Search

Dámaso Parrón Collar,1 Mario Pazos Guerra,1 Paula Rodriguez,1,2 Carolina Gotera,1,2 Ignacio Mahíllo-Fernández,2 Germán Peces-Barba,1,2 Luis M Seijo1,2 1Pulmonary Department, Universidad Autónoma de Madrid, 2Pulmonary Department, Instituto de Investigación Sanitaria, Fundación Jiménez Díaz, CIBERES, Madrid, Spain Introduction: Many patients with COPD are underdiagnosed, including patients with coexisting lung cancer. Methods: We conducted a retrospective study of COPD prevalence and outcomes among all patients diagnosed with lung cancer at our institution during a 2-year period. Patients with known COPD (group A) were compared with those who received a diagnosis of COPD at the time of their oncologic workup (group B). Results: A total of 306 patients were diagnosed with lung cancer during the study period, including 87 with COPD (28.6%). Sixty percent of patients with coexisting lung cancer and COPD were unaware of their obstructive airways disease prior to the lung cancer diagnosis. Patients in group A were older (74+9 vs 69+9 years; P=0.03), had more severe obstruction (% of predicted forced expiratory volume in one second [FEV1%] 55+17 vs 71+13; P=0.04), more emphysema (91% vs 65%; P=0.02), and worse diffusing capacity of the lungs for carbon monoxide 59+19% vs 72+22%; P=0.01) than patients in group B, but the latter had more advanced lung cancer (27.3% vs 13.8% stage IV disease; P=0.01) and consumed more outpatient resources (P=0.03). Overall mortality was similar (56% vs 58%). However, stage-adjusted mortality showed a trend toward greater mortality in group B patients (1.87 [0.91–3.85]; P=0.087). Conclusion: COPD infradiagnosis is common in patients with coexisting lung cancer and is associated with more advanced cancer stage, greater outpatient resource consumption, and may be associated with greater stage-adjusted mortality. Keywords: lung cancer, COPD, underdiagnosis, staging, survival

Luis M Seijo Pulmonary Department, Instituto de Investigación Sanitaria-Fundación Jimenez Díaz-Centro de Investigación Biomedica en Red Enfermedades Respiratorias, Madrid, Spain Abstract: Electromagnetic navigation bronchoscopy (ENB) is one of several technological advances which have broadened the indications for bronchoscopy in the diagnostic workup of lung cancer. The technique facilitates bronchoscopic sampling of peripheral pulmonary nodules as well as mediastinal lymph nodes, although wide availability and expertise in endobronchial ultrasonography has limited its application in routine clinical practice to the former. ENB in this setting is quite versatile and may be considered an established alternative to more invasive techniques, especially in selected patients with underlying pulmonary disease or comorbidities at high risk for complications from computer topography-guided fine needle aspiration or surgical resection. Nodule sampling may be performed with a variety of instruments, including forceps, cytology brushes, and transbronchial needles. Although samples are generally small, they are often suitable for molecular analysis. Keywords: lung cancer, ENB, electromagnetic navigation, bronchoscopy, diagnosis, pulmonary nodule

Background: Electromagnetic navigation bronchoscopy (ENB) has been developed as a novel ancillary tool for the bronchoscopic diagnosis of pulmonary nodules. Despite successful navigation in 90% of patients, ENB diagnostic yield does not generally exceed 70%. We sought to determine whether the presence of a bronchus sign on CT imaging conditions diagnostic yield of ENB and might account for the discrepancy between successful navigation and diagnostic yield.Methods: We conducted a prospective, single-center study of ENB in 51 consecutive patients with pulmonary nodules. ENB was chosen as the least invasive diagnostic technique in patients with a high surgical risk, suspected metastatic disease, or advanced-stage disease, or in those who demanded a preoperative diagnosis prior to undergoing curative resection. We studied patient and technical variables that might condition diagnostic yield, including size, cause, location, distance to the pleural surface, and fluorodeoxyglucose uptake of a given nodule; the presence of a bronchus sign on CT imaging; registration point divergence; and the minimum distance from the tip of the locatable guide to the nodule measured during the procedure.Results: The diagnostic yield of ENB was 67% (34/51). The sensitivity and specificity of ENB for malignancy in this study were 71% and 100%, respectively. ENB was diagnostic in 79% (30/38) patients with a bronchus sign on CT imaging but only in 4/13 (31%) with no discernible bronchus sign. Univariate analysis identified the bronchus sign (P = .005) and nodule size (P = .04) as statistically significant variables conditioning yield, but on multivariate analysis, only the bronchus sign remained significant (OR, 7.6; 95% CI, 1.8-31.7). No procedure-related complications were observed.Conclusions: ENB diagnostic yield is highly dependent on the presence of a bronchus sign on CT imaging. [ABSTRACT FROM AUTHOR]

Large-scale lung cancer screening implementation combined with improvements in early detection techniques for three major tobacco-related diseases presents a rare opportunity to markedly improve population health outcomes for millions of people. Chest CT enables routine detection of early lung cancer as well as characterizing coronary calcium and detecting early emphysema in the course of lung cancer screening. Integrated preventive care centered on comprehensive chest CT screening has the potential to bring large benefits across co-morbid diseases with a common etiology. The current one-disease/ silo paradigm of medical practice is an obstacle to maximizing chest CT screening's benefits. The large potential for improved health outcomes across the world demands careful public health, quality assurance, and health policy considerations. A systematic analysis of imaging and health data from ongoing chest CT screening could accelerate this paradigm shift through sustained optimization of screening detection, quantitation and management for the three most lethal tobacco-related co-morbidities. To coordinate this effort to advance progress with implementing the full benefit of comprehensive chest CT screening, a new multi- disciplinary professional and advocacy consortium has been developed to foster collaboration to realize the future of multi-disease chest CT screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper Use the above and set author query in the proof to confirm., (Copyright © 2025. Published by Elsevier Ltd.)

The identification of non-small cell lung cancer (NSCLC) patients who will benefit from immunotherapy remains a clinical challenge. Monitoring real-world data (RWD) in the first cycles of therapy may provide a more accurate representation of response patterns in a real-world setting. We propose a multivariate Bayesian joint model using generalized linear mixed effects, trained and validated on RWD from 424 advanced NSCLC patients retrospectively collected from three clinical centers. Center1 was used as training ( N = 212 ), while Center2 and Center3 were used as independent testing sets ( N = 137 and N = 75 , respectively). Peripheral blood data (PBD) were collected at baseline and at three follow-up time points, alongside demographic and epidemiologic features. Six models were trained to predict progression-free survival at 6 months, PFS(6), using different number of longitudinal samples (baseline, two, or four time points) of the neutrophil-to-lymphocyte ratio (NLR) or a multivariate feature selection. Long-term predictions at 12 and 24 months were also evaluated. Prediction accuracy was measured using the area under the receiver operating characteristic curve (AUC). The proposed model significantly improved prediction performance, achieving AUCs of 0.870, 0.804 and 0.827 at 6, 12 and 24 months for Center2, and 0.824, 0.822 and 0.667 for Center3. There was also a significant difference in PFS and overall survival (OS) between predicted response groups, defined by a 6-month PFS cutoff (log-rank test p < 0.001 ). Our study suggests that the integration of multiple biomarkers and monitored PBD in an RWD-based Bayesian joint model framework significantly improves immunotherapy response prediction in advanced NSCLC compared to conventional approaches involving biomarker data at baseline only., Competing Interests: Declarations. Conflict of interest: The authors ADRG, BF, JRP, and MJLC did not report any potential Conflict of interest. AVL declares contracts with AstraZeneca, speaker roles for Health in code, and participation in meetings with AstraZeneca, BMS, and Roche. JZ has served as a consultant for Sanofi, AstraZeneca, BMS, Roche, Pfizer, Novartis, and Guardant Health. He reports speakers’ honoraria from Janssen, Amgen, Sanofi, Takeda, BMS, Pfizer, Roche, Astra Zeneca, Diagnostica Longwood, and NanoString. He reports travel honoraria from Sanofi, Takeda, BMS, Pfizer, Roche, Astra Zeneca, and NanoString. He has received research support/funds from BMS, Astra Zeneca, and Roche. GPB declares grants from GSK, Chiesi, and Menarini, none of them related to the subject of the paper. LMS reports a role as scientific advisor for Sabartech, Serum, Astra Zeneca, Roche, MSD, and Median technologies, and paid honoraria as a speaker from Astra Zeneca, GSK, Roche, Menarini, and Chiesi. LPA declares grants/contracts from MSD, AstraZeneca, Pfizer, and BMS; consulting fees from Eli Lilly, MSD, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, and Daiichi Sankyo; and payment/honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Janssen, Merck, and Mirati. IGB declares advisory board/speaker roles for Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Roche, Johnson & Johnson, MSD, Pfizer, Regeneron, Sanofi, and Takeda. MDG declares consulting/advisory roles for AstraZeneca, Boehringer Ingelheim, Janssen, MSD, Pfizer, Roche, Sanofi, and Takeda; and speaker roles for AstraZeneca, BMS, MSD, Pfizer, Roche, and Takeda., (© 2025. The Author(s).)

Reduction in lung cancer mortality is achievable through low dose computed tomography (LDCT) screening in high-risk individuals. Many countries are progressing from local LDCT screening studies to national screening programs. Implementation of effective large-scale screening programs is complex and requires a multi-disciplinary approach. A recent overview of the technical aspects of implementing high quality LDCT for screening resulted from the inaugural international expert meeting of the Alliance for Global Implementation of Lung and Cardiac Early Disease Detection and Treatment (AGILE). This covers the most important aspects of the CT imaging process: standardisation in CT image acquisition and interpretation, CT protocol management, technology developments and minimal requirements, integration of lung cancer biomarkers, and the role of AI in CT lung nodule detection, segmentation, and classification, and related data security issues., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. M. Giger is contact PI for MIDRC and is on the editorial board for SPIE Journal of Medical Imaging. Dr. S. Fain serves as a scientific advisor for Polarean LLC. Dr. S. Fain also receives research funding from Polarean LLC, Siemens Healthineers INC, and GE Healthcare INC for development of pulmonary CT and MRI methods. Dr. K. Myers serves as a scientific and regulatory consultant for MIDRC, RevealDx, Annalise, and the I-ELCAP AIRS project funded by the Simons Foundation. All other authors have no competing interests to declare, (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lung cancer remains the leading cause of cancer-related deaths worldwide, mainly due to late diagnosis and the presence of metastases. Several countries around the world have adopted nation-wide LDCT-based lung cancer screening that will benefit patients, shifting the stage at diagnosis to earlier stages with more therapeutic options. Biomarkers can help to optimize the screening process, as well as refine the TNM stratification of lung cancer patients, providing information regarding prognostics and recommending management strategies. Moreover, novel adjuvant strategies will clearly benefit from previous knowledge of the potential aggressiveness and biological traits of a given early-stage surgically resected tumor. This review focuses on proteins as promising biomarkers in the context of lung cancer screening. Despite great efforts, there are still no successful examples of biomarkers in lung cancer that have reached the clinics to be used in early detection and early management. Thus, the field of biomarkers in early lung cancer remains an evident unmet need. A more specific objective of this review is to present an up-to-date technical assessment of the potential use of protein biomarkers in early lung cancer detection and management. We provide an overview regarding the benefits, challenges, pitfalls and constraints in the development process of protein-based biomarkers. Additionally, we examine how a number of emerging protein analytical technologies may contribute to the optimization of novel robust biomarkers for screening and effective management of lung cancer., (Copyright © 2024 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The impact of obstructive lung disease (OLD) and emphysema on lung cancer (LC) mortality in patients undergoing LC screening is controversial., Methods: Patients with spirometry and LC diagnosed within the first three rounds of screening were selected from the National Lung Screening Trial (NLST) and from the Pamplona International Early Lung Cancer Detection Program (P-IELCAP). Medical and demographic data, tumor characteristics, comorbidities and presence of emphysema were collected. The effect of OLD and emphysema on the risk of overall survival was assessed using unadjusted and adjusted Cox models, competing risk regression analysis, and propensity score matching., Results: Data from 353 patients with LC, including 291 with OLD and/or emphysema and 62 with neither, were analyzed. The median age was 67.3 years-old and 56.1% met OLD criteria, predominantly mild (1: 28.3%, 2: 65.2%). Emphysema was present in 69.4% of the patients. Patients with OLD and/or emphysema had worse survival on univariate analysis (HR: 1.40; 95% CI: 0.86-2.31; p=0.179). However, after adjusting for LC stage, age, and sex, the HR was 1.02 (95% CI: 0.61-1.70; p=0.952). Specific LC survival between both groups showed an adjusted HR of 0.90 (95% CI: 0.47-1.72; p=0.76). Propensity score matching found no statistically significant difference in overall survival (HR: 1.03; 95% CI: 0.59-1.9; p=0.929)., Conclusion: The survival of LC patients diagnosed in the context of screening is not negatively impacted by the coexistence of mild OLD and/or emphysema., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Intermittent hypoxaemia and obstructive sleep apnoea (OSA) have been linked to lung cancer through as yet unidentified pathophysiological mechanisms. This study evaluates the effect of OSA on serum levels of biomarkers of immunosurveillance, lymphangiogenesis and intrinsic tumour cell aggressiveness in high-risk individuals screened for lung cancer and patients with established lung cancer., Methods: Serum samples from individuals participating in a lung cancer screening cohort (SAILS study) or with newly diagnosed lung cancer (SAIL study) were analysed. All patients underwent home sleep apnoea testing. Soluble levels of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4, midkine (MDK), paraspeckle component-1 (PSPC1), transforming growth factor-β1 (TGF-β1), SMAD3, matrix metalloproteinase-2 and co-stimulus receptor of the tumour necrosis factor family of receptors (CD137) were determined by ELISA., Results: The presence of moderate-to-severe OSA was associated with increased levels of PSPC1, MDK, PD-L1 and PD-1 in screened individuals, and with higher values of PSPC1, TGF-β1, PD-L1 and PD-1 in patients with established lung cancer. The findings correlated with nocturnal intermittent hypoxaemia indices., Conclusion: Moderate-to-severe OSA is associated with increased expression of serum biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk individuals screened for lung cancer and those with established disease., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2024.)

Introduction: The Global Initiative for Obstructive Lung Disease (GOLD) recommends lung cancer screening for patients with Chronic Obstructive Pulmonary Disease (COPD), but data is lacking regarding results of screening in this high-risk population. The main goal of the present work is to explore if lung cancer screening with Low Dose Chest Tomography (LDCT) in people with COPD, allows lung cancer (LC) diagnosis in early stages with survival compatible with curative state., Methods: This is a post hoc exploratory analysis. Pamplona International Early Lung Cancer Action Program (P-IELCAP) participants with a GOLD defined obstructive pattern (post bronchodilator FEV 1 /FVC<0.70) were selected for analysis. The characteristics of those who developed LC and their survival are described. A Cox proportional analysis explored the factors associated with LC diagnosis., Results: Eight hundred and sixty-five patients (77% male, 93% in spirometric GOLD stage 1+2) were followed for 102±63 months. LC prevalence was 2.6% at baseline, with an annual LC diagnosis rate of 0.68%. Early-stage tumors predominated (74%) with a median survival (25-75th percentiles) of 139 (76-185) months. Cumulative tobacco exposure, FEV 1 %, and emphysema were the main predictors of an LC diagnosis. Eight (11%) patients with COPD had a second LC, most of them in early stage (92%), and 6 (8%) had recurrence. Median survival (25-75th percentiles) in these patients was 168 (108-191) months., Conclusions: Lung cancer screening of selected high-risk participants with COPD allowed the LC diagnosis in early stages with survival compatible with curative state., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Background: There has been debate on whether inhaled corticosteroids (ICS) reduce the incidence of lung cancer amongst patients with Chronic Obstructive Lung Disease (COPD). We aimed to perform a systematic review and dose-response meta-analysis on available observational data., Methods: We performed both a dose response and high versus low random effects meta-analysis on observational studies measuring whether lung cancer incidence was lower in patients using ICS with COPD. We report relative risk (RR) with 95% confidence intervals (CI), as well as risk difference. We use the GRADE framework to report our results., Results: Our dose-response suggested a reduction in the incidence of lung cancer for every 500 ug/day of fluticasone equivalent ICS (RR 0.82 [95% 0.68-0.95]). Using a baseline risk of 7.2%, we calculated risk difference of 14 fewer cases per 1000 ([95% CI 24.7-3.8 fewer]). Similarly, our results suggested that for every 1000 ug/day of fluticasone equivalent ICS, there was a larger reduction in incidence of lung cancer (RR 0.68 [0.44-0.93]), with a risk difference of 24.7 fewer cases per 1000 ([95% CI 43.2-5.4 fewer]). The certainty of the evidence was low to very low, due to risk of bias and inconsistency., Conclusion: There may be a reduction in the incidence for lung cancer in COPD patients who use ICS. However, the quality of the evidence is low to very low, therefore, we are limited in making strong claims about the true effect of ICS on lung cancer incidence., (© 2022. The Author(s).)

The main objective of this work is to develop and evaluate an artificial intelligence system based on deep learning capable of automatically identifying, quantifying, and characterizing COVID-19 pneumonia patterns in order to assess disease severity and predict clinical outcomes, and to compare the prediction performance with respect to human reader severity assessment and whole lung radiomics. We propose a deep learning based scheme to automatically segment the different lesion subtypes in nonenhanced CT scans. The automatic lesion quantification was used to predict clinical outcomes. The proposed technique has been independently tested in a multicentric cohort of 103 patients, retrospectively collected between March and July of 2020. Segmentation of lesion subtypes was evaluated using both overlapping (Dice) and distance-based (Hausdorff and average surface) metrics, while the proposed system to predict clinically relevant outcomes was assessed using the area under the curve (AUC). Additionally, other metrics including sensitivity, specificity, positive predictive value and negative predictive value were estimated. 95% confidence intervals were properly calculated. The agreement between the automatic estimate of parenchymal damage (%) and the radiologists' severity scoring was strong, with a Spearman correlation coefficient (R) of 0.83. The automatic quantification of lesion subtypes was able to predict patient mortality, admission to the Intensive Care Units (ICU) and need for mechanical ventilation with an AUC of 0.87, 0.73 and 0.68 respectively. The proposed artificial intelligence system enabled a better prediction of those clinically relevant outcomes when compared to the radiologists' interpretation and to whole lung radiomics. In conclusion, deep learning lesion subtyping in COVID-19 pneumonia from noncontrast chest CT enables quantitative assessment of disease severity and better prediction of clinical outcomes with respect to whole lung radiomics or radiologists' severity score., (© 2022. The Author(s).)

Low dose computed tomography (LDCT) screening, together with the recent advances in targeted and immunotherapies, have shown to improve non-small cell lung cancer (NSCLC) survival. Furthermore, screening has increased the number of early stage-detected tumors, allowing for surgical resection and multimodality treatments when needed. The need for improved sensitivity and specificity of NSCLC screening has led to increased interest in combining clinical and radiological data with molecular data. The development of biomarkers is poised to refine inclusion criteria for LDCT screening programs. Biomarkers may also be useful to better characterize the risk of indeterminate nodules found in the course of screening or to refine prognosis and help in the management of screening detected tumors. The clinical implications of these biomarkers are still being investigated and whether or not biomarkers will be included in further decision-making algorithms in the context of screening and early lung cancer management still needs to be determined. However, it seems clear that there is much room for improvement even in early stage lung cancer disease-free survival (DFS) rates; thus, biomarkers may be the key to refine risk-stratification and treatment of these patients. Clinicians' capacity to register, integrate, and analyze all the available data in both high risk individuals and early stage NSCLC patients will lead to a better understanding of the disease's mechanisms, and will have a direct impact in diagnosis, treatment, and follow up of these patients. In this review, we aim to summarize all the available data regarding the role of biomarkers in LDCT screening and early stage NSCLC from a multidisciplinary perspective. We have highlighted clinical implications, the need to combine risk stratification, clinical data, radiomics, molecular information and artificial intelligence in order to improve clinical decision-making, especially regarding early diagnostics and adjuvant therapy. We also discuss current and future perspectives for biomarker implementation in routine clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-750). The series “Implementation of CT-based screening of lung cancer” was commissioned by the editorial office without any funding or sponsorship. LMM serves as an unpaid editorial board member of Translational Lung Cancer Research from Sep 2019 to Sep 2021. DA reports other, during the conduct of the study. LMS reports personal fees from Sabartech, personal fees from Astra Zeneca, personal fees from Esteve, personal fees from Chiesi, outside the submitted work. RP has two patents licensed to Amadix: new lung cancer molecular markers, and in vitro method for the diagnosis of lung cancer. JJZ reports other from VisionGate, Inc., outside the submitted work. In addition, Dr. LMM has a patent: complement fragments for the diagnosis of lung cancer licensed. The authors have no other conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Objective: Lung cancer (LC) is the leading cause of death from cancer worldwide. More than 27,000 LCs are diagnosed annually in Spain, and most are unresectable. Early detection and treatment reduce LC mortality. This study describes surgical outcomes in a longstanding LC screening cohort in Spain., Methods: We conducted a retrospective study of surgical outcomes in a LC screening (LCS) program using low dose computed tomography (LDCT) since the year 2000. A descriptive analysis of clinical and radiological parameters, presence or absence of a preoperative diagnosis, pathological staging, morbidity, mortality, and survival was performed., Results: Ninety-seven (2.5%) LC were diagnosed in 3825 screened. Twenty individuals with LC had no surgery due to advanced stage or small cell histology. Eighty-seven surgical procedures were carried out for suspected or biopsy proven LC, detected by LDCT. Most operated patients were male (57[85%]) aged 64±9.1 years. Nine patients underwent a second operation for a metachronous primary lung cancer. Mean tumor size was 15.2±7.6mm. Eight nodules were benign (9.2%). Lobectomy was performed in 56 cases (83.6%). Adenocarcinoma (n=39; 58.2%) was the most frequent histological type followed by squamous cell carcinoma (n=17; 25.4%). Fifty-nine (88%) tumors were in Stage I. Thirteen patients (15.4%) had 16 complications. The estimated survival rates at 5 and 10 years for stage I were 93% (95% CI: 79%-98%) and 83% (95% CI: 65%-92%), respectively., Conclusion: Lung cancer screening was associated with excellent surgical outcomes with 5 and 10-year survival rates exceeding 90 and 80%, respectively., (Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT., Methods: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD ≥ 29 mm in men and ≥27 mm in women or as a PA:Ao ratio > 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models., Results: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index ≥ 30 kg/m 2 (OR 2.01; 95%CI 1.06-3.78), lower % predicted of forced expiratory volume in one second (FEV 1 ) (OR 1.03; 95%CI 1.02-1.05) and higher % of sleep time with O 2 saturation < 90% (T90) (OR 1.02; 95%CI 1.00-1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01-1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01-1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01-1.07)., Conclusions: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence.

Introduction: The prevalence of bronchiectasis in the general population and in individuals undergoing lung cancer screening with low dose computed tomography (LDCT) is unknown. The aim of this study is to estimate the prevalence and impact of bronchiectasis in a screening lung cancer program., Methods: 3028 individuals participating in an international multicenter lung cancer screening consortium (I-ELCAP) were selected from 2000 to 2012. Patients with bronchiectasis on baseline CT were identified and compared to selected controls. Detection of nodules, need for additional studies and incidence of cancer were analyzed over the follow-up period., Results: The prevalence of bronchiectasis was 11.6%(354/3028). On the baseline LDCT, the number of subjects with nodules identified was 189(53.4%) in patients with bronchiectasis compared to 63(17.8%) in controls (p<0.001). The occurrence of false positives was higher in subjects with bronchiectasis (26%vs17%;p = 0.003). During follow-up, new nodules were more common among subjects with bronchiectasis (17%vs.12%; p = 0.008). The total number of false positives during follow-up was 29(17.06%) for patients with bronchiectasis vs. 88(12.17%) for controls (p = 0.008).The incidence rate of lung cancer during follow-up was 6.8/1000 and 5.1/1000 person-years for each group respectively (p = 0.62)., Conclusions: Bronchiectasis are common among current and former smokers undergoing lung cancer screening with LDCT. The presence of bronchiectasis is associated with greater incidence of new nodules and false positives on baseline and follow-up screening rounds. This leads to an increase need of diagnostic tests, although the lung cancer occurrence is not different., Competing Interests: The authors have declared that no competing interests exist.

Study Objectives: To identify a link between sleep disordered breathing, nocturnal hypoxemia, and lung cancer., Methods: We conducted a cross-sectional study of a combined cohort of 302 individuals derived from the sleep apnea in lung cancer study (SAIL; NCT02764866) investigating the prevalence of sleep apnea in lung cancer, and the sleep apnea in lung cancer screening study (SAILS; NCT02764866) investigating the prevalence of sleep apnea in a lung cancer screening program. All subjects had spirometry and a chest CT, underwent home sleep apnea testing (HSAT), and completed a sleep related questionnaire. Subjects from the SAIL study underwent HSAT prior to initiating oncologic therapy or surgery. Subjects with an apnea-hypopnea index (AHI) > 15 were compared with a control group of individuals with an AHI < 15. Propensity score, near neighbor matching, and logistic regression adjusted for potential confounders, were used in order to evaluate the association between sleep apnea, the AHI, oxygen desaturation indices and lung cancer., Results: The prevalence of sleep apnea and lung cancer in the combined cohort was 42% and 21%, respectively. Lung cancer was 8% more prevalent in patients with an AHI >15. The difference was statistically significant when assessed by propensity score matching (p = 0.015) and nearest neighbor matching (p = 0.041). Binary logistic regression adjusted for potential confounders revealed a statistically significant association between AHI (p = 0.04), nocturnal hypoxemia, including time spent below 90% oxyhemoglobin saturation (T90%; p = 0.005), 3% oxygen desaturation index (ODI3; p = 0.02) and lung cancer., Conclusions: Sleep apnea and nocturnal hypoxemia are associated with an increased prevalence of lung cancer., Clinical Trial Registration: SAIL study (NCT02764866) and SAILS study (NCT02764866)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To assess the relationship between lung cancer and emphysema subtypes., Objective: Airflow obstruction and emphysema predispose to lung cancer. Little is known, however, about the lung cancer risk associated with different emphysema phenotypes. We assessed the risk of lung cancer based on the presence, type and severity of emphysema, using visual assessment., Methods: Seventy-two consecutive lung cancer cases were selected from a prospective cohort of 3,477 participants enrolled in the Clínica Universidad de Navarra's lung cancer screening program. Each case was matched to three control subjects using age, sex, smoking history and body mass index as key variables. Visual assessment of emphysema and spirometry were performed. Logistic regression and interaction model analysis were used in order to investigate associations between lung cancer and emphysema subtypes., Results: Airflow obstruction and visual emphysema were significantly associated with lung cancer (OR = 2.8, 95%CI: 1.6 to 5.2; OR = 5.9, 95%CI: 2.9 to 12.2; respectively). Emphysema severity and centrilobular subtype were associated with greater risk when adjusted for confounders (OR = 12.6, 95%CI: 1.6 to 99.9; OR = 34.3, 95%CI: 25.5 to 99.3, respectively). The risk of lung cancer decreases with the added presence of paraseptal emphysema (OR = 4.0, 95%CI: 3.6 to 34.9), losing this increased risk of lung cancer when it occurs alone (OR = 0.7, 95%CI: 0.5 to 2.6)., Conclusions: Visual scoring of emphysema predicts lung cancer risk. The centrilobular phenotype is associated with the greatest risk., Competing Interests: All authors have read the journal's authorship agreement and policy on disclosure of potential conflicts of interest. JJZ is a part-time employee of VisionGate, Inc. JPd-T has received consultancy fees for participating in advisory boards for Takeda Pharmaceuticals International GmbH, Menarini, and Novartis AG; he also received fees for speaking activities from GlaxoSmithKline plc, AstraZeneca, Chiesi, Menarini, Novartis AG, Merck, Sharp & Dohme Corporation, and Takeda Pharmaceuticals International GmbH. DFY is a named inventor on a number of patents and patent applications relating to the evaluation of diseases of the chest including measurement of nodules. Some of these, which are owned by Cornell Research Foundation (CRF), are non-exclusively licensed to General Electric. As an inventor of these patents, DFY is entitled to a share of any compensation which CRF may receive from its commercialization of these patents. He is also an equity owner in Accumetra, a privately held technology company committed to improving the science and practice of image-based decision making. DFY also serves on the advisory board of GRAIL. CIH is the President and serves on the board of the Early Diagnosis and Treatment Research Foundation. She receives no compensation from the Foundation. CIH is also a named inventor on a number of patents and patent applications relating to the evaluation of pulmonary nodules on CT scans of the chest which are owned by Cornell Research Foundation (CRF). Since 2009, CIH does not accept any financial benefit from these patents including royalties and any other proceeds related to the patents or patent applications owned by CRF. APR holds shares in VisionGate Inc., is owner of D4Vision Inc., and receives royalties from patents owned and licensed by Cornell Research Foundation. All other authors have no competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The present review is an update of the research and development efforts regarding the use of molecular biomarkers in the lung cancer screening setting. The two main unmet clinical needs, namely, the refinement of risk to improve the selection of individuals undergoing screening and the characterization of undetermined nodules found during the computed tomography-based screening process are the object of the biomarkers described in the present review. We first propose some principles to optimize lung cancer biomarker discovery projects. Then, we summarize the discovery and developmental status of currently promising molecular candidates, such as autoantibodies, complement fragments, microRNAs, circulating tumor DNA, DNA methylation, blood protein profiling, or RNA airway or nasal signatures. We also mention other emerging biomarkers or new technologies to follow, such as exhaled breath biomarkers, metabolomics, sputum cell imaging, genetic predisposition studies, and the integration of next-generation sequencing into study of circulating DNA. We also underline the importance of integrating different molecular technologies together with imaging, radiomics, and artificial intelligence. We list a number of completed, ongoing, or planned trials to show the clinical utility of molecular biomarkers. Finally, we comment on future research challenges in the field of biomarkers in the context of lung cancer screening and propose a design of a trial to test the clinical utility of one or several candidate biomarkers., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: Smoking is a recognized risk factor for osteoporosis. Trabecular bone score (TBS) is a novel texture parameter to evaluate bone microarchitecture. TBS and their main determinants are unknown in active and former smokers., Objective: To assess TBS in a population of active or former smokers with and without Chronic Obstructive Pulmonary Disease (COPD) and to determine its predictive factors., Methods: Active and former smokers from a pulmonary clinic were invited to participate. Clinical features were recorded and bone turnover markers (BTMs) measured. Lung function, low dose chest Computed Tomography scans (LDCT), dual energy absorptiometry (DXA) scans were performed and TBS measured. Logistic regression analysis explored the relationship between measured parameters and TBS., Results: One hundred and forty five patients were included in the analysis, 97 (67.8%) with COPD. TBS was lower in COPD patients (median 1.323; IQR: 0.13 vs 1.48; IQR: 0.16, p = 0.003). Regression analysis showed that a higher body mass index (BMI), younger age, less number of exacerbations and a higher forced expiratory volume-one second (FEV1%) was associated with better TBS (β = 0.005, 95% CI:0.000-0.011, p = 0.032; β = -0.003, 95% CI:-0.007(-)-0.000, p = 0.008; β = -0.019, 95% CI:-0.034(-)-0.004, p = 0.015; β = 0.001, 95% CI:0.000-0.002, p = 0.012 respectively). The same factors with similar results were found in COPD patients., Conclusions: A significant proportion of active and former smokers with and without COPD have an affected TBS. BMI, age, number of exacerbations and the degree of airway obstruction predicts TBS values in smokers with and without COPD. This important information should be considered when evaluating smokers at risk of osteoporosis., Competing Interests: The authors have declared that no competing interests exist.

Objective: Obstructive sleep apnea (OSA) can influence the appearance and proliferation of some tumors. The Sleep Apnea In Lung Cancer Screening (SAILS) study (NCT02764866) evaluated the prevalence of OSA and nocturnal hypoxemia in a high-risk population enrolled in a lung cancer screening program., Methods: This was a prospective study of the prevalence of OSA in a lung cancer screening program. Subjects met the National Lung Screening Trial (NLST) age and smoking criteria (age 55-75 years; pack-years >30). Participants in the study were offered annual screening with low-dose computed tomography (LDCT) and pulmonary function testing, as well as home sleep apnea testing (HSAT) and a sleep-specific questionnaire. Sleep study-related variables, symptoms, and epidemiologic data were recorded., Results: HSAT was offered to 279 subjects enrolled in our lung cancer screening program. HSAT results were available for 236 participants (mean age 63.6 years; mean tobacco exposure: 45 pack-years), of whom 59% were male and 53% were active smokers. Emphysema (74%) and chronic obstructive pulmonary disease (COPD) (62%) were common and in most cases mild in severity. OSA, including moderate to severe disease, was very common in this patient population. AHI distributions were as follows: AHI <5 (22.5%); 5-15 (36.4%); 15-30 (23.3%); and >30 (17.8%). Nocturnal hypoxemia (T90) (p = 0.003), diffusing capacity for carbon monoxide (DLCO) (p = 0.01), tobacco exposure (p = 0.024), and COPD (p = 0.023) were associated with OSA severity. Positive screening findings (nodules ≥6 mm) were associated with nocturnal hypoxemia on multivariate analysis adjusted for confounders (OR = 2.6, 95% CI = 1.12-6.09, p = 0.027)., Conclusion: Moderate to severe OSA is very prevalent in patients enrolled in a lung cancer screening program. Nocturnal hypoxemia more than doubles the risk of positive screening findings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Tobacco smoking is recognized as a major preventable cause of disease worldwide and is linked to 6 million deaths annually, 30% of which are due to cancer. The negative health consequences of smoking currently represent one of the greatest global public health challenges. Additionally, secondhand smoke, which was declared carcinogenic by the International Agency for Research on Cancer in 2004, is a major source of morbidity and premature death in nonsmokers, particularly children. Negative health effects associated with exposure to secondhand smoke have been well documented and include lung cancer, cardiovascular disease, asthma, and other respiratory diseases. International and national policies to implement cost-effective strategies to curtail smoking will have a significant impact on population health and will protect nonsmokers. Effective interventions, such as smoking bans, tobacco price increases, easy access to tobacco cessation treatments, and anti-tobacco media campaigns, should continue. Reducing tobacco use would be a major step towards the goal of decreasing health disparities by 2030, as 80% of the projected tobacco-related deaths will occur in low and middle-income countries., Competing Interests: The authors have no competing interests to declare., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.)

Background: Obstructive sleep apnea (OSA) has been linked to tumorigenesis and tumor progression., Objectives: The Sleep Apnea in Lung Cancer (SAIL) study (NCT02764866) was designed to determine the prevalence of OSA in patients with lung cancer., Methods: Cross-sectional study including consecutive patients with newly diagnosed lung cancer. All patients were offered home sleep apnea testing (HSAT) and administered a sleep-specific questionnaire prior to initiating oncologic treatment. Sleep study-related variables, symptoms, and epidemiologic data as well as cancer related variables were recorded., Results: Eighty-three patients were enrolled in the SAIL study. Sixty-six completed HSAT. The mean age was 68 ± 11 years and 58% were male with a mean body mass index of 28.1 ± 5.4. Forty-seven percent were current smokers, 42% former smokers, and 11% never smokers with a median tobacco consumption of 51 pack-years. Fifty percent had COPD with a mean FEV1 of 83 ± 22.6% of predicted and a mean DLCO of 85.5 ± 20.1%. Adenocarcinoma was the most common histologic type (46.7%), followed by squamous cell (16.7%) and small cell (16.7%). Most patients were diagnosed at an advanced stage (65% in stages III-IV). The vast majority (80%) had OSA (apnea-hypopnea index [AHI] > 5), and 50% had moderate to severe OSA (AHI > 15) with a mean Epworth Sleepiness Score of 7.43 ± 3.85. Significant nocturnal hypoxemia was common (Median T90: 10.9% interquartile range 2.4-42.2)., Conclusions: Sleep apnea and nocturnal hypoxemia are highly prevalent in patients with lung cancer., (© 2018 S. Karger AG, Basel.)

Tobacco smoking is recognized as a major preventable cause of disease worldwide and is linked to 6 million deaths annually, 30% of which are due to cancer. The negative health consequences of smoking currently represent one of the greatest public health challenges. Secondhand smoke, declared carcinogenic by the International Agency for Research on Cancer in 2004, is also a major source of morbidity and premature death in nonsmokers, particularly children. Negative health effects associated with exposure to secondhand smoke have been well documented and include lung cancer, cardiovascular disease, asthma, and other respiratory diseases. International and national policies to implement cost-effective strategies to curtail smoking will have a significant impact on population health and will protect nonsmokers. Effective interventions, such as a combination of smoke-free laws, tobacco price increases, easy access to tobacco cessation treatments, and anti-tobacco media campaigns, should continue. Reducing tobacco use would be a major step towards the goal of decreasing health disparities by 2030 as 80% of the projected tobacco-related deaths will occur in low- and middle-income countries., Competing Interests: The authors have no competing interests to declare., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.)

Lung cancer has been linked to the changes in lung function characteristic of chronic obstructive pulmonary disease (COPD) and to the changes in lung morphology seen in emphysema. It seems that a common thread of smoking-induced lung injury can be traced to all three diseases. However, the association is not as straightforward as it may seem; for example, even never-smokers with emphysema have an increased risk of lung cancer. Whether lung cancer, COPD, and emphysema are linked by common genes, mechanisms, causes, or a combination thereof, understanding the associations between them has become a priority for research regarding tobacco-related illnesses. A better delineation of the relationships between these three entities may lead to significant improvements in the effectiveness of lung cancer screening programs, and to reductions in the morbidity and mortality associated with these deadly diseases.

Objective: The LungFlag risk prediction model uses individualized clinical variables to identify individuals at high-risk of non-small cell lung cancer (NSCLC) for screening with low-dose computed tomography (LDCT). This study evaluates the cost-effectiveness of LungFlag implementation in the Spanish setting for the identification of individuals at high-risk of NSCLC., Methods: A model combining a decision-tree with a Markov model was adapted to the Spanish setting to calculate health outcomes and costs over a lifetime horizon, comparing two hypothetical scenarios: screening with LungFlag versus non-screening, and screening with LungFlag versus screening the entire population meeting 2013 US Preventive Services Task Force (USPSTF) criteria. Model inputs were obtained from the literature and the clinical practice of a multidisciplinary expert panel. Only direct costs (€of 2023), obtained from local sources, were considered. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of our results., Results: A cohort of 3,835,128 individuals meeting 2013 USPSTF criteria would require 2,147,672 LDCTs scans. However, using LungFlag would only require 232,120 LDCTs scans. Cost-effectiveness results showed that LungFlag was dominant versus non-screening scenario, and outperformed the scenario where the entire population were screened since the observed loss of effectiveness (-224,031 life years [LYs] and -97,612 quality-adjusted life years [QALYs]) was largely offset by the significant cost savings provided (€7,053 million). The resulting incremental cost-effectiveness ratio (ICER) for this strategy of screening the whole population versus using LungFlag was €72,000/QALY, showing that LungFlag is cost-effective. Various were described, such as the source of the efficacy or adherence rates, and other limitations inherent to cost-effectiveness analyses., Conclusions: Using LungFlag for the selection of high-risk individuals for NSCLC screening in Spain would be a cost-effective strategy over screening the entire population meeting USPSTF 2013 criteria and is dominant over non-screening.

Background: Bronchoalveolar lavage (BAL) may be performed using a hand-held syringe or wall suction., Objectives: The aim was to study BAL volume and diagnostic yields based on BAL technique., Methods: A total of 220 consecutive patients undergoing BAL at our center were included. Manual aspiration was performed in 115 patients (group 1), and wall suction (<50 mm Hg of negative pressure) was used in 105 patients (group 2). All bronchoscopies were performed under conscious sedation applying topical anesthesia with lidocaine. Three 50-ml sterile saline aliquots were instilled in all patients., Results: The mean total amount of fluid recovered was 67 ± 20 ml in group 1 and 55 ± 22 ml in group 2 (p < 0.001). More patients in the manual aspiration group met American Thoracic Society criteria (recovery of ≥30% of instilled fluid) for an optimal BAL (81 vs. 59%; p < 0.001). The quantity of recovered fluid was also related to BAL location (p < 0.001) and radiologic findings (p = 0.002). Forty-eight (22%) BALs were diagnostic (23 in group 1 and 25 in group 2), including 37 positive bacterial cultures, 6 positive stains for Pneumocystis, and 5 cases of malignancy. No statistically significant difference in diagnostic yield was observed between the two groups. A BAL diagnosis was more likely in patients with certain radiologic (p = 0.033) and endoscopic findings (p = 0.001). When taking into account all bronchoscopic techniques performed during the procedure (e.g. biopsies, brushing, etc.), bronchoscopy was diagnostic in 37% of patients., Conclusions: Manual aspiration is superior to wall suction during BAL yielding a larger quantity of aspirate. Diagnostic yields are similar for both techniques., (© 2016 S. Karger AG, Basel.)

Rationale: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity., Objectives: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion., Methods: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects who met NLST criteria alone, those with computed tomography-detected emphysema, and those who met NLST criteria and/or had emphysema., Measurements and Main Results: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss as many as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%., Conclusions: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed.

Introduction and Objectives: European experience regarding lung cancer screening using low-dose chest CT (LDCT) is available. However, there is limited data on the Spanish experience in this matter. Our aim is to present the results from the longest ongoing screening program in Spain., Methodology: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) is actively screening participants for lung cancer using LDCT since year 2000 following the IELCAP protocol, including spirometric assessments. Men and women, ≥40 years of age, current or former smokers with a tobacco history of ≥10 pack-years are included. Results are compared to those from other European trials., Results: A total of 2989 participants were screened until March 2014 (73% male). A median of 2 (IQR 1-3) annual screening rounds were performed. Sixty lung cancers were detected in 53 participants (73% in StageI). Adenocarcinoma was the most frequent. The lung cancer prevalence and incidence proportion was 1.0% and 1.4%, respectively, with an annual detection rate of 0.41. The estimated 10-year survival rate among individuals with lung cancer was 70%. Chronic obstructive pulmonary disease and emphysema are important lung cancer predictors., Conclusions: The experience in Spain's longest lung cancer screening program is comparable to what has been described in the rest of Europe, and confirms the feasibility and efficacy of lung cancer screening using LDCT., (Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.)

Lung volume reduction surgery is a therapeutic option for selected patients with advanced emphysema. However, it is an invasive procedure benefitting only a selected group of patients with heterogeneous upper lobe predominant disease and limited exercise capacity. The most widely studied alternatives are endobronchial valves. Hundreds of patients worldwide have undergone endobronchial valve placement. Although short-term outcomes have been described, little is known about the long-term side effects following this treatment, and endoscopic follow-up is virtually nonexistent. The images, biopsies, and microbiologic evidence accrued from this patient are witnesses to the natural evolution of endobronchial valves in the airways and should offer a word of caution with regard to valve placement in patients with life expectancies exceeding those typical of severe chronic obstructive lung disease.

Background: COPD is an independent risk factor for lung cancer, especially in patients with mild to moderate disease., Objective: To determine if performing lung cancer screening in GOLD 1 and 2 COPD patients, results in reduced lung cancer mortality., Methods: This study compared patients with mild to moderate COPD from 2 cohorts matched for age, gender, BMI, FEV1%, pack-yrs history and smoking status. The screening group (SG) had an annual low dose computed tomography (LDCT). The control group (CG) was prospectively followed with usual care. Lung cancer incidence and mortality densities were compared between groups., Results: From an initial sample of 410 (SG) and 735 (CG) patients we were able to match 333 patients from each group. At the same follow-up time lung cancer incidence density was 1.79/100 person-years in the SG and 4.14/100 person-years in the CG (p = 0.004). The most frequent histological type was adenocarcinoma in both SG and CG (65% and 46%, respectively), followed by squamous cell carcinoma (25% and 37%, respectively). Eighty percent of lung cancers in the SG (16/20) were diagnosed in stage I, and all of CG cancers (35/35) were in stage III or IV. Mortality incidence density from lung cancer (0.08 vs. 2.48/100 person-years, p < 0.001) was lower in the SG., Conclusions: This pilot study in patients with mild to moderate COPD suggests that screening with LDCT detects lung cancer in early stages, and could decrease lung cancer mortality in that high risk group. Appropriately designed studies should confirm these important findings., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widely-accepted method for obtaining both benign and malignant mediastinal lymph node samples. We present the results obtained with a modification that simplifies sampling, known as fine-needle capillary sampling or EBUS-FNC., Methods: A prospective observational study with 44 consecutive patients who underwent EBUS at the University of Navarra Clinic in Pamplona (Spain). All samples were obtained by EBUS-FNC instead of by conventional EBUS-TBNA. No suction was used, and the internal stylus was not completely withdrawn at any time., Results: The examination of the mediastinum by means of EBUS identified the presence of lymphadenopathies or mediastinal masses in 38 patients (86.4%). Samples were taken from more than one lymph node in 23 patients (52.3%). EBUS-FNC provided adequate and representative material for interpretation in all patients, and diagnostic performance was 87%. Sensitivity for the detection of lung cancer with EBUS-FNC was 84%. Mild complications were only recorded in two patients (4.5%)., Conclusions: Our study suggests that EBUS-FNC is a safe technique, comparable to EBUS-TBNA in efficacy, and is able to obtain adequate samples., (Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.)

Rationale: Low-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown., Objective: TO COMPARE THE PLASMA CYTOKINE PROFILES IN TWO GROUPS OF CURRENT OR FORMER SMOKERS WITHOUT AIRWAY OBSTRUCTION: a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individuals with CT detected emphysema., Methods: Subjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors., Results: 160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (-0.317, p = 0.01), IL-15 (-0.21, p = 0.01), IL-8 (-0.180, p = 0.02) and IL-1ra (-0.220, p = 0.03) in subjects with emphysema and normal spirometry., Conclusions: Current or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.

Background: Physicians are increasingly encountering lung nodules in their practice, and tissue diagnosis is often required. Conventional bronchoscopic sampling yields a range from 14% to 69% depending on the nodule size and location within the lung. We aimed to evaluate the diagnostic yield of electromagnetic navigation bronchoscopy (ENB) in multiple centers and to determine what factors affect the yield of ENB., Methods: A retrospective analysis of 92 consecutive ENB procedures at 5 centers was carried out. Data were collected on patient demographics, nodule characteristics, complications, type of samples obtained, diagnosis, and follow-up studies. Variables were analyzed to determine as to which factors had an impact on the diagnostic yield with multiple logistic regression analysis., Results: Ninety-two patients underwent EMB at 5 centers between December 2008 and October 2009. The average nodule size was 2.61 cm (SD 1.42) at a distance of 1.81 cm (SD 1.32) from the pleural surface. The overall yield for ENB-guided sampling of pulmonary nodules was 65% (60/92). The ENB yield for nodules ≤2 versus >2 cm in size was significantly less after controlling for the distance from the pleura (50% vs. 76%, respectively; P=0.01). The distance from the pleura did not affect the ENB diagnostic yield after controlling for nodule size (P=0.92). The lobar location of the nodule also did not affect the diagnostic yield (P=0.59)., Conclusions: The diagnostic yield of ENB-guided sampling of pulmonary nodules is impacted by the nodule size, but not by the distance from the pleura or the lobar location.

Objective: The objective of our study was to investigate whether fluorodeoxyglucose (FDG) positron emission tomography scanning uptake impacts the yield of transbronchial needle aspiration (TBNA)., Methods: We carried out a retrospective analysis of data from 140 consecutive patients (178 lymph nodes) undergoing positron emission tomography-computed tomography scanning and subsequent TBNA with rapid onsite cytologic evaluation of the specimen. Patient and lymph node characteristics, including nodal station, size, FDG uptake, number of passes with the needle, sample adequacy, and the final diagnosis were recorded., Results: The diagnostic yield of TBNA was 75%. Themean short axis lymph node diameter was 18.7±9 mm and mean maximum standardized uptake value (SUVmax) was 7.7±4. The diagnostic yield depended on the lymph node size [odds ratio (OR)=1.07 (1.00-1.14); P=0.04], clinical suspicion of malignancy [OR=5.13 (1.95-13.52); P=0.001], malignant diagnosis [OR=4.91 (1.71-14.09); P=0.003], and FDG uptake [for SUVmax cutoff of 3.0: OR=33.8 (9.2-124); P<0.001]. Only clinical suspicion of cancer [OR=6.2 (2.2-17.2); P=0.001] and FDG uptake [for SUVmax cutoff of 3.0: OR=33.8 (9.2-123.8); P<0.001] remained significant on multivariate analysis. Receiver operating characteristic curves combining 3 key variables (lymph node size, clinical suspicion of malignancy, and SUVmax) showed an area of 0.83 under the curve for a 2.5 SUVmax cutoff and 0.84 for a 3.0 cutoff., Conclusions: FDG uptake is the single most important variable impacting the TBNA yield. TBNA of lymph nodes with an SUVmax less than 3.0 is rarely diagnostic.

Background: Phenotypic characterization of patients with COPD may have potential prognostic and therapeutic implications. Available information on the relationship between emphysema and the clinical presentation in patients with COPD is limited to advanced stages of the disease. The objective of this study was to describe emphysema presence, severity, and distribution and its impact on clinical presentation of patients with mild to moderate COPD., Methods: One hundred fifteen patients with COPD underwent clinical and chest CT scan evaluation for the presence, severity, and distribution of emphysema. Patients with and without emphysema and with different forms of emphysema distribution (upper/lower/core/peel) were compared. The impact of emphysema severity and distribution on clinical presentation was determined., Results: Fifty percent of the patients had mild homogeneously distributed emphysema (1.84; 0.76%-4.77%). Upper and core zones had the more severe degree of emphysema. Patients with emphysema were older, more frequently men, and had lower FEV(1)%, higher total lung capacity percentage, and lower diffusing capacity of the lung for carbon monoxide. No differences were found between the clinical or physiologic parameters of the different emphysema distributions., Conclusions: In patients with mild to moderate COPD, although the presence of emphysema has an impact on physiologic presentation, its severity and distribution seem to have little impact on clinical presentation.