS/ERS positio paper. Eur Respir J 2004; 23: Lug fuctio testig: seectio of referece vaues ad iterpretative strategies. America Thoracic Society. Am Rev Respir Dis 1991; 144: Peegrio R, Viegi G, Brusasco V, et a. Iterpretative strategies for ug fuctio tests. Eur Respir J 2005; 26: Hardie JA, Buist AS, Vomer WM, Eigse I, Bakke PS, Morkve O. Risk of over-diagosis of COPD i asymptomatic edery ever-smokers. Eur Respir J 2002; 20: Hakiso JL, Odecratz JR, Feda KB. Spirometric referece vaues from a sampe of the geera U.S. popuatio. Am J Respir Crit Care Med 1999; 159: Sterk PJ. Let s ot forget: the GOLD criteria for COPD are based o post-brochodiator FEV1. Eur Respir J 2004; 23: Pistei F, Viegi G, Carrozzi L, Römark E, Ludäck B, Giutii C. Compedium of respiratory stadard questioaires for aduts (CORSQ). Eur Respir Rev 2001; 11: Marsh S, Adigto S, Wiiams M, et a. Physioogica associatios of computerized tomography ug desity: a factor aaysis. It J COPD 2006; 1: VOLUME 30 NUMBER 2 EUROPEAN RESPIRATORY JOURNAL

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