Juan P de Torres | Universidad de Navarra (original) (raw)

Papers by Juan P de Torres

Research paper thumbnail of Development and validation of a new comorbidity index for patients with head and neck squamous cell carcinoma in Japan

Scientific Reports, 2017

Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck s... more Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck squamous cell carcinoma (HNSCC) frequently present with comorbidities. Several comorbidity indices have been developed and validated for HNSCC. However, none have become the standard method. In this study, we developed a new comorbidity index for Japanese patients with HNSCC, which was validated against an independent data set. A Cox proportional hazards analysis of 698 patients identified dementia, connective tissue diseases, and second primary malignancies in the oesophagus, head and neck, lungs, and stomach as prognostic comorbidities for overall survival. The Osaka head and neck comorbidity index (OHNCI) was generated from the weighted points of these comorbidities. In the independent data set, the 5-year overall survival rates for the low, moderate, and high scoring OHNCI groups were 62.1%, 64.3%, and 37.7%, respectively. In the multivariate analysis, the high scoring OHNCI group was...

Research paper thumbnail of Distribution and Prognostic Validity of the New Global Initiative for Chronic Obstructive Lung Disease Grading Classification

Chest, 2013

The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) update includes airflow lim... more The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) update includes airflow limitation, history of COPD exacerbations, and symptoms to classify and grade COPD severity. We aimed to determine their distribution in 11 well-defined COPD cohorts and their prognostic validity up to 10 years to predict time to death. Spirometry in all 11 cohorts was postbronchodilator. Survival analysis and C statistics were used to compare the two GOLD systems by varying time points. 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 ( x (2) , P < .01). No differences were seen in the C statistics of old vs new GOLD grading to predict mortality at 1 year (0.635 vs 0.639, P = .53), at 3 years (0.637 vs 0.645, P = .21), or at 10 years (0.639 vs 0.642, P = .76). 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.

Research paper thumbnail of Changes and clinical consequences of smoking cessation in COPD patients: a prospective analysis from the CHAIN cohort

Chest, Jan 21, 2018

Despite the existing evidence-based smoking cessation interventions, chances of achieving that go... more Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real-life are still low among COPD patients. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of COPD patients. CHAIN is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses. One thousand and eighty-one COPD patients were included (80.8% males, 65.2 (SD 8.9) years of age, FEV60.2 (20.5)%). During the two-year follow-up time (visit 2: 906 patients; visit 3...

Research paper thumbnail of Identification of clinical phenotypes in patients with and without COPD using cluster analysis

European Respiratory Journal, 2016

COPD is an heterogeneous disease better characterized by multidimensional phenotyping. Clustering... more COPD is an heterogeneous disease better characterized by multidimensional phenotyping. Clustering is a technique used to identify discrete subgroups with similar combinations of traits. Except for pulmonary function variables, many other characteristics (6MWT, BMI, QOL) are not unique to COPD. Aim: To compare how discrete clusters form in a mixed cohort of 120 individuals with COPD and controls. Methods: Hundred and twenty patients matched by age and gender were selected, 90 with COPD of which 60 died at 3 years of follow-up. Hierarchical clustering was applied using pulmonary function, functional, anthropometric and QOL variables. Clusters were compared against a selected reference. Results: Four clusters were identified and their composition is shown in A. Cluster 4 composed with 84% controls was used as reference and the comparison and descriptions are shown in B. Conclusion: Clustering is a useful tool to discriminate clinical meaningful phenotypes and by including “controls” we showed that >10% were assigned in COPD predominant clusters. This could be important when designing exploratory studies.

Research paper thumbnail of Six-Minute Walking Distance in Women with COPD

COPD: Journal of Chronic Obstructive Pulmonary Disease, 2011

The 6-minute walk distance (6MWD) has been useful in the evaluation of men with COPD. Little is k... more The 6-minute walk distance (6MWD) has been useful in the evaluation of men with COPD. Little is known about 6MWD in women with the disease. Using healthy women as a reference, to evaluate the factors that help determine 6MWD in women with COPD. To explore if the 350 meters threshold differentiates survival in women as it does in men. Healthy women (n = 164) and with COPD (n = 223) were included in the study. Age, pack-years history, smoking status, comorbidities (Charlson Index), BMI, MRC dyspnea, spirometry and 6MWD were recorded in all participants and PaO(2) and IC/TLC in COPD women. The patients were prospectively followed and deaths registered. Factors predicting 6MWD were determined by multiple regression analysis. ROC analysis was used to calculate the best threshold value for the 6MWD with mortality as gold standard. Kaplan-Meier curves compared survival of patients that walked more or less than 350 m by age categories. The 6MWD is decreased in women with COPD. Values decrease with age and GOLD stages. Age, BMI, smoking status, comorbidities, MRC and FEV(1%) are statistical significant predictors of 6MWD. A 350 m cut-off value has a good sensitivity and specificity to predict (73% and 80% respectively) and differentiate survival (p…

Research paper thumbnail of IL-8Gene Variants are Associated with Lung Function Decline and Multidimensional BODE Index in COPD Patients But Not with Disease Susceptibility: A Validation Study

COPD: Journal of Chronic Obstructive Pulmonary Disease, 2014

COPD is a leading cause of dead worldwide and tobacco smoking is its major risk factor. IL8 is a ... more 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. 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. 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). 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.

Research paper thumbnail of Distance and Oxygen Desaturation During the 6-min Walk Test as Predictors of Long-term Mortality in Patients With COPD

Research paper thumbnail of Power of Outcome Measurements to Detect Clinically Significant Changes in Pulmonary Rehabilitation of Patients With COPD

Research paper thumbnail of Exploring the association betwen active hormonal life and the presence of emphysema/airway obstruction in female smokers

Research paper thumbnail of Comorbidities and mortality risk in adults younger than 50 years of age with chronic obstructive pulmonary disease

Respiratory Research

Rationale and objective Patients with chronic obstructive pulmonary disease (COPD), usually diagn... more Rationale and objective Patients with chronic obstructive pulmonary disease (COPD), usually diagnosed after the 6th decade, frequently suffer from comorbidities. Whether COPD patients 50 years or younger (Young COPD) have similar comorbidities with the same frequency and mortality impact as aged-matched controls or older COPD patients is unknown. Methods We compared comorbidity number, prevalence and type in 3 groups of individuals with ≥ 10 pack-years of smoking: A Young (≤ 50 years) COPD group (n = 160), an age-balanced control group without airflow obstruction (n = 125), and Old (> 50 years) COPD group (n = 1860). We also compared survival between the young COPD and control subjects. Using Cox proportional model, we determined the comorbidities associated with mortality risk and generated Comorbidomes for the “Young” and “Old” COPD groups. Results The severity distribution by GOLD spirometric stages and BODE quartiles were similar between Young and Old COPD groups. After adjus...

Research paper thumbnail of A Delphi Consensus Document on the Use of Single-Inhaler Fixed-Dose Triple Therapies in COPD Patients

International Journal of Chronic Obstructive Pulmonary Disease, 2020

Research paper thumbnail of Similar Programmed Death Ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer

Rationale: Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance... more Rationale: Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear.Methods: In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: 1) via cutting-edge digital spatial proteomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n=19); and 2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract.Results: PD-L1 expression was increased in the bronchiolar wall,...

Research paper thumbnail of Exercise Tolerance according to the Definition of Airflow Obstruction in Smokers

American Journal of Respiratory and Critical Care Medicine, 2020

Research paper thumbnail of Lung cancer screening: how do we make it better?

Quantitative Imaging in Medicine and Surgery, 2020

Research paper thumbnail of External Validation and Recalculation of the CODEX Index in COPD Patients. A 3CIAplus Cohort Study

COPD: Journal of Chronic Obstructive Pulmonary Disease, 2019

Research paper thumbnail of The Global Burden of Pulmonary Diseases: Most Prevalent Problems and Opportunities for Improvement

Annals of Global Health, 2019

Research paper thumbnail of A simple algorithm for the identification of clinical COPD phenotypes

The European respiratory journal, Nov 1, 2017

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (C... more This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses.Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative.Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respirato...

Research paper thumbnail of Bone attenuation on chest computed tomography correlates with bone mineral density on densitometry in patients with emphysema and COPD

1.12 Clinical Problems - COPD, 2016

Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk o... more Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis. In these patients, the relationship between osteoporosis measured by bone density in chest computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) is not well established. Objectives: To determine the association between the bone mineral density (BMD) measured in the first lumbar vertebra (L1) of a low dose chest CT (LDCT) with the one measured in a bone DXA. We also aim at exploring the possible association of this measurement with the severity of radiological emphysema. Methods: 43 COPD patients with emphysema were evaluated. In a LDCT we determined BMD in the central part of L1 body. DXA was in all patients. The quantification of emphysema in CT was performed using a specific software (Volume, Siemens Healthcar) considering 3 different thresholds: -900, -950 and -960 Hounsfield Units (HU), and the emphysema index (EI) was calculated. Spearman correlation coefficient was used for the statistical analysis. Results: The correlation between the BMD in L1 by CT and the lumbar spine (L1-L4) density by DXA was 0.40 (p Conclusions: There is a weak correlation between BMD measured in CT and DXA. In the same way, there is a weak inverse correlation between IE and BMD determined by CT. Further studies are needed to establish the relationship between these two diseases processes.

Research paper thumbnail of Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?

Multidisciplinary Respiratory Medicine, 2016

Research paper thumbnail of Efectos inmunomoduladores del glatirámero acetato y su potencial papel en la reactivación de la tuberculosis pulmonar

Archivos de Bronconeumología, 2015

Glatiramer acetate (GA) is a synthetic copolymer-1 approved as first-line treatment for relapsing... more Glatiramer acetate (GA) is a synthetic copolymer-1 approved as first-line treatment for relapsing-remitting multiple sclerosis (RRMS). Several studies have indicated that GA modulates different levels of the immune response, but no specific warnings regarding its use and potential reactivation of latent tuberculosis (TB) infection exist.1 A 37-year-old man, engineer, active smoker (10 pack-years), with a 6-year history of RRMS but otherwise healthy, attended our pulmonary clinic reporting a 1-week history of productive cough, fever, left side pleuritic chest pain, and malaise. He had been taking daily subcutaneous GA since his RRMS diagnosis, but no other concomitant medication. Relevant past medical history included a 9-month course of isoniazid as primary chemoprophylaxis for TB 16 years previously, after a positive tuberculin skin test as part of a TB contact study. He denied any other subsequent known contacts or exposure to high-risk environments. His physical exam was normal and blood tests showed a mild elevation of acute phase reactants. A chest computed tomography revealed left upper lobe alveolar infiltrate and a 1.8 cm lung cavity. The sputum smear was positive for acid-fast bacilli and empiric 4-drug treatment was started. Sputum culture confirmed Mycobacterium tuberculosis and the patient recovered completely after 6 months of treatment. Peripheral immunomodulatory mechanisms of GA include: binding to major histocompatiblity class II molecules, alteration

Research paper thumbnail of Development and validation of a new comorbidity index for patients with head and neck squamous cell carcinoma in Japan

Scientific Reports, 2017

Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck s... more Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck squamous cell carcinoma (HNSCC) frequently present with comorbidities. Several comorbidity indices have been developed and validated for HNSCC. However, none have become the standard method. In this study, we developed a new comorbidity index for Japanese patients with HNSCC, which was validated against an independent data set. A Cox proportional hazards analysis of 698 patients identified dementia, connective tissue diseases, and second primary malignancies in the oesophagus, head and neck, lungs, and stomach as prognostic comorbidities for overall survival. The Osaka head and neck comorbidity index (OHNCI) was generated from the weighted points of these comorbidities. In the independent data set, the 5-year overall survival rates for the low, moderate, and high scoring OHNCI groups were 62.1%, 64.3%, and 37.7%, respectively. In the multivariate analysis, the high scoring OHNCI group was...

Research paper thumbnail of Distribution and Prognostic Validity of the New Global Initiative for Chronic Obstructive Lung Disease Grading Classification

Chest, 2013

The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) update includes airflow lim... more The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) update includes airflow limitation, history of COPD exacerbations, and symptoms to classify and grade COPD severity. We aimed to determine their distribution in 11 well-defined COPD cohorts and their prognostic validity up to 10 years to predict time to death. Spirometry in all 11 cohorts was postbronchodilator. Survival analysis and C statistics were used to compare the two GOLD systems by varying time points. 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 ( x (2) , P < .01). No differences were seen in the C statistics of old vs new GOLD grading to predict mortality at 1 year (0.635 vs 0.639, P = .53), at 3 years (0.637 vs 0.645, P = .21), or at 10 years (0.639 vs 0.642, P = .76). 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.

Research paper thumbnail of Changes and clinical consequences of smoking cessation in COPD patients: a prospective analysis from the CHAIN cohort

Chest, Jan 21, 2018

Despite the existing evidence-based smoking cessation interventions, chances of achieving that go... more Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real-life are still low among COPD patients. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of COPD patients. CHAIN is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses. One thousand and eighty-one COPD patients were included (80.8% males, 65.2 (SD 8.9) years of age, FEV60.2 (20.5)%). During the two-year follow-up time (visit 2: 906 patients; visit 3...

Research paper thumbnail of Identification of clinical phenotypes in patients with and without COPD using cluster analysis

European Respiratory Journal, 2016

COPD is an heterogeneous disease better characterized by multidimensional phenotyping. Clustering... more COPD is an heterogeneous disease better characterized by multidimensional phenotyping. Clustering is a technique used to identify discrete subgroups with similar combinations of traits. Except for pulmonary function variables, many other characteristics (6MWT, BMI, QOL) are not unique to COPD. Aim: To compare how discrete clusters form in a mixed cohort of 120 individuals with COPD and controls. Methods: Hundred and twenty patients matched by age and gender were selected, 90 with COPD of which 60 died at 3 years of follow-up. Hierarchical clustering was applied using pulmonary function, functional, anthropometric and QOL variables. Clusters were compared against a selected reference. Results: Four clusters were identified and their composition is shown in A. Cluster 4 composed with 84% controls was used as reference and the comparison and descriptions are shown in B. Conclusion: Clustering is a useful tool to discriminate clinical meaningful phenotypes and by including “controls” we showed that >10% were assigned in COPD predominant clusters. This could be important when designing exploratory studies.

Research paper thumbnail of Six-Minute Walking Distance in Women with COPD

COPD: Journal of Chronic Obstructive Pulmonary Disease, 2011

The 6-minute walk distance (6MWD) has been useful in the evaluation of men with COPD. Little is k... more The 6-minute walk distance (6MWD) has been useful in the evaluation of men with COPD. Little is known about 6MWD in women with the disease. Using healthy women as a reference, to evaluate the factors that help determine 6MWD in women with COPD. To explore if the 350 meters threshold differentiates survival in women as it does in men. Healthy women (n = 164) and with COPD (n = 223) were included in the study. Age, pack-years history, smoking status, comorbidities (Charlson Index), BMI, MRC dyspnea, spirometry and 6MWD were recorded in all participants and PaO(2) and IC/TLC in COPD women. The patients were prospectively followed and deaths registered. Factors predicting 6MWD were determined by multiple regression analysis. ROC analysis was used to calculate the best threshold value for the 6MWD with mortality as gold standard. Kaplan-Meier curves compared survival of patients that walked more or less than 350 m by age categories. The 6MWD is decreased in women with COPD. Values decrease with age and GOLD stages. Age, BMI, smoking status, comorbidities, MRC and FEV(1%) are statistical significant predictors of 6MWD. A 350 m cut-off value has a good sensitivity and specificity to predict (73% and 80% respectively) and differentiate survival (p…

Research paper thumbnail of IL-8Gene Variants are Associated with Lung Function Decline and Multidimensional BODE Index in COPD Patients But Not with Disease Susceptibility: A Validation Study

COPD: Journal of Chronic Obstructive Pulmonary Disease, 2014

COPD is a leading cause of dead worldwide and tobacco smoking is its major risk factor. IL8 is a ... more 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. 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. 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). 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.

Research paper thumbnail of Distance and Oxygen Desaturation During the 6-min Walk Test as Predictors of Long-term Mortality in Patients With COPD

Research paper thumbnail of Power of Outcome Measurements to Detect Clinically Significant Changes in Pulmonary Rehabilitation of Patients With COPD

Research paper thumbnail of Exploring the association betwen active hormonal life and the presence of emphysema/airway obstruction in female smokers

Research paper thumbnail of Comorbidities and mortality risk in adults younger than 50 years of age with chronic obstructive pulmonary disease

Respiratory Research

Rationale and objective Patients with chronic obstructive pulmonary disease (COPD), usually diagn... more Rationale and objective Patients with chronic obstructive pulmonary disease (COPD), usually diagnosed after the 6th decade, frequently suffer from comorbidities. Whether COPD patients 50 years or younger (Young COPD) have similar comorbidities with the same frequency and mortality impact as aged-matched controls or older COPD patients is unknown. Methods We compared comorbidity number, prevalence and type in 3 groups of individuals with ≥ 10 pack-years of smoking: A Young (≤ 50 years) COPD group (n = 160), an age-balanced control group without airflow obstruction (n = 125), and Old (> 50 years) COPD group (n = 1860). We also compared survival between the young COPD and control subjects. Using Cox proportional model, we determined the comorbidities associated with mortality risk and generated Comorbidomes for the “Young” and “Old” COPD groups. Results The severity distribution by GOLD spirometric stages and BODE quartiles were similar between Young and Old COPD groups. After adjus...

Research paper thumbnail of A Delphi Consensus Document on the Use of Single-Inhaler Fixed-Dose Triple Therapies in COPD Patients

International Journal of Chronic Obstructive Pulmonary Disease, 2020

Research paper thumbnail of Similar Programmed Death Ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer

Rationale: Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance... more Rationale: Programmed Death Ligand 1 (PD-L1) is crucial in regulating the immunological tolerance in non-small cell lung cancer (NSCLC). Alveolar macrophage (AM)-derived PD-L1 binds to its receptor, PD-1, on surveilling lymphocytes, leading to lymphocyte exhaustion. Increased PD-L1 expression is associated with cigarette smoke (CS)-exposure. However, the PD-L1 role in CS-associated lung diseases associated with NSCLC, such as chronic obstructive pulmonary disease (COPD), is still unclear.Methods: In two different cohorts of ever smokers with COPD or NSCLC, and ever and never smoker controls, we evaluated PD-L1 expression: 1) via cutting-edge digital spatial proteomic profiling (Geomx) of formalin-fixed paraffin-embedded (FFPE) lung tissue sections (n=19); and 2) via triple immunofluorescence staining of bronchoalveolar lavage (BAL) AMs (n = 83). PD-L1 mRNA expression was also quantified in BAL AMs exposed to CS extract.Results: PD-L1 expression was increased in the bronchiolar wall,...

Research paper thumbnail of Exercise Tolerance according to the Definition of Airflow Obstruction in Smokers

American Journal of Respiratory and Critical Care Medicine, 2020

Research paper thumbnail of Lung cancer screening: how do we make it better?

Quantitative Imaging in Medicine and Surgery, 2020

Research paper thumbnail of External Validation and Recalculation of the CODEX Index in COPD Patients. A 3CIAplus Cohort Study

COPD: Journal of Chronic Obstructive Pulmonary Disease, 2019

Research paper thumbnail of The Global Burden of Pulmonary Diseases: Most Prevalent Problems and Opportunities for Improvement

Annals of Global Health, 2019

Research paper thumbnail of A simple algorithm for the identification of clinical COPD phenotypes

The European respiratory journal, Nov 1, 2017

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (C... more This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses.Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative.Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respirato...

Research paper thumbnail of Bone attenuation on chest computed tomography correlates with bone mineral density on densitometry in patients with emphysema and COPD

1.12 Clinical Problems - COPD, 2016

Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk o... more Introduction: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis. In these patients, the relationship between osteoporosis measured by bone density in chest computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) is not well established. Objectives: To determine the association between the bone mineral density (BMD) measured in the first lumbar vertebra (L1) of a low dose chest CT (LDCT) with the one measured in a bone DXA. We also aim at exploring the possible association of this measurement with the severity of radiological emphysema. Methods: 43 COPD patients with emphysema were evaluated. In a LDCT we determined BMD in the central part of L1 body. DXA was in all patients. The quantification of emphysema in CT was performed using a specific software (Volume, Siemens Healthcar) considering 3 different thresholds: -900, -950 and -960 Hounsfield Units (HU), and the emphysema index (EI) was calculated. Spearman correlation coefficient was used for the statistical analysis. Results: The correlation between the BMD in L1 by CT and the lumbar spine (L1-L4) density by DXA was 0.40 (p Conclusions: There is a weak correlation between BMD measured in CT and DXA. In the same way, there is a weak inverse correlation between IE and BMD determined by CT. Further studies are needed to establish the relationship between these two diseases processes.

Research paper thumbnail of Increased expression of A Proliferation-inducing Ligand (APRIL) in lung leukocytes and alveolar epithelial cells in COPD patients with non small cell lung cancer: a possible link between COPD and lung cancer?

Multidisciplinary Respiratory Medicine, 2016

Research paper thumbnail of Efectos inmunomoduladores del glatirámero acetato y su potencial papel en la reactivación de la tuberculosis pulmonar

Archivos de Bronconeumología, 2015

Glatiramer acetate (GA) is a synthetic copolymer-1 approved as first-line treatment for relapsing... more Glatiramer acetate (GA) is a synthetic copolymer-1 approved as first-line treatment for relapsing-remitting multiple sclerosis (RRMS). Several studies have indicated that GA modulates different levels of the immune response, but no specific warnings regarding its use and potential reactivation of latent tuberculosis (TB) infection exist.1 A 37-year-old man, engineer, active smoker (10 pack-years), with a 6-year history of RRMS but otherwise healthy, attended our pulmonary clinic reporting a 1-week history of productive cough, fever, left side pleuritic chest pain, and malaise. He had been taking daily subcutaneous GA since his RRMS diagnosis, but no other concomitant medication. Relevant past medical history included a 9-month course of isoniazid as primary chemoprophylaxis for TB 16 years previously, after a positive tuberculin skin test as part of a TB contact study. He denied any other subsequent known contacts or exposure to high-risk environments. His physical exam was normal and blood tests showed a mild elevation of acute phase reactants. A chest computed tomography revealed left upper lobe alveolar infiltrate and a 1.8 cm lung cavity. The sputum smear was positive for acid-fast bacilli and empiric 4-drug treatment was started. Sputum culture confirmed Mycobacterium tuberculosis and the patient recovered completely after 6 months of treatment. Peripheral immunomodulatory mechanisms of GA include: binding to major histocompatiblity class II molecules, alteration