Javier Zulueta | Universidad de Navarra (original) (raw)

Papers by Javier Zulueta

Research paper thumbnail of Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe

Cancers, 2020

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the Nati... more Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and pr...

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Research paper thumbnail of Quantitative Estimation of Individual Lung Cancer Risk

PURPOSE To evaluate the performance of a new and quantitative method for estimating individual lu... more PURPOSE To evaluate the performance of a new and quantitative method for estimating individual lung cancer risk based on CT HU values at airway bifurcations and FEV1/FVC. METHOD AND MATERIALS 108 subjects with spirometry and thin slice CT (<= 1.25mm) data were selected from a CT screening study including 15 early lung cancers and 93 age and pack year matched controls. A subset of 7 cancer and 72 control cases were scanned with 1mm CT slice thickness, representing a high resolution case subset (HR). A quantitative lung cancer risk index (LCRI) method was developed based on airway bifurcation HU values combined with FEV1/FVC. Cochran-Mantel-Haenszel (CMH) and conditional logistic regression tests were used to analyze performance. RESULTS CMH crude analysis revealed a cancer detection sensitivity and specificity of 69% and 71% for all cases and 100% and 73% for the HR case subset, respectively. Conditional logistic regression showed that a 0.1 increase in LCRI was associated with an...

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Research paper thumbnail of Hot Topic: A Quantitative Method for Estimating Individual Lung Cancer Risk

PURPOSE To evaluate the performance of a novel method for estimating individual lung cancer risk ... more PURPOSE To evaluate the performance of a novel method for estimating individual lung cancer risk based on the combined measurement of CT calcification density at airway bifurcations and FEV1/FVC. METHOD AND MATERIALS Thirteen early lung cancer patients were selected from a CT screening study based on the availability of low dose, whole lung CT data with <= 1.25mm slice thickness and good image quality. 91 cancer-free control subjects were also selected with these criteria plus the requirement that each subject’s age was within +/-10 years and pack years was within +/-10 years of a cancer case. 7/13 (54%) cancer positive and 70/91 (77%) cancer negative scans were performed with 1.0mm slice thickness. 2 cancer cases and 14 control cases were female. Siemens scanners and the B60f reconstruction kernel were used, except for 2 control cases that used the B80f kernel. Pulmonary function tests were administered at CT scan time according to ATS spirometry guidelines. A quantitative metho...

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Research paper thumbnail of PD-055 CT screening for lung cancer: Staging of multiple lung cancerswithout other evidence of metastases

Lung Cancer, 2005

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Research paper thumbnail of O-046 CT Screening for lung cancer: The relationship of disease stageto tumor size

Lung Cancer, 2005

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Research paper thumbnail of A Quantitative Method for Estimating Individual Lung Cancer Risk

Academic Radiology, 2010

Lung cancer is caused primarily by repeated exposure to carcinogenic particulate matter and noxio... more Lung cancer is caused primarily by repeated exposure to carcinogenic particulate matter and noxious gasses with high particulate deposition localized to airway bifurcations and the lung periphery. The quantitative measurement and analysis of these sites has the potential to stratify lung cancer risk. The aim of this preliminary study was to assess the performance of a new method for estimating individual lung cancer risk based on the analysis of airway bifurcations on high-resolution (HR) computed tomographic (CT) scanning and spirometry. One hundred eight subjects with spirometry and thin-slice CT data were selected from a CT screening study including 15 patients with early lung cancer and 93 age-matched and pack-year-matched controls. A subset of seven patients with cancer and 72 controls were scanned with 1-mm CT slice thickness, representing an HR case subset. A quantitative lung cancer risk index method was developed on the basis of airway bifurcation x-ray attenuation combined with the ratio of forced expiratory volume in 1 second to forced vital capacity. Cochran-Mantel-Haenszel and conditional logistic regression tests were used to analyze performance. Cochran-Mantel-Haenszel crude analysis revealed a cancer detection sensitivity and specificity of 67% and 72% for all cases and 100% and 73% for the HR case subset, respectively. Conditional logistic regression showed that a 0.0328 increase in lung cancer risk index was associated with odds ratios of 1.84 (95% confidence interval, 1.18-2.85) for the full data set (P = .0067) and 2.89 (95% confidence interval, 1.02-8.19) for the HR subset (P = .0467). A preliminary evaluation of a new lung cancer risk estimation method based on thin slice CT and spirometry showed a statistically significant association with lung cancer.

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Research paper thumbnail of Pulmonary arterial enlargement predicts long-term survival in COPD patients

PloS one, 2018

Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmon... more Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers. In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival. During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the mul...

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Research paper thumbnail of A novel protein-based prognostic signature improves risk stratification to guide clinical management in early lung adenocarcinoma patients

The Journal of pathology, Jan 13, 2018

Each of the pathological stages (I-IIIa) in which surgically resected non-small cell lung cancer ... more Each of the pathological stages (I-IIIa) in which surgically resected non-small cell lung cancer patients are classified conceals hidden biological heterogeneity, manifested in heterogeneous outcomes within each stage. Thus, the finding of robust and precise molecular classifiers to assess individual patient risk is an unmet medical need. Here we identified and validated the clinical utility of a new prognostic signature based on three proteins (BRCA1, QKI and SLC2A1) to stratify early lung adenocarcinoma patients according to their risk of recurrence or death. Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (8 edition, 2018). A test cohort (n=239) was used to assess the value of this new prognostic index (PI) based on the three proteins. The prognostic signature was developed by Cox regression following stringent statistical criteria (TRIPOD: Transparent reporting of a multivariable prediction model for individu...

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Research paper thumbnail of Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Cancer medicine, Jan 15, 2018

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We ... more 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 = 5.66 × 10 ; OR = 2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p = 1.02 × 10 ; OR = 2.57), an intronic v...

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Research paper thumbnail of Complement C4d-specific antibodies for the diagnosis of lung cancer

Oncotarget, Jan 19, 2018

Development of molecular markers that help to identify high-risk individuals or diagnose indeterm... more Development of molecular markers that help to identify high-risk individuals or diagnose indeterminate pulmonary nodules could have a major impact on lung cancer clinical management. In this study, we evaluated the diagnostic potential of a newly-developed ELISA that specifically detects complement C4d. We measured this marker in five independent cohorts of plasma and bronchoalveolar lavage samples from lung cancer patients and controls. In case-control studies, the area under the ROC curve for the diagnosis of lung cancer was 0.82 (95%CI = 0.72-0.92) in plasma samples, and 0.80 (95%CI = 0.69 to 0.90) in bronchoalveolar lavage fluids. In a set of plasma samples from the MILD CT-screening trial, the assay was unable to discriminate between asymptomatic high-risk individuals with or without early stage lung cancer. On the contrary, in two independent cohorts of individuals with indeterminate pulmonary nodules, plasma samples from patients with lung cancer nodules presented higher leve...

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Research paper thumbnail of Telomere length, COPD and emphysema as risk factors for lung cancer

European Respiratory Journal, 2016

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Research paper thumbnail of Clinical Features of Smokers with Radiological Emphysema but without Airway Limitation

Chest, 2017

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Research paper thumbnail of Assessment of indeterminate pulmonary nodules detected in lung cancer screening: Diagnostic accuracy of FDG PET/CT

Lung Cancer, 2016

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Research paper thumbnail of Lung cancer screening in patients with chronic obstructive pulmonary disease

Annals of Translational Medicine, 2016

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Research paper thumbnail of Is COPD a Progressive Disease? A Long Term Bode Cohort Observation

PloS one, 2016

The Global Initiative for Obstructive Lung Diseases (GOLD) defines COPD as a disease that is usua... more The Global Initiative for Obstructive Lung Diseases (GOLD) defines COPD as a disease that is usually progressive. GOLD also provides a spirometric classification of airflow limitation. However, little is known about the long-term changes of patients in different GOLD grades. Explore the proportion and characteristics of COPD patients that change their spirometric GOLD grade over long-term follow-up. Patients alive for at least 8 years since recruitment and those who died with at least 4 years of repeated spirometric measurements were selected from the BODE cohort database. We purposely included the group of non survivors to avoid a "survival selection" bias. The proportion of patients that had a change (improvement or worsening) in their spirometric GOLD grading was calculated and their characteristics compared with those that remained in the same grade. A total of 318 patients were included in the survivor and 217 in the non-survivor groups. Nine percent of survivors and ...

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Research paper thumbnail of The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development

Lung Cancer, 2016

Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of... more Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of cancer diagnosis have been associated to poor prognosis in various cancers. There is no data on their natural progression before the cancer diagnosis has been established. We aim to evaluate whether or not the annual changes in these ratios could be early indicators of lung cancer development. Participants recruited into the Pamplona International Early Lung Cancer Action Program (P-IELCAP, n=3061) between 2001 and 2015 were considered. Complete blood counts (CBC) were registered at annual intervals between enrolment and time of diagnosis. Linear regression was used to calculate the mean annual change in NLR and PLR in participants with ≥3CBCs. Changes were expressed relative to baseline values. Lung cancer incidence density and lung cancer risk (Cox regression analysis) were calculated for different NLR and PLR annual thresholds (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0%, ≥0%, ≥1%, ≥2%, ≥4%). Results were compared to a matched group of participants who did not develop lung cancer. After a median follow-up of 80 months and a median of 4 (IQR 3-6) CBCs, subjects who developed lung cancer (n=32) showed greater NLR and PLR annual changes than matched controls (n=103) (2.56% vs. 0.27% [p=0.25] per year; and 3.75% vs. 0.33% [p=0.053] per year, respectively). Lung cancer incidence density per 100 person-years increased with higher annual NLR and PLR thresholds. On multivariable analysis (adjusting for emphysema and baseline lung-function), NLR and PLR were not significant lung cancer predictors. However, among individuals with emphysema, for each relative unit increase in PLR, lung cancer risk increased 5% (p=0.03). There was a significant supra-additive risk effect between PLR increase and emphysema. Annual NLR change was not a significant lung cancer predictor. In a lung cancer screening setting, the assessment of annual PLR change could help predict lung cancer development.

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Research paper thumbnail of Chronic obstructive pulmonary disease (COPD) as syndrome of accelerated aging

http://isrctn.org/>, 2013

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Research paper thumbnail of Massive acute gases intoxication: Clinical presentation and outcomes

On Oct 30th, 2008, a car bomb exploded on the University of Navarre (UN) campus, causing serious ... more On Oct 30th, 2008, a car bomb exploded on the University of Navarre (UN) campus, causing serious damages and several fires. On Nov 5th, during the repairing works, gases retained inside the false ceiling were released, causing intoxication by inhalation in about 300 people. A longitudinal observational study was performed to assess the presentation and outcomes of 230 patients assisted at the Emergency Room (ER) of the UN Hospital. Employees and students were affected: 104 men and 126 women, with mean age 31±12 y, 23% smokers and 13% with previous respiratory disease. 65% of patients got to the ER on Nov 5th. At the first 6 h commonest complaints were cough (80%), dyspnea (51%), sore throat (38%), and chest tightness (32%). People coming after 6 h had more frequently fever (31%), headache (30%), nausea (25%), asthenia (18%), dizziness (16%), and vomiting (7%). Chest xray (n=218) showed infiltrates in 17.5% and chest CT (n=19) interstitial/alveolar infiltrates in 68%. Blood analysis (n=101) revealed leukocytosis in 65%, and high CRP in 85%. 80 patients were hospitalised (34.8%) with a median length of stay of 1 day (max 5 d). At the ER, patients received bronchodilators (62%) and steroids (54%). Upon discharge, bronchodilators (82%), steroids (30%) and N-acetyl cysteine (82%) were prescribed. One month after discharge, 206 patients were re-evaluated: 41 (20%) had symptoms, consisting in dyspnea (12%) and cough (11%). Chest xray (n=162) was normal in all the cases. Chest CT (n=36) showed alveolar-interstitial infiltrates in 5 patients. Spirometry (n=193) was normal in all the cases. We describe the clinical features of an acute intoxication by unknown gases, with a biphasic presentation of symptoms and short clinical resolution.

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Research paper thumbnail of Emphysema, COPD and lung cancer screening. Update of an ongoing study

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Research paper thumbnail of Improving Selection Criteria for Lung Cancer Screening. The Potential Role of Emphysema

American Journal of Respiratory and Critical Care Medicine, 2015

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Research paper thumbnail of Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe

Cancers, 2020

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the Nati... more Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and pr...

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Research paper thumbnail of Quantitative Estimation of Individual Lung Cancer Risk

PURPOSE To evaluate the performance of a new and quantitative method for estimating individual lu... more PURPOSE To evaluate the performance of a new and quantitative method for estimating individual lung cancer risk based on CT HU values at airway bifurcations and FEV1/FVC. METHOD AND MATERIALS 108 subjects with spirometry and thin slice CT (<= 1.25mm) data were selected from a CT screening study including 15 early lung cancers and 93 age and pack year matched controls. A subset of 7 cancer and 72 control cases were scanned with 1mm CT slice thickness, representing a high resolution case subset (HR). A quantitative lung cancer risk index (LCRI) method was developed based on airway bifurcation HU values combined with FEV1/FVC. Cochran-Mantel-Haenszel (CMH) and conditional logistic regression tests were used to analyze performance. RESULTS CMH crude analysis revealed a cancer detection sensitivity and specificity of 69% and 71% for all cases and 100% and 73% for the HR case subset, respectively. Conditional logistic regression showed that a 0.1 increase in LCRI was associated with an...

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Research paper thumbnail of Hot Topic: A Quantitative Method for Estimating Individual Lung Cancer Risk

PURPOSE To evaluate the performance of a novel method for estimating individual lung cancer risk ... more PURPOSE To evaluate the performance of a novel method for estimating individual lung cancer risk based on the combined measurement of CT calcification density at airway bifurcations and FEV1/FVC. METHOD AND MATERIALS Thirteen early lung cancer patients were selected from a CT screening study based on the availability of low dose, whole lung CT data with <= 1.25mm slice thickness and good image quality. 91 cancer-free control subjects were also selected with these criteria plus the requirement that each subject’s age was within +/-10 years and pack years was within +/-10 years of a cancer case. 7/13 (54%) cancer positive and 70/91 (77%) cancer negative scans were performed with 1.0mm slice thickness. 2 cancer cases and 14 control cases were female. Siemens scanners and the B60f reconstruction kernel were used, except for 2 control cases that used the B80f kernel. Pulmonary function tests were administered at CT scan time according to ATS spirometry guidelines. A quantitative metho...

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Research paper thumbnail of PD-055 CT screening for lung cancer: Staging of multiple lung cancerswithout other evidence of metastases

Lung Cancer, 2005

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Research paper thumbnail of O-046 CT Screening for lung cancer: The relationship of disease stageto tumor size

Lung Cancer, 2005

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Research paper thumbnail of A Quantitative Method for Estimating Individual Lung Cancer Risk

Academic Radiology, 2010

Lung cancer is caused primarily by repeated exposure to carcinogenic particulate matter and noxio... more Lung cancer is caused primarily by repeated exposure to carcinogenic particulate matter and noxious gasses with high particulate deposition localized to airway bifurcations and the lung periphery. The quantitative measurement and analysis of these sites has the potential to stratify lung cancer risk. The aim of this preliminary study was to assess the performance of a new method for estimating individual lung cancer risk based on the analysis of airway bifurcations on high-resolution (HR) computed tomographic (CT) scanning and spirometry. One hundred eight subjects with spirometry and thin-slice CT data were selected from a CT screening study including 15 patients with early lung cancer and 93 age-matched and pack-year-matched controls. A subset of seven patients with cancer and 72 controls were scanned with 1-mm CT slice thickness, representing an HR case subset. A quantitative lung cancer risk index method was developed on the basis of airway bifurcation x-ray attenuation combined with the ratio of forced expiratory volume in 1 second to forced vital capacity. Cochran-Mantel-Haenszel and conditional logistic regression tests were used to analyze performance. Cochran-Mantel-Haenszel crude analysis revealed a cancer detection sensitivity and specificity of 67% and 72% for all cases and 100% and 73% for the HR case subset, respectively. Conditional logistic regression showed that a 0.0328 increase in lung cancer risk index was associated with odds ratios of 1.84 (95% confidence interval, 1.18-2.85) for the full data set (P = .0067) and 2.89 (95% confidence interval, 1.02-8.19) for the HR subset (P = .0467). A preliminary evaluation of a new lung cancer risk estimation method based on thin slice CT and spirometry showed a statistically significant association with lung cancer.

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Research paper thumbnail of Pulmonary arterial enlargement predicts long-term survival in COPD patients

PloS one, 2018

Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmon... more Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers. In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival. During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the mul...

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Research paper thumbnail of A novel protein-based prognostic signature improves risk stratification to guide clinical management in early lung adenocarcinoma patients

The Journal of pathology, Jan 13, 2018

Each of the pathological stages (I-IIIa) in which surgically resected non-small cell lung cancer ... more Each of the pathological stages (I-IIIa) in which surgically resected non-small cell lung cancer patients are classified conceals hidden biological heterogeneity, manifested in heterogeneous outcomes within each stage. Thus, the finding of robust and precise molecular classifiers to assess individual patient risk is an unmet medical need. Here we identified and validated the clinical utility of a new prognostic signature based on three proteins (BRCA1, QKI and SLC2A1) to stratify early lung adenocarcinoma patients according to their risk of recurrence or death. Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (8 edition, 2018). A test cohort (n=239) was used to assess the value of this new prognostic index (PI) based on the three proteins. The prognostic signature was developed by Cox regression following stringent statistical criteria (TRIPOD: Transparent reporting of a multivariable prediction model for individu...

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Research paper thumbnail of Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Cancer medicine, Jan 15, 2018

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We ... more 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 = 5.66 × 10 ; OR = 2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p = 1.02 × 10 ; OR = 2.57), an intronic v...

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Research paper thumbnail of Complement C4d-specific antibodies for the diagnosis of lung cancer

Oncotarget, Jan 19, 2018

Development of molecular markers that help to identify high-risk individuals or diagnose indeterm... more Development of molecular markers that help to identify high-risk individuals or diagnose indeterminate pulmonary nodules could have a major impact on lung cancer clinical management. In this study, we evaluated the diagnostic potential of a newly-developed ELISA that specifically detects complement C4d. We measured this marker in five independent cohorts of plasma and bronchoalveolar lavage samples from lung cancer patients and controls. In case-control studies, the area under the ROC curve for the diagnosis of lung cancer was 0.82 (95%CI = 0.72-0.92) in plasma samples, and 0.80 (95%CI = 0.69 to 0.90) in bronchoalveolar lavage fluids. In a set of plasma samples from the MILD CT-screening trial, the assay was unable to discriminate between asymptomatic high-risk individuals with or without early stage lung cancer. On the contrary, in two independent cohorts of individuals with indeterminate pulmonary nodules, plasma samples from patients with lung cancer nodules presented higher leve...

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Research paper thumbnail of Telomere length, COPD and emphysema as risk factors for lung cancer

European Respiratory Journal, 2016

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Clinical Features of Smokers with Radiological Emphysema but without Airway Limitation

Chest, 2017

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Assessment of indeterminate pulmonary nodules detected in lung cancer screening: Diagnostic accuracy of FDG PET/CT

Lung Cancer, 2016

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Research paper thumbnail of Lung cancer screening in patients with chronic obstructive pulmonary disease

Annals of Translational Medicine, 2016

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Research paper thumbnail of Is COPD a Progressive Disease? A Long Term Bode Cohort Observation

PloS one, 2016

The Global Initiative for Obstructive Lung Diseases (GOLD) defines COPD as a disease that is usua... more The Global Initiative for Obstructive Lung Diseases (GOLD) defines COPD as a disease that is usually progressive. GOLD also provides a spirometric classification of airflow limitation. However, little is known about the long-term changes of patients in different GOLD grades. Explore the proportion and characteristics of COPD patients that change their spirometric GOLD grade over long-term follow-up. Patients alive for at least 8 years since recruitment and those who died with at least 4 years of repeated spirometric measurements were selected from the BODE cohort database. We purposely included the group of non survivors to avoid a "survival selection" bias. The proportion of patients that had a change (improvement or worsening) in their spirometric GOLD grading was calculated and their characteristics compared with those that remained in the same grade. A total of 318 patients were included in the survivor and 217 in the non-survivor groups. Nine percent of survivors and ...

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Research paper thumbnail of The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development

Lung Cancer, 2016

Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of... more Elevated neutrophil-to-lymphocyte ratios (NLR) and platelet-to-lymphocyte ratios (PLR) at time of cancer diagnosis have been associated to poor prognosis in various cancers. There is no data on their natural progression before the cancer diagnosis has been established. We aim to evaluate whether or not the annual changes in these ratios could be early indicators of lung cancer development. Participants recruited into the Pamplona International Early Lung Cancer Action Program (P-IELCAP, n=3061) between 2001 and 2015 were considered. Complete blood counts (CBC) were registered at annual intervals between enrolment and time of diagnosis. Linear regression was used to calculate the mean annual change in NLR and PLR in participants with ≥3CBCs. Changes were expressed relative to baseline values. Lung cancer incidence density and lung cancer risk (Cox regression analysis) were calculated for different NLR and PLR annual thresholds (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0%, ≥0%, ≥1%, ≥2%, ≥4%). Results were compared to a matched group of participants who did not develop lung cancer. After a median follow-up of 80 months and a median of 4 (IQR 3-6) CBCs, subjects who developed lung cancer (n=32) showed greater NLR and PLR annual changes than matched controls (n=103) (2.56% vs. 0.27% [p=0.25] per year; and 3.75% vs. 0.33% [p=0.053] per year, respectively). Lung cancer incidence density per 100 person-years increased with higher annual NLR and PLR thresholds. On multivariable analysis (adjusting for emphysema and baseline lung-function), NLR and PLR were not significant lung cancer predictors. However, among individuals with emphysema, for each relative unit increase in PLR, lung cancer risk increased 5% (p=0.03). There was a significant supra-additive risk effect between PLR increase and emphysema. Annual NLR change was not a significant lung cancer predictor. In a lung cancer screening setting, the assessment of annual PLR change could help predict lung cancer development.

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Research paper thumbnail of Chronic obstructive pulmonary disease (COPD) as syndrome of accelerated aging

http://isrctn.org/>, 2013

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Research paper thumbnail of Massive acute gases intoxication: Clinical presentation and outcomes

On Oct 30th, 2008, a car bomb exploded on the University of Navarre (UN) campus, causing serious ... more On Oct 30th, 2008, a car bomb exploded on the University of Navarre (UN) campus, causing serious damages and several fires. On Nov 5th, during the repairing works, gases retained inside the false ceiling were released, causing intoxication by inhalation in about 300 people. A longitudinal observational study was performed to assess the presentation and outcomes of 230 patients assisted at the Emergency Room (ER) of the UN Hospital. Employees and students were affected: 104 men and 126 women, with mean age 31±12 y, 23% smokers and 13% with previous respiratory disease. 65% of patients got to the ER on Nov 5th. At the first 6 h commonest complaints were cough (80%), dyspnea (51%), sore throat (38%), and chest tightness (32%). People coming after 6 h had more frequently fever (31%), headache (30%), nausea (25%), asthenia (18%), dizziness (16%), and vomiting (7%). Chest xray (n=218) showed infiltrates in 17.5% and chest CT (n=19) interstitial/alveolar infiltrates in 68%. Blood analysis (n=101) revealed leukocytosis in 65%, and high CRP in 85%. 80 patients were hospitalised (34.8%) with a median length of stay of 1 day (max 5 d). At the ER, patients received bronchodilators (62%) and steroids (54%). Upon discharge, bronchodilators (82%), steroids (30%) and N-acetyl cysteine (82%) were prescribed. One month after discharge, 206 patients were re-evaluated: 41 (20%) had symptoms, consisting in dyspnea (12%) and cough (11%). Chest xray (n=162) was normal in all the cases. Chest CT (n=36) showed alveolar-interstitial infiltrates in 5 patients. Spirometry (n=193) was normal in all the cases. We describe the clinical features of an acute intoxication by unknown gases, with a biphasic presentation of symptoms and short clinical resolution.

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Research paper thumbnail of Emphysema, COPD and lung cancer screening. Update of an ongoing study

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Improving Selection Criteria for Lung Cancer Screening. The Potential Role of Emphysema

American Journal of Respiratory and Critical Care Medicine, 2015

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