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Jessica González, 1 Pilar Rivera-Ortega, 1 Macarena Rodríguez-Fraile, 2 Patricia Restituto, 3 Inmaculada Colina, 4 María de los Desamparados Calleja, 5 Ana B Alcaide, 1 Aránzazu Campo, 1 Juan Bertó, 1 Luis Seijo, 6 Maria Teresa Pérez-Warnisher, 6 Javier J Zulueta, 1 Nerea Varo, 3 Juan P de-Torres 7 1Pulmonary Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain; 2Nuclear Medicine Department, Clínica Universidad de Navarra, Pamplona, Spain; 3Biochemistry Department, Clínica Universitaria de Navarra, Pamplona, Spain; 4Department of Internal Medicine, Clínica Universidad de Navarra, Pamplona, Spain; 5Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain; 6Pulmonary Department, Clínica Universidad de Navarra, Madrid, Spain; 7Respirology Division, Queen’s University, Kingston, ON, CanadaCorrespondence: Jessica GonzálezPulmonary department, Hospital Universitari Arnau de Vilanova, Lleida, SpainEmail jgonzalezgutierrez@gmail.comRationale: 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=< 0.001) and severe in those with low BMD. Multivariable analysis adjusting for other significant cofactors (age, sex, FEV 1, and severity of emphysema) showed that BMI (OR=0.91, 95% CI: 0.76– 0.92) and centrilobular emphysema (OR=26.19, 95% CI: 1.71 to 399.44) were associated with low BMD.Conclusion: Low BMD is highly prevalent in current and former smokers. BMI and centrilobular emphysema are strong and independent predictors of its presence, which suggests that they should be considered when evaluating smokers at risk for low BMD.Keywords: emphysema, COPD, low bone mineral density, osteopenia, osteoporosis; smokers

El estudio de las bronquiectasias ha generado un interés creciente. Se continúa investigando sobre la verdadera prevalencia (los escasos trabajos publicados muestran resultados muy dispares), los mecanismos implicados o su relación con otras patologías. Además, se desconocen los datos en la población asintomática. Los individuos sin síntomas que participan en un programa de cribado de cáncer de pulmón mediante Tomografía Computarizada de baja dosis de radiación (TCBD), son una población idónea para estudiar enfermedades en estadios precoces. En un programa de cribado la aparición de falsos positivos suponen un problema. Las bronquiectasias podrían dar lugar a falsos positivos que supongan un daño para el paciente. Por último, cabe plantearse si las bronquiectasias comparten algún mecanismo que pueda influir en el desarrollo del cáncer. Se estudiaron los pacientes incluidos en el programa I-ELCAP (International Early Lung Cancer Program) en la Clínica Universidad de Navarra, entre los años 2000 y 2012, seguidos hasta el 2014. En la evaluación inicial se realizó una TCBD basal, un cuestionario epidemiológico y una espirometría. En función de los hallazgos de las TCBD se aplicó el protocolo de I-ELCAP del que se extrajo un listado de los sujetos con bronquiectasias. La elección de los individuos sin bronquiectasias se realizó mediante emparejamiento 1:1 por sexo, tabaquismo y edad. Para la medición de la gravedad y extensión de las bronquiectasias se utilizó la escala de Bhalla. Se incluyeron en el programa P-IELCAP 3028 sujetos y se identificaron 354 individuos con bronquiectasias, predominantemente varones (73%), con una edad media de 60,9 años y un consumo medio de tabaco de 40 paquetes-año. Por tanto, la prevalencia de bronquiectasias fue del 11,7%. Tras aplicar la escala de Bhalla, se observó que la mediana de puntuación de las bronquiectasias fue de 7 puntos. Se identificaron 307 pacientes con grado de enfermedad leve, 46 moderada y solo 1 paciente con afectación grave. Un 45% de los pacientes las presentaba de forma bilateral. La afectación por generaciones resultó ser homogénea. El daño de ambos lóbulos superiores se presentó en 42 casos y de ambos lóbulos inferiores en 67. Los pacientes con bronquiectasias mostraban más frecuentemente obstrucción al flujo aéreo, mayor gravedad de la misma y mayor presencia de enfisema. No se observaron diferencias en la prevalencia de antecedentes de infección u otras enfermedades. De los 354 individuos con bronquiectasias en la TCBD inicial se observaron nódulos pulmonares en un 53% y un 17% en los que no las presentaban. Los falsos positivos fueron mayores entre los pacientes con bronquiectasias (26% vs. 17%), lo que condujo a una mayor proporción de TCBD en los sujetos con bronquiectasias y más indicaciones de toma de antibióticos. No hubo diferencias en el número de cánceres. En los TCBD de seguimiento se encontraron más nódulos nuevos en pacientes con bronquiectasias que en los sujetos control (17% y 12%). El número de falsos positivos durante el seguimiento fue de 129 para los pacientes con bronquiectasias frente a 88 para el otro grupo. La necesidad de pruebas adicionales o antibióticos en los pacientes con bronquiectasias versus sujetos sin bronquiectasias fue mayor para TCBD y toma de antibiótico. Trece pacientes fueron diagnosticados de cáncer, 6 en el grupo de bronquiectasias y 7 en sus respectivos controles (p= 0,77). En las espirometrías basales se observa un 55% de obstrucción al flujo aéreo en el grupo de bronquiectasias y un 45% en los individuos sin ellas. Del total de 708 sujetos, se estudian 203 pacientes con datos de función pulmonar tanto al inicio como al final del programa. En ambos grupos se observa una caída del FEV1 significativa, sin diferencias entre ambos grupos. La caída del FEV1 tanto total como anual se asocia a la cantidad de paquetes-año fumados, pero no a la presencia de bronquiectasias, la edad ni el sexo.

Rationale: Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs) have shown benefit in other inflammatory diseases. Objectives: To evaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF. Methods: A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, three patients were included sequentially in three dose cohorts (10x10(6), 50x10(6) and 100x10(6) cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with pulmonary function testing, 6-min walk test and St George's Respiratory Questionnaire was done at 1, 2, 3, 6 and 12 months, and with computed tomography at 3, 6 and 12 months. Results: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at 3 months and three (23%) at 12 months. Conclusions:..

1. INTRODUCIÓN En España se detectan anualmente más de 23.000 casos de cáncer de pulmón (CP) con una tasa de supervivencia del 18 % luego de cinco años. Determinada básicamente por la naturaleza asintomática del CP durante los estadios iniciales, solo un 16% de los casos se diagnostican en esta etapa. El cribado de CP con TCBD ha mostrado eficacia en la detección y diagnóstico del CP en fase inicial. Un tema muy debatido en el cribado son los falsos positivos, pacientes sanos con nódulos pulmonares indeterminados que se someten a procedimientos quirúrgicos o no, con consecuencias físicas y emocionales. Luego de dos décadas del inicio del programa PELCAP, el de mayor duración en Europa, el número de pacientes quirúrgicos diagnosticados con CP nos permitió analizar y describir sus resultados y las posibles causas de los falsos positivos (FP). 2. OBJETIVOS 1. Describir las características y resultados obtenidos en pacientes tratados quirúrgicamente. 2. Analizar el subgrupo sometido a cirugía y cuyo diagnóstico final no fue de CP. 3. Comparar a partir de tres encuestas validadas, el nivel de satisfacción y la CDV entre los intervenidos quirúrgicamente y cuyo diagnóstico final fue cáncer o enfermedad benigna. 3. MATERIAL Y METODOS El universo considerado fueron los pacientes reclutados entre septiembre de 2000 y diciembre de 2019 y que fueron sometidos a cirugía. 1. Antes de la resección pulmonar, el mediastino se evaluó en función de los hallazgos del TCBD o PET, a través de EBUS, EUS o mediastinoscopia. En todos los casos, un equipo multidisciplinario decidió las intervenciones quirúrgicas u oncológicas. 2. Revisión detallada de las historias clínicas e imágenes de los FP, permitiendo así una auditoría basada en la valoración de cada prueba realizada y contrastarla con la información incluida en los algoritmos. 3. Se evaluaron mediante tres encuestas validadas a 24 pacientes, 8 FP junto a 16 diagnosticados de CP como grupo control emparejado (1:2). El comité de ética de la Universidad de Navarra aprobó el protocolo de estudio y todos los sujetos firmaron un consentimiento. 4. RESULTADOS 1. Participaron 3825 sujetos en el programa de cribado, 97 (2.5%) CP fueron diagnosticados en 95 pacientes. Solo 14 pacientes (16,1%) tuvieron un diagnóstico preoperatorio no quirúrgico de CP. Se realizaron 87 cirugías en 75 pacientes por sospecha de CP. 59 (88,1%) fueron diagnosticados en estadio I. Las tasas de supervivencia para los pacientes en estadio I a los 5 y 10 años fueron de 93% y 83% respectivamente. 2. 7 de los 8 pacientes FP del proceso de cribado no siguieron correctamente el algoritmo I-ELCAP. 3. El grupo de FP mostró un alto grado de satisfacción respecto a la calidad asistencial en el EORTC IN-PATSAT32, una excelente CDV en sus dimensiones física y emocional en el SF12, y un alto grado de satisfacción respeto a la percepción de su salud en el SATISCORE. En este último, el 100% de los encuestados afirmaron que se someterían de nuevo a cirugía bajo las mismas circunstancias. 5. CONCLUSIONES 1. El cribado de CP mediante TCBD anual permite su diagnóstico precoz. 2. Las tasas de supervivencia a largo plazo en pacientes diagnosticados supera el 80%. 3. El porcentaje de FP fue de 9,2%. 4. El seguimiento riguroso del protocolo, asociado a una gestión multidisciplinar integrada y coordinada, podría resultar en una baja tasa de FP. 5. La provisión de información adecuada y oportuna sobre beneficios y riesgos del cribado, junto con una asistencia integral de alta calidad, favorecen un alto grado de satisfacción y la disminución del impacto psicosocial en pacientes intervenidos por lesiones benignas o no. 6. Los sujetos falsos positivos en ausencia de complicaciones, mostraron alto grado de satisfacción y CDV en sus dimensiones física y mental.

Introduction: The Spanish COPD guidelines (GesEPOC) have been recently modified. The aim of this study is to assess this revision and evaluate the prognosis of patients according to the new classification of severity. Methods: A total of 700 COPD patients (83.9% men) were prospectively followed up for a mean period of 5 years in tertiary hospitals in Spain and the USA. Anthropometric data, lung function tests, dyspnea (according to the mMRC scale), BODE and Charlson index were collected. We calculated mortality at 5 years following the risk criteria proposed by the new GesEPOC. Results: Mean age was 66 ± 9.6 years and mean FEV1% was 59.7 ± 20.2. The proportion of patients in the low-risk group was 40.43%. Patients in the high-risk group had a significantly higher BODE index than those in the low-risk group (2.92 ± 0, 66 vs. 0.52 ± 1.91, p < 0.001), while the Charlson index score was similar in both groups. Mortality at 60 months was significantly higher in the high-risk group (31.7% vs. 15.5%, p < 0.001). Dyspnea and FEV1% were also independent predictors of mortality (p < 0.001), and neither was inferior to the risk classification proposed by GesEPOC. Conclusions: The new severity index proposed by GesEPOC accurately predicts 5-year mortality. However, dyspnea and FEV1% have the same strength in predicting mortality.

Trials have been carried out with Holm oak and Cork oak acorns, in the same edafoclimatic conditions in land in Extremadura, in order to establish germination losses by growth temperatures and loss of humidity. The results show that temperature does not affect germination until it rises above 55º C, therefore it does not have a negative effect, whatever the type of storage. In Holm oak, the loss of humidity of 15 p. 100 brings about a mayor decrease in the germination, which is absolute from 20 p. 100. In the Cork oak, there is an acceptable level of germination between a loss of 25-30 p. 100 and nil germination from 40 p. 100. With the drying of the air, under trial conditions, the Holm oak acorns did not germinate after 21 days, and the Cork oak after 38 days., En bellotas de alcornoque y encina, situados en iguales condiciones edafoclimáticas en una dehesa extremeña, se han hecho ensayos para determinar pérdidas de germinación por temperaturas y pérdidas de humedad crecientes. Los resultados muestran que la temperatura no afecta a la germinación hasta superar 55º C, por lo que no tiene efecto negativo en cualquier sistema de almacenaje. En encina la pérdida de humedad del 15 p. 100 supone una importante disminución de la germinación, que es total a partir del 20 p. 100. En alcornoque hay aceptable germinación entre una pérdida de 25-30 p. 100 y la germinación es nula al llegar al 40 p. 100. Con la desecasción al aire, en las condiciones del ensayo, las bellotas de encina no germinan después de 21 días y las de alcornoque después de 38 días.

EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events

OBJECTIVE: Our objective was to assess the usefulness of emphysema scores in predicting death from COPD and lung cancer. METHODS: Emphysema was assessed with low-dose CT scans performed on 9,047 men and women for whom age and smoking history were documented. Each scan was scored according to the presence of emphysema as follows: none, mild, moderate, or marked. Follow-up time was calculated from time of CT scan to time of death or December 31, 2007, whichever came first. Cox regression analysis was used to calculate the hazard ratio (HR) of emphysema as a predictor of death. RESULTS: Median age was 65 years, 4,433 (49%) were men, and 4,133 (46%) were currently smoking or had quit within 5 years. Emphysema was identified in 2,637 (29%) and was a significant predictor of death from COPD (HR, 9.3; 95% CI, 4.3-20.2; P < .0001) and from lung cancer (HR, 1.7; 95% CI, 1.1-2.5; P = .013), even when adjusted for age and smoking history. CONCLUSIONS: Visual assessment of emphysema on CT scan is a significant predictor of death from COPD and lung cancer.

Recensión

F.H.W. Morley (director de la edición), 1981. Grazing Animals. World Animal Science, B-1, 411 páginas. Elsevier Scientific Publishing Company, Amsterdam-Oxford-New York. ISBN 0-444-41835-0

Jeffrey, CH. Nomenclatura Biológica. Código Internacional de Nomenclatura Botánica. Código Internacional de Nomenclatura Zoológica. Editorial H. Blume

Epidermal growth factor receptor (EGFR) and K-ras mutations guide treatment selection in non-small cell lung cancer (NSCLC) patients. Although mutation status is routinely assessed in biopsies, cytological specimens are frequently the only samples available. We determined EGFR and K-ras mutations in cytological samples. METHODS: DNA was extracted from 150 consecutive samples, including 120 Papanicolau smears (80%), 10 cell blocks (7%), nine fresh samples (6%), six ThinPrep(R) tests (4%), and five body cavity fluids (3.3%). Papanicolau smears were analyzed when they had >50% malignant cells. Polymerase chain reaction and direct sequencing of exons 18-21 of EGFR and exon 2 of K-ras were performed. EGFR mutations were simultaneously determined in biopsies and cytological samples from 20 patients. Activity of EGFR tyrosine kinase inhibitors (TKIs) was assessed. RESULTS: The cytological diagnosis was adenocarcinoma in 110 samples (73%) and nonadenocarcinoma in 40 (27%) samples. EGFR mutations were identified in 26 samples (17%) and K-ras mutations were identified in 18 (12%) samples. EGFR and K-ras mutations were mutually exclusive. In EGFR-mutated cases, DNA was obtained from stained smears in 24 cases (92%), pleural fluid in one case (4%), and cell block in one case (4%). The response rate to EGFR TKIs in patients harboring mutations was 75%. The mutation status was identical in patients who had both biopsies and cytological samples analyzed. CONCLUSION: Assessment of EGFR and K-ras mutations in cytological samples is feasible and comparable with biopsy results, making individualized treatment selection possible for NSCLC patients from whom tumor biopsies are not available.

Commonwealth Bureau of Pastures and Field Crops (CAB), 1978: Measurements of grassland vegetation and animal production. Boletín 52,260 p. (Edición dirigida por L'.tMannerje.) Farnham Royal, Bucks, England. ISBN 0-85198-404-5

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.

Rationale: Idiopathic pulmonary fibrosis (IPF) has a dismal prognosis. Mesenchymal stromal cells (MSCs) have shown benefit in other inflammatory diseases. Objectives: To evaluate the safety and feasibility of endobronchial administration of bone marrow autologous MSCs (BM-MSC) in patients with mild-to-moderate IPF. Methods: A phase I multicentre clinical trial (ClinicalTrials.gov NCT01919827) with a single endobronchial administration of autologous adult BM-MSCs in patients diagnosed with mild-to-moderate IPF. In a first escalating-dose phase, three patients were included sequentially in three dose cohorts (10×106, 50×106 and 100×106 cells). In a second phase, nine patients received the highest tolerated dose. Follow-up with pulmonary function testing, 6-min walk test and St George’s Respiratory Questionnaire was done at 1, 2, 3, 6 and 12 months, and with computed tomography at 3, 6 and 12 months. Results: 21 bone marrow samples were obtained from 17 patients. Three patients were excluded from treatment due to chromosome aberrations detected in MSCs after culture, and one patient died before treatment. Finally, 13 patients received the BM-MSC infusion. No treatment-related severe adverse events were observed during follow-up. Compared to baseline, the mean forced vital capacity showed an initial decline of 8.1% at 3 months. The number of patients without functional progression was six (46%) at 3 months and three (23%) at 12 months. Conclusions: The endobronchial infusion of BM-MSCs did not cause immediate serious adverse events in IPF patients, but a relevant proportion of patients suffered clinical and/or functional progression. Genomic instability of BM-MSCs during culture found in three patients may be troublesome for the use of autologous MSCs in IPF patients.

Identification of risk factors for lung cancer can help in selecting patients who may benefit the most from smoking cessation interventions, early detection, or chemoprevention. OBJECTIVE: To evaluate whether the presence of emphysema on low-radiation-dose CT (LDCT) of the chest is an independent risk factor for lung cancer. METHODS: The study used data from a prospective cohort of 1,166 former and current smokers participating in a lung cancer screening study. All individuals underwent a baseline LDCT and spirometry followed by yearly repeat LDCT studies. The incidence density of lung cancer among patients with and without emphysema on LDCT was estimated. Stratified and multiple regression analyses were used to assess whether emphysema is an independent risk factor for lung cancer after adjusting for age, gender, smoking history, and the presence of airway obstruction on spirometry. RESULTS: On univariate analysis, the incidence density of lung cancer among individuals with and without emphysema on LDCT was 25.0 per 1,000 person-years and 7.5 per 1,000 person-years, respectively (risk ratio [RR], 3.33; 95% confidence interval [CI], 1.41 to 7.85). Emphysema was also associated with increased risk of lung cancer when the analysis was limited to individuals without airway obstruction on spirometry (RR, 4.33; 95% CI, 1.04 to 18.16). Multivariate analysis showed that the presence of emphysema (RR, 2.51; 95% CI, 1.01 to 6.23) on LDCT but not airway obstruction (RR, 2.10; 95% CI, 0.79 to 5.58) was associated with increased risk of lung cancer after adjusting for potential cofounders. CONCLUSIONS: Results suggest that the presence of emphysema on LDCT is an independent risk factor for lung cancer.

A lung transplant is usually the final therapeutic option for patients with respiratory insufficiency. In spite of the many advances in immunology and the management of complications, mortality and morbidity associated with this transplant are far higher than with others. Acute rejection is an almost universal problem in the first year, while obliterative bronchitis reduces long term survival. Respiratory infections also play a significant role in the complications associated with lung transplants due to the constant exposure of the graft to the outside. However, the success of this therapeutic option, which basically depends on a suitable selection of donor and recipient, are evident, above all with respect to quality of life.

El cáncer de pulmón es una de las causas de muerte más frecuentes en el mundo occidental. La supervivencia global de los pacientes no supera el 15% a los 5 años, debido principalmente a que la mayor parte de los casos se diagnostican en estadios avanzados. Además de la prevención primaria, mediante la reducción del consumo de tabaco, son necesarias nuevas tecnologías para el diagnóstico precoz de la enfermedad. Estudios recientes han demostrado que el TAC helicoidal del tórax es efectivo en la detección de nódulos pulmonares malignos en estadios precoces. En la actualidad se está valorando su eficacia en series amplias de pacientes de alto riesgo. Recientemente se ha desarrollado una nueva técnica de citogenética molecular, el FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms). Esta técnica permite el análisis simultáneo de marcadores inmunofenotípicos y alteraciones genéticas presentes en las células tumorales. El objetivo de nuestro proyecto es su puesta a punto para el estudio de muestras de esputo y lavado broncoalveolar de pacientes con cáncer de pulmón. El fin último es estudiar la posibilidad de que esta técnica pueda ser utilizada, junto con el TAC helicoidal, en programas de detección precoz de cáncer de pulmón, para pacientes de alto riesgo. En este trabajo presentamos una revisión de la contribución de las distintas técnicas de citogenética al estudio del cáncer de pulmón y la metodología de trabajo que vamos a llevar a cabo en nuestro proyecto.