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Enormous progress has been made on the epic journey towards implementation of lung cancer screening in Europe. A breakthrough for lung health has been achieved with the EU proposal for a Council recommendation on cancer screening.

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 ± 7.6 mm. 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.

Rationale Emphysema and osteoporosis are tobacco-related diseases. Many studies have shown that emphysema is a strong and independent predictor of low bone mineral density (BMD) in smokers; however, none of them explored its association with different emphysema subtypes. Objective To explore the association between the different emphysema subtypes and the presence of low bone mineral density in a population of active or former smokers with and without chronic obstructive pulmonary disease (COPD). Methods One hundred and fifty-three active and former smokers from a pulmonary clinic completed clinical questionnaires, pulmonary function tests, a low-dose chest computed tomography (LDCT) and a dual-energy absorptiometry (DXA) scans. Subjects were classified as having normal BMD or low BMD (osteopenia or osteoporosis). Emphysema was classified visually for its subtype and severity. Logistic regression analysis explored the relationship between the different emphysema subtypes and the presence of low BMD adjusting for other important factors. Results Seventy-five percent of the patients had low BMD (78 had osteopenia and 37 had osteoporosis). Emphysema was more frequent (66.1 vs 26.3%, p=

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 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.

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 &gt, 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/m2 (OR 2.01, 95%CI 1.06–3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03, 95%CI 1.02–1.05) and higher % of sleep time with O2 saturation &lt, 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.

Lung cancer (LC) is a major public health issue. Despite recent advances in treatment, primary prevention and early diagnosis are key to reducing the incidence and mortality of this disease. A recent clinical trial demonstrated the efficacy of selective screening by low-dose computed tomography (LDCT) in reducing the risk of both lung cancer mortality and all-cause mortality in high-risk individuals. This article contains the reflections of an expert group on the use of LDCT for early diagnosis of LC in high-risk individuals, and how to evaluate its implementation in Spain. The expert group was set up by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), the Spanish Society of Thoracic Surgery (SECT), the Spanish Society of Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM).

Resumen El cancer de pulmon (CP) constituye un problema de salud publica de primer orden. A pesar de los recientes avances en su tratamiento, la prevencion primaria y el diagnostico precoz son las claves para reducir su incidencia y mortalidad. Un ensayo clinico reciente demostro la eficacia del cribado selectivo con tomografia computarizada de baja dosis (TCBD) en la reduccion del riesgo de muerte en personas de alto riesgo, tanto por CP como global. Este articulo recoge las reflexiones de un grupo de expertos designados por la Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), la Sociedad Espanola de Cirugia Toracica (SECT), la Sociedad Espanola de Radiologia Medica (SERAM) y la Sociedad Espanola de Oncologia Medica (SEOM) sobre el uso de la TCBD para el diagnostico precoz del CP en personas con riesgo elevado de padecerlo y los pasos necesarios para evaluar su implementacion en nuestro pais.

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

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.

BackgroundTo assess the relationship between lung cancer and emphysema subtypes.ObjectiveAirflow 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.MethodsSeventy-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.ResultsAirflow 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).ConclusionsVisual scoring of emphysema predicts lung cancer risk. The centrilobular phenotype is associated with the greatest risk.

To identify a link between sleep disordered breathing, nocturnal hypoxemia, and lung cancer.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.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 AHI15. 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.Sleep apnea and nocturnal hypoxemia are associated with an increased prevalence of lung cancer.SAIL study (NCT02764866) and SAILS study (NCT02764866).

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.

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.

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.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.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.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%.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.

Resumen Introduccion y objetivos La experiencia europea en relacion con el cribado de cancer de pulmon con tomografia de baja dosis de radiacion (TBDR) es amplia. Sin embargo, la evidencia sobre la experiencia en Espana es limitada. Nuestro objetivo es presentar los resultados del programa de cribado de cancer de pulmon mas largo de Espana. Metodos El Programa Internacional de Deteccion Precoz de Cancer de Pulmon con TBDR de Pamplona (P-IELCAP) viene reclutando individuos de manera activa desde el ano 2000 siguiendo el protocolo IELCAP. Se incluyen individuos ≥ 40 anos de edad, fumadores o ex fumadores (consumo acumulado ≥ 10 paquetes-ano). Los resultados se comparan con los de otros estudios europeos. Resultados Un total de 2.989 participantes fueron reclutados hasta marzo de 2014 (73% varones), realizando una mediana de 2 (IQR 1-3) rondas de cribado por individuo. Se detectaron 60 canceres de pulmon en 53 participantes (73% en estadio i ). Adenocarcinoma fue el tipo histologico mas frecuente. La proporcion de prevalencia e incidencia de cancer de pulmon fue del 1,0 y del 1,4%, respectivamente, con una tasa de deteccion anual de 0,41. La tasa de supervivencia a 10 anos de los pacientes con cancer de pulmon fue del 70%. La enfermedad pulmonar obstructiva cronica y el enfisema son importantes factores de riesgo para desarrollar cancer de pulmon. Conclusiones La experiencia del programa de cribado de cancer de pulmon mas largo de Espana es comparable con lo descrito en el resto de Europa y confirma la viabilidad y la eficacia del cribado mediante TBDR.

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 the 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 Stage I). 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.

Introduction: A link between some tumors and Obstructive Sleep Apnea Syndrome (OSAS) has been reported. We studied the prevalence of OSAS in patients with a recent diagnosis of lung cancer. Methods: Prospective registered multicenter study (NCT02764866). The study was offered to 66 consecutive patients with lung cancer, including Home Sleep Testing (HST) and a sleep-related questionnaire. Anthropometric and epidemiologic data were recorded along with Apnea-hypopnea Index (AHI), Oxygen Desaturation Index (ODI), Snore Index (SI) and % of time with oxygen levels Results: Nine of the 66 patients refused to participate, 13 failed to comply with HST, and 2 studies were invalid. A total of 42 HST were valid for analysis. Mean BMI was 27.4 Kg/m2 (+5.5). A majority of patients snored (57%), 31% had witnessed apneas, and 20% had excessive daytime sleepiness. Mean sleep duration was 7 hours (+1.5) and mean Epworth score was 7.28 (+3.9). Median AHI was 20.09, and T90 10.5% (IQR: 2.8-39). Sleep disordered breathing was ruled out in 7 patients (16%), while 11 (26%) had mild, 13 (30.1%) had moderate, and 11 (26%) had severe OSAS. Conclusions: Preliminary results of the prospective SAIL study suggest that sleep disordered breathing may be very prevalent in patients with lung cancer.

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

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.

Lung cancer is the most common cause of cancer death in the world, with most patients having a dismal prognosis. As many as 40 % of lung cancers are diagnosed in stage IV, with current 5-year survival rates well below 20 %. Conventional chest radiography has been historically derided as a valid screening tool for this dreaded disease. A recent National Cancer Institute-sponsored study known as the Prostate, Lung, Colorectal, and Ovarian cancer screening trial found no benefit from such screening in patients at risk. In recent years, low-dose computed tomography (LDCT) of the chest has emerged as a promising screening tool. Recent evidence from the National Lung Screening Trial (NLST) demonstrated a 20 % reduction in mortality from lung cancer in patients undergoing three rounds of LDCT screening. Opponents of lung cancer screening favor its limited use in the setting of well-designed trials claiming excessive false-positive findings, overdiagnosis, and morbidity and mortality associated with invasive testing. That notwithstanding, leading medical societies such as ASCO and ATS have positioned themselves recently in favor of screening subjects meeting the NLST criteria.

New evidence regarding the protective effect of inhaled steroids in patients with COPD suggests that a controlled clinical trial is needed to investigate the potential benefit of inhaled steroids in preventing lung cancer in patients with COPDhttp://bit.ly/2PTBTCO

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.

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.

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 (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.

With the publication of the national lung cancer screening trial (NLST), screening for lung cancer is expected to become more commonplace. The discovery of pulmonary nodules that require further management will, therefore, increase as well and will generate a growing need for tissue given the recent inroads in the pursuit of individualized therapies for lung cancer. This, coupled with imaging advances in screening process, have all conspired to raise the bar on the limits of the bronchoscope, especially in the pursuit of small peripheral lesions. This review highlights advances in navigational bronchoscopy and tissue processing which may help the bronchoscopist of the 21st century meet these and other challenges.

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.

A major hallmark of non-small cell lung cancer (NSCLC) and other solid tumors is a desmoplastic tumor stroma rich in activated fibroblasts and fibrillar collagens. Previous studies have revealed that these tumor-associated fibroblasts contribute to virtually all steps of tumor progression and even therapy resistance. However, our knowledge of the prognostic value of markers of activated fibroblasts in NSCLC is very scarce. To fill this gap of knowledge we conducted a retrospective multicentric study of the prognostic value of the standard markers of activated fibroblasts α-SMA and fibrillar collagens by quantitative image analysis of α-SMA immunostaining and picrosirius red (PSR) staining, respectively. For this purpose tissue microarrays from a cohort of 222 patients with early-stage (I-IIp) NSCLC recruited in Spain for the International Association for the Study of Lung Cancer TNM-16 staging project were analyzed. A percentage of positive staining area/image was obtained for each marker and patient. Kaplan-Meier analysis revealed that PSR was associated with poor survival when using data obtained from both bright-field (p = 0.04) and polarized microscopy (p = 0.002), whereas α-SMA was not (p = 0.7). Remarkably, the prognostic value of PSR was independent of TNM stage, and patients with PSR above the cut-offs exhibited a 55% (for bright-field; HR=1.55, 95%CI (1.0-2.4)) and 109% (for polarized microscopy; HR=2.09, 95%CI (1.3-3.2)) increased risk of 3 year mortality. These results reveal that the content of stromal fibrillar collagens, assessed from image analysis of picrosirius red staining (particularly using polarized microscopy) is associated with adverse prognosis independently of the tumor stage. This new prognostic biomarker may help predict which patients subject to therapeutic surgery are at higher risk of progression and death. Moreover it supports that antifibrotic drugs aiming to target stromal fibrillar collagens may be an effective therapeutic approach to improve survival in NSCLC. Citation Format: Jordi Alcaraz, Laura Millares, Josep-Lluís Carrasco, Iuliana-Cristiana Benchea, Francisco-Javier Fernández, Esther Barreiro, Anabel Martínez, Julio Sánchez, María Ángeles González-Castro, Ana Blanco, Rosa Sánchez-Gil, Mireia Serra, Ramon Rami-Porta, Jaume Sauleda, Esther Fernández, Rosario Melchor, Luis Seijo, Leonardo de Esteban, Eduard Monsó. High stromal fibrillar collagen predicts poor survival in surgical non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1554.

Introduccion El objetivo del estudio ha sido analizar la eficacia y seguridad del cateter de drenaje pleural permanente en el manejo de pacientes con diagnostico de derrame pleural maligno. Pacientes y metodos Se ha realizado un estudio prospectivo y multicentrico de 63 pacientes consecutivos de 4 hospitales espanoles. Se incluyo a 43 varones y 20 mujeres, con una mediana de edad de 67 anos, diagnosticados de derrame pleural maligno sintomatico. En 7 casos el tratamiento se indico tras fracaso de pleurodesis, en 5 por encontrarse el pulmon atrapado, en otros 5 tras toracocentesis repetidas y en el resto como indicacion preferente a la pleurodesis. A todos los pacientes se les inserto de forma ambulatoria un cateter tunelizado permanente (PleurX®, Denver Biomedical). Resultados La mayoria de los pacientes (95,4%) refirio mejoria parcial o completa de los sintomas respiratorios (tos y disnea) y de su capacidad funcional. La mediana de duracion de uso del cateter fue de 45 dias (rango: 6�222). La mediana diaria de liquido pleural drenado fue de 75ml. En 22 casos (34,9%) se produjo una pleurodesis espontanea. No se registraron complicaciones durante la insercion del cateter. Las complicaciones durante el seguimiento fueron las siguientes: empiema (3 casos), dolor toracico (2 casos) y diseminaciones del tumor por el lugar de insercion del tubo (3 casos). Conclusiones El cateter de drenaje pleural permanente es eficaz en el manejo ambulatorio del paciente con derrame pleural maligno sintomatico. Es un procedimiento sencillo que no precisa ingreso hospitalario, de facil manejo para el paciente en su domicilio y con escasas complicaciones. Palabras clave: Derrame pleural maligno. Cateter pleural tunelizado permanente. Paciente ambulatorio.

Introduction: To analyse the effectiveness and safety of the indwelling pleural catheter in the management of recurrent malignant pleural effusion. Patients and methods: A prospective multicentre study was performed in 63 consecutive outpatients from four Spanish hospitals. A total of 43 men and 20 women were included, with a median age of 67 years. In seven of the cases treatment with pleurodesis had failed; in fi ve other cases their lung was trapped; in another fi ve cases after repeat therapeutic thoracocentesis, and the rest of them as a preference choice to pleurodesis. All patients had an indwelling pleural catheter inserted (PleurX

Lung cancer screening using computed tomography (CT) is effective in detecting early stage disease. However, concerns regarding adherence have been raised. The current authors conducted a retrospective observational study of 641 asymptomatic smokers enrolled in a lung cancer screening programme between 2000 and 2003. Adherent subjects were compared with nonadherent subjects with regard to lung function, sex, age, motivation for enrollment, smoking status, distance to the referral centre, family history of lung cancer, asbestos exposure, education, the presence and type of nodule(s) seen on initial CT, and exposure to a nursing intervention designed to improve adherence. Overall, early adherence to the study protocol was 65%. Multivariate analysis confirmed the importance of sex, proximity to the referral centre, the presence of noncalcified nodules, and the nursing intervention as factors conditioning adherence to the study protocol. Patients encouraged to participate in the study were more adherent, as were former smokers. Sex interactions were observed in multivariate analysis. The nursing intervention was significant for females, while abnormal lung function improved male adherence. Adherence to lung cancer screening is particularly good among females and subjects living near the referral centre. The present study suggests the need to develop new strategies, especially those targeting males and subjects with low risk perception, in order to improve adherence.

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre.

La navegaci?n electromagn?tica es una t?cnica novedosa capaz de facilitar la obtenci?n mediante broncoscopio de muestras de lesiones nodulares perif?ricas de peque?o tama?o y adenopat?as mediast?nicas. Permite realizar tanto biospias transbronquiales como punciones con aguja citol?gica, y por ello es muy vers?til. Publicamos el resultado de 2 casos en los que la combinaci?n de navegaci?n con el sistema superDimension/Bronchus y de t?cnicas diagn?sticas convencionales facilit? el diagn?stico definitivo mediante broncoscopia. La navegaci?n electromagn?tica ofrece la posibilidad de evitar m?todos diagn?sticos invasivos como la cirug?a, con el consiguiente ahorro econ?mico, de tiempo y de complicaciones.