The role of coronary artery disease in lung transplantation: a propensity-matched analysis.

BACKGROUND AND AIMS: Candidate selection for lung transplantation (LuTx) is pivotal to ensure individual patient benefit as well as optimal donor organ allocation. The impact of coronary artery disease (CAD) on post-transplant outcomes remains controversial. We provide comprehensive data on the relevance of CAD for short- and long-term outcomes following LuTx and identify risk factors for mortality. METHODS: We retrospectively analyzed all adult patients (≥ 18 years) undergoing primary and isolated LuTx between January 2000 and August 2021 at the LMU University Hospital transplant center. Using 1:1 propensity score matching, 98 corresponding pairs of LuTx patients with and without relevant CAD were identified. RESULTS: Among 1,003 patients having undergone LuTx, 104 (10.4%) had relevant CAD at baseline. There were no significant differences in in-hospital mortality (8.2% vs. 8.2%, p > 0.999) as well as overall survival (HR 0.90, 95%CI [0.61, 1.32], p = 0.800) between matched CAD and non-CAD patients. Similarly, cardiovascular events such as myocardial infarction (7.1% CAD vs. 2.0% non-CAD, p = 0.170), revascularization by percutaneous coronary intervention (5.1% vs. 1.0%, p = 0.212), and stroke (2.0% vs. 6.1%, p = 0.279), did not differ statistically between both matched groups. 7.1% in the CAD group and 2.0% in the non-CAD group (p = 0.078) died from cardiovascular causes. Cox regression analysis identified age at transplantation (HR 1.02, 95%CI [1.01, 1.04], p < 0.001), elevated bilirubin (HR 1.33, 95%CI [1.15, 1.54], p < 0.001), obstructive lung disease (HR 1.43, 95%CI [1.01, 2.02], p = 0.041), decreased forced vital capacity (HR 0.99, 95%CI [0.99, 1.00], p = 0.042), necessity of reoperation (HR 3.51, 95%CI [2.97, 4.14], p < 0.001) and early transplantation time (HR 0.97, 95%CI [0.95, 0.99], p = 0.001) as risk factors for all-cause mortality, but not relevant CAD (HR 0.96, 95%CI [0.71, 1.29], p = 0.788). Double lung transplant was associated with lower all-cause mortality (HR 0.65, 95%CI [0.52, 0.80], p < 0.001), but higher in-hospital mortality (OR 2.04, 95%CI [1.04, 4.01], p = 0.039). CONCLUSION: In this cohort, relevant CAD was not associated with worse outcomes and should therefore not be considered a contraindication for LuTx. Nonetheless, cardiovascular events in CAD patients highlight the necessity of control of cardiovascular risk factors and a structured cardiac follow-up.

Long-term multicenter comparison shows equivalent efficacy of monoclonal antibodies in severe asthma therapy.

BACKGROUND: Monoclonal antibodies (biologics) drastically changed severe asthma therapy. Mepolizumab (anti-interleukin (IL) 5), benralizumab (anti-IL5 receptor alpha), and dupilumab (anti-IL4/13) are the most used biologics in this context. While all biologics are efficient individually, the choice of biologic is complicated by insufficient data on their comparative long-term treatment efficacy. Here, we compare the real-life efficacy of these biologics in asthma therapy over 12 months. METHODS: 280 severe asthma patients treated with mepolizumab (129/280, 46%), benralizumab (83/280, 30%) or dupilumab (68/280, 24%) for one year were analyzed retrospectively. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels as well as responder status measured by the recently published "Biologic Asthma Response Score" (BARS). RESULTS: All biologics led to significant improvements in PF, ACT and OCS dose. Only Mepolizumab and Benralizumab significantly decreased the exacerbation rate, while only Mepolizumab and Dupilumab significantly decreased FeNO. Responder rates measured by BARS were high across all groups: roughly half of all patients achieved full response and most of the remainder achieved at least partial responder status. Overall, outcomes were similar between groups after both 6 and 12 months. CONCLUSIONS: All biologics showed great efficacy in individual parameters and high responder rates measured by BARS without a clinically relevant advantage for any antibody. Response was usually achieved after 6 months and retained at 12 months, emphasizing the utility of early response assessment.

[Therapeutic Pathways in Sarcoidosis. A Position Paper of the German Society of Respiratory Medicine (DGP)]. / Therapie der Sarkoidose. Ein Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin (DGP).

The present recommendations on the therapy of sarcoidosis of the German Respiratory Society (DGP) was written in 2023 as a German-language supplement and update of the international guidelines of the European Respiratory Society (ERS) from 2021. It contains 5 PICO questions (Patients, Intervention, Comparison, Outcomes) agreed in the consensus process, which are explained in the background text of the four articles: Confirmation of diagnosis and monitoring of the disease under therapy, general therapy recommendations, therapy of cutaneous sarcoidosis, therapy of cardiac sarcoidosis.

Sfrp1 inhibits lung fibroblast invasion during transition to injury-induced myofibroblasts.

BACKGROUND: Fibroblast-to-myofibroblast conversion is a major driver of tissue remodelling in organ fibrosis. Distinct lineages of fibroblasts support homeostatic tissue niche functions, yet their specific activation states and phenotypic trajectories during injury and repair have remained unclear. METHODS: We combined spatial transcriptomics, multiplexed immunostainings, longitudinal single-cell RNA-sequencing and genetic lineage tracing to study fibroblast fates during mouse lung regeneration. Our findings were validated in idiopathic pulmonary fibrosis patient tissues in situ as well as in cell differentiation and invasion assays using patient lung fibroblasts. Cell differentiation and invasion assays established a function of SFRP1 in regulating human lung fibroblast invasion in response to transforming growth factor (TGF)ß1. MEASUREMENTS AND MAIN RESULTS: We discovered a transitional fibroblast state characterised by high Sfrp1 expression, derived from both Tcf21-Cre lineage positive and negative cells. Sfrp1 + cells appeared early after injury in peribronchiolar, adventitial and alveolar locations and preceded the emergence of myofibroblasts. We identified lineage-specific paracrine signals and inferred converging transcriptional trajectories towards Sfrp1 + transitional fibroblasts and Cthrc1 + myofibroblasts. TGFß1 downregulated SFRP1 in noninvasive transitional cells and induced their switch to an invasive CTHRC1+ myofibroblast identity. Finally, using loss-of-function studies we showed that SFRP1 modulates TGFß1-induced fibroblast invasion and RHOA pathway activity. CONCLUSIONS: Our study reveals the convergence of spatially and transcriptionally distinct fibroblast lineages into transcriptionally uniform myofibroblasts and identifies SFRP1 as a modulator of TGFß1-driven fibroblast phenotypes in fibrogenesis. These findings are relevant in the context of therapeutic interventions that aim at limiting or reversing fibroblast foci formation.

Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multilineage cell circuit dynamics in human lung fibrogenesis.

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage circuit of fibrogenic cell states in hPCLS. We showed that these cell states were highly similar to the in vivo cell circuit in a multicohort lung cell atlas from patients with pulmonary fibrosis. Using micro-CT-staged patient tissues, we characterized the appearance and interaction of myofibroblasts, an ectopic endothelial cell state, and basaloid epithelial cells in the thickened alveolar septum of early-stage lung fibrosis. Induction of these states in the hPCLS model provided evidence that the basaloid cell state was derived from alveolar type 2 cells, whereas the ectopic endothelial cell state emerged from capillary cell plasticity. Cell-cell communication routes in patients were largely conserved in hPCLS, and antifibrotic drug treatments showed highly cell type-specific effects. Our work provides an experimental framework for perturbational single-cell genomics directly in human lung tissue that enables analysis of tissue homeostasis, regeneration, and pathology. We further demonstrate that hPCLS offer an avenue for scalable, high-resolution drug testing to accelerate antifibrotic drug development and translation.

Domestic Parasitic Infections in Patients with Asthma and Eosinophilia in Germany - Three Cases with Learnings in the Era of Anti- IL5 Treatments.

Eosinophilic inflammation is a hallmark of asthma, and blood eosinophilia has been established as a biomarker for phenotyping asthma and predicting the response to anti-IL5 treatments. Although parasitic infections are rare in European adults, they remain an important differential diagnosis for blood eosinophilia. We present three patients with both domestic parasitic infections and asthma to raise awareness of the potential challenge of eosinophilia and to provide experience in the management of parasitic infections in the setting of planned or ongoing anti-IL5 treatment. One, a patient from Croatia with moderate asthma but severe blood eosinophilia had an underlying Strongyloides stercoralis infection, with positive stool cultures. Second, a patient with severe allergic asthma and gastrointestinal symptoms had a positive S. stercoralis titer in serology with a clinical response to treatment with ivermectin. Third, a patient with severe nonallergic eosinophilic asthma and eosinophilic granulomatosis with polyangiitis (EGPA) showed an increasing hepatic tumour under anti-IL5-receptor therapy. Positive serology confirmed the diagnosis of Echinococcus multilocularis, and albendazole therapy was initiated. Anti-IL5 therapies were safely started (Patient 2) or resumed (Patient 3) after the initiation of antiparasitic treatment. Screening for parasitic infections is useful in cases of hypereosinophilia, extrapulmonary symptoms or stay in endemic regions.

[Pulmonary hypertension associated with lung disease]. / Pulmonale Hypertonie assoziiert mit Lungenerkrankungen.

Lung diseases and hypoventilation syndromes are often associated with pulmonary hypertension (PH). In most cases, PH is not severe. This is defined hemodynamically by a mean pulmonary arterial pressure (PAPm) > 20 mmHg, a pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance of ≤ 5 Wood units (WU). Both the non-severe (PVR ≤ 5 WU) and much more the severe PH (PVR > 5 WU) have an unfavorable prognosis.If PH is suspected, it is recommended to primarily check whether risk factors for pulmonary arterial hypertension (PAH, group 1 PH) or chronic thromboembolic pulmonary hypertension (CTEPH, group 4 PH) are present. If risk factors are present or there is a suspicion of severe PH in lung patients, it is recommended that the patient should be presented to a PH outpatient clinic promptly.For patients with severe PH associated with lung diseases, personalized, individual therapy is recommended - if possible within the framework of therapy studies. Currently, a therapy attempt with PH specific drugs should only be considered in COPD patients if the associated PH is severe and a "pulmonary vascular" phenotype (severe precapillary PH, but typically only mild to moderate airway obstruction, no or mild hypercapnia and DLCO < 45 % of predicted value) is present. In patients with severe PH associated with interstitial lung disease phosphodiesterase-5-inhibitors may be considered in individual cases. Inhaled treprostinil may be considered also in non-severe PH in this patient population.

Mass spectrometry-based autoimmune profiling reveals predictive autoantigens in idiopathic pulmonary fibrosis.

Autoimmunity plays a role in certain types of lung fibrosis, notably connective tissue disease-associated interstitial lung disease (CTD-ILD). In idiopathic pulmonary fibrosis (IPF), an incurable and fatal lung disease, diagnosis typically requires clinical exclusion of autoimmunity. However, autoantibodies of unknown significance have been detected in IPF patients. We conducted computational analysis of B cell transcriptomes in published transcriptomics datasets and developed a proteomic Differential Antigen Capture (DAC) assay that captures plasma antibodies followed by affinity purification of lung proteins coupled to mass spectrometry. We analyzed antibody capture in two independent cohorts of IPF and CTL-ILD patients over two disease progression time points. Our findings revealed significant upregulation of specific immunoglobulins with V-segment bias in IPF across multiple cohorts. We identified a predictive autoimmune signature linked to reduced transplant-free survival in IPF, persisting over time. Notably, autoantibodies against thrombospondin-1 were associated with decreased survival, suggesting their potential as predictive biomarkers.

Mechanical Power Density Predicts Prolonged Ventilation Following Double Lung Transplantation.

Prolonged mechanical ventilation (PMV) after lung transplantation poses several risks, including higher tracheostomy rates and increased in-hospital mortality. Mechanical power (MP) of artificial ventilation unifies the ventilatory variables that determine gas exchange and may be related to allograft function following transplant, affecting ventilator weaning. We retrospectively analyzed consecutive double lung transplant recipients at a national transplant center, ventilated through endotracheal tubes upon ICU admission, excluding those receiving extracorporeal support. MP and derived indexes assessed up to 36 h after transplant were correlated with invasive ventilation duration using Spearman's coefficient, and we conducted receiver operating characteristic (ROC) curve analysis to evaluate the accuracy in predicting PMV (>72 h), expressed as area under the ROC curve (AUROC). PMV occurred in 82 (35%) out of 237 cases. MP was significantly correlated with invasive ventilation duration (Spearman's ρ = 0.252 [95% CI 0.129-0.369], p < 0.01), with power density (MP normalized to lung-thorax compliance) demonstrating the strongest correlation (ρ = 0.452 [0.345-0.548], p < 0.01) and enhancing PMV prediction (AUROC 0.78 [95% CI 0.72-0.83], p < 0.01) compared to MP (AUROC 0.66 [0.60-0.72], p < 0.01). Mechanical power density may help identify patients at risk for PMV after double lung transplantation.

Impact of ILD-Specific Therapies on Perioperative Course in Patients with Progressive Interstitial Lung Disease Undergoing Lung Transplantation.

Immunosuppressants and antifibrotics are currently used to treat patients with various interstitial lung diseases, which may undergo lung transplantation (LTx). The retrospective study aimed to evaluate the potential effects of therapeutic regimen on the perioperative course in patients with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) undergoing LTx. All patients with IPF and PPF undergoing LTx between January 2014 and December 2021 were included. We retrospectively screened for previous use of immunosuppressants and antifibrotic therapy. We analyzed perioperative courses, short-term outcomes, and safety retrospectively. In total, 286 patients with diagnosis of IPF or PPF were analyzed. According to the treatment regimen before LTx, the study cohort was divided into four groups and compared. No differences between antifibrotic monotherapy, combined antifibrotic and immunosuppressive therapy with regard to postoperative complications were observed. Length of mechanical ventilation was shorter in patients with antifibrotics prior to LTx. Pretreatment with antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy, lower body mass index (BMI) and lower blood loss, were independently associated with primary graft dysfunction grades 0-3 72 hours after LTx (p < 0.001). Finally, patients with antifibrotic monotherapy developed significantly less de novo donor-specific antibodies (DSA) (p = 0.009). Higher intraoperative blood loss, etiology of interstitial lung disease (ILD) and older age were independently associated with shorter survival after LTx. Use of antifibrotic monotherapy and a combination of antifibrotic drugs with immunosuppressive therapy in IPF/PPF patients undergoing LTx, proved to be safe and might lead to beneficial effects after LTx.

Case report: Central venous catheter thrombosis complicated by chronic thromboembolic disease/pulmonary hypertension in two children requiring parenteral nutrition.

Chronic thromboembolic pulmonary hypertension is a rare but life-threatening complication of long-term central venous catheters (CVC) in children. However, evidence in terms of potential treatment strategies and outcome data remains scarce. We describe two cases of CVC-related thrombosis (Hickman-catheter) complicated by recurrent pulmonary emboli. One patient experienced a complete thromboembolic obstruction of the right pulmonary artery with normal pulmonary pressures and the second patient suffered from a central thromboembolic obstruction of both pulmonary arteries associated with severe pulmonary hypertension. Both patients successfully underwent surgical thromboendarterectomy with deep hypothermic circulatory arrest.

Clinical Impact of Physical Activity and Cough on Disease Progression in Fibrotic Interstitial Lung Disease.

Physical activity limitations and cough are common in patients with interstitial lung disease (ILD), potentially leading to reduced health-related quality of life. We aimed to compare physical activity and cough between patients with subjective, progressive idiopathic pulmonary fibrosis (IPF) and fibrotic non-IPF ILD. In this prospective observational study, wrist accelerometers were worn for seven consecutive days to track steps per day (SPD). Cough was evaluated using a visual analog scale (VAScough) at baseline and weekly for six months. We included 35 patients (IPF: n = 13; non-IPF: n = 22; mean ± SD age 61.8 ± 10.8 years; FVC 65.3 ± 21.7% predicted). Baseline mean ± SD SPD was 5008 ± 4234, with no differences between IPF and non-IPF ILD. At baseline, cough was reported by 94.3% patients (mean ± SD VAScough 3.3 ± 2.6). Compared to non-IPF ILD, patients with IPF had significantly higher burden of cough (p = 0.020), and experienced a greater increase in cough over six months (p = 0.009). Patients who died or underwent lung transplantation (n = 5), had significantly lower SPD (p = 0.007) and higher VAScough (p = 0.047). Long-term follow up identified VAScough (HR: 1.387; 95%-CI 1.081-1.781; p = 0.010) and SPD (per 1000 SPD: HR 0.606; 95%-CI: 0.412-0.892; p = 0.011) as significant predictors for transplant-free survival. In conclusion, although activity didn't differ between IPF and non-IPF ILD, cough burden was significantly greater in IPF. SPD and VAScough differed significantly in patients who subsequently experienced disease progression and were associated with long-term transplant-free survival, calling for better acknowledgement of both parameters in disease management.

Response to Biologics and Clinical Remission in the Adult German Asthma Net Severe Asthma Registry Cohort.

BACKGROUND: Recently, criteria for evaluation of response to biologics have been proposed and the concept of clinical remission has gained attention as a possible goal even in severe asthma. OBJECTIVE: To analyze the response and remission in the German Asthma Net severe asthma registry cohort. METHODS: We included adults not using a biologic at baseline (V0) and compared patients treated between V0 and 1-year visit (V1) without using a biologic (group A) to patients starting with a biologic after V0 and continuing it up to V1 (group B). We applied the Biologics Asthma Response Score to quantify composite response in good, intermediate, or insufficient. We defined clinical remission (R) as absence of significant symptoms (Asthma Control Test score ≥ 20 at V1) in the absence of exacerbations and oral corticosteroid therapy. RESULTS: Group A included 233 and group B 210 patients, the latter receiving omalizumab (n = 33), mepolizumab (n = 40), benralizumab (n = 81), reslizumab (n = 1), or dupilumab (n = 56). At baseline, group B had less often an allergic phenotype (35.2% vs 41.6%), lower Asthma Control Test score (median, 12 vs 14), more exacerbations in the past year (median, 3 vs 2), and more often high-dose inhaled corticosteroid treatment (71.4% vs 51.5%) than group A. After 1 year of treatment, rates of response (good: 61.4% vs 34.8%; intermediate: 26.7% vs 42.9%; insufficient: 11.9% vs. 22.3%) and/or clinical remission (37.6% vs 17.2%) were higher in group B than in group A. CONCLUSIONS: Despite more severe asthma at baseline, patients treated with biologics had a markedly higher probability of achieving good clinical response and/or remission than patients treated without biologics.

Predictive value of molecular matching tools for the development of donor specific HLA-antibodies in patients undergoing lung transplantation.

Molecular matching is a new approach for virtual histocompatibility testing in organ transplantation. The aim of our study was to analyze whether the risk for de novo donor-specific HLA antibodies (dnDSA) after lung transplantation (LTX) can be predicted by molecular matching algorithms (MMA) and their combination. In this retrospective study we included 183 patients undergoing LTX at our center from 2012-2020. We monitored dnDSA development for 1 year. Eplet mismatches (epMM) using HLAMatchmaker were calculated and highly immunogenic eplets based on their ElliPro scores were identified. PIRCHE-II scores were calculated using PIRCHE-II algorithm (5- and 11-loci). We compared epMM and PIRCHE-II scores between patients with and without dnDSA using t-test and used ROC-curves to determine optimal cut-off values to categorize patients into four groups. We used logistic regression with AIC to compare the predictive value of PIRCHE-II, epMM, and their combination. In total 28.4% of patients developed dnDSA (n = 52), 12.5% class I dnDSA (n = 23), 24.6% class II dnDSA (n = 45), and 8.7% both class II and II dnDSA (n = 16). Mean epMMs (p-value = 0.005), mean highly immunogenic epMMs (p-value = 0.003), and PIRCHE-II (11-loci) (p = 0.01) were higher in patients with compared to without class II dnDSA. Patients with highly immunogenic epMMs above 30.5 and PIRCHE-II 11-loci above 560.0 were more likely to develop dnDSA (31.1% vs. 14.8%, p-value = 0.03). The logistic regression model including the grouping variable showed the best predictive value. MMA can support clinicians to identify patients at higher or lower risk for developing class II dnDSA and might be helpful tools for immunological risk assessment in LTX patients.

Efficacy of pre-exposure prophylaxis to prevent SARS-CoV-2 infection after lung transplantation: a two center cohort study during the omicron era.

PURPOSE: Lung transplant (LTx) recipients are at risk for poor outcomes from coronavirus disease 2019 (COVID-19). The aim of the study was to assess the outcome of patients receiving pre-exposure prophylaxis (PrEP) with tixagevimab and cilgavimab after LTx. METHODS: All LTx recipients with outpatient visits from February 28th to October 31st, 2022 at two German centers were included. Baseline characteristics were recorded and patients followed until November 30rd, 2022. Infections with SARS-CoV-2, disease severity, and COVID-19-associated death were compared between patients with and without PrEP. RESULTS: In total, 1438 patients were included in the analysis, and 419 (29%) received PrEP. Patients receiving PrEP were older and earlier after transplantation, had lower glomerular filtration rates, and lower levels of SARS-CoV-2-S antibodies. In total, 535 patients (37%) developed SARS-CoV-2 infection during a follow-up of median of 209 days. Fewer infections occurred in patients with PrEP during the study period (31% vs. 40%, p = 0.004). Breakthrough SARS-CoV-2 infections after PrEP occurred in 77 patients (19%). In total, 37 infections (8%) were severe or critical. No difference in severity of COVID-19 was observed between patients with and without PrEP. There were 15 COVID-19-associated deaths (n = 1 after PrEP). Compared to matched controls, there was a non-significant difference towards a lower risk for moderate to critical COVID-19 (p 0.184). CONCLUSION: The number of SARS-CoV-2 infections was lower in LTx recipients with PrEP. Despite being at higher risk for worse outcome severity of COVID-19 and associated mortality were similar in patients with and without PrEP.

[SARS-CoV-2-Infection and Interstitial Lung Disease: Position paper of the German Respiratory Society]. / SARS-CoV-2-Infektion und interstitielle Lungenerkrankungen ­ Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin.

The SARS-CoV-2 pandemic had a tremendous impact on diagnosis and treatment of interstitial lung diseases (ILD). Especially in the early phase of the pandemic, when the delta variant was prevailling, a huge number of viral pneumonias were observed, which worsened pre-existing, triggered de novo occurence or discovery of previously subclincal interstitial lung diseases. The effect of SARS-CoV-2 infection - without or with accompanying viral pneumonia - on the further development of pre-existing ILD as well of new pulmonary inflitrates and consolidiations is difficult to predict and poses a daily challenge to interdisciplinary ILD boards. This position paper of the German Respiratory Society (DGP e.V.) provides answers to the most pressing questions based on current knowledge.

Ventilatory ratio and mechanical power in prolonged mechanically ventilated COVID-19 patients versus respiratory failures of other etiologies.

BACKGROUND: Evidence suggests differences in ventilation efficiency and respiratory mechanics between early COVID-19 pneumonia and classical acute respiratory distress syndrome (ARDS), as measured by established ventilatory indexes, such as the ventilatory ratio (VR; a surrogate of the pulmonary dead-space fraction) or mechanical power (MP; affected, e.g., by changes in lung-thorax compliance). OBJECTIVES: The aim of this study was to evaluate VR and MP in the late stages of the disease when patients are ready to be liberated from the ventilator after recovering from COVID-19 pneumonia compared to respiratory failures of other etiologies. DESIGN: A retrospective observational cohort study of 249 prolonged mechanically ventilated, tracheotomized patients with and without COVID-19-related respiratory failure. METHODS: We analyzed each group's VR and MP distributions and trajectories [repeated-measures analysis of variance (ANOVA)] during weaning. Secondary outcomes included weaning failure rates between groups and the ability of VR and MP to predict weaning outcomes (using logistic regression models). RESULTS: The analysis compared 53 COVID-19 cases with a heterogeneous group of 196 non-COVID-19 subjects. VR and MP decreased across both groups during weaning. COVID-19 patients demonstrated higher values for both indexes throughout weaning: median VR 1.54 versus 1.27 (p < 0.01) and MP 26.0 versus 21.3 Joule/min (p < 0.01) at the start of weaning, and median VR 1.38 versus 1.24 (p < 0.01) and MP 24.2 versus 20.1 Joule/min (p < 0.01) at weaning completion. According to the multivariable analysis, VR was not independently associated with weaning outcomes, and the ability of MP to predict weaning failure or success varied with lung-thorax compliance, with COVID-19 patients demonstrating consistently higher dynamic compliance along with significantly fewer weaning failures (9% versus 30%, p < 0.01). CONCLUSION: COVID-19 patients differed considerably in ventilation efficiency and respiratory mechanics among prolonged ventilated individuals, demonstrating significantly higher VRs and MP. The differences in MP were linked with higher lung-thorax compliance in COVID-19 patients, possibly contributing to the lower rate of weaning failures observed.

Lung Ultrasound as a Promising Diagnostic Tool for Primary Graft Dysfunction after Lung Transplantation.

PURPOSE: The aim of the study was to evaluate whether the quantification of B-lines via lung ultrasound after lung transplantation is feasible and correlates with the diagnosis of primary graft dysfunction. METHODS: Following lung transplantation, patients underwent daily lung ultrasound on postoperative days 1-3. B-lines were quantified by an ultrasound score based on the number of single and confluent B-lines per intercostal space, using a four-region protocol. The ultrasound score was correlated with the diagnosis of primary graft dysfunction. Furthermore, correlation analyses and receiver operating characteristics analyses taking into account ultrasound score, chest radiographs, and PaO2/FiO2 ratio were performed. RESULTS: A total of 32 patients (91 ultrasound measurements) were included, whereby 10 were diagnosed with primary graft dysfunction. The median B-line score was 5 [IQR: 4, 8]. There was a significant correlation between B-line score and the diagnosis of primary graft dysfunction (r = 0.59, p < 0.001). A significant correlation could also be seen between chest X-rays and primary graft dysfunction (r = 0.34, p = 0.008), but the B-line score showed superiority over chest X-rays with respect to diagnosing primary graft dysfunction in the receiver operating characteristics curves with an area under the curve value of 0.921 versus 0.708. There was a significant negative correlation between B-line score and PaO2/FiO2 ratio (r = -0.41, p < 0.001), but not between chest X-rays and PaO2/FiO2 ratio (r = -0.14, p = 0.279). CONCLUSION: The appearance of B-lines correlated well with primary graft dysfunction and outperformed chest radiographs.

Outcome of lung transplant recipients infected with SARS-CoV-2/Omicron/B.1.1.529: a Nationwide German study.

PURPOSE: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is currently the major threat for immunocompromised individuals. The course of COVID-19 in lung transplant recipients in the Omicron era remains unknown. The aim of the study was to assess outcome and associated factors in lung transplant recipients in a German-wide multicenter approach. METHODS: All affected individuals from January 1st to March 20th, 2022 from 8 German centers during the Omicron wave were collected. Baseline characteristics and antiviral measures were associated with outcome. RESULTS: Of 218 patients with PCR-proven SARS-CoV-2 infection 166 patients (76%) received any early (< 7 days) antiviral therapy median 2 (interquartile range 1-4) days after symptom onset. Most patients received sotrovimab (57%), followed by remdesivir (21%) and molnupiravir (21%). An early combination therapy was applied in 45 patients (21%). Thirty-four patients (16%) developed a severe or critical disease severity according to the WHO scale. In total, 14 patients (6.4%) died subsequently associated with COVID-19. Neither vaccination and antibody status, nor applied treatments were associated with outcome. Only age and glomerular filtration rate < 30 ml/min/1.73m2 were independent risk factors for a severe or critical COVID-19. CONCLUSION: COVID-19 due to Omicron remains an important threat for lung transplant recipients. In particular, elderly patients and patients with impaired kidney function are at risk for worse outcome. Prophylaxis and therapy in highly immunocompromised individuals need further improvement.

Posterior reversible encephalopathy syndrome after lung transplantation: Risk factors and management.

INTRODUCTION: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation. METHODS: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19). RESULTS: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES. CONCLUSION: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.