The modified BODE index: validation with mortality in COPD

Transcription

1 Eur Respir J 2008; 32: DOI: / CopyrightßERS Jourals Ltd 2008 The modified BODE idex: validatio with mortality i COPD C.G. Cote*, V.M. Pito-Plata #, J.M. Mari ", H. Nekach +, L.J. Dordelly + ad B.R. Celli # ABSTRACT: Peak oxyge uptake (V9O 2 ) remais the gold stadard measuremet of exercise capacity ad has bee associated with survival. A modified BODE (body mass idex, airflow obstructio, dyspoea, exercise capacity) idex replacig the 6-mi walk distace (6MWD) with V9O 2 as % predicted (mbode%) has bee developed ad foud to have excellet correlatio with the covetioal BODE idex. The objectives of the preset study were to compare the ability of the covetioal BODE ad the mbode% to predict mortality i 444 patiets with chroic obstructive pulmoary disease (COPD) followed for a mea SD period of moths. Athropometrics, spirometry, lug volumes, comorbidity, cardiopulmoary cyclo-ergometry test ad 6MWD were determied at etry. The mea BODE idices for the cohort were: BODE ad mbode% Both idices were sigificatly correlated with mortality. Logistic regressio aalysis with COPD survival as the depedet variable idetified the BODE idex, Charlso s ad exercise capacity (i W) as variables associated with this outcome. I coclusio, the covetioal BODE idex, which uses the 6-mi walk distace, predicts mortality i chroic obstructive pulmoary disease as well as the modified idex usig peak oxyge uptake. The results support the use of the simpler idex, which icludes the 6-mi walk distace i the comprehesive evaluatio of patiets with chroic obstructive pulmoary disease. KEYWORDS: Chroic obstructive pulmoary disease, exercise capacity, mortality The oxyge uptake measured at peak exercise (V9O 2 ) durig icremetal cardiopulmoary exercise testig (CPET) is cosidered to be the gold stadard for the evaluatio of exercise capacity. V9O 2 helps predict survival i patiets udergoig lug resectio [1, 2] ad lug volume reductio surgery (LVRS) [3], ad i patiets with chroic obstructive pulmoary disease (COPD) [4] ad heart failure [5]. The 6-mi walk test (6MWT) is easy to perform ad has bee stadardised [6], ad also predicts mortality i COPD [7, 8] ad i pulmoary hypertesio [9]. The 6MWT is cosidered a submaximal test; however, CASAS et al. [10] have show that patiets with COPD walk at a pace close to their maximal exercise capacity while the V9O 2 measured at the ed of a icremetal protocol i COPD is ot a true maximal oxyge uptake [11, 12]. This idicates that the differeces betwee tests i the patiets with COPD may ot be as large as otherwise suspected. There is a modest but sigificat correlatio betwee V9O 2 ad 6- mi walkig distace (6MWD) [13, 14], implyig that the tests are ot equal; however, as it relates to the capacity to predict survival i COPD, the curret authors have recetly show that the 6MWD is equal to, if ot better tha, V9O 2 at predictig this outcome [15]. The BODE idex, which icorporates measuremets of utritio (body mass idex), airflow obstructio (forced expiratory volume i oe secod (FEV1)), dyspoea (Modified Medical Research Coucil dyspoea scale) ad exercise capacity as measured by the 6MWD, predicts mortality [16, 17], hospitalisatios [18] ad reflects disease modificatio after LVRS [19], osurgical volume reductio [20], ad pulmoary rehabilitatio [21]. It also reflects the deleterious effects of exacerbatios ad hospitalisatios [22]. CARDOSO et al. [23] recetly developed a modified BODE idex (mbode) by replacig the 6MWD with V9O 2. A excellet correlatio betwee BODE ad mbode whe the V9O 2 value was expressed as % predicted was reported (mbode%), which was better tha with that with mbode whe V9O 2 was expressed i ml?kg -1?mi -1. The purpose of the preset study was to test the hypothesis that the mbode% idex usig V9O 2 expressed as % pred had a similar predictive AFFILIATIONS *Pulmoary ad Critical Care, Bay Pies Veteras Admiistratio Medical Ceter, + The Bay Pies Research Foudatio, Bay Pies, FL, # Pulmoary ad Critical Care, Caritas St. Elizabeth s Medical Ceter, Bosto, MA, USA. " Hospital Miguel Servet, Zaragoza, Spai. CORRESPONDENCE C.G. Cote Pulmoary ad Critical Care Medicie Bay Pies Veteras Admiistratio Health Care System 10,000 Bay Pies Boulevard Bay Pies FL USA Fax: claudia.cote@med.va.gov Received: October Accepted after revisio: Jue STATEMENT OF INTEREST Noe declared. Europea Respiratory Joural Prit ISSN Olie ISSN c EUROPEAN RESPIRATORY JOURNAL VOLUME 32 NUMBER

2 MULTIDIMENSIONAL INDICES C.G. COTE ET AL. TABLE 1 Baselie characteristics i a cohort of 444 patiets with chroic obstructive pulmoary disease Variable Subjects 444 Age yrs 66 8 (37 83) Smokig history pack-yrs (10 250) Pa,O2 mmhg (52 96) BMI kg?m (14 50) FEV1 % (15 90) FVC % (32 120) FEV1/FVC % (16 70) MMRC 2.3 (0 4) 6MWD m (54 712) BODE idex (0 10) mbode% idex (0 10) Data are preseted as mea SD (rage), uless otherwise stated. Pa,O 2: partial arterial pressure of oxyge; BMI: body mass idex; FEV1: forced expiratory volume i oe secod; FVC: forced vital capacity; MMRC: Modified Medical Research Coucil dyspoea scale; 6MWD: 6-mi walkig distace; mbode%: modified BODE idex usig peak oxyge uptake as % predicted. power for mortality to the origial BODE idex, which icludes the 6MWD i a cohort of patiets with COPD. METHODS Patiets The cohort cosisted of 444 patiets with COPD, recruited at the Bay Pies Veteras Admiistratio Health Care System (Bay Pies, FL, USA; 5292), St Elizabeth s Medical Ceter (Bosto, MA, USA; 5119) ad the Miguel Servet Hospital (Zaragoza, Spai; 533) betwee 1996 ad 2006 ad followed util Jue The huma research committees at each istitutio approved the study ad all patiets gave iformed coset. Erolmet criteria have bee previously published [16]. The patiets were cliically stable for 6 weeks ad had to be able to perform both tests. Measuremets Spirometry ad 6MWD were completed followig the America Thoracic Society (ATS) recommedatios [6, 24]. Comorbidity was determied with the Charlso score [25]. For exercise ergometry, the patiets started with a 2-mi period of uloaded pedallig at 60 cycles?mi -1, followed by a W?mi -1 icremet [26] ad were ecouraged to cycle util exhaustio. Heart rate ad blood pressure were moitored cotiuously. Miute vetilatio ad its compoets were measured usig a peumotachograph. The cocetratios of expired oxyge ad carbo dioxide were aalysed breath by breath. The preset study used 30-s averages of miute vetilatio, tidal volume, respiratory rate, oxyge uptake, carbo dioxide output ad gas exchage ratio. Predicted maximal oxyge cosumptio was calculated usig stadard equatios [26]. The heart rate reserve was calculated as 220 mius the patiet s age mius the observed peak heart rate. CPET ad the 6MWD were performed o separate days, at least 1 day apart ad withi 1 moth of erolmet ito the study. To avoid bias, the two tests were performed i radom order. The BODE idices The BODE idex was calculated as previously reported [16]. The mbode% idex was calculated by replacig the 6MWD by the V9O 2 expressed as % pred as follows: score 0 for.70% pred; score 1 for 60 69% pred; score 2 for 40 59% pred; ad score 3 for,40% pred [27]. I the study of CARDOSO et al. [23], as well as i calculatios coducted i the preset cohort (data ot preseted), the V9O 2 expressed as % pred offered similar, if ot better, discrimiatig power tha the absolute value. Statistical aalysis The data are preseted as mea SD ad rage. The differeces i physical characteristics, pulmoary fuctio test ad exercise parameters i patiets stratified by BODE quartiles were evaluated usig ANOVA. Pearso s correlatio test was used to assess the relatioship betwee the idices ad mortality. Mortality was evaluated over time usig Kapla Meier aalysis. TABLE 2 Exercise parameters of patiets with chroic obstructive pulmoary disease stratified by BODE ad modified BODE idex (mbode%) quartiles Variable Quartile 1 Quartile 2 Quartile 3 Quartile 4 BODE mbode% BODE mbode% BODE mbode% BODE mbode% Exercise capacity W * * * * V9O2 ml?kg -1?mi * * V9O 2 % pred * 49 57* 41 46* Restig fc beats?mi Peak fc beats?mi fc reserve % Maximal V9E L * * * V9E L?mi * * * Breathig reserve % Data are preseted as mea SD, uless otherwise stated. V9O 2: oxyge uptake; fc: cardiac frequecy; V9E: miute vetilatio. *: p, VOLUME 32 NUMBER 5 EUROPEAN RESPIRATORY JOURNAL

3 C.G. COTE ET AL. MULTIDIMENSIONAL INDICES TABLE 3 Logistic regressio aalysis ad odds ratios (ORs) for survival amog patiets with chroic obstructive pulmoary disease Parameter OR (95% CI) Likelihood ratio test Chi-squared Df p-value BODE ( ) Charlso ( ) Exercise capacity # 2158 ( ) CI: cofidece iterval. # : measured i W. a) Survival fuctio Logistic regressio aalysis was used to ivestigate the relatioship betwee the idexes ad mortality. Receiver operatig curves (ROC) were used to assess the diagostic power of both idices with mortality as a outcome. A p-value,5 was cosidered sigificat. RESULTS The characteristics of the 444 patiets are show i table 1. The cohort was predomiatly male (87%) ad Caucasia (99%), ad 23% of the patiets were oxyge depedet. Usig ATS/ Europea Respiratory Society (ERS)/Global Iitiative for Chroic Obstructive Lug Disease (GOLD) criteria, 2% were classified as stage 1 COPD patiets, 27% were stage 2, 47% were stage 3 ad 24% were stage 4. Whe the patiets were stratified by the covetioal BODE idex, 23% were i quartile 1, 35% were i quartile 2, 29% were i quartile 3 ad 13% were i quartile 4. Coversely, whe stratified by mbode%, 10% were i quartile 1, 22% were i quartile 2, 32% were i quartile 3 ad 36% were i quartile 4. The mea BODE idex for the cohort was ad the mbode% idex was (p,01) with a differece of 1.4 poits. b) Survival fuctio Follow-up moths FIGURE 1. Kapla Meier survival curves for a) the origial BODE idex that uses the 6-mi walk distace ad b) the modified BODE idex (mbode%) usig the peak oxyge uptake % predicted. Both are divided i quartiles as follows. : quartile 1 (BODE or mbode% idex score 0 2); : quartile 2 (score 3 4);?????: quartile 3 (score 5 6);?? : quartile 4 (score 7 10). The origial idex differetiated to a level similar to that of the modified BODE. See also table 4. TABLE 4 Survival probability of chroic obstructive pulmoary disease patiets stratified by BODE ad modified BODE (mbode%) idices Survival probability % Baselie 12 moths 24 moths 36 moths 48 moths 60 moths 72 moths 84 moths 96 moths 8-yr survival BODE Quartile Quartile Quartile Quartile mbode% Quartile Quartile Quartile Quartile Quartile 1: BODE or mbode% idex score 0 2; quartile 2: score 3 4; quartile 3: score 5 6; quartile 4: score See also figure 1. c EUROPEAN RESPIRATORY JOURNAL VOLUME 32 NUMBER

4 MULTIDIMENSIONAL INDICES C.G. COTE ET AL. Exercise parameters Table 2 shows that the exercise capacity was severely reduced at all stages except for quartile 1, whether patiets were stratified by the traditioal BODE idex or the modified BODE idex. The preset authors observed that oly 39 (8.7%) patiets i the cohort had ormal exercise capacity (V9O 2.70% pred). With exemptio of cardiac parameters, which showed o differeces, BODE reflected exercise impairmet better tha the mbode. Mortality There were 206 deaths durig the study, with a mea SD time from erolmet to death of moths. A total of 107 (51.4%) were due to COPD ad 40 (19.4%) to lug cacer. The remaiig deaths were due to cardiovascular disease, cacers other tha lug cacer ad other medical reasos. Mortality was very high for patiets who had a V9O 2,40% pred (61%) or a walkig distace,350 m (63%). Coversely, COPD mortality amog patiets exceedig these values was low (18 ad 15%, respectively). Logistic regressio aalysis idetified the covetioal BODE idex, Charlso s comorbidity ad exercise capacity as variables associated with COPD mortality. The model explaied 17.16% of the deviace; odds ratios are show i table 3. Kapla Meier survival aalysis (fig. 1 ad table 4) also idetified a better stratificatio betwee BODE quartiles tha mbode% quartiles. The Chi-squared for BODE was 58 versus 40 for mbode% (pf0001). Mortality was higher i all of the covetioal BODE quartiles, i particular i quartile 4, compared with the correspodig mbode% idex quartile. A ROC aalysis showed discrimiative values of 0.73 for BODE ad 0.72 for mbode% (fig. 2). Correlatios Pearso s correlatio calculatios betwee the idices were performed ad they were foud to correlate very well (fig. 3). Sesitivity specificity FIGURE 2. Receiver operatig curves for the covetioal BODE idex (h)usig the 6-mi walk distace ad the modified BODE idex (mbode%; &) usig peak oxyge uptake % predicted. No differeces were observed betwee tests i their capacity to predict survival i chroic obstructive pulmoary disease. The area uder the curve for the BODE idex was 0.73 (95% cofidece iterval (CI) ; SE 29). The correspodig value for mbode% was 0.72 (95% CI ; SE 30). The correlatio betwee 6MWD ad V9O 2 was modest but highly statistically sigificat, as it has bee demostrated previously. DISCUSSION The preset study shows that i patiets with a wide rage of COPD severity, the covetioal BODE idex predicts mortality as well as the modified BODE idex which replaces the 6MWD with V9O 2 % pred obtaied durig CPET. The curret authors have previously show that the BODE idex is a better predictor of mortality tha FEV1 [16]. The BODE idex also predicts hospitalisatios ad outcome followig LVRS ad pulmoary rehabilitatio [17 21]. The BODE idex icorporates the 6MWD as a measure of exercise capacity. Differet modificatios of the covetioal BODE idex have bee proposed, amog them oe that icorporates V9O 2 ad ot the 6MWD. I oe study, the modified BODE idex was reported to have a excellet correlatio with the covetioal BODE (r50.97) but its predictive value for mortality was ot evaluated [23]. I the preset study, these fidigs of CARDOSO et al. [23] were cofirmed, ad the modest a) mbode% b) 150 V O 2 % pred BODE MWD m FIGURE 3. a) Pearso s correlatios betwee the traditioal BODE idex ad the modified BODE idex (mbode%). Although the correlatio betwee the two idexes is excellet, b) a more modest but sigificat correlatio is see betwee 6- mi walk distace (6MWD) ad peak oxyge uptake (V9O2) VOLUME 32 NUMBER 5 EUROPEAN RESPIRATORY JOURNAL

5 C.G. COTE ET AL. MULTIDIMENSIONAL INDICES but sigificat correlatio betwee the 6MWD ad V9O 2 % pred was further corroborated. Ideed, it seems logical that V9O 2, which represets the itegral fuctio of the cardiopulmoary system, should be superior at predictig outcome i COPD ad to reflect better the multisystemic compromise of these patiets tha the 6MWD. It is also reasoable to expect that the 6MWD, which is cosidered a submaximal test, to have less of a overall predictive capacity, because it has bee thought of as beig less objective ad accurate tha V9O 2. Surprisigly, as show i figures 1 ad 2, the covetioal BODE idex, which uses 6MWD, performed equally well, if ot better tha, the modified BODE idex usig V9O 2 the predictio of mortality i this cohort of patiets. It is possible that the differet methodology durig CPET iflueces the iformatio obtaied with this test. A icremetal load protocol durig exercise testig may ot be sustaiable for patiets with more severe COPD. Ideed, i the preset cohort of 444 patiets (27% stage 1 ad 2, as defied by ATS/ERS/GOLD) oly 39 (8.7%) patiets had V9O 2.70% pred. This impairmet i exercise capacity, eve at lower stages of ATS/ERS/GOLD disease severity, has bee reported before ad its aetiology is ot clear. Ususpected pulmoary hypertesio, right vetricular afterload ad impaired oxyge utilisatio have bee proposed to be possible mechaisms [27]. Whe patiets i ATS/ERS/GOLD stages 0 2 (120 patiets, 27% of the cohort) were aalysed separately, their V9O 2 was oly 57 16% pred, which suggests that this methodology of testig with icremetal load might ot be sustaiable, eve for patiets with mild disease. It is likely that the patiets i the preset cohort developed symptoms of shortess of breath ad/or leg fatigue, which made them stop the exercise before they reached a true V9O 2. As see i table 2, all patiets had a reduced breathig reserve at all stages of disease by BODE ad mbode% idices. Coversely, whe patiets are physically uable to walk more tha a very short distace durig the 6MWD, i spite of beig allowed to pace themselves ad to pause as eeded, this iability to walk may represet a greater vital compromise tha that provided by a reduced V9O 2. The preset study has some limitatios. First, the patiets icluded here were mostly males attedig specialised cetres ad, therefore, the fidigs may ot be exteded to female patiets or to COPD patiets attedig other settigs. However, the wide rage of airflow obstructio i the cohort represet most patiets with COPD see by cliicias. Secodly, oly patiets capable of performig both tests were icluded. Thus, the results may ot apply to patiets with coditios that limit the ability to walk. 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