Ciro Casanova

Harvard Medical School, Boston, Massachusetts, United States

Are you Ciro Casanova?

Claim your profile

Publications (63)311.16 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The modified Medical Research Council (mMRC) dyspnea, the Chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) have been interchangeably proposed by the GOLD initiative for assessing symptoms in COPD patients. However, there are no data on the prognostic value of these tools in terms of mortality. To evaluate the prognostic value of the CAT and CCQ scores and compare with modified Medical Research Council (mMRC) dyspnea. We analyzed the ability of these tests to predict mortality in an observational cohort of 768 COPD patients (82% males; FEV1 60%) from the CHAIN study, a multicenter observational Spanish cohort who were monitored annually for a mean follow-up time of 38 months. Subjects who died (n=73; 9.5%) had higher CAT (14 vs. 11, p=0.022), CCQ (1.6 vs. 1.3, p=0.033), and mMRC dyspnea scores (2 vs. 1, p<0.001) than survivors. Receiver operating characteristic analysis showed that higher CAT, CCQ, and dyspnea scores were associated with higher mortality (area under the curve: 0.589, 0.588, and 0.649, respectively). CAT scores ≥17 and CCQ scores >2.5 provided a similar sensitivity than mMRC dyspnea scores ≥2 to predict all-cause mortality. The CAT and the CCQ have similar ability for predicting all-cause mortality in patients with chronic obstructive pulmonary disease, but were inferior to mMRC dyspnea scores. We suggest new thresholds for CAT and CCQ scores based on mortality risk that could be useful for the new GOLD grading classification. ClinicalTrials.gov Identifier: NCT01122758.
    Chest 01/2015; · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Indications for inhaled corticosteroids (IC) in combination with long-acting bronchodilators (LABD) are well defined in clinical practice guidelines. However, there are some doubts about their efficacy and safety. The aim of this document is to establish an expert consensus to clarify these issues. A coordinator group was formed, which systematically reviewed the scientific evidence with the aim of identifying areas of uncertainty about the efficacy of ICs, the adverse effects associated with their use and criteria for withdrawal. Their proposals were submitted to a panel of experts and the Delphi technique was used to test the level of consensus. Twenty-five experts participated in the panel, and consensus was reached on the use of IC in the mixed chronic obstructive pulmonary disease (COPD)-asthma phenotype and in frequent exacerbators, and on not using IC in association with LABD for improving lung function in COPD. There was no general consensus on restricting the use of IC to prevent adverse effects. The panel did agree that IC withdrawal is feasible but should be undertaken gradually, and patients who have discontinued must be evaluated in the short term. Consensus was reached regarding the indication of IC in mixed COPD-asthma and frequent exacerbator phenotypes. The potential for adverse effects must be taken into consideration, but there is no consensus on whether limiting use is justified. The withdrawal of ICs was uniformly agreed to be feasible. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.
    Archivos de bronconeumologia. 12/2014;
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim We analyzed the genome of individuals presenting extreme phenotypes of sensitivity and resistance to develop tobacco induced NSCLC to identify SNPs associated with these phenotypes. For this purpose, we used one of the most powerful GWAS platforms available. We hypothesized that SNPs may modulate individual susceptibility to carcinogens and that selection of extreme phenotypes would enrich the frequencies of alleles that contribute to the trait, thus increasing the power to identify them. Methods From an identification cohort (n=3631) we selected caucasian heavy smokers that either developed NSCLC at an early age (cancer-cohort) or that did not present NSCLC at an advanced age (cancer-free cohort). We analyzed their genomic DNA using the array Illumina HumanOmni 2.5 Quad that includes over 2 million powerful markers selected from the 1000 Genomes Project, targeting genetic variation down to 1% minor allele frequency. Statistical significance of SNPs was calculated using logistic regression and Fisher´s test. Results 96 patients (48 per cohort) were selected. Mean age for the cancer and cancer-free cohorts was 49 years (range 38-55) and 76 years (72-84). Mean tobacco consumption was 41 pack-years (range 18-99) and 68 pack-years (40-120). GWAS identified 8 SNPs differentially expressed by logistic regression and 54 SNP by Fisher´s test (p<10-5). Odds-ratio ranged between 0.08-0.29 for protective SNPs and 3.4-11.2 for SNPs that increased NSCLC risk. Candidate SNPs were located within or in adjacent regions of genes that have been previously related with cancer and that constitute potentially relevant targets (table 1): Function, Gene and Position - Oncogenes: MSX2 rs17064225 SOX11 rs6727285 - Tumor supressors: CSMD1 rs13253703 FOXF1 rs8055638 - Tobacco induced NSCLC: ABCB5 rs10281505, rs78057207, rs2390348 - Regulators of transcription: DROSHA rs17405280 HDAC9 rs13232564, rs2240419, rs10246722 KIAA0947 rs2913366 - Regulators of inflammation: PellinoE3 rs1189107, rs1300661 TRIM9 rs4375571 - Related with cancer ABHD6 rs7640259 GRIK1 rs465835 RAB40B rs2306911 SCN1A rs1020852 SLC24A2 rs4977304, rs4391516 SLC25A26 rs28544143 ZFYVE26 rs2235967 Conclusions We identified candidate SNPs associated with the risk of developing tobacco-induced NSCLC in individuals with extreme phenotypes. Several identified SNPs were located within or near genes that constitute potentially relevant targets for modulation of cancer risk. Validation of the most significant SNPs in an independent set of individuals with similar phenotypes, selected from the EPIC-Spain project (www.epic-spain.com, n=40,000) is ongoing.
    ESMO 2014 Congress, Abstract 1576P (poster presentation) http://www.poster-submission.com/search/sresult, Madrid; 09/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim We analyzed the genome of individuals presenting extreme phenotypes of sensitivity and resistance to develop tobacco induced NSCLC to identify SNPs associated with these phenotypes. For this purpose, we used one of the most powerful GWAS platforms available. We hypothesized that SNPs may modulate individual susceptibility to carcinogens and that selection of extreme phenotypes would enrich the frequencies of alleles that contribute to the trait, thus increasing the power to identify them. Methods From an identification cohort (n=3631) we selected caucasian heavy smokers that either developed NSCLC at an early age (cancer-cohort) or that did not present NSCLC at an advanced age (cancer-free cohort). We analyzed their genomic DNA using the array Illumina HumanOmni 2.5 Quad that includes over 2 million powerful markers selected from the 1000 Genomes Project, targeting genetic variation down to 1% minor allele frequency. Statistical significance of SNPs was calculated using logistic regression and Fisher´s test. Results 96 patients (48 per cohort) were selected. Mean age for the cancer and cancer-free cohorts was 49 years (range 38-55) and 76 years (72-84). Mean tobacco consumption was 41 pack-years (range 18-99) and 68 pack-years (40-120). GWAS identified 8 SNPs differentially expressed by logistic regression and 54 SNP by Fisher´s test (p<10-5). Odds-ratio ranged between 0.08-0.29 for protective SNPs and 3.4-11.2 for SNPs that increased NSCLC risk. Candidate SNPs were located within or in adjacent regions of genes that have been previously related with cancer and that constitute potentially relevant targets (table 1): Function Gene Position Oncogenes MSX2 rs17064225 SOX11 rs6727285 Tumor supressors CSMD1 rs13253703 FOXF1 rs8055638 Tobacco induced NSCLC ABCB5 rs10281505, rs78057207, rs2390348 Regulators of transcription DROSHA rs17405280 HDAC9 rs13232564, rs2240419, rs10246722 KIAA0947 rs2913366 Regulators of inflammation PellinoE3 rs1189107, rs1300661 TRIM9 rs4375571 Related with cancer ABHD6 rs7640259 GRIK1 rs465835 RAB40B rs2306911 SCN1A rs1020852 SLC24A2 rs4977304, rs4391516 SLC25A26 rs28544143 ZFYVE26 rs2235967 Conclusions We identified candidate SNPs associated with the risk of developing tobacco-induced NSCLC in individuals with extreme phenotypes. Several identified SNPs were located within or near genes that constitute potentially relevant targets for modulation of cancer risk. Validation of the most significant SNPs in an independent set of individuals with similar phenotypes, selected from the EPIC-Spain project (www.epic-spain.com, n=40,000) is ongoing.
    ESMO 2014 Congress, Abstract 1576P (poster presentation), Madrid; 09/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Global Obstructive Lung Disease (GOLD) 2011 revision recommends the multidimensional assessment of COPD including comorbidities and has developed a disease categories system (ABCD) attempting to implement this strategy. The added value provided by quantifying comorbidities and integrating them to multidimensional indices has not been explored.
    Thorax 06/2014; · 8.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and objective: COPD is a leading cause of dead worldwide and tobacco smoking is its major risk factor. IL8 is a proinflammatory chemokine mainly involved in the acute inflammatory reaction. The aim of this study was to test the association of IL-8, CXCR1 and CXCR2 gene variants and COPD susceptibility as part of a replication study and explore the effect of these variations in disease progression. Methods: 9 tagSNPs were genotyped in 728 Caucasian individuals (196 COPD patients, 80 smokers and 452 non-smoking controls). Pulmonary compromise was evaluated using spirometry and clinical parameters at baseline and annually over a 2 years period. We also determined plasma levels of TNF-α, IL-6, IL-8 and IL-16 in COPD patients. Results: There was a lack of association between gene variants or haplotypes with predisposition to COPD. No correlation was observed between the polymorphisms and cytokines levels. Interestingly, significant associations were found between carriers of the rs4073A (OR = 3.53, CI 1.34-9.35, p = 0.01), rs2227306C (OR = 5.65, CI 1.75–18.88, p = 0.004) and rs2227307T (OR = 4.52, CI = 1.49–12.82, p = 0.007) alleles in the IL-8 gene and patients who scored higher in the BODE index and showed an important decrease in their FEV1 and FVC during the 2 years follow-up period (p < 0.05). Conclusions: Despite no association was found between the studied genes and COPD susceptibility, three polymorphisms in the IL-8 gene appear to be involved in a worse progression of the disease, with an affectation beyond the pulmonary function and importantly, a reduction in lung function along the follow-up years.
    COPD Journal of Chronic Obstructive Pulmonary Disease 06/2014; 12(1). · 2.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic obstructive pulmonary disease (COPD), although frequent in older individuals, can also occur at younger age; this latter population has not been well described.We reviewed the functional progression of 1708 patients with COPD attending pulmonary clinics. Those with three or more annual spirometries were divided into those who, at enrolment, were ≤55 (n = 103) or ≥65 (n = 463) years of age (younger and older COPD, respectively). Baseline and annual changes in lung function (forced expiratory volume in 1 s (FEV1)) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) score were recorded and compared between both groups.Severity distribution by Global Initiative for Chronic Obstructive Lung Disease and BODE scores were similar in both groups, except for mild obstruction, which was higher in the younger group. Mean FEV1 decline was 38.8 and 40.6 mL·year(-1), while BODE scores increased 0.19 and 0.23 units per year, for younger and older COPD, respectively. Both groups had similar proportion of FEV1 rapid decliners (42% and 46%, respectively).The severity distribution and progression of disease in younger patients with COPD is similar to that of patients of older age. This observation suggests that younger individuals presenting with COPD develop the disease from an already compromised pulmonary and systemic status, complementing the model of steeper decline of lung function proposed by Fletcher and Peto.
    European Respiratory Journal 04/2014; · 7.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: FEV1 is universally used as a measure of severity in COPD. Current thresholds are based on expert opinion and not on evidence. We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients. We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS). Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival. A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%). Overall 975 (28.1%) patients died at 5 years. The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56-69%, severe 36-55%, and very severe ≤35%. Survival at 5 years was 0.89 for patients with FEV1≥70 vs. 0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69-7.74). The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001). Prognostic reliability is maintained at 1, 3, 5, and 10 years. In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear. The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56-69%, 36-55%, and ≤35%. These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs.
    PLoS ONE 02/2014; 9(2):e89866. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT RATIONALE: The Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was proposed for assessing health status in COPD, but little is known about its longitudinal changes. OBJECTIVE: To evaluate one-year CAT variability in stable COPD patients and relate its variations to changes in other disease markers. METHODS: We evaluated the following variables in smokers with and without COPD at baseline and after one year: CAT score, age, gender, smoking status, pack-years history, BMI, modified Medical Research Council (MMRC) scale, 6MWD, lung function, BODE index, hospital admissions, Hospital and Depression Questionnaire, and the Charlson comorbidity score. In COPD patients we explored the association of CAT scores and its one-year changes with the studied parameters. RESULTS: 824 smokers with COPD and 126 without were evaluated at baseline, and 441 smokers with COPD and 66 without one year later. At 1 year, CAT scores for COPD patients were similar (±4 points) in 56%, higher in 27%, and lower in 17%. Interestingly, MMRC scores were similar (± 1 point) in 46% of patients, worse in 36% and better in 18% at 1 year. One-year CAT changes were best predicted by changes in MMRC scores (β coefficient 0.47, p<0.001). A similar behavior was found for CAT and MMRC in smokers without COPD. CONCLUSIONS: One-year longitudinal data shows variability in CAT scores among stable COPD patients, similar to what happened to MMRC that was the best predictor of one-year CAT changes. Further longitudinal studies should confirm the long-term CAT variability and it clinical applicability.
    Chest 02/2014; · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rationale: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index.
    Respiratory research 01/2014; 15(1):3. · 3.38 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The value and timing of multidimensional assessments in COPD remains unclear because there is little information about their variability and relationship to outcome.Determine progression of COPD using clinical and spirometric variability over time with mortality as the outcome.We determined the annual intra-individual variability of the FEV1 and the BODE index in 403 patients with at least 5 measurements. The pattern was defined as "stable" if the annual change remained constant in at least 66% of the observations and "unstable" if it did not meet that threshold. We explored the minimal number of yearly observations that related to mortality in the 704 patients of the cohort.The "unstable" pattern of FEV1 was seen in53% of patients using a threshold of 40 mL·yr(-1) and 40% for 100 mL·yr(-1). There was a slightly more "stable" pattern in the BODE index (62% for 1 unit). One baseline and yearly for 2 years BODE measurements but not its individual components including the FEV1 defined a profile associated with mortality (p<0.001).The progression of COPD using the FEV1 is inconsistent and relates poorly to outcome. Monitoring the more stable BODE index better helps assess disease progression.
    European Respiratory Journal 09/2013; · 7.13 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: COPD is an independent risk factor for lung cancer, especially in patients with mild to moderate disease. OBJECTIVE: To determine if performing lung cancer screening in GOLD 1 and 2 COPD patients, results in reduced lung cancer mortality. METHODS: This study compared patients with mild to moderate COPD from 2 cohorts matched for age, gender, BMI, FEV1%, pack-yrs history and smoking status. The screening group (SG) had an annual low dose computed tomography (LDCT). The control group (CG) was prospectively followed with usual care. Lung cancer incidence and mortality densities were compared between groups. RESULTS: From an initial sample of 410 (SG) and 735 (CG) patients we were able to match 333 patients from each group. At the same follow-up time lung cancer incidence density was 1.79/100 person-years in the SG and 4.14/100 person-years in the CG (p = 0.004). The most frequent histological type was adenocarcinoma in both SG and CG (65% and 46%, respectively), followed by squamous cell carcinoma (25% and 37%, respectively). Eighty percent of lung cancers in the SG (16/20) were diagnosed in stage I, and all of CG cancers (35/35) were in stage III or IV. Mortality incidence density from lung cancer (0.08 vs. 2.48/100 person-years, p < 0.001) was lower in the SG. CONCLUSIONS: This pilot study in patients with mild to moderate COPD suggests that screening with LDCT detects lung cancer in early stages, and could decrease lung cancer mortality in that high risk group. Appropriately designed studies should confirm these important findings.
    Respiratory medicine 02/2013; · 2.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Guidelines recommend to define COPD by airflow obstruction and other factors, but no studies evaluated the ability of existing multicomponent indices to predict mortality up to 10 years.We conducted a patient-based pooled analysis. Survival analysis and C-statistics were used to determine the best COPD index/indices according to several construct variables and by varying time points. Individual data of 3,633 patients from eleven COPD cohorts were collected, totalling the experience of 15,878 person-years.Overall, there were 1,245 death events within our cohorts, with a K-M survival of 0.963 at 6-months, down to 0.432 at 10 years. In all patients, ADO, BODE and e-BODE were the best indices to predict 6-months mortality. The ADO index was the best to predict 12-month mortality (C-statistic 0.702), 5-yr mortality (C-statistic 0.695), and 10-yr mortality (C-statistic 0.698), significantly better than BODE (all p<0.05). The best indices to predict death by C-statistics when adjusting by age were eBODE, BODEx, and BODE.No index predicts well short-term survival. All BODE modifications score better than ADO after age adjustment.. The ADO and BODE indices are overall the most valid multicomponent indices to predict time to death in all COPD patients.
    European Respiratory Journal 12/2012; · 7.13 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionThis present paper describes the method and the organization of the study known as the COPD History Assessment In SpaiN (CHAIN), whose main objective is to evaluate the long-term natural history of a chronic obstructive pulmonary disease (COPD) patient cohort from a multidimensional standpoint and to identify clinical phenotypes, in comparison with another non-COPD control cohort.Patients and methodsCHAIN is a multicenter, observational study of prospective cohorts carried out at 36 Spanish hospitals. Both cohorts will be followed-up during a 5-year study period with complete office visits every 12 months and telephone interviews every 6 months in order to evaluate exacerbations and the vital state of the subjects. The recruitment period for cases was between 15 January 2010 and 31 March 2012. At each annual visit, information will be collected on: (i) clinical aspects (socio-economic situation, anthropometric data, comorbidities, smoking, respiratory symptoms, exacerbations, quality of life, anxiety-depression scale, daily life activities, treatments); (ii) respiratory function (spirometry, blood gases, hyperinflation, diffusion, respiratory pressures); (iii) BODE index (main study variable); (iv) peripheral muscle function, and (v) blood work-up (including IgE and cardiovascular risk factors). In addition, a serum bank will be created for the future determination of biomarkers. The data of the patients are anonymized in a database with a hierarchical access control in order to guarantee secure information access. The CHAIN study will provide information about the progression of COPD and it will establish a network of researchers for future projects related with COPD.
    Archivos de Bronconeumología 12/2012; 48(12):453–459. · 2.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IntroductionThis present paper describes the method and the organization of the study known as the COPD History Assessment In SpaiN (CHAIN), whose main objective is to evaluate the long-term natural history of a chronic obstructive pulmonary disease (COPD) patient cohort from a multidimensional standpoint and to identify clinical phenotypes, in comparison with another non-COPD control cohort.Patients and methodsCHAIN is a multicenter, observational study of prospective cohorts carried out at 36 Spanish hospitals. Both cohorts will be followed-up during a 5-year study period with complete office visits every 12 months and telephone interviews every 6 months in order to evaluate exacerbations and the vital state of the subjects. The recruitment period for cases was between 15 January 2010 and 31 March 2012. At each annual visit, information will be collected on: (i) clinical aspects (socio-economic situation, anthropometric data, comorbidities, smoking, respiratory symptoms, exacerbations, quality of life, anxiety-depression scale, daily life activities, treatments); (ii) respiratory function (spirometry, blood gases, hyperinflation, diffusion, respiratory pressures); (iii) BODE index (main study variable); (iv) peripheral muscle function, and (v) blood work-up (including IgE and cardiovascular risk factors). In addition, a serum bank will be created for the future determination of biomarkers. The data of the patients are anonymized in a database with a hierarchical access control in order to guarantee secure information access. The CHAIN study will provide information about the progression of COPD and it will establish a network of researchers for future projects related with COPD.ResumenIntroducciónEl presente trabajo describe el método y la organización del trabajo del estudio COPD History Assessment in SpaiN (CHAIN), cuyo objetivo principal es evaluar a largo plazo la historia natural de una cohorte de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) desde un punto de vista multidimensional y la identificación de fenotipos clínicos comparándola con otra cohorte control sin EPOC.Pacientes y métodoCHAIN es un estudio observacional multicéntrico de cohortes prospectivas realizado en 36 hospitales españoles. Ambas cohortes se seguirán durante un periodo de 5 años con visitas completas cada 12 meses y controles telefónicos cada 6 meses para valorar las exacerbaciones y el estado vital del sujeto. El periodo de reclutamiento de casos se realizó entre el 15 de enero de 2010 y el 31 de marzo de 2012. En cada visita anual se recoge información sobre: (a) aspectos clínicos (situación socioeconómica, datos antropométricos, comorbilidades, tabaquismo, clínica respiratoria, exacerbaciones, calidad de vida, escala ansiedad-depresión, actividades de la vida diaria, tratamientos); (b) función respiratoria (espirometría, gasometría arterial, hiperinsuflación, difusión, presiones respiratorias); (c) índice BODE (variable principal del estudio); (d) función muscular periférica, y (e) analítica sanguínea (incluida IgE y factores de riesgo cardiovascular). Además, se creará una seroteca para la futura determinación de biomarcadores. Los datos de los pacientes son anonimizados en una base de datos con un acceso jerárquico para garantizar la seguridad en los accesos a la información. El estudio CHAIN aportará información sobre la progresión de la EPOC y establecerá una red de investigadores para futuros proyectos relacionados con la enfermedad.
    Archivos de Bronconeumología 12/2012; 48(12):453–459. · 2.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT BACKGROUND: The new GOLD update includes airflow limitation, history of COPD exacerbations and symptoms to classify and grade COPD severity. We aimed to determine their distribution in eleven, well defined COPD cohorts, and their prognostic validity up to 10 years to predict time to death. METHODS: Spirometry in all eleven cohors was post-bronchodilator. Survival analysis and C-statistics were used to compare the two GOLD systems by varying time points. RESULTS: Of 3,633 patients, 1,064 (33.6%) were in new GOLD patient group A (low risk, less symptoms); 515 (16.3%) were B (low risk, more symptoms); 561 (17.7%) were C (high risk, less symptoms); and 1,023 (32.3%) were D (high risk, more symptoms). There was great heterogeneity of this distribution within the cohorts (Chi2 p value < 0.01). No differences were seen in the C statistics of old versus new GOLD grading to predict mortality at one year (0.635 vs. 0.639, p=0.53, at three years (0.637 vs. 0.645, p=0.21) or at 10 years (0.639 vs. 0.642, p=0.76). CONCLUSIONS: The new GOLD grading produces an uneven split of the COPD population, one third each in A and D patient groups, and its prognostic validity to predict time to death is no different than the old GOLD staging based in spirometry only.1Fundación Caubet-Cimera Illes Balears, Bunyola, Spain; 2Hospital Universitario Valme, Sevilla; 3Internal Medicine, Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona; 4Hospital Nuestra Señora de la Candelaria, Tenerife; 5Hospital Galdakao-Usansolo, Galdakao, Bizkaia 6Unidad de Neumología, Servicio de Medicina Interna, Hospital General de Requena, Valencia; 7Clınica Universidad de Navarra, Pamplona; 8CAIBER, Oficina de Investigación Biosanitaria de Asturias, Oviedo; 9Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; 10Harvard University, Brigham and Women's Hospital, Pulmonary and Critical Care Medicine, Boston, MA, USA; 11Hospital Universitario Miguel Servet, Zaragoza, SpainAuthor for correspondence: Dr. Joan B Soriano Director, Program of Epidemiology & Clinical Research CIMERA. Recinte Hospital Joan March, Carretera Soller Km 12. 07110 - Bunyola, Illes Balears; Spain Email: jbsoriano@caubet-cimera.esFINANCIAL DISCLOSURE INFORMATION: No funding was required/available for COCOMICS.
    Chest 09/2012; · 7.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair. METHODS: We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF alpha) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot]. RESULTS: Levels of the inflammatory markers IL-6, TNF alpha were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05). CONCLUSIONS: In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.
    Respiratory research 08/2012; 13(1):71. · 3.38 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • American Journal of Respiratory and Critical Care Medicine 05/2012; 185(10):1128-1129. · 11.99 Impact Factor

Publication Stats

3k Citations
311.16 Total Impact Points

Institutions

  • 2012
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2005–2012
    • Hospital Universitario Nuestra Señora de Candelaria
      Cancelaria, Canary Islands, Spain
  • 2011
    • Universidad de Navarra
      Iruña, Navarre, Spain
    • Clínica Universidad de Navarra
      Madrid, Madrid, Spain
  • 2008
    • Aragon Health Sciences Institute
      Caesaraugusta, Aragon, Spain
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
  • 2007
    • Universidad de La Laguna
      San Cristóbal de La Laguna, Canary Islands, Spain
  • 2000
    • Hospital Universitario de Canarias
      San Cristóbal de La Laguna, Canary Islands, Spain