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Rationale: The use of extracorporeal membrane oxygenation (ECMO) in patients who are awake and spontaneously breathing may represent a novel bridging strategy toward lung transplantation (LuTx). Objectives: To evaluate the outcomes of patients treated with the 'awake ECMO' concept as bridge to transplantation. Methods: We performed a retrospective, single-center, intention-to-treat analysis of consecutive LuTx candidates with terminal respiratory or cardiopulmonary failure receiving awake ECMO support. The outcomes were compared with a historical control group of patients treated with conventional mechanical ventilation (MV group) as bridge to transplant. Measurements and Main Results: Twenty-six patients (58% female; median age, 44 yr; range, 23-62) were included in the awake ECMO group and 34 patients (59% female; median age, 36 yr; range, 18-59) in the MV group. The duration of ECMO support or MV, respectively, was comparable in both groups (awake ECMO: median, 9 d; range, 1-45. MV: median, 15 d; range, 1-71; P = 0.25). Six (23%) of 26 patients in the awake ECMO group and 10 (29%) of 34 patients in the MV group died before a donor organ was available (P = 0.20). Survival at 6 months after LuTx was 80% in the awake ECMO group versus 50% in the MV group (P = 0.02). Patients in the awake ECMO group required shorter postoperative MV (P = 0.04) and showed a trend toward a shorter postoperative hospital stay (P = 0.06). Conclusions: ECMO support in patients who are awake and nonintubated represents a promising bridging strategy, which should be further evaluated to determine its role in patients with end-stage lung disease awaiting LuTx. [ABSTRACT FROM AUTHOR]

Introduction: The Seraph 100 Microbind Affinity blood filter eliminate bacteria, viruses, fungi and toxins from blood stream., Methods: This is a prospective multicenter observational biomarker trial in PCR-positive SARS-CoV-2 patients with acute respiratory failure. Biomarkers were sequentially tested at three time points., Results: Forty-two patients with SARS-CoV-2 detected by PCR with acute respiratory failure were included. When receiving hemoperfusion treatment, 27 (64%) patients were on mechanical ventilation, 41 (98%) patients were treated in the ICU. The 3-month survival was 52%. After one hemoperfusion treatment cycle, D-dimer (p = 0.014), hemoglobin (p = 0.003) and LDH (p = 0.001) concentrations were significantly reduced 4 days after treatment. From the multiplex assay IL-1b, CXCL8/ IL-8, IL-10, IL-13, IL-15, CCL11/Eotaxin, G-CSF, and CXCL10/IP-10 were significantly reduced 1 h after treatment, however not 4 days later., Conclusion: Hemoperfusion with Seraph 100 Microbind Affinity Filter in patients with severe COVID-19 can transiently reduce several inflammatory biomarkers in the blood., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Background: Many hospitalized patients decline in functional status after discharge, but functional decline in emergency admissions with hypoxemia is unknown. The primary aim of this study was to study functional outcomes as a clinical endpoint in a cohort of patients with acute hypoxemia., Methods: A multicenter prospective observational study was conducted in patients with new-onset hypoxemia emergently admitted to two respiratory departments at a university hospital and an academic teaching hospital. Using the WHO scale, the patients' functional status 4 weeks before admission and at hospital discharge was assessed. The type and duration of oxygen therapy, hospital length of stay and survival and risk of hypercapnic failure were recorded., Results: A total of 151 patients with a median age of 74 were included. Two-thirds declined in functional status by at least one grade at discharge. A good functional status (OR 4.849 (95% CI 2.209-10.647)) and progressive cancer (OR 6.079 (1.197-30.881)) were more associated with functional decline. Most patients were treated with conventional oxygen therapy (n = 95, 62%). The rates of in-hospital mortality and need for intubation were both 8%., Conclusions: Patients with acute hypoxemia in the emergency room have a poorer functional status after hospital discharge. This decline may be of multifactorial origin., Competing Interests: Jens Gottlieb reports institutional research grants from Zambon/Breath Therapeutics, German Center of Lung Research, Deutsche Forschungsgemeinschaft. He also received fees for advisory/consultancy from Theravance, Pierre Fabre, Atheneum, Merck, Springer Healthcare and the European Research Network, and speaker fees from Novartis, Astra Zeneca and CSL Behring. He owns stock options from Pfizer. He serves as a member of the ScanCLAD study’s data safety monitoring board. All disclosures are unrelated to the current work. Susanne Simon, Ina Burchart and René Abu Isneineh report no disclosures. Thomas Fuehner reports speaker fees from Novartis and Astra Zeneca. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: Chronic lung allograft dysfunction (CLAD) is a leading cause of graft loss in lung transplantation. Despite this, convincing treatment data is lacking, and protocols vary widely between centers. CLAD phenotypes exist, but phenotype transitioning has increased the challenge of designing clinically relevant studies. Extracorporeal photopheresis (ECP) has long been a suggested salvage treatment, but efficacy appears unpredictable. This study describes our experiences with photopheresis, using novel temporal phenotyping to illustrate the clinical course., Methods: Retrospective analysis of patients completing ≥3 months of ECP for CLAD between 2007 and 2022 was performed. A latent class analysis employing a mixed-effects model was performed, deriving patient subgroups based on spirometry trajectory over the 12 months prior to photopheresis until graft loss or 4 years post photopheresis initiation. The resulting temporal phenotypes were compared in terms of treatment response and survival outcomes. Linear discriminatory analysis was used to assess phenotype predictability, relying solely on data available at photopheresis initiation., Results: Data from 5,169 outpatient attendances in 373 patients was used to construct the model. Five trajectories were identified, with uniform spirometry changes evident following 6 months of photopheresis. Outcomes were poorest in Fulminant patients (N = 25, 7%) with median survival of 1 year. In the remainder, poorer lung function at initiation led to poorer outcomes. The analysis revealed important confounders, affecting both decision-making and outcome interpretation., Conclusions: Temporal phenotyping provided novel insights into ECP treatment response in CLAD, particularly the importance of timely intervention. Limitations in % Baseline values in guiding treatment decisions warrant further analysis. Photopheresis may have a more uniform effect than previously thought. Predicting survival at ECP initiation appears feasible., Competing Interests: Disclosure statement MG has previously received speaker fees from Therakos. Neither Therakos nor any of their partners were involved or indeed had any prior knowledge of the manuscript at any stage prior to publication. JMM reports institutional grants and speaker fees from Boehringer Ingelheim. FI reports consulting and speaker fees as well as travel support grants from Biotest AG. TW has received research grants from the German Ministry for Research and Education for projects unrelated to this manuscript. None of the other authors reported any relevant financial interests., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Obstructive airway complications (OACs) represent a significant problem after lung transplantation (LTx). Bilateral OACs after double lung transplantation are infrequently reported., Objectives: The aim of this study was to investigate management and outcome of OAC., Design: Retrospective single-center cohort study., Methods: Adult patients with bilateral LTx performed between 2010 and 2021 were included. Patients with follow-ups of less than 3 months and after heart-lung transplantation were excluded. OAC was defined either as the need for stenting, surgical revision, or balloon dilatation. Outcome parameters included graft survival, graft function, quality of life, and management., Results: During the study period, 1,170 patients were included. Hundred thirty-five (11.5%) patients developed OAC. Forty-six (4.4%) patients had significant bilateral OAC. Thirty-seven (80%) bilateral OAC patients were treated by stent insertion; in 34 patients, biodegradable stents were used. The median number of bronchoscopies in bilateral OAC was 26 during the first postoperative year compared with nine in controls ( p  < 0.001). Fourteen OAC patients ( n  = 10 bilateral) underwent surgical revision including six re-do transplantations. Graft loss occurred significantly more frequently in patients with bilateral OAC with a graft survival of 63% and 50% in these after 3 and 5 years compared with 83% and 73% in controls without OAC ( p  < 0.001). Baseline forced expiratory volume in 1 s (FEV1) in patients with bilateral OAC was median 58% predicted in comparison with 90% in controls ( p  < 0.001). Quality of life was significantly reduced., Conclusion: Bilateral OACs impose a high burden of disease on patients after lung transplantation and were associated with early and late graft loss. Affected patients' OAC demonstrated reduced graft function and impaired quality of life. Most OACs were managed by bronchoscopy preferably by non-permanent stenting. Surgery including re-do transplantation was used in selected cases.

Background: The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global crisis challenging the worldwide healthcare systems. Many patients present with a mismatch of profound hypoxemia and few signs of respiratory distress (i.e., silent hypoxemia). This particular clinical presentation is often cited, but data are limited., Main Body: We describe dyspnea sensation as assessed by using the BORG scale in pulmonary patients admitted to the emergency room during a 4-week period and transferred to the respiratory department of Siloah Hospital, Hannover, Germany. From October 1 to November 1, 2020, 82 patients with hypoxemia defined as oxygen demand to achieve an oxygen saturation (SpO2) ≥92% were included. In 45/82 (55%) patients, SARS-CoV-2 was detected by PCR on admission. Among non-COVID patients, exacerbation of COPD was the main diagnosis (15/37, 41%). All subjects rated their perceived dyspnea using the modified Borg CR10 scale. Patients in the non-COVID group suffered from more dyspnea on the modified Borg CR10 scale (median 1, IQR: 0-2 vs. median 5, IQR: 3-6, p < 0.001). In multivariate analysis, "silent hypoxemia" as defined by the dyspnea Borg CR10 scale ≥5 was independently associated with COVID-19 and presence of severe hypocapnia with an odds ratio of 0.221 (95% confidence interval 0.054, 0.907, p 0.036)., Conclusion: Among pulmonary patients with acute hypoxemia defined as oxygen demand, patients suffering from COVID-19 experience less dyspnea compared to non-COVID patients. "Silent" hypoxemia was more common in COVID-19 patients., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

Background: Bronchoscopy is widely used and regarded as standard of care in most intensive care units (ICUs). Data concerning recommendations for on-call bronchoscopy are lacking., Objectives: Evaluation of recommendations, complications, and outcome of on-call bronchoscopies., Method: A retrospective single-centre analysis was conducted in a large university hospital. All on-call bronchoscopies performed outside normal working hours in the year before (period 1) and after (period 2) establishing a catalogue of recommendations for indications of on-call bronchoscopy on November 1, 2016, were included., Results: Overall, 924 bronchoscopies in 538 patients were analysed. A relative reduction of 83.6% from 794 bronchoscopies in 432 patients (1.84 per patient) during period 1 to 130 in 107 patients (1.21 per patient) during period 2 was observed. Most bronchoscopies (812/924, 87.9%) were performed in ICUs, and 416 patients (77.3%) were intubated. Bronchoscopies for excessive secretions decreased significantly during period 2. Fifty-three of 130 bronchoscopies (40.8%) fulfilled the specified recommendations during period 2, in comparison with 16.8% in period 1 (p < 0.001). Complications were recorded in 58 of 924 procedures (6.3%) and were more frequent in period 2, especially moderate bleeding. In-hospital mortality of patients undergoing on-call bronchoscopy did not differ between periods and was 28.7 and 30.2% in periods 1 and 2, respectively., Conclusion: The introduction of recommendations for on-call bronchoscopy led to a significant decline of on-call bronchoscopies without negatively affecting outcome. More evidence is needed in on-call bronchoscopy, especially for ICU patients with intrinsic higher complication rates., (© 2021 S. Karger AG, Basel.)