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Appropriate isolation methods are essential for unravelling the relative contribution of extracellular vesicles (EVs) and the EV-free secretome to homeostasis and disease. We hypothesized that ultrafiltration followed by size exclusion chromatography (UF-SEC) provides well-matched concentrates of EVs and free secreted molecules for proteomic and functional studies. Conditioned media of BEAS-2B bronchial epithelial cells were concentrated on 10 kDa centrifuge filters, followed by separation of EVs and free protein using sepharose CL-4B SEC. Alternatively, EVs were isolated by ultracentrifugation. EV recovery was estimated by bead-coupled flow cytometry and tuneable resistive pulse sensing. The proteomic composition of EV isolates and SEC protein fractions was characterized by nano LC-MS/MS. UF-SEC EVs tended to have a higher yield and EV-to-protein rate of purity than ultracentrifugation EVs. UF-SEC EVs and ultracentrifugation EVs showed similar fold-enrichments for biological pathways that were distinct from those of UF-SEC protein. Treatment of BEAS-2B cells with UF-SEC protein, but not with either type of EV isolate increased the IL-8 concentration in the media whereas EVs, but not protein induced monocyte adhesion to endothelial cells. Thus, UF-SEC is a useful alternative for ultracentrifugation and allows comparing the proteomic composition and functional effects of EVs and free secreted molecules.

Background: Disturbances of intestinal integrity, manifested by increased gastro-intestinal (GI) permeability, have been found in chronic obstructive pulmonary disease (COPD) patients during physical activity, often associated with intermittent hypoxic periods. Evidence about extrapulmonary organ disturbances, especially of the GI tract, during hospitalised acute exacerbation of COPD (AE-COPD) with hypoxaemic respiratory failure (RF) is lacking. Objective: The aim was to assess changes in GI permeability in patients with AE-COPD and during recovery 4 weeks later. Methods: All patients admitted to our hospital with AE-COPD accompanied by hypoxaemia at admission (PaO 2 <8.7 kPa or O 2 saturation <93%) were screened between October 2013 and February 2014. Patients with a history of GI or renal disease, chronic heart failure, or use of non-steroidal anti-inflammatory drugs in the 48 h before the test were excluded. GI permeability was assessed by evaluating urinary excretion ratios of the orally ingested sugars lactulose/L-rhamnose (L/R ratio), sucrose/L-rhamnose (Su/R ratio) and sucralose/erythritol (S/E ratio). Results: Seventeen patients with severe to very severe COPD completed the study. L/R ratio (×10 3 ) at admission of AE-COPD was significantly higher than in the recovery condition (40.9 [29.4–49.6] vs. 27.3 [19.5–47.7], p = 0.039), indicating increased small intestinal permeability. There were no significant differences in the individual sugar levels in urine nor in the 0- to 5-h urinary S/E and Su/R ratios between the 2 visits. Conclusion: This is the first study showing increased GI permeability during hospitalised AE-COPD accompanied by hypoxaemic RF. Therefore, GI integrity in COPD patients is an attractive target for future research and for the development of interventions to alleviate the consequences of AE-COPD.

Background Severe respiratory failure in patients with cystic fibrosis (CF) requiring invasive mechanical ventilation is associated with poor clinical outcomes. The purpose of this study was to evaluate the role of extracorporeal membrane oxygenation (ECMO) in this clinical setting. Methods In this descriptive retrospective monocentric cohort study, we collected data by using electronic medical records from all patients with CF who received ECMO therapy during the period 2012–2021. Setting A monocentric setting at the non-surgical intensive care unit of the University Hospital of Frankfurt, Germany (tertiary care level center and nationally certified CF center). Results During the study period 72 cases of CF patients with intensive care treatment were detected. Of these, 46 cases required mechanical ventilation. Nine patients received ECMO therapy for severe respiratory failure due to pulmonary exacerbation. Eight of the nine patients died in the hospital. This corresponds to an in-hospital mortality rate of 88.9%. None of the patients underwent lung transplantation. The most common CF mutation was the p.Phe508del homo- or heterozygous genotype. Pseudomonas aeruginosa colonization was significantly associated with the in-hospital mortality. Conclusions ECMO support in CF patients and severe hypoxemic failure is associated with high mortality and its use must take into account the increased risk and poor patient outcome in this clinical setting. Clinical trial number This was a retrospective, unregistered analysis. A clinical trial number is not applicable.

[This corrects the article DOI: 10.3389/fimmu.2025.1597635.].

ObjectivesThe objective of this study was to evaluate epidemiological characteristics, clinical course and outcome of mechanically ventilated non-surgical intensive care unit (ICU) patients, with the aim of improving the strategic planning of ICU capacities.DesignWe conducted a retrospective observational cohort analysis. Data from mechanically ventilated intensive care patients were obtained by investigating electronic health records. The association between clinical parameters and ordinal scale data of clinical course was evaluated using Spearman correlation and Mann-Whitney U test. Relations between clinical parameters and in-hospital mortality rates were examined using binary logistic regression analysis.SettingA single-centre study at the non-surgical ICU of the University Hospital of Frankfurt, Germany (tertiary care-level centre).ParticipantsAll cases of critically ill adult patients in need of mechanical ventilation during the years 2013–2015 were included. In total, 932 cases were analysed.ResultsFrom a total of 932 cases, 260 patients (27.9%) were transferred from peripheral ward, 224 patients (24.1%) were hospitalised via emergency rescue services, 211 patients (22.7%) were admitted via emergency room and 236 patients (25.3%) via various transfers. In 266 cases (28.5%), respiratory failure was the reason for ICU admission. The length of stay was higher in non-geriatric patients, patients with immunosuppression and haemato-oncological disease or those in need of renal replacement therapy. 431 patients died, which corresponds to an all-cause in-hospital mortality rate of 46.2%. 92 of 172 patients with presence of immunosuppression (53.5%), 111 of 186 patients (59.7%) with pre-existing haemato-oncological disease, 27 of 36 patients (75.0%) under extracorporeal membrane oxygenation (ECMO) therapy, and 182 of 246 patients (74.0%) undergoing renal replacement therapy died. In logistic regression analysis, these subgroups and older age were significantly associated with higher mortality rates.ConclusionsRespiratory failure was the main reason for ventilatory support at this non-surgical ICU. Immunosuppression, haemato-oncological diseases, the need for ECMO or renal replacement therapy and older age were associated with higher mortality.

Extracellular vesicles (EVs), including microvesicles and exosomes, are emerging as important regulators of homeostasis and pathophysiology. During pro-inflammatory and pro-oxidant conditions, EV release is induced. As EVs released under such conditions often exert pro-inflammatory and procoagulant effects, they may actively promote the pathogenesis of chronic diseases. There is evidence that thiol group-containing antioxidants can prevent EV induction by pro-inflammatory and oxidative stimuli, likely by protecting protein thiols of the EV-secreting cells from oxidation. As the redox state of protein thiols greatly impacts three-dimensional protein structure and, consequently, function, redox modifications of protein thiols may directly modulate EV release in response to changes in the cell’s redox environment. In this review article, we discuss targets of redox-dependent thiol modifications that are known or expected to be involved in the regulation of EV release, namely redox-sensitive calcium channels, N -ethylmaleimide sensitive factor, protein disulfide isomerase, phospholipid flippases, actin filaments, calpains and cell surface-exposed thiols. Thiol protection is proposed as a strategy for preventing detrimental changes in EV signaling in response to inflammation and oxidative stress. Identification of the thiol-containing proteins that modulate EV release in pro-oxidant environments could provide a rationale for broad application of thiol group-containing antioxidants in chronic inflammatory diseases.

The incidence of adverse events during endobronchial ultrasound is low. Nevertheless, it is unclear, whether patients with impaired pulmonary function have an increased risk of respiratory events during the intervention. A monocentric prospective observational study was performed at the Department of Respiratory Medicine, University Hospital Frankfurt/Main, Germany. Adult patients undergoing an endobronchial ultrasound examination with propofol-sedation were included. Pre-interventional screening included pulmonary function testing, laboratory tests and electrocardiogram. The occurrence of hypercapnia >55 mmHg or reduced oxygen saturation <85% was defined as a respiratory event was recorded and compared between patients with normal and impaired pulmonary function tests. In total, 126 patients were included. Pulmonary function testing revealed a median FEV1 of 2.2 l (range 0.4-6.04l) and a predicted FEV1 of 79.5% (range 20-127.8%) respectively. The median FVC was 3.0 l (range 0.87-7.28l), the median predicted FVC was 82% (range 31.4-128.4%). In 72 examinations (60%) pCO levels >55 mmHg were measured. Transient oxygen desaturation <85% occurred in 31 cases (25.8%). The Mann Whitney U-test showed a significantly lower FEV1 (% predicted value) in patients with respiratory events ( = 0.007). ROC analysis identified a predicted FEV1 of 78.5% as the optimal cut-off with a sensitivity of 58% and a specificity of 71%. Using Z-score instead of predicted values, there was no significant association between a lower Z- score of FEV or FVC and hypercapnic or hypoxic events. However, both a lower absolute value of FEV1/FVC and a lower Z-score of the FEV1/FVC index were associated with the occurrence of respiratory events. In binary logistic regression analysis, we could not demonstrate any association with other relevant parameters (age, BMI, sedation dosage, sedation duration, or ASA-score). An impaired forced expiratory volume is associated with the frequency of respiratory events during endobronchial ultrasound examination under propofol-sedation.

The airway epithelium provides a crucial barrier against infection with respiratory pathogens. This barrier can be impaired following viral infection, paving the way for bacterial superinfections. Type I interferons (IFNs) are important antiviral mediators, and inhaled formulations of these glycoproteins are considered a potential approach for the treatment of respiratory viral infections. To investigate if type I IFNs can also protect against virus-induced epithelial barrier dysfunction, differentiated primary bronchial epithelial cells were pre-treated with IFN-β1a and subsequently infected with human rhinovirus (HRV) for 24 to 72h. Moreover, to functionally assess the effects of IFN-β1a pre-treatment on barrier integrity, we conducted co-infection experiments, in which cells were initially infected with HRV, and superinfected with Streptococcus pneumoniae 24 to 72 h later. In untreated cells, HRV infection significantly damaged ZO-1 positive tight junctions and cilia, and transiently increased permeability, whereas the barrier of cultures pre-treated with IFN-β1a remained intact. In co-infection experiments, bacteria were able to penetrate deeper into the cell layers of HRV-infected cultures than into those of uninfected cells. IFN-β1a pre-treatment abrogated virus-induced damage to the epithelial barrier. Taken together, these data demonstrate a beneficial effect of IFN-β in protecting epithelial barrier function in addition to its antiviral effects.

IntroductionmHealth refers to digital technologies that, via smartphones, mobile apps and specialised digital sensors, yield real-time assessments of patient’s health status. In the context of the COVID-19 pandemic, these technologies enable remote patient monitoring, with the benefit of timely recognition of disease progression to convalescence, deterioration or postacute sequelae. This should enable appropriate medical interventions and facilitate recovery. Various barriers, both at patient and technology levels, have been reported, hindering implementation and use of mHealth telemonitoring. As systematised and synthesised evidence in this area is lacking, we developed this protocol for a scoping review on mHealth home telemonitoring of acute COVID-19.Methods and analysisWe compiled a search strategy following the PICO (Population, Intervention, Comparator, Outcome) and PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendation for Scoping Reviews) guidelines. MEDLINE, Embase and Web of Science will be searched from 1 March 2020 to 31 August 2021. Following the title and abstract screening, we will identify, systematise and synthesise the available knowledge. Based on pilot searches, we preview three themes for descriptive evidence synthesis. The first theme relates to implementation and use of mHealth telemonitoring, including reported barriers. The second theme covers the interactions of the telemonitoring team within and between different levels of the healthcare system. The third theme addresses how this telemonitoring warrants the continuity of care, also during disease transition into deterioration or postacute sequelae.Ethics and disseminationThe studied evidence is in the public domain, therefore, no specific ethics approval is required. Evidence dissemination will be via peer-reviewed publications, conference presentations and reports to the policy makers.