Casanova, C. (Ciro)
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- Somatotypes trajectories during adulthood and their association with COPD phenotypes(European Respiratory Society, 2020) Bastarrika, G. (Gorka); Hersh, C.P. (Craig P.); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Divo, M. (Miguel); Silverman, E. (Edwin); Marín-Oto, M. (Marta); DeMeo, D. (Dawn); Polverino, F. (Francesca); Torres, J.P. (Juan P.) de; Maguire, C. (Cherie); Ezponda, A. (Ana); Cabrera-Lopez, C. (Carlos); Pinto-Plata, V. (Víctor); Marin-Trigo, J.M. (Jose Maria); Ross, J.C. (James C.)Rationale: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation. Objectives: We hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood follow different trajectories to reach distinct phenotypes. Methods: Using the validated Stunkard’s Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory. Measurements and main results: At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2 ) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m−2 ). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and DLCO (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1), DLCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype. Conclusions: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD.
- 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.
- Role of HIF1A, VEGFA and VEGFR2 SNPs in the susceptibility and progression of COPD in a spanish population(2016) Casanova, C. (Ciro); Espizona-Jiménez, A. (Adriana); Almeida-González, D. (Delia); Baz-Dávila, R. (Rebeca); Cordoba-Lanus, E. (Elizabeth); Montejo, Á. (Ángela); Aguirre-Jaime, A. (Armando); Rodríguez-Pérez, M.C. (María C.); Zulueta, J. (Javier); Varo-Cenarruzabeitia, M.N. (Miren Nerea)Hypoxia is involved in the development of chronic inflammatory processes. Under hypoxic conditions HIF1A, VEGF and VEGFR2 are expressed and mediate the course of the resultant disease. The aim of the present study was to define the associations between tSNPs in these genes and COPD susceptibility and progression in a Spanish cohort. The T alleles in rs3025020 and rs833070 SNPs (VEGFA gene) were less frequent in the group of COPD cases and were associated with a lower risk of developing the disease (OR = 0.60; 95% CI = 0. 39-0.93; p = 0.023 and OR = 0.60; 95% CI = 0.38-0.96; p = 0.034, respectively) under a dominant model of inheritance. The haplotype in which both SNPs presented the T allele confirmed the association found (OR = 0.02; 95% CI = 0.00 to 0.66; p = 0.03). Moreover, patients with COPD carrying the T allele in homozygosis in rs3025020 SNP showed higher lung function values and this association remained constant during 3 years of follow-up. In conclusion, T allele in rs833070 and rs3025020 may confer a protective effect to COPD susceptibility in a Spanish population and the association of the SNP rs3025020 with lung function may be suggesting a role for VEGF in the progression of the disease.
- 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.
- 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.
- Natural course of the diffusing capacity of the lungs for carbon monoxide in COPD: importance of sex(2021) Cabrera, C. (Carlos); Cosio, B.G. (Borja G.); Martinez-Gonzalez, C. (Cristina); Celli, B.R. (Bartolomé R.); Casanova, C. (Ciro); Divo, M. (Miguel); Marín-Oto, M. (Marta); Marin, J.M. (José M.); Ojeda, E. (Elena); Torres, J.P. (Juan P.) de; Fuster, A. (Antonia); Solanes-García, I. (Ingrid); Feu-Collado, N. (Nuria); Balcells, E. (Eva); González-Dávila, E. (Enrique); Pinto-Plata, V. (Víctor); Golpe, R. (Rafael); Amado, C. (Carlos); Calle, M. (Myriam); Lopez-Campos, J.L. (José Luis); Peces-Barba, G. (German)Background: The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression. Research question: What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression? Study design and methods: We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time. Results: The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039). Interpretation: Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function. Trial registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.
- EPOC en la mujer(Elsevier, 2010) Casanova, C. (Ciro); Torres, J.P. (Juan P.) deThe prevalence of chronic obstructive pulmonary disease (COPD) is increasing worldwide, mainly due to the increase in women. In developed countries, COPD in women is mainly a result of exposure to tobacco smoke and in developing countries to inhalation of biomass combustion products. Underdiagnosis of COPD is more common in women since this disease has classically been associated with men. Moreover, COPD in women shows certain differential features, such as a greater expression of aspects related to perception (dyspnea and health-related quality of life), a high prevalence of malnutrition, anxiety and depression, and a distinct distribution of emphysema from that in men. Better phenotypical characterization of COPD in women would allow its impact on the health system to be more accurately evaluated and more individualized therapeutic strategies to be designed
- 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.
- 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.
- Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer(2018) Pajares, M.J. (María José); Gil-Bazo, I. (Ignacio); Patiño-García, A. (Ana); Pio, R. (Rubén); Lozano, M.D. (María Dolores); Alonso, R. (Rosario); Casanova, C. (Ciro); Perez-Gracia, J.L. (Jose Luis); Benitez, J. (Javier); Rodriguez-Ruiz, M.E. (María Esperanza); Agudo, A. (Antonio); Baz-Dávila, R. (Rebeca); Bou-i-Sala, N. (Núria); Lopez-Picazo, J.M. (José M.); Fusco, J.P. (Juan Pablo); Torres, J.P. (Juan P.) de; Gurpide, A. (Alfonso); Andueza, M.P. (Maria P.); Montuenga-Badia, L.M. (Luis M.); Melero, I. (Ignacio); Ardanaz, E. (Eva); González, Á. (Álvaro); Gonzalez-Neira, A. (Anna); Alvarez, N. (Nuria); Fernandez-Sanmamed, M. (Miguel); Zulueta, J. (Javier); Pita, G. (Guillermo)Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC.