The Role of Inflammatory Phenotype in Patients With Exacerbation-prone Asthma and Ongoing Therapy

Introduction: The risk factors for having frequent exacerbations are not well documented in cohort studies of patients with asthma on existing therapy. The objective of the present study was to compare the clinical and inflammatory characteristics of patients with exacerbation-prone asthma (EPA) with a history of two or more exacerbations in the previous year with those who had presented just one or no exacerbation. Methods: An ambispective observational study was conducted in a tertiary hospital. Patients diagnosed with moderate or severe asthma and ongoing therapy, whose inflammatory profile was determined by means of allergy and atopy status, blood eosinophilia and induced sputum were included. Patients were classified according to the number of asthma exacerbations in EPA (≥2 exacerbations in the previous year) vs. non-exacerbators (≤1 exacerbation in the previous year). Clinical, lung function and inflammatory characteristics of the two groups were compared. Results: Three hundred ten patients were visited in the Asthma Unit in 2018 and the combination of atopy and allergy status, blood eosinophilia and induced sputum was obtained in 96 (31%) patients. Of this latter group, 46 patients (47%) presented EPA compared to 50 (53%) non-exacerbators. Airway and blood eosinophilic inflammation did not differ between EPA and non-exacerbators in patients with asthma and ongoing therapy, and it was not a risk factor for EPA in our cohort. Conclusion: Airway or blood type 2 inflammation status is not a valid tool for recognizing EPA or predicting asthma exacerbations in asthma patients following controller therapy. (AU)

The Role of Inflammatory Phenotype in Patients With Exacerbation-prone Asthma and Ongoing Therapy.

INTRODUCTION: The risk factors for having frequent exacerbations are not well documented in cohort studies of patients with asthma on existing therapy. The objective of the present study was to compare the clinical and inflammatory characteristics of patients with exacerbation-prone asthma (EPA) with a history of two or more exacerbations in the previous year with those who had presented just one or no exacerbation. METHODS: An ambispective observational study was conducted in a tertiary hospital. Patients diagnosed with moderate or severe asthma and ongoing therapy, whose inflammatory profile was determined by means of allergy and atopy status, blood eosinophilia and induced sputum were included. Patients were classified according to the number of asthma exacerbations in EPA (≥2 exacerbations in the previous year) vs. non-exacerbators (≤1 exacerbation in the previous year). Clinical, lung function and inflammatory characteristics of the two groups were compared. RESULTS: Three hundred ten patients were visited in the Asthma Unit in 2018 and the combination of atopy and allergy status, blood eosinophilia and induced sputum was obtained in 96 (31%) patients. Of this latter group, 46 patients (47%) presented EPA compared to 50 (53%) non-exacerbators. Airway and blood eosinophilic inflammation did not differ between EPA and non-exacerbators in patients with asthma and ongoing therapy, and it was not a risk factor for EPA in our cohort. CONCLUSION: Airway or blood type 2 inflammation status is not a valid tool for recognizing EPA or predicting asthma exacerbations in asthma patients following controller therapy.

Therapeutic reconditioning of damaged lungs by transient heat stress during ex vivo lung perfusion.

Ex vivo lung perfusion (EVLP) may serve as a platform for the pharmacologic repair of lung grafts before transplantation (LTx). We hypothesized that EVLP could also permit nonpharmacologic repair through the induction of a heat shock response, which confers stress adaptation via the expression of heat shock proteins (HSPs). Therefore, we evaluated whether transient heat application during EVLP (thermal preconditioning [TP]) might recondition damaged lungs before LTx. TP was performed during EVLP (3 hours) of rat lungs damaged by warm ischemia by transiently heating (30 minutes, 41.5 °C) the EVLP perfusate, followed by LTx (2 hours) reperfusion. We also assessed the TP (30 minutes, 42 °C) during EVLP (4 hours) of swine lungs damaged by prolonged cold ischemia. In rat lungs, TP induced HSP expression, reduced nuclear factor κB and inflammasome activity, oxidative stress, epithelial injury, inflammatory cytokines, necroptotic death signaling, and the expression of genes involved in innate immune and cell death pathways. After LTx, heated lungs displayed reduced inflammation, edema, histologic damage, improved compliance, and unchanged oxygenation. In pig lungs, TP induced HSP expression, reduced oxidative stress, inflammation, epithelial damage, vascular resistance, and ameliorated compliance. Collectively, these data indicate that transient heat application during EVLP promotes significant reconditioning of damaged lungs and improves their outcomes after transplantation.

Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs / Ensayo piloto de conservación pulmonar hipotérmica prolongada para analizar la lesión de isquemia-reperfusión en cerdos

Background: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. Methods: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. Results: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1β and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion. (AU)

Antecedentes: En el trasplante de pulmón (TP), la duración del tiempo de isquemia es controvertida, ya que se estableció de forma arbitraria. Sería útil explorar el impacto del tiempo de isquemia fría (TIF) prolongado sobre la lesión de isquemia-reperfusión en un modelo experimental. Métodos: Ensayo piloto experimental aleatorizado de grupos paralelos y análisis ciego final utilizando un modelo de TP en cerdos. Se extrajeron los órganos de los animales donantes (n=8). Los pulmones se conservaron durante 6 horas (n=4) o 12 horas (n=4) en hipotermia aeróbica. El pulmón izquierdo se trasplantó y reperfundió durante 4 horas. Se obtuvieron biopsias de pulmón (i) al comienzo del TIF, (ii) al final del TIF, (iii) 30 minutos después de la reperfusión y (iv) 4 horas después de la reperfusión. Los injertos de pulmón se evaluaron histológicamente mediante la puntuación de daño histológico pulmonar y la relación de peso húmedo y peso seco. La respuesta inflamatoria se valoró mediante la determinación de citoquinas inflamatorias. Se determinó la actividad de caspasa-3 como marcador de apoptosis. Resultados: No observamos diferencias en la puntuación de daño histológico pulmonar o en la relación de peso húmedo y peso seco en un momento dado entre los pulmones sometidos a 6 h-TIF o 12 h-TIF. Las IL-1β e IL-6 mostraron una tendencia ascendente durante la reperfusión en ambos grupos. El TNF-α alcanzó su punto máximo dentro de los 30 minutos posteriores a la reperfusión. Apenas se detectó IFN-γ. La inmunoexpresión de caspasa-3 se clasificó semicuantitativamente por el porcentaje de células teñidas. Se observó un 20% de células apoptóticas 30 minutos después de la reperfusión. (AU)

Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs.

BACKGROUND: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. METHODS: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. RESULTS: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1ß and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion. CONCLUSIONS: We observed that 6 and 12h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.

Pilot Trial of Extended Hypothermic Lung Preservation to Analyze Ischemia-reperfusion Injury in Pigs.

BACKGROUND: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model. METHODS: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker. RESULTS: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1ß and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion. CONCLUSIONS: We observed that 6 and 12h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild.

Neumotórax iatrogénico tras malposición de sonda nasogástrica / Iatrogenic Pneumothorax Following Nasogastric Tube Misplacement

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Amiloidosis pulmonar: un desafío diagnóstico / Pulmonary amyloidosis: A diagnostic challenge

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EV-associated miRNAs from pleural lavage as potential diagnostic biomarkers in lung cancer.

Lung cancer is the leading cause of cancer-related deaths among men and women in the world, accounting for the 25% of cancer mortality. Early diagnosis is an unmet clinical issue. In this work, we focused to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the pleural lavage, a proximal fluid in lung cancer patients, as a source of potential biomarkers. We isolated EVs by ultracentrifuge method from 25 control pleural fluids and 21 pleural lavages from lung cancer patients. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 288 out of the 754 miRNAs that were contained in the OpenArray. The differential expression analysis yielded a list of 14 miRNAs that were significantly dysregulated (adj. p-value < 0.05 and logFC lower or higher than 3). Using Machine Learning approach we discovered the lung cancer diagnostic biomarkers; miRNA-1-3p, miRNA-144-5p and miRNA-150-5p were found to be the best by accuracy. Accordance with our finding, these miRNAs have been related to cancer processes in previous studies. This results opens the avenue to the use of EV-associated miRNA of pleural fluids and lavages as an untapped source of biomarkers, and specifically, identifies miRNA-1-3p, miRNA-144-5p and miRNA 150-5p as promising biomarkers of lung cancer diagnosis.

[Pulmonary metastasectomy]. / Métastases pulmonaires†: une maladie chirurgicale†?

The lung is the second site of metastasis after the liver, affecting 30 to 40 % of all patients with a malignant tumor. Chemotherapy seems to be ineffective for some types of tumor. Although there are no prospective randomized studies that confirm the benefit of surgical pulmonary metastasectomy, many studies have shown the existence of a group of patients with pulmonary metastases who benefit from a complete resection for curative purposes in case of complete resection of lung metastases. Different approaches are known to achieve a complete resection with maximum lung parenchyma sparing. Minimal invasive approaches appear to offer a better quality of life and have equivalent oncologic outcomes compared to the open approach.

Au cours d'un cancer, 40 % des patients vont développer des métastases pulmonaires et dans cette situation un traitement seul de chimiothérapie est généralement peu efficace. Même s'il n'existe pas d'études randomisées prospectives qui confirment le bénéfice de la métastasectomie pulmonaire chirurgicale, diverses études ont montré l'existence d'un groupe de patients atteints de métastases pulmonaires qui bénéficient d'une résection à visée curative en cas de résection complète des métastases pulmonaires. Différentes approches chirurgicales peuvent être utilisées ayant pour but principal une résection complète et une épargne maximale du parenchyme pulmonaire. Les approches minimales invasives semblent offrir une meilleure qualité de vie et un résultat oncologique équivalent à l'approche par voie ouverte.

Three dimensional computed tomography for preoperative assessment of the pulmonary artery in patients undergoing endoscopic lobectomy or segmentectomy. / Rentabilidad de la reconstrucción volumétrica de la arteria pulmonar para la planificación de lobectomías y segmentectomías endoscópicas.

BACKGROUND: The interest for endoscopic pulmonary anatomic resections has grown exponentially during the last decade. During thoracoscopic procedures surgeons cannot rely on digital handling and operative field is viewed on a two-dimensional video monitor, thus frequently encountering anatomical difficulties. The hypothesis is that foreknowledge of the anatomy of each patient would greatly contribute to the safety and accuracy of the operation. The aim of the study was to evaluate the effectiveness of 3dimensional multidetector computed tomography (3D-MDCT) software to identify the pulmonary artery branching pattern during the preoperative study of endoscopic lobectomies and segmentectomies. METHODS: Descriptive prospective study of 25consecutive patients scheduled from November 2015 to July 2016 in a tertiary referral academic hospital for VATS lobectomy or segmentectomy and evaluated about branching pattern of the pulmonary artery with preoperative 16-row 3D-MDCT angiography. Intraoperative findings of the pulmonary branching pattern were compared with the preoperative 3D-MDCT angiography images. RESULTS: According to the intraoperative findings, 67 out of 68 (98%) of pulmonary artery branches were well defined in the 3D-MDCT angiography images. There was a unique 2mm undetected branch. No conversion to open thoracotomy was needed because of intraoperative bleending. CONCLUSION: 3D-MDCT angiography imaging is useful for preoperative identification of the pulmonary artery branching pattern.

Rentabilidad de la reconstrucción volumétrica de la arteria pulmonar para la planificación de lobectomías y segmentectomías endoscópicas / Three dimensional computed tomography for preoperative assessment of the pulmonary artery in patients undergoing endoscopic lobectomy or segmentectomy

INTRODUCCIÓN: El número de resecciones pulmonares mayores endoscópicas ha presentado un incremento exponencial durante la última década. La realización de la videotoracoscopia (VTC) puede ocasionar dificultades para la correcta interpretación de la anatomía torácica debido a la ausencia de exploración manual y de la visión en profundidad en el caso de trabajar con monitores bidimensionales. En consecuencia, el hecho de conocer con exactitud la anatomía de cada paciente contribuiría enormemente a la realización de una cirugía segura y precisa. El objetivo del estudio es analizar la eficacia de las reconstrucciones volumétricas realizadas mediante angiotomografía computarizada multidetector para identificar el patrón de ramificación de la arteria pulmonar en el preoperatorio de lobectomías y segmentectomías endoscópicas. MÉTODOS: Estudio descriptivo prospectivo de 25 pacientes seleccionados de noviembre de 2015 a julio de 2016 para realización de lobectomía/segmentectomía VTC en un hospital de tercer nivel. En todos los casos se realizó una reconstrucción volumétrica de la arteria pulmonar mediante angiotomografía computarizada multidetector de 16 coronas. Se analizaron comparativamente el número de ramas arteriales identificadas mediante reconstrucción volumétrica y las observadas durante la resección pulmonar. RESULTADOS: En total 67 de las 68 (98%) ramas de la arteria pulmonar fueron correctamente identificadas mediante la reconstrucción volumétrica preoperatoria. La única rama no objetivada mediante la reconstrucción volumétrica presentaba un diámetro menor a 2mm. No fue precisa ninguna conversión a toracotomía abierta debido a accidente vascular. CONCLUSIONES: La reconstrucción volumétrica es útil como herramienta diagnóstica preoperatoria para la correcta identificación del patrón de ramificación de la arteria pulmonar

BACKGROUND: The interest for endoscopic pulmonary anatomic resections has grown exponentially during the last decade. During thoracoscopic procedures surgeons cannot rely on digital handling and operative field is viewed on a two-dimensional video monitor, thus frequently encountering anatomical difficulties. The hypothesis is that foreknowledge of the anatomy of each patient would greatly contribute to the safety and accuracy of the operation. The aim of the study was to evaluate the effectiveness of 3dimensional multidetector computed tomography (3D-MDCT) software to identify the pulmonary artery branching pattern during the preoperative study of endoscopic lobectomies and segmentectomies. METHODS: Descriptive prospective study of 25consecutive patients scheduled from November 2015 to July 2016 in a tertiary referral academic hospital for VATS lobectomy or segmentectomy and evaluated about branching pattern of the pulmonary artery with preoperative 16-row 3D-MDCT angiography. Intraoperative findings of the pulmonary branching pattern were compared with the preoperative 3D-MDCT angiography images. RESULTS: According to the intraoperative findings, 67 out of 68 (98%) of pulmonary artery branches were well defined in the 3D-MDCT angiography images. There was a unique 2mm undetected branch. No conversion to open thoracotomy was needed because of intraoperative bleending. CONCLUSION: 3D-MDCT angiography imaging is useful for preoperative identification of the pulmonary artery branching pattern

Division of the intersegmental plane during thoracoscopic segmentectomy: is stapling an issue?

BACKGROUND: Stapling is becoming the method of choice for dividing the intersegmental plane during thoracoscopic segmentectomies. The technique however is controversial as it can impair re-expansion of preserved segments. We have analyzed the morbidity and lung re-expansion on a series of 175 thoracoscopic segmentectomies. METHODS: A total of 175 patients underwent a thoracoscopic anatomic segmentectomy. Ten patients were excluded due to conversion into thoracotomy. There were 89 females (54%) and 76 males (46%). Mean age was 63 years (range, 18-83 years). Indications for segmentectomy were as follows: primary lung cancer (n=100, 61%), metastases (n=27, 16%), benign non-infectious lesions (n=20, 12%) and benign infectious lesions (n=18, 11%). The intersegmental plane was divided with an endostapler in all patients. Lung re-expansion assessment included chest roentgenograms at discharge and at one-month consultation. RESULTS: The overall complication rate was 17%. There were 0.6% major complications and 16% minor complications. The average duration of drainage was 3 days (range, 1-13 days) and average length of stay was 5.7 days (range, 2-22 days). At discharge and at 1-month follow-up chest radiography, incomplete lung re-expansion was observed in 12 (7.4%) and 4 patients (2.8%) respectively. Patients who underwent upper lobe segmentectomy had significantly more incomplete re-expansion at discharge and at 1-month follow-up. On univariate analysis, mean drainage duration was significantly longer in patients who underwent upper segmentectomy (mean 3.7 days; range, 1-13) than those who underwent lower segmentectomy (mean 2.7 days; range, 1-5). CONCLUSIONS: Although stapling of the intersegmental plane most likely slightly impairs lung re-expansion, clinical and radiological consequences are minimal.

Thoracoscopic anatomical resection of congenital lung malformations in adults.

Congenital lung malformations (CLM) are a heterogeneous group of disorders that may require surgical resection to prevent complications. Thoracoscopic resection of CLM has been reported in infants. Our goal was to state whether it can also be a viable option in adults. Between 2007 and 2014, 11 patients had a thoracoscopic resection of a CLM (six lobectomies and five anatomic segmentectomies) with satisfactory results. Although being more challenging in adults due to infectious sequellae, this approach is safe.