Marin, J.M. (José M.)
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- Metallomic signatures of lung cancer and chronic obstructive pulmonary disease(2023) Santana, R. (Rafael); Gotera-Rivera, C. (Carolina); Marin, J.M. (José M.); Sánchez-Espirilla, S. (Saida); García-Cosio, B. (Borja); Díaz-Olivares, I. (Isabel); Callejón-Leblic, B. (Belén); Fuster, A. (Antonia); Solanes-García, I. (Ingrid); Casanova-Macario, C. (Ciro)Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.
- Sex differences in mortality in patients with COPD(European Respiratory Society, 2009) Oca, M.M. (M.M.) de; Nekach, V. (V.); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Cote, C.G. (C.G.); Marin, J.M. (José M.); Torres, J.P. (Juan P.) de; Aguirre-Jaime, A. (Armando); Lopez, M.V. (M.V.); Diaz, O. (O.); Pinto-Plata, V. (Víctor); Dordelly, L.J. (L. J.)Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George’s Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan–Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second.
- Long term management of obstructive sleep apnea and its comorbidities(PAGEPress Publications, 2019) Marín-Oto, M. (Marta); Marin, J.M. (José M.); Vicente, E.E. (Eugenio E.)Obstructive sleep apnea (OSA) is a worldwide highly prevalent disease associated with systemic consequences, including excessive sleepiness, impairment of neurocognitive function and daytime performance, including driving ability. The long-term sequelae of OSA include and increase risk for cardiovascular, cerebrovascular and metabolic syndrome disorders that ultimately lead to premature death if untreated. To ensure optimal long-term outcomes, the assessment and management of OSA should be personalized with the involvement of the appropriate specialist. Most studies have demonstrated inmediate improvement in daytime somnolence and quality of life with CPAP and other therapies, but the effect of long-term treatment on mortality is still under debate. Currently, the long-term management of OSA should be based on a) identifying physiological or structural abnormalities that are treatable at the time of patient evaluation and b) comprehensive lifestyle interventions, especially weight-loss interventions, which are associated with improvements in OSA severity, cardiometabolic comorbidities, and quality of life. In long-term management, attention should be paid to the clinical changes related to a potential reoccurrence of OSA symptoms and it is also necessary to monitor throughout the follow up how the main associated comorbidities evolve.
- Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data(European respiratory society, 2020) Sobradillo, P. (Patricia); Sternberg, A. (Alice); Esteban, C. (Cristóbal); Navarro, A. (Annie); Cosio, B.G. (Borja G.); Johannessen, A. (Ane); García-Castillo, E. (Elena); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Han, M.K. (Meilan K.); Burgel, P.R.(Pierre-Régis); Soler-Cataluña, J.J. (Juan José); Ramírez-García-Luna, A.S. (Ana S.); Lamprecht, B. (Bernd); Turner, A.M. (Alice M.); Ancochea-Bermúdez, J. (Julio); García-Aymerich, J. (Judith); Marin, J.M. (José M.); Langhammer, A. (Arnulf); Oga, T. (Toru); Almagro, P. (Pere); Torres, J.P. (Juan P.) de; Soriano, J.B. (Joan B.); Carrasco, L. (Laura); Bakke, P. (Per); Alonso-Pérez, T. (Tamara); Roche, N. (Nicolás); Aalberg-Vikjord, S.A. (Sigrid Ana); Martinez-Camblor, P. (Pablo); Leivseth, L. (Linda); Miravitlles, M. (Marc); Pastor-Sanz, M.T. (Maria Teresa); Antó, J.M. (Josep M.); Lange, P. (Peter); Echazarreta, A. (Andrés); Puhan, M.A. (Milo A.); Kaiser, B. (Bernhard); Lopez-Campos, J.L. (José Luis); Alfageme, I. (Inmaculada); Sin, D.D. (Don D.); Rodríguez-Carballeira, M. (Mónica); Riet, G. (Gerben) terIn 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A–4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66–0.68) for GOLD 2015 and 0.65 (95% CI 0.63–0.66) for GOLD 2019.
- Forkhead Box P3 Methylation and Expression in Men with Obstructive Sleep Apnea(2020) Martin-Burriel, I. (Inmaculada); Marín-Oto, M. (Marta); Marin, J.M. (José M.); Sanz-Rubio, D. (David); Cubero, P. (Pablo); Bolea, R. (Rosa); Sanz, A. (Arianne); Forner, M. (Marta); Varona, L. (Luis); Gil, A.V. (Ana V.)Background: Epigenetic changes in obstructive sleep apnea (OSA) have been proposed as a mechanism for end-organ vulnerability. In children with OSA, Forkhead Box P3 (FOXP3) DNA methylation were associated with inflammatory biomarkers; however, the methylation pattern and its effect in the expression of this gene have not been tested in adults with OSA. Methods: Plasma samples from subjects without comorbid conditions other than OSA were analyzed (the Epigenetics Status and Subclinical Atherosclerosis in Obstructive Sleep Apnea (EPIOSA) Study: NCT02131610). In 16 patients with severe OSA (Apnea-Hypopnea Index—AHI- > 30 events/h) and seven matched controls (AHI < 5), methylation of FOXP3 gen was evaluated by PCR of the promoter and by pyrosequencing of the intron 1 Treg-specific demethylated region (TSDR). In another 74 patients with OSA (AHI > 10) and 31 controls, we quantified FOXP3 protein expression by ELISA and gene expression by quantitative real-time PCR. C-reactive protein (CRP) and plasma Treg cells were also evaluated. Results: Neither the levels of the promoter nor the TSDR demethylated region were different between controls and patients with OSA, whether they were grouped by normal or high CRP. FOXP3 protein and mRNA expression did not differ between groups. Conclusions: FOXP3 methylation or its expression is not altered in adults with OSA, whatever their inflammatory status.
- New GOLD classification: longitudinal data on group assignment(BioMed Central, 2014) Ramos, P. (Pilar); Galdiz, J.B. (Juan Bautista); Cosio, B.G. (Borja G.); Martinez-Gonzalez, C. (Cristina); Casanova, C. (Ciro); Soler-Cataluña, J.J. (Juan José); Agüero, R. (Ramón); Marin, J.M. (José M.); Calle-Rubio, M. (Miryam); Marin, M. (Margarita); Torres, J.P. (Juan P.) de; Irigaray, R. (Rosa); Soriano, J.B. (Joan B.); Diego-Damia, A. (Alfredo) de; Solanes-García, I. (Ingrid); Feu-Collado, N. (Nuria); Balcells, E. (Eva); Llunell, A. (Antonia); Lopez-Campos, J.L. (José Luis); Alfageme, I. (Inmaculada); Mir-Viladrich, I. (Isabel); Peces-Barba, G. (German)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.
- Clinical and prognostic impact of low diffusing capacity for carbon monoxide values in patients with global initiative for obstructive lung disease I COPD(2021) Cabrera, C. (Carlos); Cosio, B.G. (Borja G.); Martinez-Gonzalez, C. (Cristina); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Marin, J.M. (José M.); Gonzalez-Gutierrez, J. (Jessica); Torres, J.P. (Juan P.) de; Fuster, A. (Antonia); Ezponda, A. (Ana); Solanes-García, I. (Ingrid); Marin-Marin, M. (Marta); O'Donnell, D.E. (Denis E.); Neder, J.A. (J. Alberto)Background The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored. Research Question Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients? Study Design and Methods GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years’ history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality. Results A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) Interpretation In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined.
- Impact of applying the global lung initiative criteria for airway obstruction in GOLD defined COPD cohorts: the BODE and CHAIN experience(2024) Cabrera, C. (Carlos); Cosio, B.G. (Borja G.); Bastarrika, G. (Gorka); Celli, B.R. (Bartolomé R.); Gotera-Rivera, C. (Carolina); Casanova, C. (Ciro); Sangro, M. (Matilde); Marin, J.M. (José M.); Torres, J.P. (Juan P.) de; Fuster, A. (Antonia); Alcaide, A.B. (Ana Belén); Ezponda, A. (Ana); Solanes-García, I. (Ingrid); Feu-Collado, N. (Nuria); Marin-Marin, M. (Marta); Martínez, C. (Cristina); Calle, M. (Myriam); Marin, A. (Alicia); Peces-Barba, G. (German)Introduction: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. Methods: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. Results: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality - 33% and 22% respectively. Conclusions: An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice.
- Large-scale external validation and comparison of prognostic models: an application to chronic obstructive pulmonary disease(2018) Sobradillo, P. (Patricia); Haile, S.R. (Sara R.); Esteban, C. (Cristóbal); 3CIA collaboration; Cosio, B.G. (Borja G.); Johannessen, A. (Ane); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Han, M.K. (Meilan K.); Ramirez, A.S. (Ana S.); Burgel, P.R.(Pierre-Régis); Soler-Cataluña, J.J. (Juan José); Lamprecht, B. (Bernd); Turner, A.M. (Alice M.); Ancochea-Bermúdez, J. (Julio); García-Aymerich, J. (Judith); Marin, J.M. (José M.); Langhammer, A. (Arnulf); Oga, T. (Toru); Almagro, P. (Pere); Torres, J.P. (Juan P.) de; Soriano, J.B. (Joan B.); Bakke, P. (Per); Guerra, B. (Beniamino); Roche, N. (Nicolás); Martinez-Camblor, P. (Pablo); Leivseth, L. (Linda); Miravitlles, M. (Marc); Antó, J.M. (Josep M.); Lange, P. (Peter); Echazarreta, A. (Andrés); Puhan, M.A. (Milo A.); Kaiser, B. (Bernhard); Alfageme, I. (Inmaculada); Sin, D.D. (Don D.); Riet, G. (Gerben) terBackground: External validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD. Methods: We relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores. Results: Depending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile-3rd quartile = 0.655-0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUC(ADO) - AUC(BODE) = 0.015 [95% confidence interval (CI) = - 0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUCBODE updated - AUCBODE = 0.008 [95% CI = -0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency. Conclusions: Our analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research.
- Psoas muscle density evaluated by chest CT and long-term mortality in COPD patients(2021) Cabrera, C. (Carlos); Bastarrika, G. (Gorka); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Divo, M. (Miguel); Martin-Palmero, A. (Ángela); Marín-Oto, M. (Marta); Marin, J.M. (José M.); Torres, J.P. (Juan P.) de; Ezponda, A. (Ana); Pinto-Plata, V. (Víctor); Zulueta, J. (Javier)Rationale: Poor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality. Methods: At baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65 ± 8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48–119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality. Results: PsD was lower in COPD patients than in controls (40.5 vs 42.5, p = 0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV1%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02–1.12, p = 0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94–0.99, p = 0.023) were the variables independently associated with all-cause mortality. Conclusions: In COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.