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a multidimensional parameter that includes body mass index &#40;B&#41;&#44; degree of airflow obstruction &#40;O&#41;&#44; functional dyspnea &#40;D&#41; and exercise capacity &#40;E&#41;&#46; It was reported to be better than forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s &#40;FEV<span class="elsevierStyleInf">1</span>&#41; to reflect the severity of COPD&#44; and it is effective in the prediction of mortality in patients with the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> In this population of patients&#44; it has also been described that the BODE score is applicable for predicting an individual&#39;s need for hospitalization&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> determining the lung function changes of the follow-up during pulmonary rehabilitation<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and the transbronchoscopic application of one-way valves&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> predicting survival after lung volume reduction surgery<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and reflecting modifications of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In clinical practice&#44; it is foreseeable that the combination of the levels of serum CRP concentrations and the BODE score would be a better predictor for survival between patients with COPD&#44; because serum CRP is an important systemic inflammatory marker and the BODE score is a clinical parameter of great use for patients with the disease&#46; The objective of the present study was to determine the predictive value of CRP serum concentrations combined with the BODE score for mortality in patients with stable COPD&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Study Design</span><p id="par0020" class="elsevierStylePara elsevierViewall">We carried out a prospective study to select clinically stable COPD patients and register their characteristics in order to identify the prognostic longitudinal mortality variables&#46; The variables included age&#44; sex&#44; current tobacco use&#44; pack-years&#44; maximal inspiratory pressure&#44; maximal expiratory pressure&#44; severity of COPD&#44; modified Medical Research Council dyspnea scale &#40;MMRC&#41;&#44; body mass index&#44; diffusion capacity&#44; 6-minute walk test &#40;6MWT&#41;&#44; serum CRP concentration&#44; serum fibrinogen concentration and BODE score&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Study Subjects</span><p id="par0025" class="elsevierStylePara elsevierViewall">The study was approved by the Research Committee of the Chang Gung Memorial Hospital&#44; which also provided financing&#46; A total of 125 patients were consecutively selected with variable COPD severity from April 2005 to July 2006 from the Division of Pulmonary Medicine outpatient clinic&#44; Chang Gung Memorial Hospital-Kaohsiung Medical Center&#44; a hospital with 2300 primary-care beds and a tertiary reference center in Taiwan &#40;China&#41;&#46; These patients underwent spirometry and lung volume determinations in accordance with the recommendations published by the American Thoracic Society and according to standard references&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Each recruited COPD patient was over the age of 40 and had been a heavy smoker&#44; with smoking histories of at least 10 pack-years&#46; The diagnosis of COPD was established based on anamnesis&#44; physical exploration and the spirometric data of the patient indicative of a post-bronchodilator FEV<span class="elsevierStyleInf">1</span> &#40;forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s&#41;&#47;forced vital capacity &#40;FVC&#41; ratio of less than 0&#46;7&#44; with a reversibility by means of inhaled bronchodilator of FEV<span class="elsevierStyleInf">1</span>&#60;15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In the selected patients&#44; other causes of airway limitation were excluded&#44; such as pulmonary tuberculosis&#44; bronchial asthma&#44; bronchiectasis and heart failure&#44; identified by reviewing chest radiographies and medical files&#46; We also excluded those patients with diagnosis of cardiovascular disease&#44; such as coronary artery disease&#44; peripheral vasculopathy or cerebral vascular disease&#46; After 6 weeks of appropriate treatment&#44; the patients with clinically stable COPD were included&#59; for these patients&#44; the BODE index was calculated and serum CRP concentrations determined&#46; The patients who experienced an exacerbation in their COPD &#40;fever&#44; increase in purulent sputum or dyspnea&#41; or hospitalizations for any reason during the 6-week treatment period were excluded from the study&#46; After their inclusion&#44; the patients were seen approximately every 3 months based on the medical histories and the computerized information&#46; If a patient was lost to follow-up at our hospital&#44; the research assistant communicated with the patient or his&#47;her family and acquired information regarding mortality in a telephone interview&#46; The final data of the study were collected on 7 August 2008&#46; During the follow-up period&#44; the mortality due to any cause was used as an analyzed variable&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">CRP Determination</span><p id="par0035" class="elsevierStylePara elsevierViewall">Fasting blood samples were obtained while the patients were at rest and before carrying out any other test&#46; The CRP concentrations were determined with a high-sensitivity immunoanalysis&#46; The analytical sensitivity of this analysis was 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; and the determination range was 0&#46;1&#8211;20<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#46; We divided the COPD patients into two subgroups with an initial cut value for the CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l or &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l because&#44; in studies published about cardiovascular medicine<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> and in the COPD cohort described by Dahl et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> it has been previously demonstrated that this value is a determinant for patient survival&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Evaluation With the BODE Index</span><p id="par0040" class="elsevierStylePara elsevierViewall">Each patient was assigned a BODE score&#44; which was calculated using an empirical model as has previously been described&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The body mass index &#40;BMI&#41; was calculated as the weight of the patient in kilograms divided by height in meters squared&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The degree of airflow obstruction was determined by means of FEV<span class="elsevierStyleInf">1</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> dyspnea was determined using the MMRC dyspnea scale<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> and exercise capacity was determined with the distance walked in 6<span class="elsevierStyleHsp" style=""></span>minutes &#40;6MWT&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> For each value of FEV<span class="elsevierStyleInf">1</span>&#44; MMRC dyspnea scale and 6MWT&#44; each patient received points that varied from 0 to 3&#59; for the body mass index&#44; each patient received 0 or 1 point&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The points for each component of the BODE index were added&#44; and the score varied between 0 and 10 points for each patient&#46; In addition&#44; the BODE score was classified in quartiles as previously described&#58; quartile 1 included patients with a score of 0&#8211;2&#59; quartile 2&#44; 3&#8211;4 points&#59; quartile 3&#44; 5&#8211;6 points&#59; and quartile 4&#44; 7&#8211;10 points&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical Analyses</span><p id="par0045" class="elsevierStylePara elsevierViewall">The continuous variables are presented as means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation and the categorical variables are presented as absolute numbers and percentages&#46; The relationship between the BODE quartile and the patients with a serum concentration of CRP &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l was analyzed by means of a non-parametric test&#46; The difference in the BODE scores between patients with a serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l was evaluated using the Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#46; In order to identify the most significant prognostic factors for survival and calculate the hazard ratios &#40;HR&#41; for mortality and the 95&#37; confidence intervals &#40;CI&#41;&#44; we used a Cox proportional hazards regression model&#46; The variables whose <span class="elsevierStyleItalic">P</span> values were &#60;&#46;05 in the univariate analysis were also analyzed in a multivariate analysis&#46; Survival was estimated by means of the Kaplan&#8211;Meier method with a <span class="elsevierStyleItalic">log-rank</span> test&#46; A two-tailed <span class="elsevierStyleItalic">P</span> value&#60;&#46;05 was considered statistically significant&#46; The statistical analyses were done using the SPSS program &#40;version 13&#46;0&#59; SPSS Inc&#46;&#44; Chicago&#44; IL&#44; United States&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Characteristics of the Study Participants</span><p id="par0050" class="elsevierStylePara elsevierViewall">We initially selected 125 patients for the present study&#46; However&#44; 6 of them were excluded due to the exacerbation of the symptoms or to hospitalization during the initial 6-week observational period&#46; Out of the 119 cases included in the study&#44; we could not obtain information about the mortality in 5 because they had either changed residence or telephone&#44; or due to the lack of cooperation of the patient or his&#47;her family&#46; Therefore&#44; in the final analysis we include a total of 114 patients&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the characteristics of the study participants&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Correlation Between the Serum Concentration of CRP and the BODE Score</span><p id="par0055" class="elsevierStylePara elsevierViewall">There were no significant differences in the BODE scores between patients whose serum CRP concentrations were &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and those in whom it was &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l &#40;3&#46;11 compared with 3&#46;34&#59; <span class="elsevierStyleItalic">P</span>&#61;&#46;62&#41;&#46; The non-parametric analysis also did not demonstrate a correlation between the BODE quartile and the serum concentration of CRP &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;87&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Predictive Variables for Survival in Patients <span class="elsevierStyleItalic">W</span>ith Chronic Obstructive Pulmonary Disease</span><p id="par0060" class="elsevierStylePara elsevierViewall">In the univariate analysis&#44; it was demonstrated that parameters such as age&#44; FEV1&#47;FVC&#44; MMRC dyspnea scale&#44; 6MWT&#44; serum concentration of CRP&#44; carbon monoxide diffusion capacity &#40;DLCO&#41;&#44; maximum inspiratory pressure &#40;PI<span class="elsevierStyleInf">MAX</span>&#41; and BODE scores were significantly associated with mortality &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; However&#44; despite treating the serum concentration of CRP with either total data or divided by categories&#44; or treating the BODE score as either a continuous variable or divided in quartile categories&#44; the multivariate analysis demonstrated that the serum CRP concentration and the BODE scores were independent prognostic variables for mortality &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; A serum CRP concentration &#62;3 simultaneous with a BODE score in quartile 3&#8211;4 predicted a greater mortality than any of the two factors alone or in the absence of both in patients with clinically stable COPD &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Survival of Patients With Chronic Obstructive Pulmonary Disease</span><p id="par0065" class="elsevierStylePara elsevierViewall">During the periods of the present study&#44; 17 &#40;14&#46;9&#37;&#41; patients died &#40;17&#47;114&#41;&#46; In patients with clinically stable COPD and a serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; we identified a lower accumulative survival rate than in those with a value &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In the subgroup with a concentration of CRP &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; there was a mortality rate of 27&#37; &#40;12&#47;44&#41; during the study period&#46; In comparison&#44; in the group with values &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; the mortality rate was 6&#46;3&#37; &#40;4&#47;63&#41;&#46; In patients with a BODE score in quartile 3&#8211;4&#44; there was a lower accumulative survival rate than in those with a BODE score in quartile 1&#8211;2 &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;02&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In the subgroup of quartile 3&#8211;4&#44; there was a mortality rate of 27&#37; &#40;10&#47;37&#41; during the study period&#46; In comparison&#44; the mortality rate of the subgroup of quartile 1&#8211;2 was 9&#46;1&#37; &#40;7&#47;77&#41;&#46; The accumulative survival rates of the COPD patients were classified from the worst to the best in the following manner&#58; serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2&#59; serum CRP concentration &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2 &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The mortality rates of the COPD subgroups during the study period were likewise classified&#58; serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2&#59; serum CRP concentration &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2 were 7&#47;14 &#40;50&#37;&#41;&#59; 5&#47;30 &#40;16&#46;7&#37;&#41;&#59; 2&#47;11 &#40;9&#46;5&#37;&#41; and 2&#47;45 &#40;4&#46;4&#37;&#41;&#44; respectively&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">The results of the present longitudinal study revealed that serum CRP concentrations and the BODE score are independent prognostic variables for mortality in patients with stable COPD&#46; The accumulative survival rates of the COPD patients were classified from the worst to the best in the following manner&#58; serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2&#59; serum CRP concentration &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2 &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46; This indicates that the use of the concentration of this reactive and the BODE score combined produced a greater predictive value for mortality in these patients than either parameter alone&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The concentration of CRP is also related to the presence of airflow obstruction&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> de Torres et al&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> found a significant relationship between the concentration and other clinical variables in patients with the disease&#46; Their results demonstrated that the concentration correlated with various clinical parameters&#44; including FEV<span class="elsevierStyleInf">1</span>&#44; FVC&#44; CI&#47;CPT&#44; classification of COPD severity based on the GOLD initiative&#44; BODE score&#44; PaO<span class="elsevierStyleInf">2</span> and 6MWT in a multivariate analysis&#46; However&#44; only these last two parameters were associated with CRP concentration in the multivariate linear regression analysis&#46; de Torres et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> also compared the clinical parameters of COPD patients with initial CRP values &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l or &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l in another study with a different population&#44; and they did not find any significant differences in FEV<span class="elsevierStyleInf">1</span>&#44; FVC&#44; CI&#47;CPT&#44; GOLD stage&#44; MMRC scale or BODE score&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> In a later study&#44; only BMI and PaO<span class="elsevierStyleInf">2</span> were significantly different between groups with CRP &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l in the univariate analysis&#46; The population of this latter study included patients with moderate or very severe COPD from two pulmonology clinics at two hospitals&#44; which represented a difference from the previous study&#46; Therefore&#44; the correlation between the serum CRP levels and the clinical parameters is conflictive&#46; In the present study&#44; the serum CRP values did not correlate with the BODE scores&#44; not even in the subgroup of patients with levels of FEV<span class="elsevierStyleInf">1</span>&#60;50&#37; of the reference value or FEV<span class="elsevierStyleInf">1</span>&#8805;50&#37; of the reference value&#46; The univariate and multivariate analyses also showed that CRP and the BODE score were significant factors for the survival of these patients&#46; This indicates that the correlation between both parameters was not significant in the population of the present study&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">CRP is a circulating pentraxin largely&#44; although not exclusively&#44; produced by the hepatocytes as part of an acute phase response&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The <span class="elsevierStyleItalic">in vitro</span> studies have demonstrated that it can activate the classic complement cascade&#44; up-regulate adhesion molecules and chemoattractive cytokines and induce the synthesis of inflammatory cytokines&#44; such as interleukin &#40;IL&#41;-8 and IL-6&#44; which together amplify the initial inflammatory signal and propagate the chronic inflammatory processes&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Serum CRP is usually considered an important prognostic variable for cardiovascular mortality&#46; Nevertheless&#44; contradictory findings have been published about whether its concentration is associated with the survival of COPD patients&#46; The results of the de Torres et al&#46; study<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> demonstrated that the concentration is not associated with survival in patients with moderate or very severe disease compared with other prognostic clinical parameters&#44; such as the BODE index&#44; MMRC scale&#44; 6MWT&#44; percentage of the FEV<span class="elsevierStyleInf">1</span> reference value&#44; CI&#47;CPT ratio &#60;0&#46;25 and PaO<span class="elsevierStyleInf">2</span>&#46; Nevertheless&#44; the conclusions of the study do not coincide with the two epidemiological studies mentioned&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> which demonstrated that the increase in CRP concentrations was independently associated with global and cardiovascular mortality in COPD patients with mild or moderate obstruction of the airways&#46; The present study also showed that the concentration was significantly associated with survival after being adjusted for age&#44; sex and FEV<span class="elsevierStyleInf">1</span>&#44; even in the subgroup of patients with levels &#60;50&#37; the reference levels&#46; The reason for these conflictive findings can be the different study designs&#44; populations or COPD phenotypes&#44; sample size and other known or unknown factors that probably influence CRP concentrations&#46; Consequently&#44; additional longitudinal studies are required in this direction in order to clarify this problem in more detail&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">As the accumulated tests suggest that the mortality in patients with COPD is associated with multiple factors&#44; the progress in the comprehension of the disease and its components will lead to the development of multidimensional scores&#44; such as the frequently used BODE index&#46; The importance of this index is that the prognosis of COPD patients is not associated with an individual factor but instead with different factors that span different phenotypes&#46; This index is an invaluable instrument in the prediction of the need for hospitalization of an individual&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and it determines the effect of interventions&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;11</span></a> In spite of the continued controversy about the possible causal role of CRP&#44; its serum levels correlate with the future risk for morbidity and mortality in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a> The present study demonstrates that the combination of CRP with the BODE index can stratify the patients with stable COPD into different risk levels for mortality&#46; The combination of a low-grade systemic inflammation marker and a multidimensional score for predicting mortality in these patients is superior to an individual biological marker or any clinical parameter alone&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">This present study has several limitations&#46; In the first place&#44; we evaluate the cardiovascular disease using only the clinical information that is registered&#44; and we have not formally evaluated the presence of an active disease&#46; In addition&#44; the causes of mortality of the patients were not clearly divided into &#8220;cardiovascular&#44; respiratory or other&#8221; from the clinical histories or from the communication with the families&#46; Second of all&#44; some patients treated with oral or inhaled steroids presented lower concentrations of CRP than the non-treated patients&#59; nevertheless&#44; this difference was not statistically significant&#46; The reason could be the small sample size with a reduced statistical power&#46; Although&#44; in general&#44; inhaled corticosteroid treatment with a long-acting &#946;2 adrenergic agonist does not reduce the concentration of CRP or IL-6 in the serum of patients with COPD for 4 weeks&#44; we consider that some corticosteroids used and their actual effect on this parameter have yet to be clarified&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In short&#44; our study confirms that the serum concentration of CRP as well as the BODE score do not correlate and that both are independent prognostic variables for the survival in patients with stable COPD&#46; A serum CRP concentration &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and a BODE score in quartile 3&#8211;4 are poorer prognostic variables of COPD compared with CRP concentration &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and a BODE score in quartile 1&#8211;2&#46; The combination of both precisely predicted the survival of patients with stable COPD&#46; Additional cohort studies with a larger size sample will determine their validity&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Funding</span><p id="par0100" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleGrantSponsor" id="gs0005">Chang Gung Memorial Hospital</span> provided funding for this study &#40;<span class="elsevierStyleGrantNumber" refid="gs0005">CMRPG840421</span>&#41;&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare having no economic relationships with commercial entities with interests in this topic of research&#46;</p></span></span>"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec156315"
          "palabras" => array:3 [
            0 => "Enfermedad pulmonar obstructiva cr&#243;nica"
            1 => "Puntuaci&#243;n BODE"
            2 => "Prote&#237;na C reactiva"
          ]
        ]
      ]
    ]
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Both BODE score &#40;body mass index&#44; degree of airflow obstruction&#44; functional dyspnea&#44; and exercise capacity&#41; and serum C-reactive protein &#40;CRP&#41; are validated predictors of mortality in patients with chronic obstructive pulmonary disease &#40;COPD&#41;&#46; The aim of this study is to investigate the predictive value of combined serum CRP and BODE score for mortality in COPD patients&#46;</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A cohort of 114 clinically stable COPD patients was assessed for predictors of longitudinal mortality&#46; Variables included age&#44; gender&#44; current smoking status&#44; pack-years&#44; maximal inspiratory&#47;expiratory pressure&#44; BODE score &#40;body mass index&#44; degree of airflow obstruction&#44; functional dyspnea&#44; and exercise capacity&#41;&#44; serum CRP&#44; and fibrinogen&#46; Predictors were assessed by Cox proportional hazards regression model&#46; Survival was estimated by Kaplan&#8211;Meier method and log-rank test&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Serum CRP &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;005&#59; HR&#61;1&#46;042&#59; 95&#37; CI&#61;1&#46;019&#8211;1&#46;066&#41; and BODE score &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;032&#59; HR&#61;1&#46;333&#59; 95&#37; CI&#61;1&#46;025&#8211;1&#46;734&#41; were independent predictors of survival in the multivariate analysis&#46; The cumulative survival rates of COPD patients were sorted from the worst to the best as following&#58; serum CRP&#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP&#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2&#59; serum CRP &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP&#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2 &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Serum CRP and BODE score are independent predictors of survival in stable COPD patients&#46; Combination of serum CRP and BODE score has higher predictive value in clinical practice&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Tanto la puntuaci&#243;n BODE &#40;&#237;ndice de masa corporal&#44; grado de obstrucci&#243;n del flujo a&#233;reo&#44; disnea funcional y capacidad de ejercicio&#41; como la concentraci&#243;n s&#233;rica de prote&#237;na C reactiva &#40;PCR&#41; son variables pron&#243;sticas validadas de mortalidad en pacientes con enfermedad pulmonar obstructiva cr&#243;nica &#40;EPOC&#41;&#46; El objetivo del presente estudio fue investigar el valor predictivo de la combinaci&#243;n de la concentraci&#243;n s&#233;rica de PCR y la puntuaci&#243;n BODE para la mortalidad en pacientes con EPOC&#46;</p> <span class="elsevierStyleSectionTitle">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se evalu&#243; una cohorte de 114 pacientes con EPOC&#44; cl&#237;nicamente estables&#44; en busca de las variables pron&#243;sticas de mortalidad longitudinal&#46; Las variables incluyeron la edad&#44; sexo&#44; tabaquismo actual&#44; paquetes-a&#241;o&#44; presi&#243;n inspiratoria&#47;espiratoria m&#225;xima&#44; puntuaci&#243;n BODE <span class="elsevierStyleItalic">&#40;body mass index&#44; degree of airflow obstruction&#44; functional dyspnea&#44; and exercise capacity&#41;</span>&#44; concentraci&#243;n s&#233;rica de PCR y fibrin&#243;geno&#46; Las variables pron&#243;sticas se evaluaron mediante un modelo de regresi&#243;n de riesgos proporcionales de Cox&#46; La supervivencia se estim&#243; mediante el m&#233;todo de Kaplan&#8211;Meier y la prueba del <span class="elsevierStyleItalic">log-rank</span>&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La concentraci&#243;n s&#233;rica de PCR &#40;<span class="elsevierStyleItalic">P</span>&#61;0&#46;005&#59; CR&#61;1&#46;042&#59; IC del 95&#37;&#61;1&#46;019&#8211;1&#46;066&#41; y la puntuaci&#243;n BODE &#40;<span class="elsevierStyleItalic">P</span>&#61;0&#46;032&#59; CR&#61;1&#46;333&#59; IC del 95&#37;&#61;1&#46;025&#8211;1&#46;734&#41; fueron variables pron&#243;sticas independientes de la supervivencia en el an&#225;lisis multivariante&#46; Las tasas de supervivencia acumulativas de los pacientes con EPOC se clasificaron desde las peores hasta las mejores del modo siguiente&#58; concentraci&#243;n s&#233;rica de PCR&#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l y cuartil 3&#8211;4&#59; concentraci&#243;n s&#233;rica de PCR&#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l y cuartil 1&#8211;2&#59; concentraci&#243;n s&#233;rica de PCR &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l y cuartil 3&#8211;4&#59; concentraci&#243;n s&#233;rica de PCR &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l y cuartil 1&#8211;2 &#40;<span class="elsevierStyleItalic">P</span>&#60;0&#44;001&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La concentraci&#243;n s&#233;rica de PCR y la puntuaci&#243;n BODE son variables pron&#243;sticas independientes de la supervivencia en pacientes con EPOC estable&#46; La combinaci&#243;n de la concentraci&#243;n s&#233;rica de PCR y la puntuaci&#243;n BODE posee el mayor valor predictivo en la pr&#225;ctica cl&#237;nica&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Liu S-F&#44; et al&#46; Alto valor de la combinaci&#243;n de la concentraci&#243;n s&#233;rica de prote&#237;na C reactiva y la puntuaci&#243;n BODE para la predicci&#243;n de la mortalidad en pacientes con EPOC estable&#46; Arch Bronconeumol&#46; 2011&#59;47&#58;427&#8211;32&#46;</p>"
      ]
    ]
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        "etiqueta" => "Fig&#46; 1"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">In clinically stable COPD patients whose serum CRP concentration was &#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l&#44; there was a lower accumulative survival rate than in those with levels &#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;003&#41;&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">In patients with clinically stable COPD with BODE scores in quartile 3&#8211;4&#44; there was a lower accumulative survival rate than in those with a score in quartile 1&#8211;2 &#40;<span class="elsevierStyleItalic">P</span>&#61;&#46;02&#41;&#46;</p>"
        ]
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The accumulative survival rates of the patients with COPD were classified from the worst to the best in the following manner&#58; serum CRP concentration&#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration&#62;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2&#59; serum CRP concentration&#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 3&#8211;4&#59; serum CRP concentration&#8804;3<span class="elsevierStyleHsp" style=""></span>mg&#47;l and quartile 1&#8211;2 &#40;<span class="elsevierStyleItalic">P</span>&#60;&#46;001&#41;&#46;</p>"
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        "identificador" => "tbl0005"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">FVC&#44; forced vital capacity&#59; FEV<span class="elsevierStyleInf">1</span>&#44; maximum expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s&#59; COPD&#44; chronic obstructive pulmonary disease&#59; BODE&#44; body mass index&#44; degree of airflow obstruction&#44; functional dyspnea and exercise capacity&#59; MMRC&#44; modified Medical Research Council dyspnea scale&#59; 6MWT&#44; 6-mi