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Chronic thromboembolic pulmonary hypertension (CTEPH) has a poor prognosis if left untreated but can be cured by pulmonary endarterectomy (PEA). Massive endobronchial pulmonary hemorrhage is a potentially fatal complication of PEA, occurring in 0.5%of patients. We describe the use of an endobronchial blocker (EBB) as an additional method to successfully treat massive, focal pulmonary hemorrhage during PEA. [ABSTRACT FROM AUTHOR]

Background: Transbronchial cryobiopsy (TBCB) of the lung parenchyma is a minimally invasive alternative for surgical lung biopsy in interstitial lung disease (ILD) patients. Drawbacks are the nondiagnostic rate and complication risk of pneumothorax and bleeding. Fluoroscopy is the current guidance tool for TBCB, which is limited by 2D imaging and a radiation dose for the patient. Confocal laser endomicroscopy (CLE) is a high-resolution imaging technique that provides immediate feedback during bronchoscopy about the elastin fiber network of peripheral lung areas. Both the visceral pleura and fibrotic lung areas consist of elastin fibers and are therefore potentially detectable with CLE. Objectives: To investigate whether CLE is capable of (1) distinguishing fibrotic from normal alveolar areas and (2) identifying the pleura. Methods: In and ex vivo CLE imaging obtained during bronchoscopy was compared with histology of lung biopsies in 14 ILD patients. Results: CLE imaging of the alveolar compartment was feasible in all patients without adverse events. Based on CLE imaging, key characteristics that influence both diagnostic yield (dense fibrotic areas) and complication rate (pleura and subpleural space) were visualized. Conclusions: CLE seems a promising alternative to fluoroscopy as a guidance tool for TBCB procedures. [ABSTRACT FROM AUTHOR]

Bronchial thermoplasty (BT) is a bronchoscopic treatment for patients with severe asthma who remain symptomatic despite optimal medical therapy. In this “expert best practice” paper, the background and practical aspects of BT are highlighted. Randomized, controlled clinical trials have shown BT to be safe and effective in reducing severe exacerbations, improving quality of life, and decreasing emergency department visits. Five-year follow-up studies have provided evidence of the functional stability of BT-treated patients with persistence of a clinical benefit. The Global Initiative for Asthma (GINA) guidelines state that BT can be considered as a treatment option for adult asthma patients at step 5. Patient selection for BT requires close collaboration between interventional pulmonologists and severe asthma specialists. Key patient selection criteria for BT will be reviewed. BT therapy is delivered in 3 separate bronchoscopy sessions at least 3 weeks apart, covering different regions of the lung separately. Patients are treated with 50 mg/day of prednisolone or equivalent for 5 days, starting treatment 3 days prior to the procedure. The procedure is performed under moderate-to-deep sedation or general anesthesia. At bronchos­copy a single-use catheter with a basket design is inserted through the instrument channel and the energy is delivered by a radiofrequency (RF) generator (AlairTM Bronchial Thermoplasty System). BT uses temperature-controlled RF energy to impact airway remodeling, including a reduction of excessive airway smooth muscle within the airway wall, which has been recognized as a predominant feature of asthma. The treatment should be performed in a systemic manner, starting at the most distal part of the (sub)segmental airway, then moving proximally to the main bronchi, ensuring that the majority of the airways are treated. In general, 40–70 RF activations are provided in the lower lobes, and between 50 and 100 activations in the upper lobes combined. The main periprocedural adverse events are exacerbation of asthma symptoms and increased cough and sputum production. Occasionally, atelectasis has been observed following the procedure. The long-term safety of BT is excellent. An optimized BT responder profile – i.e., which specific asthma phenotype benefits most – is a topic of current research. [ABSTRACT FROM AUTHOR]

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fasttwitch muscle fibers of CTEPH patients, resulting in a ~40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 μM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients. [ABSTRACT FROM AUTHOR]

Aims: Structural adaptation of the vessel wall in response to sustained alterations in haemodynamic forces is known as vascular remodelling. Detailed knowledge on the mechanism underlying this vascular response is limited, and we aimed to study the function of Nur77 in smooth muscle cells (SMCs) in arterial remodelling. [ABSTRACT FROM PUBLISHER]

A 44-year-old woman with a history of pulmonary embolism and abdominal echinococcosis complained of sudden thoracic pain and shortness of breath. A D-dimer of 77.5 mg/l (reference ≤0.5 mg/l) was found. Chest CT scan revealed obstruction of the right lower and middle lobe pulmonary artery (PA). Anticoagulation therapy was initiated for the presumed diagnosis of recurrent pulmonary embolism. However, due to persistent symptoms of dyspnea, follow-up CT angiography of the chest was performed 3 months later. A persistent PA obstruction was found and the presumed diagnosis of embolism was questioned. Subsequently, endobronchial ultrasound (EBUS) imaging was performed to support an alternative diagnosis. EBUS imaging showed an inhomogeneous, sharply demarcated, intravascular lesion with round hypoechoic areas compatible with cysts. The diagnosis of embolism was rejected and treatment with albendazole was initiated for pulmonary echinococcosis. Echinococcosis is a parasitic disease and cystic spread in the PA is exceptional. The patient has remained stable for more than 4 years. In case of disease progression, including progressive PA obstruction or life-threatening hemoptysis, surgical resection will be considered. [ABSTRACT FROM AUTHOR]

Nur77, Nurr1, and NOR-1 form the NR4A subfamily of the nuclear hormone receptor superfamily of transcription factors and have been described in the regulation of differentiation, proliferation, apoptosis, and survival of many different cell types. The expression of NR4A nuclear receptors in vascular pathologies has only recently been revealed, after which studies on the functional involvement of NR4A receptors in vascular disease were initiated. This review summarizes our current view on involvement of Nur77, Nurr1, and NOR-1 in atherosclerotic vascular disease and discusses NR4A function in vascular response to injury. [Copyright &y& Elsevier]

Introduction: Persistent air leak (PAL) is associated with prolonged hospitalization, high morbidity and increased treatment costs. Conservative treatment consists of observation, chest tube drainage, and pleurodesis. Guidelines recommend surgical evaluation if air leak does not respond after 3–5 days. One-way endobronchial valves (EBV) have been proposed as a treatment option for patients with PAL in which surgical treatment is not feasible, high risk or has failed. We aimed to provide a comprehensive overview of reported EBV use for PAL and issue best practice recommendations based on multicenter experience. Methods: We conducted a retrospective observational case-series study at four different European academic hospitals and provided best practice recommendations based on our experience. A systematic literature review was performed to summarize the current knowledge on EBV in PAL. Results: We enrolled 66 patients, male (66.7%), median age 59.5 years. The most common underlying lung disease was chronic obstructive pulmonary disease (39.4%) and lung cancer (33.3%). The median time between pneumothorax and valve placement was 24.5 days (interquartile range: 14.0–54.3). Air leak resolved in 40/66 patients (60.6%) within 30 days after EBV treatment. Concerning safety outcome, no procedure-related mortality was reported and complication rate was low (6.1%). Five patients (7.6%) died in the first 30 days after intervention. Conclusion: EBV placement is a treatment option in patients with PAL. In this multicenter case-series of high-risk patients not eligible for lung surgery, we show that EBV placement resulted in air leak resolution in 6 out of 10 patients with a low complication rate. Considering the minimally invasive nature of EBV to treat PAL as opposed to surgery, further research should investigate if EBV treatment should be expanded in low to intermediate risk PAL patients. [ABSTRACT FROM AUTHOR]

Serum biomarkers and lung ultrasound are important measures for prognostication and treatment allocation in patients with COVID-19. Currently, there is a paucity of studies investigating relationships between serum biomarkers and ultrasonographic biomarkers derived from lung ultrasound. This study aims to assess correlations between serum biomarkers and lung ultrasound findings. This study is a secondary analysis of four prospective observational studies in adult patients with COVID-19. Serum biomarkers included markers of epithelial injury, endothelial dysfunction and immune activation. The primary outcome was the correlation between biomarker concentrations and lung ultrasound score assessed with Pearson's (r) or Spearman's (rs) correlations. Forty-four patients (67 [41–88] years old, 25% female, 52% ICU patients) were included. GAS6 (rs = 0.39), CRP (rs = 0.42) and SP-D (rs = 0.36) were correlated with lung ultrasound scores. ANG-1 (rs = −0.39) was inversely correlated with lung ultrasound scores. No correlations were found between lung ultrasound score and several other serum biomarkers. In patients with COVID-19, several serum biomarkers of epithelial injury, endothelial dysfunction and immune activation correlated with lung ultrasound findings. The lack of correlations with certain biomarkers could offer opportunities for precise prognostication and targeted therapeutic interventions by integrating these unlinked biomarkers. [ABSTRACT FROM AUTHOR]

Background and Objective: Needle‐based confocal laser endomicroscopy (nCLE) allows real‐time microscopic imaging at the needle tip. nCLE malignancy criteria are used for tool‐in‐lesion confirmation during bronchoscopic lung nodule analysis. However, to date, nCLE criteria for granulomas are lacking. The aim was to identify and validate nCLE granuloma criteria and assess if blinded raters can distinguish malignant from granulomatous nCLE videos. Methods: In patients with suspected sarcoidosis, nCLE‐imaging of mediastinal lymph nodes was performed during endoscopic ultrasound procedures, followed by needle aspiration. nCLE granuloma criteria were identified by comparison with pathology and final diagnoses. Additionally, nCLE‐videos of granulomatous lung nodules part of prospective trials and clinical care were compared to the proposed nCLE granuloma criteria. Blinded raters validated nCLE videos of sarcoid and reactive mediastinal lymph nodes and malignant and granulomatous lung nodules twice. Results: Granuloma criteria were identified (brighter‐toned, homogeneous and well‐demarcated lesions) based on nCLE‐imaging in 14 sarcoidosis patients. Raters evaluated 26 nCLE‐videos obtained in lymph nodes (n = 15 sarcoidosis; n = 11 reactive and total of 260 ratings). Granuloma criteria were recognized with 88% accuracy. The inter‐observer (κ = 0.63, 95% CI 0.54–0.72) and intra‐observer reliability (κ = 0.70 ± 0.06) were substantial. Based on 12 nCLE‐videos obtained in lung nodules (n = 4 granulomas, n = 6 malignancy, n = 2 malignancy + granulomas and total of 120 ratings) granuloma and malignancy criteria were recognized with 92% and 75% accuracy. Conclusion: nCLE imaging facilitates real‐time granuloma visualization. Blinded raters accurately and consistently recognized granulomas on nCLE‐imaging and distinguished nCLE granuloma criteria from malignancy. Our data show the potential of nCLE as a real‐time bronchoscopic guidance tool for lung nodule analysis. nCLE imaging of mediastinal lymph nodes and pulmonary nodules enables real‐time granuloma visualization. Blinded raters accurately validated novel nCLE granuloma criteria through two separate validation sessions and distinguished nCLE granuloma criteria from malignancy. nCLE has the potential to become a useful adjunct to bronchoscopy for real‐time nodule detection and characterization. [ABSTRACT FROM AUTHOR]

Background: In diseases such as interstitial lung diseases (ILDs), patient diagnosis relies on diagnostic analysis of bronchoalveolar lavage fluid (BALF) and biopsies. Immunological BALF analysis includes differentiation of leukocytes by standard cytological techniques that are labor-intensive and time-consuming. Studies have shown promising leukocyte identification performance on blood fractions, using third harmonic generation (THG) and multiphoton excited autofluorescence (MPEF) microscopy. Objective: To extend leukocyte differentiation to BALF samples using THG/MPEF microscopy, and to show the potential of a trained deep learning algorithm for automated leukocyte identification and quantification. Methods: Leukocytes from blood obtained from three healthy individuals and one asthma patient, and BALF samples from six ILD patients were isolated and imaged using label-free microscopy. The cytological characteristics of leukocytes, including neutrophils, eosinophils, lymphocytes, and macrophages, in terms of cellular and nuclear morphology, and THG and MPEF signal intensity, were determined. A deep learning model was trained on 2D images and used to estimate the leukocyte ratios at the image-level using the differential cell counts obtained using standard cytological techniques as reference. Results: Different leukocyte populations were identified in BALF samples using label-free microscopy, showing distinctive cytological characteristics. Based on the THG/MPEF images, the deep learning network has learned to identify individual cells and was able to provide a reasonable estimate of the leukocyte percentage, reaching >90% accuracy on BALF samples in the hold-out testing set. Conclusions: Label-free THG/MPEF microscopy in combination with deep learning is a promising technique for instant differentiation and quantification of leukocytes. Immediate feedback on leukocyte ratios has potential to speed-up the diagnostic process and to reduce costs, workload and inter-observer variations. [ABSTRACT FROM AUTHOR]

Background and Objective: Robotic bronchoscopy has demonstrated high navigational success in small peripheral lung nodules but the diagnostic yield is discrepantly lower. Needle based confocal laser endomicroscopy (nCLE) enables real‐time microscopic imaging at the needle tip. We aim to assess feasibility, safety and needle repositioning based on real‐time nCLE‐guidance during robotic bronchoscopy in small peripheral lung nodules. Methods: Patients with suspected peripheral lung cancer underwent fluoroscopy and radial EBUS assisted robotic bronchoscopy. After radial EBUS nodule identification, nCLE‐imaging of the target area was performed. nCLE‐malignancy and airway/lung parenchyma criteria were used to identify the optimal sampling location. In case airway was visualized, repositioning of the biopsy needle was performed. After nCLE tool‐in‐nodule confirmation, needle passes and biopsies were performed at the same location. Measurements and Main Results: Twenty patients were included (final diagnosis n = 17 (lung) cancer) with a median lung nodule size of 14.5 mm (range 8–28 mm). No complications occurred. In 19/20 patients, good quality nCLE‐videos were obtained. In 9 patients (45%), real‐time nCLE‐imaging revealed inadequate positioning of the needle and repositioning was performed. After repositioning, nCLE‐imaging provided tool‐in‐nodule‐confirmation in 19/20 patients. Subsequent ROSE demonstrated representative material in 9/20 patients (45%) and overall diagnostic yield was 80% (16/20). Of the three patients with malignant nCLE‐imaging but inadequate pathology, two were diagnosed with malignancy during follow‐up. Conclusion: Robotic bronchoscopic nCLE‐imaging is feasible and safe. nCLE‐imaging in small, difficult‐to‐access lung nodules provided additional real‐time feedback on the correct needle positioning with the potential to optimize the sampling location and diagnostic yield. [ABSTRACT FROM AUTHOR]

Introduction: High flow nasal cannula (HFNC) reduces the need for intubation in patients with hypoxaemic acute respiratory failure (ARF), but its added value in patients with severe coronavirus disease 2019 (COVID‐19) and a do‐not‐intubate (DNI) order is unknown. We aimed to assess (variables associated with) survival in these patients. Materials and methods: We described a multicentre retrospective observational cohort study in five hospitals in the Netherlands and assessed the survival in COVID‐19 patients with severe acute respiratory failure and a DNI order who were treated with high flow nasal cannula. We also studied variables associated with survival. Results and discussion: One‐third of patients survived after 30 days. Survival was 43.9% in the subgroup of patients with a good WHO performance status and only 16.1% in patients with a poor WHO performance status. Patients who were admitted to the hospital for a longer period prior to HFNC initiation were less likely to survive. HFNC resulted in an increase in ROX values, reflective of improved oxygenation and/or decreased respiratory rate. Conclusion: Our data suggest that a trial of HFNC could be considered to increase chances of survival in patients with ARF due to COVID‐19 pneumonitis and a DNI order, especially in those with a good WHO performance status. [ABSTRACT FROM AUTHOR]

We recently reported in the phase 3 PANAMO trial that selectively blocking complement 5a (C5a) with vilobelimab led to improved survival in critically ill COVID-19 patients. C5a is an important contributor to the innate immune system and can also activate the coagulation system. High C5a levels have been reported in severely ill COVID-19 patients and correlate with disease severity and mortality. Previously, we assessed the potential benefit and safety of vilobelimab in severe COVID-19 patients. In the current substudy of the phase 2 PANAMO trial, we aim to explore the effects of vilobelimab on various biomarkers of inflammation and coagulation. Between March 31 and April 24, 2020, 17 patients with severe COVID-19 pneumonia were enrolled in an exploratory, open-label, randomised phase 2 trial. Blood markers of complement, endothelial activation, epithelial barrier disruption, inflammation, neutrophil activation, neutrophil extracellular trap (NET) formation and coagulopathy were measured using enzyme-linked immunosorbent assay (ELISA) or utilizing the Luminex platform. During the first 15 days after inclusion, change in biomarker concentrations between the two groups were modelled with linear mixed-effects models with spatial splines and compared. Eight patients were randomized to vilobelimab treatment plus best supportive care (BSC) and nine patients were randomized to BSC only. A significant decrease over time was seen in the vilobelimab plus BSC group for C5a compared to the BSC only group (p < 0.001). ADAMTS13 levels decreased over time in the BSC only group compared to the vilobelimab plus BSC group (p < 0.01) and interleukin-8 (IL-8) levels were statistically more suppressed in the vilobelimab plus BSC group compared to the BSC group (p = 0.03). Our preliminary results show that C5a inhibition decreases the inflammatory response and hypercoagulability, which likely explains the beneficial effect of vilobelimab in severe COVID-19 patients. Validation of these results in a larger sample size is warranted. [ABSTRACT FROM AUTHOR]

Background: Transfusion‐related acute lung injury (TRALI) is a severe complication of blood transfusion that is thought of as a two‐hit event: first the underlying patient condition (e.g., sepsis), and then the transfusion. Transfusion factors include human leukocyte antigen antibodies or biologic response modifiers (BRMs) accumulating during storage. Preclinical studies show an increased TRALI risk with longer stored platelets, clinical studies are conflicting. We aim to discover whether longer platelet concentrate (PC) storage time increases TRALI risk in a controlled human experiment. Study Design and Methods: In a randomized controlled trial, 18 healthy male volunteers received a first hit of experimental endotoxemia (2 ng/kg lipopolysaccharide), and a second hit of fresh (2‐day old) or aged (7‐day old) autologous PC, or physiological saline. After 6 h, changes in TRALI pathways were determined using spirometry, chest X‐ray, and bronchoalveolar lavage (BAL). Results: All subjects reacted adequately to lipopolysaccharide infusion and satisfied SIRS criteria (increased pulse [>90/min] and temperature [>38°C]). There were no differences between the saline, fresh, and aged PC groups in BAL‐fluid protein (95 ± 33 μg/ml; 83 ± 21 μg/ml and 104 ± 29 μg/ml, respectively) and relative neutrophil count (1.5 ± 0.5%; 1.9 ± 0.8% and 1.3 ± 0.8%, respectively), nor in inflammatory BAL‐fluid BRMs (Interleukin‐6, CXCL8, TNFα , and myeloperoxidase), clinical respiratory parameters, and spirometry results. All chest X‐rays were normal. Conclusions: In a human endotoxemia model of autologous platelet transfusion, with an adequate first hit and platelet storage lesion, transfusion of 7‐day‐old PC does not increase pulmonary inflammation compared with 2‐day‐old PC. [ABSTRACT FROM AUTHOR]

Background: Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. Objectives: This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. Method: The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30–60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. Results: Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, p = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227, not statistically significant). Symptom scores and lung function showed stability. Conclusions: AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD. [ABSTRACT FROM AUTHOR]

Background: Patients with interstitial lung diseases (ILDs) frequently present with nondiagnostic high-resolution CT (HRCT) scan and bronchoalveolar lavage (BAL) results, resulting in the need for invasive surgical or cryo-lung biopsy that is associated with significant morbidity. Confocal laser endomicroscopy (CLE) and optical coherence tomography (OCT) are high-resolution laser and light-based techniques that provide real-time imaging of the alveolar compartment during bronchoscopy with a different depth and field of view. Objectives: The aim of the study was to correlate OCT and CLE imaging to HRCT imaging in ILD. Methods: This is a retrospective case series of 20 ILD patients who underwent alveolar CLE and OCT imaging during a standard bronchoscopy with BAL, followed by a lung biopsy when indicated. CLE and OCT imaging were compared to four main HRCT patterns and histology. The final diagnosis was based on the multidisciplinary discussion diagnosis. Results: Bronchoscopic CLE and OCT imaging were feasible and safe and provided additional high-detailed anatomical information compared to the HRCT. Bronchoscopic real-time CLE was capable of identification of "alveolar cells" (ground glass opacities) and lung fibrosis (increased alveolar elastin fibers). Bronchoscopic real-time OCT allowed for visualization of "patchy fibrotic disease", "honeycombing" (microcysts), and mucosal granulomas in the airways. Conclusions: Bronchoscopic CLE and OCT of the alveolar compartment is feasible and safe and enables minimally invasive, high-resolution detection of specific ILD features with the potential to improve ILD diagnostics and monitoring and decrease the need for surgical or cryo-lung biopsies. [ABSTRACT FROM AUTHOR]

Antecedentes: Con frecuencia, los pacientes con enfermedades pulmonares intersticiales (EPI) presentan resultados no-diagnósticos en la tomografía computarizada de alta resolución (TCAR) y el lavado broncoalveolar (LBA), lo que hace necesario realizar una biopsia quirúrgica o criopulmonar invasiva, que se asocia con morbilidad significativa. La endomicroscopía láser confocal (CLE) y la tomografía de coherencia óptica (OCT) son técnicas de alta resolu-ción basadas en el láser y la luz, que proporcionan imágenes en tiempo real del compartimento alveolar durante la broncoscopía, con distinta profundidad y campo de visión. Objetivos: El objetivo del estudio fue correlacionar las imágenes por OCT y CLE con imágenes por TCAR en la EPI. Métodos: Presentamos una serie retrospectiva con casos de 20 pacientes con EPI, en quienes se tomaron imágenes por CLE y OCT alveolares durante una broncoscopía estándar con LBA, seguida de una biopsia pulmonar cuando ésta estaba indicada. Las imágenes por CLE y OCT se compararon con cuatro patrones principales de TCAR y con la histología. El diagnóstico final se basó en una discusión multidisciplinaria. Resultados: La obtención de imágenes por CLE y OCT broncoscópicas fue factible y segura, y proporcionó información anatómica adicional de gran detalle en comparación con la TCAR. La CLE broncoscópica en tiempo real fue capaz de identificar «células alveolares» (opacidades con aspecto de vidrio esmerilado) y fibrosis pulmonar (aumento de las fibras de elastina alveolares). La OCT broncoscópica en tiempo real permitió visualizar la «enfermedad fibrótica en parches», el «panal de abejas» (microquistes) y granulomas en la mucosa respiratoria. Conclusiones: La CLE y la OCT broncoscópicas del compartimento alveolar son factibles y seguras, y permiten detectar de forma mínimamente invasiva y con alta resolución las características específicas de la EPI, con potencial para mejorar el diagnóstico y el seguimiento de la enfermedad, y reducir la necesidad de realizar biopsias quirúrgicas o criopulmonares. [ABSTRACT FROM AUTHOR]

Dexamethasone improves clinical outcomes in COVID-19 patients requiring supplementary oxygen. We investigated possible mechanisms of action by comparing sixteen plasma host response biomarkers in general ward patients before and after implementation of dexamethasone as standard of care. 48 patients without and 126 patients with dexamethasone treatment were sampled within 48 h of admission. Endothelial cell and coagulation activation biomarkers were comparable. Dexamethasone treatment was associated with lower plasma interleukin (IL)-6 and IL-1 receptor antagonist levels, whilst other inflammation parameters were not affected. These data argue against modification of vascular-procoagulant responses as an early mechanism of action of dexamethasone in COVID-19. [ABSTRACT FROM AUTHOR]

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death. Advancements in navigational bronchoscopy have shown encouraging results but the diagnostic yield of small lung nodules by bronchoscopic techniques is still below that of transthoracic needle aspiration. The development of robotic bronchoscopy has demonstrated a significantly improved navigational success but the diagnostic yield is regularly limited by near-miss of the target nodule. Needle-based confocal laser endomicroscopy is a novel imaging technique that allows for the real-time visualization of individual cells and structures with microscopic resolution at the tip of the needle. We present the first reported case of confocal laser endomicroscopy guided robotic bronchoscopy for the real-time diagnosis of a small, partially cystic lung nodule. [ABSTRACT FROM AUTHOR]

Acute pyelonephritis, frequently caused by Escherichia coli, is a substantial health problem. Plasminogen activator inhibitor type-1 (PAI-1) not only inhibits plasminogen activation but is also involved in cell migration. To determine if it has a role in host defense, we induced pyelonephritis in PAI-1 gene knockout and wild-type mice by intravesical inoculation with uropathogenic E. coli 1677. Bacterial growth was determined on blood agar plates in portions of the kidneys homogenized in sterile saline. Kidney levels of PAI-1 were increased in infected compared to control mice, suggesting a physiological role for PAI-1 during pyelonephritis. The knockout mice had significantly more bacterial outgrowth in kidney homogenates compared to the wild-type mice. Strikingly, higher colony-forming units were accompanied by increased levels of the cytokines TNF-α, IL-1β, and IL-6 in the kidneys of knockout mice, but levels of the chemokines KC and MIP-2 were not different. Remarkably, plasma levels of KC were higher, but renal neutrophil influx was significantly lower, in the knockout than in the wild-type mice. Our study shows that PAI-1 is critically involved in host defense against E. coli-induced acute pyelonephritis, in part, by modulating neutrophil influx.Kidney International (2009) 75, 52–59; doi:10.1038/ki.2008.454; published online 17 September 2008 [ABSTRACT FROM AUTHOR]

Aims: Altered blood flow affects vascular tone, attracts inflammatory cells, and leads to microvascular remodelling. We tested the hypothesis that inflammation facilitates the remodelling response, but that vascular tone determines its direction (inward or outward). [ABSTRACT FROM PUBLISHER]

Background and objective: Endosonography with intrathoracic nodal sampling is proposed as the single test with the highest granuloma detection rate in suspected sarcoidosis stage I/II. However, most studies have been performed in limited geographical regions. Studies suggest that oesophageal endosonographic nodal sampling has higher diagnostic yield than endobronchial endosonographic nodal sampling, but a head‐to‐head comparison of both routes has never been performed. Methods: Global (14 hospitals, nine countries, four continents) randomized clinical trial was conducted in consecutive patients with suspected sarcoidosis stage I/II presenting between May 2015 and August 2017. Using an endobronchial ultrasound (EBUS) scope, patients were randomized to EBUS or endoscopic ultrasound (EUS)‐B‐guided nodal sampling, and to 22‐ or 25‐G ProCore needle aspiration (2 × 2 factorial design). Granuloma detection rate was the primary study endpoint. Final diagnosis was based on cytology/pathology outcomes and clinical/radiological follow‐up at 6 months. Results: A total of 358 patients were randomized: 185 patients to EBUS‐transbronchial needle aspiration (EBUS‐TBNA) and 173 to EUS‐B‐fine‐needle aspiration (FNA). Final diagnosis was sarcoidosis in 306 patients (86%). Granuloma detection rate was 70% (130/185; 95% CI, 63–76) for EBUS‐TBNA and 68% (118/173; 95% CI, 61–75) for EUS‐B‐FNA (p = 0.67). Sensitivity for diagnosing sarcoidosis was 78% (129/165; 95% CI, 71–84) for EBUS‐TBNA and 82% (115/141; 95% CI, 74–87) for EUS‐B‐FNA (p = 0.46). There was no significant difference between the two needle types in granuloma detection rate or sensitivity. Conclusion: Granuloma detection rate of mediastinal/hilar nodes by endosonography in patients with suspected sarcoidosis stage I/II is high and similar for EBUS and EUS‐B. These findings imply that both diagnostic tests can be safely and universally used in suspected sarcoidosis patients. This global RCT in patients with suspected sarcoidosis stage I/II with an indication for endosonographic nodal sampling showed a similarly high granuloma detection rate and sensitivity for diagnosing sarcoidosis with endobronchial ultrasound versus endoscopic ultrasound‐B. The findings imply that both diagnostic tests (endobronchial/oesophageal) can be used safely and universally in suspected sarcoidosis patients. [ABSTRACT FROM AUTHOR]

Background and objective: Patients with coronavirus disease 2019 (COVID‐19) pneumonia present with typical findings on chest computed tomography (CT), but the underlying histopathological patterns are unknown. Through direct regional correlation of imaging findings to histopathological patterns, this study aimed to explain typical COVID‐19 CT patterns at tissue level. Methods: Eight autopsy cases were prospectively selected of patients with PCR‐proven COVID‐19 pneumonia with varying clinical manifestations and causes of death. All had been subjected to chest CT imaging 24–72 h prior to death. Twenty‐seven lung areas with typical COVID‐19 patterns and two radiologically unaffected pulmonary areas were correlated to histopathological findings in the same lung regions. Results: Two dominant radiological patterns were observed: ground‐glass opacity (GGO) (n = 11) and consolidation (n = 16). In seven of 11 sampled areas of GGO, diffuse alveolar damage (DAD) was observed. In four areas of GGO, the histological pattern was vascular damage and thrombosis, with (n = 2) or without DAD (n = 2). DAD was also observed in five of 16 samples derived from areas of radiological consolidation. Seven areas of consolidation were based on a combination of DAD, vascular damage and thrombosis. In four areas of consolidation, bronchopneumonia was found. Unexpectedly, in samples from radiologically unaffected lung parenchyma, evidence was found of vascular damage and thrombosis. Conclusion: In COVID‐19, radiological findings of GGO and consolidation are mostly explained by DAD or a combination of DAD and vascular damage plus thrombosis. However, the different typical CT patterns in COVID‐19 are not related to specific histopathological patterns. Microvascular damage and thrombosis are even encountered in the radiologically normal lung. [ABSTRACT FROM AUTHOR]

• Lungtumors positioned adjacent to the central airways can be visualized by EBUS. • EBUS imaging can assess the presence or absence of mediastinal/vascular tumor invasion. • EBUS provides important additional staging information complementary to CT findings. • T4 assessment by EBUS cab be considered following an nodal examination. In lung cancer patients, accurate assessment of mediastinal and vascular tumor invasion (stage T4) is crucial for optimal treatment allocation and to prevent unnecessary thoracotomies. We assessed the diagnostic accuracy of linear endobronchial ultrasound (EBUS) for T4-status in patients with centrally located lung cancer. This is a retrospective study among consecutive patients who underwent EBUS for diagnosis and staging of lung cancer in four hospitals in The Netherlands (Amsterdam, Leiden), Italy (Bologna) and Poland (Zakopane) between 04–2012 and 04−2019. Patients were included if the primary tumor was detected by EBUS and subsequent surgical-pathological staging was performed, which served as the reference standard. T4-status was extracted from EBUS and pathology reports. Chest CT's were re-reviewed for T4-status. 104 patients with lung cancer in whom EBUS detected the primary tumour, and who underwent subsequent surgical-pathological staging were included. 36 patients (35 %) had T4-status, based on vascular (n = 17), mediastinal (n = 15), both vascular and mediastinal (n = 3), or oesophageal invasion (n = 1). For EBUS, sensitivity, specificity, PPV and NPV for T4-status were (n = 104): 63.9 % (95 %CI 46.2–79.2 %), 92.6 % (83.7–97.6 %), 82.1 % (65.6–91.7 %), and 82.9 % (75.7–88.2 %), respectively. For chest CT (n = 72): 61.5 % (95 %CI 40.6–79.8 %), 37.0 % (23.2–52.5 %), 35.6 % (27.5–44.6 %), and 63.0 % (47.9–75.9 %), respectively. When combining CT and EBUS with concordant T4 status (n = 33): 90.9 % (95 %CI 58.7–99.8 %), 77.3 % (54.6–92.20 %), 66.7 % (47.5–81.6 %), and 94.4 % (721−99.1%), respectively. Both EBUS and CT alone are inaccurate for assessing T4-status as standalone test. However, combining a negative EBUS with a negative CT may rule out T4-status with high certainty. [ABSTRACT FROM AUTHOR]

The addition of LPS to HDM mimics a natural allergen exposure as LPS is a widespread pollutant and coexisting with HDM in house dust.7 After seven hours, a bilateral bronchoalveolar lavage (BAL) was performed. We have shown previously that intrabronchial HDM/LPS challenge induces a mixed eosinophilic and neutrophil airways inflammation in asthma patients.5 Therefore, we hypothesize that exposure of AM to HDM/LPS would upregulate genes associated with eosinophil and neutrophil signaling. Comparing HDM/LPS challenge to saline identified 1013 significantly altered transcripts (fold expression <=-1.2 or >=1.2), of which 485 were upregulated and 528 downregulated as consequence of HDM/LPS challenge (Figure 1B). [Extracted from the article]

Introduction: Obtaining a tissue diagnosis of centrally located lung tumors in patients presenting without endobronchial abnormalities is challenging, and therefore a considerable diagnostic problem. Objective: The objective of this study was to evaluate the performance of linear endobronchial ultrasound guided-transbronchial-needle aspiration (EBUS-TBNA) for the diagnosis of centrally located lung tumors. Methods: We performed a systematic review (PROSPERO, CRD42017080968) and searched MEDLINE, Embase, BIOSIS Previews, and Web of Science till November 18, 2018 for studies that evaluated the yield and/or sensitivity of EBUS-TBNA for diagnosing centrally located lung tumors. We assessed the study quality using QUADAS-2 and performed random-effects meta-analysis. Results: A total of 5,657 manuscripts were identified; of these 14 were considered for the study, including 1,175 patients who underwent EBUS-TBNA for diagnosing an intrapulmonary tumor. All studies had a high risk of bias or applicability concerns, predominately regarding patient selection. The average yield of EBUS-TBNA for diagnosing centrally located lung tumors was 0.89 (95% CI 0.84–0.92) and average sensitivity for diagnosing malignant tumors was 0.91 (95% CI 0.88–0.94). Among studies reporting this information, EBUS-related complications occurred in 5.4% of patients (42/721). Conclusion: EBUS-TBNA has a high yield and sensitivity for diagnosing centrally located lung tumors and is safe in selected patients. Prospective studies are recommended to evaluate the routine use of this procedure for diagnosing intrapulmonary tumors. [ABSTRACT FROM AUTHOR]

Diagnosing and monitoring pulmonary diseases is highly dependent on imaging, physiological function tests and tissue sampling. Optical coherence tomography (OCT) and confocal laser endomicroscopy (CLE) are novel imaging techniques with near-microscopic resolution that can be easily and safely combined with conventional bronchoscopy. Disease-related pulmonary anatomical compartments can be visualized, real time, using these techniques. In obstructive lung diseases, airway wall layers and related structural remodelling can be identified and quantified. In malignant lung disease, normal and malignant areas of the central airways, lung parenchyma, lymph nodes and pleura can be discriminated. A growing number of interstitial lung diseases (ILDs) have been visualized using OCT or CLE. Several ILD-associated structural changes can be imaged: fibrosis, cellular infiltration, bronchi(ol)ectasis, cysts and microscopic honeycombing. Although not yet implemented in clinical practice, OCT and CLE have the potential to improve detection and monitoring pulmonary diseases and can contribute in unravelling the pathophysiology of disease and mechanism of action of novel treatments. Indeed, assessment of the airway wall layers with OCT might be helpful when evaluating treatments targeting airway remodelling. By visualizing individual malignant cells, CLE has the potential as a real-time lung cancer detection tool. In the future, both techniques could be combined with laser-enhanced fluorescent-labelled tracer detection. This review discusses the value of OCT and CLE in pulmonary medicine by summarizing the current evidence and elaborating on future perspectives. [ABSTRACT FROM AUTHOR]

Background: Bronchial Thermoplasty (BT) is an endoscopic treatment for severe asthma using radiofrequency energy to target airway remodeling including smooth muscle. The correlation of pulmonary function tests and BT response are largely unknown. Forced Oscillation Technique (FOT) is an effort-independent technique to assess respiratory resistance (Rrs) by using pressure oscillations including small airways.Aim: To investigate the effect of BT on pulmonary function, assessed by spirometry, bodyplethysmography and FOT and explore associations between pulmonary function parameters and BT treatment response.Methods: Severe asthma patients recruited to the TASMA trial were analyzed in this observational cohort study. Spirometry, bodyplethysmography and FOT measurements were performed before and 6 months after BT. Asthma questionnaires (AQLQ/ACQ-6) were used to assess treatment response.Results: Twenty-four patients were analyzed. AQLQ and ACQ improved significantly 6 months after BT (AQLQ 4.15 (±0.96) to 4.90 (±1.14) and ACQ 2.64 (±0.60) to 2.11 (±1.04), p = 0.004 and p = 0.02 respectively). Pulmonary function parameters remained stable. Improvement in FEV1 correlated with AQLQ change (r = 0.45 p = 0.03). Lower respiratory resistance (Rrs) at baseline (both 5 Hz and 19 Hz) significantly correlated to AQLQ improvement (r = - 0.52 and r = - 0.53 respectively, p = 0.01 (both)). Borderline significant correlations with ACQ improvement were found (r = 0.30 p = 0.16 for 5 Hz and r = 0.41 p = 0.05 for 19 Hz).Conclusion: Pulmonary function remained stable after BT. Improvement in FEV1 correlated with asthma questionnaires improvement including AQLQ. Lower FOT-measured respiratory resistance at baseline was associated with favorable BT response, which might reflect targeting of larger airways with BT.Trial Registration: ClinicalTrials.gov Identifier: NCT02225392; Registered 26 August 2014. [ABSTRACT FROM AUTHOR]

Disease course was complicated by thromboembolic events in 3 of 6 patients (50%), acute kidney injury in 4 of 6 patients (67%) and superinfections in 4 of 6 patients (67%). Here we describe clinical characteristics of COVID-19 patients with auto-Abs neutralizing IFN-I, a subset of patients described by Bastard et al. [[1]]. [Extracted from the article]

Background: Pleural biopsies in patients with suspected malignant pleural mesothelioma (MPM) are often inconclusive resulting in repeat diagnostic procedures. Confocal laser endomicroscopy (CLE) enables real-time imaging on a cellular level. We investigated pleural CLE imaging as a biopsy guidance technique to distinguish malignant from benign pleural disease.Methods: Prospective, multicenter study in patients with (suspected) MPM based on PET-CT imaging who were scheduled for pleural biopsies. Patients received 2.5 mL fluorescein intravenously preceding the procedure. In vivo through-the-needle CLE imaging of the pleura and ex vivo CLE imaging of the biopsies were correlated with histology. CLE characteristics for various pleural entities were identified, and their interpretability was tested by CLE video scoring by multiple blinded raters.Results: CLE imaging was successfully obtained in 19 of 20 diagnostic pleural biopsy procedures (thoracoscopy: n = 4, surgical excision: n = 3, CT scan: n = 3, ultrasound: n = 9, esophageal ultrasound guided: n = 1) in 15 patients. CLE videos (n = 89) and corresponding pleural biopsies (n = 105) were obtained. No study-related adverse events occurred. Tumor deposits of MPM were distinguished from areas with pleural fibrosis based on CLE imaging and recognized by raters (n = 3) (interobserver agreement, 0.56; 95% CI, 0.49-0.64).Conclusions: CLE imaging was feasible and safe regardless of the biopsy method. Real-time visualization of pleural abnormalities in epithelial and sarcomatoid MPM could be distinguished from pleural fibrosis. Therefore, CLE has potential as a guidance biopsy tool to reduce the current substantial rate of repeat biopsy procedures by identification of areas with malignant cells in vivo (smart needle).Trial Registry: ClinicalTrials.gov; No.: NCT02689050; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Activated eosinophils cause major pathology in stable and exacerbating asthma; however, they can also display protective properties like an extracellular antiviral activity. Initial murine studies led us to further explore a potential intracellular antiviral activity by eosinophils. Methods: To follow eosinophil‐virus interaction, respiratory syncytial virus (RSV) and influenza virus were labeled with a fluorescent lipophilic dye (DiD). Interactions with eosinophils were visualized by confocal microscopy, electron microscopy, and flow cytometry. Eosinophil activation was assessed by both flow cytometry and ELISA. In a separate study, eosinophils were depleted in asthma patients using anti‐IL‐5 (mepolizumab), followed by a challenge with rhinovirus‐16 (RV16). Results: DiD‐RSV and DiD‐influenza rapidly adhered to human eosinophils and were internalized and inactivated (95% in ≤ 2 hours) as reflected by a reduced replication in epithelial cells. The capacity of eosinophils to capture virus was reduced up to 75% with increasing severity of asthma. Eosinophils were activated by virus in vitro and in vivo. In vivo this correlated with virus‐induced loss of asthma control. Conclusions: This previously unrecognized and in asthma attenuated antiviral property provides a new perspective to eosinophils in asthma. This is indicative of an imbalance between protective and cytotoxic properties by eosinophils that may underlie asthma exacerbations. [ABSTRACT FROM AUTHOR]

The article offers information on the airway smooth muscle reduction after bronchial thermoplasty (BT) in severe asthma correlates with FEV. It mentions bronchoscopic treatment for severe asthma patients in whom the airways are treated with radio-frequency energy to improve asthma symptoms by reducing airway smooth muscle (ASM); and also mentions ASM mass significantly decreased 6 months following BT-treatment.

• The PD-L1 suitability rate between the 22G Acquire TBNB and Expect TBNA needle is similar. • Both needles have high sensitivities for diagnosing and staging lung cancer. • Acquire TBNB needle procures improved quality tissue specimens with more tissue cores. Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has an important role in the diagnosis and staging of lung cancer. Evaluation of programmed death ligand 1 (PD-L1) expression and molecular profiling has become standard of care but cytological samples frequently contain insufficient tumor cells. The 22G Acquire needle with Franseen needle tip was developed to perform transbronchial needle biopsy (TBNB) with improved tissue specimens. This study evaluated if the 22G Acquire TBNB needle results in enhanced PD-L1 suitability rate compared to the regular Expect 22G TBNA needle. in this multi-center randomized clinical trial (Netherlands Trial Register NL7701), patients with suspected (N)SCLC and an indication for mediastinal/hilar staging or lung tumor diagnosis were recruited in five university and general hospitals in the Netherlands, Poland, Italy and Czech Republic. Patients were randomized (1:1) between the two needles. Two blinded reference pathologists evaluated the samples. The primary outcome was PD-L1 suitability rate in patients with a final diagnosis of lung cancer. In case no malignancy was diagnosed, the reference standard was surgical verification or 6 month follow-up. 154 patients were randomized (n = 76 Acquire TBNB; n = 78 Expect TBNA) of which 92.9% (n = 143) had a final malignant diagnosis. Suitability for PD-L1 analysis was 80.0% (n = 56/70; 95 %CI 0.68–0.94) with the Acquire needle and 76.7% (n = 56/73; 95 %CI 0.65–0.85) with the Expect needle (p = 0.633). Acquire TBNB needle specimens provided more frequent superior quality (65.3% (95 %CI 0.57–0.73) vs 49.4% (95 %CI 0.41–0.57, p = 0.005) and contained more tissue cores (72.0% (95 %CI 0.60-0.81) vs 41.0% (95 %CI 0.31–0.54, p < 0.01). There were no statistically significant differences in tissue adequacy, suitability for molecular analysis and sensitivity for malignancy and N2/N3 disease. The 22G Acquire TBNB needle procured improved quality tissue specimens compared to the Expect TBNA needle but this did not result in an improved the suitability rate for PD-L1 analysis. [ABSTRACT FROM AUTHOR]

Effect of C1-inhibitor in adults with mild asthma: A randomized controlled trial To the Editor, Several newly approved monoclonal antibodies targeting type 2 inflammation have shown remarkable beneficial effects in patients with severe asthma. GLO:1X5/01apr20:all14053-fig-0002.jpg PHOTO (COLOR): Intravenous C1-inhibitor infusion reduces vascular leak following HDM/LPS challenge in the airways of asthma patients. [Extracted from the article]

Background: Bronchial thermoplasty (BT) is an endoscopic treatment for severe asthma targeting airway smooth muscle (ASM) with radiofrequent energy. Although implemented worldwide, the effect of BT treatment on the airways is unclear. Optical coherence tomography (OCT) is a novel imaging technique, based on near-infrared light, that generates high-resolution cross-sectional airway wall images. Objective: To assess the safety and feasibility of OCT in severe asthma patients and determine acute airway effects of BT by OCT and compare these to the untreated right middle lobe (RML). Methods: Severe asthma patients were treated with BT (TASMA trial). During the third BT procedure, OCT imaging was performed immediately following BT in the airways of the upper lobes, the right lower lobe treated 6 weeks prior, and the untreated RML. Results: 57 airways were imaged in 15 patients. No adverse events occurred. Three distinct OCT patterns were discriminated: low-intensity scattering pattern of (1) bronchial and (2) peribronchial edema and (3) high-intensity scattering pattern of epithelial sloughing. (Peri)bronchial edema was seen in all BT-treated airways, and less pronounced in only 1/3 of the RML airways. These effects extended beyond the ASM layer and more distal than the directly BT-treated areas and were reduced, but not resolved, after 6 weeks. Epithelial sloughing occurred in 11/14 of the BT-treated airways and was absent in untreated RML airways. Conclusions: Acute BT effects can be safely assessed with OCT and 3 distinct patterns were identified. The acute effects extended beyond the targeted ASM layer and distal of directly BT-treated airway areas, suggesting that BT might also target smaller distal airways. [ABSTRACT FROM AUTHOR]

Background Mediastinal and central large vessels (T4) invasion by lung cancer is often difficult to assess preoperatively due to the limited accuracy of computed tomography (CT) scan of the chest. Esophageal ultrasound (EUS) can visualize the relationship of para-esophageally located lung tumors to surrounding mediastinal structures. Aim To assess the value of EUS for detecting mediastinal invasion (T4) of centrally located lung tumors. Methods Patients who underwent EUS for the diagnosis and staging of lung cancer and in whom the primary tumor was detected by EUS and who subsequently underwent surgical- pathological staging (2000–2016) were retrospectively selected from two university hospitals in The Netherlands. T status of the lung tumor was reviewed based on EUS, CT and thoracotomy findings. Surgical- pathological staging was the reference standard. Results In 426 patients, a lung malignancy was detected by EUS of which 74 subjects subsequently underwent surgical- pathological staging. 19 patients (26%) were diagnosed with stage T4 based on vascular (n = 8, 42%) or mediastinal (n = 8, 42%) invasion or both (n = 2, 11%), one patient (5%) had vertebral involvement. Sensitivity, specificity, PPV and NPV for assessing T4 status were: for EUS (n = 74); 42%, 95%, 73%, 83%, for chest CT (n = 66); 76%, 61%, 41%, 88% and the combination of EUS and chest CT (both positive or negative for T4, (n = 34); 83%, 100%, 100% 97%. Conclusion EUS has a high specificity and NPV for the T4 assessment of lung tumors located para-esophageally and offers further value to chest CT scan. [ABSTRACT FROM AUTHOR]

Background: High-resolution computed tomography has limitations in the assessment of airway wall layers and related remodeling in obstructive lung diseases. Near infrared-based optical coherence tomography (OCT) is a novel imaging technique that combined with bronchoscopy generates highly detailed images of the airway wall. The aim of this study is to identify and quantify human airway wall layers both ex-vivo and in-vivo by OCT and correlate these to histology. Methods: Patients with lung cancer, prior to lobectomy, underwent bronchoscopy including in-vivo OCT imaging. Ex-vivo OCT imaging was performed in the resected lung lobe after needle insertion for matching with histology. Airway wall layer perimeters and their corresponding areas were assessed by two independent observers. Airway wall layer areas (total wall area, mucosal layer area and submucosal muscular layer area) were calculated. Results: 13 airways of 5 patients were imaged by OCT. Histology was matched with 51 ex-vivo OCT images and 39 in-vivo OCT images. A significant correlation was found between ex-vivo OCT imaging and histology, in-vivo OCT imaging and histology and ex-vivo OCT imaging and in-vivo OCT imaging for all measurements (p < 0.0001 all comparisons). A minimal bias was seen in Bland-Altman analysis. High inter-observer reproducibility with intra-class correlation coefficients all above 0.90 were detected. Conclusions: OCT is an accurate and reproducible imaging technique for identification and quantification of airway wall layers and can be considered as a promising minimal-invasive imaging technique to identify and quantify airway remodeling in obstructive lung diseases. [ABSTRACT FROM AUTHOR]

Background: Bronchial thermoplasty (BT) is a novel treatment for severe asthma based on radiofrequency energy delivery to the larger airways. Although impressive radiological abnormalities have been reported, the incidence, pattern, and behavior over time of acute radiological abnormalities following BT are not well established. Objective: To assess the incidence pattern and behavior over time of acute radiological abnormalities following BT. Methods: This is a prospective, observational imaging study of severe asthma patients participating in the TASMA trial. Imaging of the lung (chest X-ray and/or computed tomography [CT]) was performed routinely before and directly after BT, within 6 weeks and at 6 months' follow-up. Results: Thirty-four chest X-rays were performed within <5 h following 34 BT procedures in 12 patients. In 91% of cases, radiological abnormalities were seen, designated as peribronchial consolidations (97%) and/or atelectasis (29%). Ultra-low-dose (ULD) chest CTs were performed following 16 BT procedures showing abnormalities in all. Four different radiological patterns were identified: peribronchial consolidations with surrounding ground glass opacities (94%), atelectasis (38%), partial bronchial occlusions (63%), and bronchial dilatations (19%). No bronchoscopic intervention was needed. At 6 months' follow-up, in a single patient, high-resolution chest CT showed a focal bronchiectasis in a single airway. Conclusions: There is a high incidence of acute radiological abnormalities after BT. Four distinct radiological patterns can be identified on ULD chest CT, which resolve without clinical impact in virtually all cases. [ABSTRACT FROM AUTHOR]

Introduction In patients with lung cancer, left adrenal glands (LAG) suspected for distant metastases (M1b) based on imaging require further evaluation for a definitive diagnosis. Tissue acquisition is regularly performed using conventional EUS-FNA. The aim of this study was to investigate the success rate of endoscopic ultrasound guided fine-needle aspiration using the EBUS scope (EUS-B-FNA) for LAG analysis. Methods This is a prospective multicenter study in consecutive patients with (suspected) lung cancer and suspected mediastinal and LAG metastases. Following complete mediastinal staging using the EBUS scope (EBUS + EUS-B), the LAG was evaluated and sampled by both EUS-B (experimental procedure) and conventional EUS (current standard of care). Results The success rate for LAG analysis (visualized, sampled and adequate tissue obtained) was 89% (39/44; 95% CI 76–95%) for EUS-B-FNA, and 93% (41/44; 95%CI 82–98%) for EUS-FNA. In the absence of metastases at EUS-B and/or EUS, surgical verification of the LAG or 6 months clinical and radiological follow-up was obtained, but missing for 5 patients. The prevalence of LAG metastases was 54% (21/39). In patients in whom LAG was seen and sampled, sensitivity for LAG metastases was at least 87% (95%CI 65–97%) for EUS-B, and at least 83% (95%CI 62–95%) for conventional EUS. Conclusion LAG analysis by EUS-B shows a similar high success rate in comparison to conventional EUS. Implication Both a mediastinal nodal and LAG evaluation can be adequately performed with just an EBUS scope and single endoscopist. This staging strategy is likely to reduce patient-burden and costs. [ABSTRACT FROM AUTHOR]

Background: Bronchial thermoplasty (BT) is a rapidly emerging bronchoscopic treatment for patients with moderate-to-severe asthma. Different sedation strategies are currently used, ranging from mild midazolam sedation to general anesthesia requiring tracheal intubation. Objectives: The aim of this study was to assess the feasibility, safety, and both patients' and bronchoscopists' satisfaction with propofol and remifentanil sedation administered by specialized sedation anesthesiology nurses during BT in severe asthma patients. Methods: A prospective observational cohort study in BT-treated severe asthma patients of the TASMA trial was designed. Patients were asked to rate their overall BT procedure satisfaction and tolerance with propofol/remifentanil sedation using a visual analogue scale (VAS) ranging from 0 to 10. Similarly, bronchoscopists were asked to rate patient cooperation and tolerance. Sedation-associated adverse events and the number of BT activations were recorded. Results: Thirty-two BT procedures in 13 severe asthma patients were performed under moderate target-controlled infusion (TCI) propofol/remifentanil sedation. Patients' median VAS scores were as follows: overall satisfaction 9.6 (interquartile range [IQR] 8.5-10.0), dyspnea 0.0 (IQR 0.0-0.6), pain 0.1 (IQR 0.0-1.0), cough 0.5 (IQR 0.0-2.1), and anxiety 0.1 (IQR 0.00.7). Bronchoscopists' median VAS scores were as follows: overall patient cooperation 9.1 (IQR 8.5-9.6), dyspnea 0.3 (IQR 0.0-0.9), pain 0.2 (IQR 0.0-1.3), cough 1.2 (IQR 0.7-2.0), and discomfort 0.6 (IQR 0.3-1.5). All patients were willing to undergo the procedure again and would recommend this form of sedation to their best friend. One case of conversion to general anesthesia occurred and no serious adverse events were reported. Conclusions: Moderate sedation with propofol and remifentanil TCI provided by specialized sedation anesthesiology nurses is feasible and safe and results in high satisfaction rates of both patients and bronchoscopists. [ABSTRACT FROM AUTHOR]

Objective: Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. Preclinical studies have shown that aged RBCs can induce transfusion-related acute lung injury in the presence of a "first hit" (e.g., sepsis). Clinical studies, however, show conflicting results on this matter. We tested whether maximally stored RBCs are able to induce lung injury in the presence of a "first hit" in humans (Dutch Trial Register: NTR4455).Design: Open-label, randomized controlled trial.Patients: Healthy male volunteers.Interventions: Eighteen healthy male volunteers donated one unit of autologous RBCs 2 or 35 days before the experiment. The experiment was started by infusion of 2 ng/kg lipopolysaccharide ("first hit"). After 2 hours, volunteers received normal saline (n = 6), 2-day stored transfusion (n = 6), or 35-day stored transfusion (n = 6) ("second hit"). Blood was sampled hourly. Six hours after transfusion, the diffusion capacity of the lungs for carbon monoxide was tested and volunteers underwent spirometry, chest x-ray study, and a bronchoalveolar lavage.Measurements and Main Results: All volunteers fulfilled sepsis criteria after lipopolysaccharide injection. The stored blood transfusion did not result in significant changes in either hemodynamic or respiratory variables compared with the control groups. Furthermore, chest x-rays, lung function, and PaO2/FIO2 ratios did not differ between groups. Transfusion of stored autologous RBCs did not result in an increased level of protein in the lungs or neutrophil influx.Conclusions: Transfusion of 35-day stored autologous RBCs in the presence of endotoxemia does not result in lung injury in humans. [ABSTRACT FROM AUTHOR]

Ectopic pancreas located in the mediastium is an extremely rare anomaly. We present a case of an ectopic pancreas located in a giant mediastinal cyst in an 18-year-old man. He presented with symptoms of dyspnea due to external compression of the cyst on the left main bronchus. Complete surgical resection was performed through median sternotomy, with relief of the bronchial compression postoperatively. Literature review showed 20 previously reported cases. These masses were usually large (>10 cm), almost exclusively located in the anterior mediastinum, predominately cystic in nature and generally benign. Surgical resection was performed in all reported cases with a favorable prognosis. Due to the size of these masses, operative treatment can be challenging and should be carefully planned, with specific considerations regarding anesthetic and surgical management. [ABSTRACT FROM AUTHOR]

Most macrophages generate energy to mount an inflammatory cytokine response by increased glucose metabolism through intracellular glycolysis. Previous studies have suggested that alveolar macrophages (AMs), which reside in a glucose-poor natural environment, are less capable to utilize glycolysis and instead rely on other substrates to fuel oxidative phosphorylation (OXPHOS) for energy supply. At present, it is not known whether AMs are capable to use glucose metabolism to produce cytokines when other metabolic options are blocked. Here, we studied human AMs retrieved by bronchoalveolar lavage from healthy subjects, and examined their glucose metabolism in response to activation by the gram-negative bacterial component lipopolysaccharide (LPS) ex vivo. The immunological and metabolic responses of AMs were compared to those of cultured blood monocyte-derived macrophages (MDMs) from the same subjects. LPS stimulation enhanced cytokine release by both AMs and MDMs, which was associated with increased lactate release by MDMs (reflecting glycolysis), but not by AMs. In agreement, LPS induced higher mRNA expression of multiple glycolytic regulators in MDMs, but not in AMs. Flux analyses of [13C]-glucose revealed no differences in [13C]-incorporation in glucose metabolism intermediates in AMs. Inhibition of OXPHOS by oligomycin strongly reduced LPS-induced cytokine production by AMs, but not by MDMs. Collectively, these results indicate that human AMs, in contrast to MDMs, do not use glucose metabolism during LPS-induced activation and fully rely on OXPHOS for cytokine production. • Human alveolar and monocyte-derived macrophages have different metabolic responses. • Activated alveolar macrophages have no metabolic shift towards glycolysis. • Inhibition of oxidative phosphorylation blocks cytokine induction in alveolar macrophages. • Activated human alveolar macrophages fully rely on oxidative phosphorylation. [ABSTRACT FROM AUTHOR]