Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services.

BACKGROUND: The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. METHODS: To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. RESULTS: The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. CONCLUSIONS: The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.

A randomised trial of lung sealant versus medical therapy for advanced emphysema.

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.

Lung inflammatory pattern and antibiotic treatment in pneumonia.

BACKGROUND: In community-acquired pneumonia host inflammatory response against the causative microorganism is necessary for infection resolution. However an excessive response can have deleterious effects. In addition to antimicrobial effects, macrolide antibiotics are known to possess immunomodulatory properties. METHODS: A prospective study was performed on 52 admitted patients who developed an inadequate response after 72 hours of antibiotic treatment - non-responders community-acquired pneumonia - (blood and bronchoalveolar lavage), and two control groups: 1) community-acquired pneumonia control (blood) and 2) non-infection control (blood and bronchoalveolar lavage). Cytokine profiles (interleukin (IL)-6, IL-8, IL-10), tumour necrosis factor α and clinical outcomes were assessed. RESULTS: Non-responders patients treated with macrolide containing regimens showed significantly lower levels of IL-6 and TNF-α in bronchoalveolar lavage fluid and lower IL-8 and IL-10 in blood than those patients treated with non-macrolide regimens. Clinical outcomes showed that patients treated with macrolide regimens required fewer days to reach clinical stability (p < 0.01) and shorter hospitalization periods (p < 0.01). CONCLUSIONS: After 72 hours of antibiotic effect, patients who received macrolide containing regimens exhibited lower inflammatory cytokine levels in pulmonary and systemic compartments along with faster stabilization of infectious parameters.

Quality-of-Life assessment in malignant pleural effusion treated with indwelling pleural catheter: a prospective study.

BACKGROUND: Malignant pleural effusion is a clinical problem that impairs Quality of Life in patients with advanced malignancies. An indwelling pleural catheter is an alternative treatment to palliate some of the symptoms. AIM: To evaluate the Quality of Life of outpatients with malignant pleural effusion who were treated with an indwelling pleural catheter. Questionnaire compliance, catheter patency time, and survival were analyzed. DESIGN: A multicenter observational study was conducted across five hospitals in Spain. Quality of Life was assessed at three different time points (before catheter placement and at 30 and 60 days post-placement) using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire QLQ-C30. For lung cancer patients, the QLQ-LC13 was also used. PARTICIPANTS: Patients with recurrent malignant pleural effusion treated with an indwelling pleural catheter. RESULTS: A total of 51 outpatients completed the baseline QLQ-C30 questionnaire. Of these, 28 completed the questionnaire at 30 days. Of these 28 patients, 13 completed the questionnaire at 60 days. Scores showed a significant improvement in symptoms scales at 30 days (p = 0.03). Global health status and functional scales showed a non-significant trend to improvement at 30 and 60 days. A total of 27 lung cancer patients completed the QLQ-LC13 questionnaire. Items assessing dyspnea showed a significant improvement following catheter placement (p = 0.002). CONCLUSION: Indwelling pleural catheter is useful for palliative management of recurrent malignant pleural effusion in that it benefits Quality of Life in outpatients with advanced malignancies. In lung cancer patients, scores indicated that indwelling pleural catheter also provides significant relief of dyspnea.

Utility of Next-Generation Sequencing in the Reconstruction of Clonal Architecture in a Patient with an EGFR Mutated Advanced Non-Small Cell Lung Cancer: A Case Report.

EGFR tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, targeted therapies impose a strong selective pressure against the coexisting tumor populations that lead to the emergence of resistant clones. Molecular characterization of the disease is essential for the clinical management of the patient, both at diagnosis and after progression. Next-generation sequencing (NGS) has been established as a technique capable of providing clinically useful molecular profiling of the disease in tissue samples and in non-invasive liquid biopsy samples (LB). Here, we describe a case report of a patient with metastatic NSCLC harboring EGFR mutation who developed two independent resistance mechanisms (EGFR-T790M and TP53 + RB1 mutations) to dacomitinib. Osimertinib given as a second-line treatment eliminated the EGFR-T790M population and simultaneously consolidated the proliferation of the TP53 + RB1 clone that eventually led to the histologic transformation to small-cell lung cancer (SCLC). Comprehensive NGS profiling revealed the presence of the TP53 + RB1 clone in the pretreatment biopsy, while EGFR-T790M was only detected after progression on dacomitinib. Implementation of NGS studies in routine molecular diagnosis of tissue and LB samples provides a more comprehensive view of the clonal architecture of the disease in order to guide therapeutic decision-making.

Translation of a tissue epigenetic signature to circulating free DNA suggests BCAT1 as a potential noninvasive diagnostic biomarker for lung cancer.

Lung cancer patients are diagnosed at late stages when curative treatments are no longer possible; thus, molecular biomarkers for noninvasive detection are urgently needed. In this sense, we previously identified and validated an epigenetic 4-gene signature that yielded a high diagnostic performance in tissue and invasive pulmonary fluids. We analyzed DNA methylation levels using the ultrasensitive digital droplet PCR in noninvasive samples in a cohort of 83 patients. We demonstrated that BCAT1 is the candidate that achieves high diagnostic efficacy in circulating DNA derived from plasma (area under the curve: 0.85). Impact of potentially confounding variables was also explored.

Development, Implementation and Assessment of Molecular Diagnostics by Next Generation Sequencing in Personalized Treatment of Cancer: Experience of a Public Reference Healthcare Hospital.

The establishment of precision medicine in cancer patients requires the study of several biomarkers. Single-gene testing approaches are limited by sample availability and turnaround time. Next generation sequencing (NGS) provides an alternative for detecting genetic alterations in several genes with low sample requirements. Here we show the implementation to routine diagnostics of a NGS assay under International Organization for Standardization (UNE-EN ISO 15189:2013) accreditation. For this purpose, 106 non-small cell lung cancer (NSCLC) and 102 metastatic colorectal cancer (mCRC) specimens were selected for NGS analysis with Oncomine Solid Tumor (ThermoFisher). In NSCLC the most prevalently mutated gene was TP53 (49%), followed by KRAS (31%) and EGFR (13%); in mCRC, TP53 (50%), KRAS (48%) and PIK3CA (16%) were the most frequently mutated genes. Moreover, NGS identified actionable genetic alterations in 58% of NSCLC patients, and 49% of mCRC patients did not harbor primary resistance mechanisms to anti-EGFR treatment. Validation with conventional approaches showed an overall agreement >90%. Turnaround time and cost analysis revealed that NGS implementation is feasible in the public healthcare context. Therefore, NGS is a multiplexed molecular diagnostic tool able to overcome the limitations of current molecular diagnosis in advanced cancer, allowing an improved and economically sustainable molecular profiling.

Bronchoscopic Lung Volume Reduction.

Since the publication of the National Emphysema Treatment Trial study, lung volume reduction (LVR) has been considered a therapeutic alternative for patients with advanced obstructive lung disease. The high complication rate of surgical LVR has led to the development of bronchoscopic LVR (BLVR). Of the currently available BLVR alternatives, coils and unidirectional endobronchial valves lead the list. The choice of each device depends on emphysema characteristics and presence of collateral ventilation. Evaluation of these patients at centers with expertise in interventional pulmonology and management of BLVR is strongly recommended.

Benefit of Chest Ultrasonography in the Diagnosis of Peripheral Thoracic Lesions in an Interventional Pulmonology Unit. / Utilidad de la ecografía en el diagnóstico de lesiones torácicas periféricas realizadas en una unidad de técnicas de neumología.

INTRODUCTION AND OBJECTIVES: The use of ultrasound in peripheral thoracic lesions offers advantages over other radiological guiding methods. This diagnostic procedure has been applied in most studies published by radiologists. Our aim was to determine the diagnostic efficacy of percutaneous ultrasound-guided punctures and biopsies of peripheral thoracic lesions performed by pulmonologists. METHODOLOGY: A retrospective analysis of 58 patients who underwent real-time ultrasound-guided transthoracic punctures and biopsy of peripheral thoracic lesions between March 2011 and September 2014 in the pulmonology department of our hospital. Cases were classified into the following diagnostic categories: malignant, benign and non-diagnostic (non-specific benign without evidence of malignancy and insufficient specimen). RESULTS: A conclusive diagnosis was obtained in 47 procedures (81%), of which 13 (22.4%) were specific benign lesions and 34 (58.6%) cancers. In the remaining 11 (19%) patients, a non-diagnostic result was obtained [non-specific benign in 5 cases (8.6%) and insufficient specimen in 6 (10.3%)]. Sensitivity was 75.6%, negative predictive value was 54.2%, specificity and positive predictive value were 100%, and diagnostic accuracy was 81%. Excluding procedures with insufficient specimens, the results were 87.2%, 72.3%, 100%, 100% and 90.4% respectively. There were no serious complications. CONCLUSIONS: Percutaneous ultrasound-guided puncture and biopsy in the diagnosis of peripheral thoracic lesions performed by pulmonologists is a safe procedure with high diagnostic accuracy. We achieved similar results to those previously obtained by radiologists.

Determinants of false-negative results in non-small-cell lung cancer staging by endobronchial ultrasound-guided needle aspiration.

OBJECTIVES: False-negative results of endobronchial ultrasound-guided transbronchial needle aspiration in non-small-cell lung cancer staging have shown significant variability in previous studies. The aim of this study was to identify procedure- and tumour-related determinants of endobronchial ultrasound-guided transbronchial needle aspiration false-negative results. METHODS: We conducted a prospective study that included non-small-cell lung cancer patients staged as N0/N1 by endobronchial ultrasound-guided transbronchial needle aspiration and undergoing therapeutic surgery. The frequency of false-negative results in the mediastinum was calculated. Procedure-related, first, and tumour-related, second, determinants of false-negative results in stations reachable and non-reachable by endobronchial ultrasound were determined by multivariate logistic regression. RESULTS: False-negative endobronchial ultrasound-guided transbronchial needle aspiration results were identified in 23 of 165 enrolled patients (13.9%), mainly in stations reachable by endobronchial ultrasound (17 cases, 10.3%). False-negative results were related to the extensiveness of endobronchial ultrasound sampling: their prevalence was low (2.4%) when sampling of three mediastinal stations was satisfactory, but rose above 10% when this requirement was not fulfilled (P = 0.043). In the multivariate analysis, abnormal mediastinum on computer tomography/positron emission tomography [odds ratio (OR) 7.77, 95% confidence interval (CI) 2.19-27.51, P = 0.001] and extensiveness of satisfactory sampling of mediastinal stations (OR 0.37, 95% CI 0.16-0.89, P = 0.026) were statistically significant risk factors for false-negative results in stations reachable by endobronchial ultrasound. False-negative results in non-reachable nodes were associated with a left-sided location of the tumour (OR 10.11, 95% CI 1.17-87.52, P = 0.036). CONCLUSIONS: The presence of false-negative ultrasound-guided transbronchial needle aspiration results were observed in nearly 15% of non-small-cell lung cancer patients but in only 3% when satisfactory samples were obtained from three mediastinal stations. False-negative results in stations reachable by endobronchial ultrasound were associated with the extensiveness of sampling, and in stations out of reach of endobronchial ultrasound with left-sided tumours. These results suggest that satisfactory sampling of at least three mediastinal stations by EBUS-TBNA may be a quality criterion to be recommended for EBUS-TBNA staging.

Utilización del catéter tunelizado permanente para administración de quimioterapia intrapleural a largo plazo: a propósito de 2 casos / Two cases of permanent indwelling catheter for long-term administration of intrapleural chemotherapy

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Utilidad de la ecografía en el diagnóstico de lesiones torácicas periféricas realizadas en una unidad de técnicas de neumología / Benefit of Chest Ultrasonography in the Diagnosis of Peripheral Thoracic Lesions in an Interventional Pulmonology Unit

Introducción y objetivos: La ecografía como guía en la punción percutánea de lesiones torácicas periféricas (LTP) ofrece ventajas frente a otras técnicas de imagen. La mayoría de los estudios con esta técnica han sido comunicados por radiólogos intervencionistas. El objetivo de este estudio ha sido analizar la rentabilidad diagnóstica de la punción percutánea guiada por ecografía en una unidad de técnicas de neumología. Metodología: Estudio retrospectivo de 58 pacientes con LTP puncionadas con visualización ecográfica en tiempo real, entre el 1 de marzo de 2011 y el 1 de septiembre de 2014. Los resultados fueron divididos en 3 categorías diagnósticas: maligna, benigna y no diagnóstica (ND); esta última incluye los resultados de benignidad no específica (SD) y los de muestra insuficiente para diagnóstico (MID). Resultados: Se obtuvo: resultado maligno en 34 (58,6%) de los procedimientos, resultado benigno en 13 (22,4%) y ND en 11 (19%) (SD en 5 [8,6%] y MID en 6 [10,3%]). En 5 de los casos ND el resultado final fue de malignidad y en 4 de ellos se tratada de una MID. La sensibilidad diagnóstica obtenida fue del 75,6%, el valor predictivo negativo del 54,2%, y la especificidad y el valor predictivo positivo del 100%, con una rentabilidad diagnóstica del 81%. Cuando se excluyeron los casos con MID los valores fueron del 87,2%, 72,3%, 100% y 100%, respectivamente, con una rentabilidad diagnóstica del 90,4%. No hubo complicaciones graves con la técnica. Conclusiones: La punción percutánea bajo guía ecográfica en LTP realizada por neumólogos intervencionistas es una técnica segura y con una alta rentabilidad diagnóstica

Introduction and objectives: The use of ultrasound in peripheral thoracic lesions offers advantages over other radiological guiding methods. This diagnostic procedure has been applied in most studies published by radiologists. Our aim was to determine the diagnostic efficacy of percutaneous ultrasound-guided punctures and biopsies of peripheral thoracic lesions performed by pulmonologists. Methodology: A retrospective analysis of 58 patients who underwent real-time ultrasound-guided transthoracic punctures and biopsy of peripheral thoracic lesions between March 2011 and September 2014 in the pulmonology department of our hospital. Cases were classified into the following diagnostic categories: malignant, benign and non-diagnostic (non-specific benign without evidence of malignancy and insufficient specimen). Results: A conclusive diagnosis was obtained in 47 procedures (81%), of which 13 (22.4%) were specific benign lesions and 34 (58.6%) cancers. In the remaining 11 (19%) patients, a non-diagnostic result was obtained [non-specific benign in 5 cases (8.6%) and insufficient specimen in 6 (10.3%)]. Sensitivity was 75.6%, negative predictive value was 54.2%, specificity and positive predictive value were 100%, and diagnostic accuracy was 81%. Excluding procedures with insufficient specimens, the results were 87.2%, 72.3%, 100%, 100% and 90.4% respectively. There were no serious complications. Conclusions: Percutaneous ultrasound-guided puncture and biopsy in the diagnosis of peripheral thoracic lesions performed by pulmonologists is a safe procedure with high diagnostic accuracy. We achieved similar results to those previously obtained by radiologists

[Use of indwelling pleural catheter in the outpatient management of recurrent malignant pleural effusion]. / Uso del drenaje pleural permanente en el manejo ambulatorio del derrame pleural maligno recidivante.

BACKGROUND AND OBJECTIVE: 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 five other cases their lung was trapped; in another five 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), Denver Biomedical). RESULTS: Most of patients (94.5%) reported an improvement in their respiratory symptoms (cough and dyspnoea) and their ability to function independently. Average length of the catheterisation was 45 days (6-222). Average amount of drained pleural effusion was 75ml, with a frequency of drainage of between 3 and 4 times per week and once fortnightly. Spontaneous pleurodesis was achieved following 34.9% of procedures. No complications occurred during the insertion of the catheter. The post-catheterisation complications were empyema (3 cases), chest pain (2 cases), and tumour metastasis (3 cases). CONCLUSIONS: The use of an indwelling pleural catheter is an effective palliative treatment in the outpatient management for patients suffering malignant pleural effusion. It is also a simple treatment that can be easily applied, does not require hospitalisation and can be easily managed by the patient at home, with a low rate of complications.

Uso del drenaje pleural permanente en el manejo ambulatorio del derrame pleural maligno recidivante / Use of Indwelling Pleural Catheter in the Outpatient Management of Recurrent Malignant Pleural Effusion

IntroducciónEl objetivo del estudio ha sido analizar la eficacia y seguridad del catéter de drenaje pleural permanente en el manejo de pacientes con diagnóstico de derrame pleural maligno.Pacientes y métodosSe ha realizado un estudio prospectivo y multicéntrico de 63 pacientes consecutivos de 4 hospitales españoles. Se incluyó a 43 varones y 20 mujeres, con una mediana de edad de 67 años, diagnosticados de derrame pleural maligno sintomático. En 7 casos el tratamiento se indicó tras fracaso de pleurodesis, en 5 por encontrarse el pulmón atrapado, en otros 5 tras toracocentesis repetidas y en el resto como indicación preferente a la pleurodesis. A todos los pacientes se les insertó de forma ambulatoria un catéter tunelizado permanente (PleurX®, Denver Biomedical).ResultadosLa mayoría de los pacientes (95,4%) refirió mejoría parcial o completa de los síntomas respiratorios (tos y disnea) y de su capacidad funcional. La mediana de duración de uso del catéter fue de 45 días (rango: 6–222). La mediana diaria de líquido pleural drenado fue de 75ml. En 22 casos (34,9%) se produjo una pleurodesis espontánea. No se registraron complicaciones durante la inserción del catéter. Las complicaciones durante el seguimiento fueron las siguientes: empiema (3 casos), dolor torácico (2 casos) y diseminaciones del tumor por el lugar de inserción del tubo (3 casos).ConclusionesEl catéter de drenaje pleural permanente es eficaz en el manejo ambulatorio del paciente con derrame pleural maligno sintomático. Es un procedimiento sencillo que no precisa ingreso hospitalario, de fácil manejo para el paciente en su domicilio y con escasas complicaciones(AU)

Background and objectiveTo analyse the effectiveness and safety of the indwelling pleural catheter in the management of recurrent malignant pleural effusion.Patients and methodsA 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 five other cases their lung was trapped; in another five 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®, Denver Biomedical).ResultsMost of patients (94.5%) reported an improvement in their respiratory symptoms (cough and dyspnoea) and their ability to function independently. Average length of the catheterisation was 45 days (6–222). Average amount of drained pleural effusion was 75ml, with a frequency of drainage of between 3 and 4 times per week and once fortnightly. Spontaneous pleurodesis was achieved following 34.9% of procedures. No complications occurred during the insertion of the catheter. The post-catheterisation complications were empyema (3 cases), chest pain (2 cases), and tumour metastasis (3 cases).ConclusionsThe use of an indwelling pleural catheter is an effective palliative treatment in the outpatient management for patients suffering malignant pleural effusion. It is also a simple treatment that can be easily applied, does not require hospitalisation and can be easily managed by the patient at home, with a low rate of complications(AU)