Patients after lung transplantation are at risk for life-threatening infections. Recently, several publications on COVID-19 outcomes in this patient population appeared, but knowledge on optimal ...treatment, mortality, outcomes, and appropriate risk predictors is limited. A retrospective analysis was performed in a German high-volume lung transplant center between 19.sup.th March 2020 and 18.sup.th May 2021. Impact of COVID-19 on physical and psychological health, clinical outcomes, and mortality were analyzed including follow-up visits up to 12 weeks after infection in survivors. Predictive parameters on survival were assessed using univariate and multivariate proportional hazards regression models. Out of 1,046 patients in follow-up, 31 acquired COVID-19 during the pandemic. 12 of 31 (39%) died and 26 (84%) were hospitalized. In survivors a significant decline in exercise capacity (p = 0.034), TLC (p = 0.02), and DLCO (p = 0.007) was observed at follow-up after 3 months. Anxiety, depression, and self-assessed quality of life remained stable. Charlson comorbidity index predicted mortality (HR 1.5, 1.1-2.2; p = 0.023). In recipients with pre-existing CLAD, mortality and clinical outcomes were inferior. However, pre-existing CLAD did not predict mortality. COVID-19 remains a life-threatening disease for lung transplant recipients, particularly in case comorbidities. Further studies on long term outcomes and impact on pre-existing CLAD are needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interleukin-5 (IL-5) antibodies represent a promising therapeutic option for patients with severe eosinophilic asthma. To date, no official treatment response criteria exist. In this study, simple ...criteria for treatment response applicable to all asthma patients were used to evaluate clinical efficacy and predictors for treatment response in a real-life setting.
Data from 42 patients with severe eosinophilic asthma treated with mepolizumab for at least six months were analysed. Simple criteria to assess treatment response in clinical practice were used: increase of FEV
≥ 12% or ≥ 200 ml, reduction of blood eosinophils (< 150/μl or < 80% from baseline) and improvement of subjective condition (patient-judged subjective improvement or worsening following therapy). Patients were considered treatment responders if two criteria were fulfilled.
Thirty-two out of 42 patients (76% 61-87%) were classified as responders. Within the groups (responder vs non-responder), treatment with mepolizumab led to significant increase in FEV
(+ 600 ml vs -100 ml, p = 0.003), oxygenation (+ 8 mmHg vs -3 mmHg, p = 0.001), quality of life (visual analogue scale; + 28% vs - 5%, p = 0.004) and Asthma Control Test (+ 8 vs + 1 points, p = 0.002). In the responder group a significant decrease in the exacerbation rate over 12 months (1.45 vs 0.45, p = 0.002) was observed. Baseline characteristics (sex, BMI, smoking history, allergies, baseline level of eosinophils) did not predict treatment response.
Using improvement of lung function, decrease of eosinophils and improvement of subjective condition as response criteria, 76% of treated patients could be classified as treatment responders, demonstrating the efficacy of anti-IL-5 therapy in clinical practice.
Non-adherence to therapy is associated with impaired outcome in solid organ allograft recipients. Outcome data are limited after lung transplantation. In a single-center cohort study, adherence was ...assessed in 427 patients undergoing lung transplantation from 2010 to 2013. Objective criteria of adherence were judged by health care workers on every visit on a five item Likert scale including trough level monitoring, home spirometry and contact with an overall rating of adherence between 0 and 100%. Cut-off values for good vs. suboptimal adherence were defined retrospectively. Primary outcome was allograft survival, secondary outcomes were patient survival, prevalence of chronic lung allograft dysfunction, hospitalizations, renal function and quality of life. Follow-up ended on 31st December 2018. Median adherence was 86% on 6,623 visits, this cut-off was used as a discriminator between good and suboptimal adherers. Patients with good adherence within the first three years showed better 5-year allograft (74% vs. 60%, p = 0.003) and patient survival (79% vs. 64%, p<0.001) and lower prevalence of chronic allograft dysfunction (33% vs. 45%, p = 0.011) after 5 years compared to patients with suboptimal adherence. A multidimensional adherence score proved to be a simple tool to assess adherence in clinical practice. Suboptimal adherence was associated with impaired outcome in lung transplant patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. Previous studies from the United Kingdom and Spain have reported incidence rates of 1.75 and 0.9 per ...million, respectively. These figures, however, may underestimate the true incidence of CTEPH.
Methods
We prospectively enrolled patients newly diagnosed with CTEPH within 2016 in Germany. Data were obtained from the three German referral centers and from the German branch of COMPERA, a European pulmonary hypertension registry. The CTEPH incidence was calculated based on German population data, and patient characteristics and treatment patterns were described.
Results
A total of 392 patients were newly diagnosed with CTEPH within 2016 in Germany, yielding an incidence of 5.7 new cases per million adults. The (mean ± standard deviation) age was 63.5 ± 15.0 years; males and females were equally affected; 76.3% of the patients had a history of venous thromboembolism. A total of 197 (50.3%) patients underwent pulmonary endarterectomy. Almost all non-operated patients received targeted drug therapy, and 49 patients (25.1% of the non-operated patients) were treated with balloon pulmonary angioplasty.
Conclusion
The incidence of CTEPH in Germany 2016 was 5.7 per million adults and thus higher than previously reported from other countries. Half of the patients were operated while the remaining patients received medical or interventional therapies.
Clinical trials registration
http://www.clinicaltrials.gov
NCT02660463 and NCT01347216.
SARS-CoV-2 infected patients show heterogeneous clinical presentations ranging from mild symptoms to severe respiratory failure and death. Consequently, various markers reflect this wide spectrum of ...disease presentations.
Our pilot cohort included moderate (n = 10) and severe (n = 10) COVID-19 patients, and 10 healthy controls. We determined plasma levels of nine acute phase proteins (APPs) by nephelometry, and full-length (M65), caspase-cleaved (M30) cytokeratin 18, and ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif 13) by ELISA. In addition, we examined whole plasma N-glycosylation by capillary gel electrophoresis coupled to laser-induced fluorescence detection (CGE-LIF).
When compared to controls, COVID-19 patients had significantly lower concentrations of ADAMTS13 and albumin (ALB) but higher M30, M65, α1-acid glycoprotein (AGP), α1-antitrypsin (AAT), ceruloplasmin (CP), haptoglobin (HP), and high-sensitivity C-reactive protein (hs-CRP). The concentrations of α1-antichymotrypsin (ACT), α2-macroglobulin (A2MG) and serum amyloid A (SAA) proteins did not differ. We found significantly higher levels of AAT and M65 but lower ALB in severe compared to moderate COVID-19 patients. N-glycan analysis of the serum proteome revealed increased levels of oligomannose- and sialylated di-antennary glycans and decreased non-sialylated di-antennary glycan A2G2 in COVID-19 patients compared to controls.
COVID-19-associated changes in levels and N-glycosylation of specific plasma proteins highlight complexity of inflammatory process and grant further investigations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with significant mortality and morbidity. Approval of antifibrotic therapy has ameliorated disease progression, but therapy response is ...heterogeneous and to date, adequate biomarkers predicting therapy response are lacking. In recent years metabolomic technology has improved and is broadly applied in cancer research thus enabling its use in other fields. Recently both aberrant metabolic and lipidomic pathways have been described to influence profibrotic responses. We thus aimed to characterize the metabolomic and lipidomic changes between IPF and healthy volunteers (HV) and analyze metabolomic changes following treatment with nintedanib and pirfenidone. We collected serial serum samples from two IPF cohorts from Germany (
n
= 122) and Spain (
n
= 21) and additionally age-matched healthy volunteers (n = 16). Metabolomic analysis of 630 metabolites covering 14 small molecule and 12 different lipid classes was carried out using flow injection analysis tandem mass spectrometry for lipids and liquid chromatography tandem mass spectrometry for small molecules. Levels were correlated with survival and disease severity. We identified 109 deregulated analytes in IPF compared to HV in cohort 1 and 112 deregulated analytes in cohort 2. Metabolites which were up-regulated in both cohorts were mainly triglycerides while the main class of down-regulated metabolites were phosphatidylcholines. Only a minority of de-regulated analytes were small molecules. Triglyceride subclasses were inversely correlated with baseline disease severity (GAP-score) and a clinical compound endpoint of lung function decline or death. No changes in the metabolic profiles were observed following treatment with pirfenidone. Nintedanib treatment induced up-regulation of triglycerides and phosphatidylcholines. Patients in whom an increase in these metabolites was observed showed a trend towards better survival using the 2-years composite endpoint (HR 2.46,
p
= 0.06). In conclusion, we report major changes in metabolites in two independent cohorts testing a large number of patients. Specific lipidic metabolite signatures may serve as biomarkers for disease progression or favorable treatment response to nintedanib.
Abstract Objectives This study sought to investigate the prognostic importance of a low diffusion capacity of the lung for carbon monoxide (DLCO) in patients with a catheter-based diagnosis of ...pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). Background In patients with pulmonary arterial hypertension, a low DLCO is associated with poor outcome. It is unclear whether the same is true in patients with PH-HFpEF. Methods This study retrospectively analyzed clinical characteristics, smoking history, lung function measurements, chest computed tomography, hemodynamics, and survival in 108 patients with PH-HFpEF. The presence of post-capillary PH was determined by right heart catheterization. Patients with moderate or severe lung function abnormalities were excluded. Results On the basis of previous studies and receiver-operating characteristic curve analysis, the study cohort was divided into patients with a DLCO <45% of the predicted value (DLCO<45% , low DLCO; n = 52) and patients with a DLCO ≥45% of the predicted value (DLCO≥45% ; n = 56). DLCO<45% was associated with male sex (odds ratio OR: 2.71; 95% confidence interval CI: 1.05 to 6.99; p = 0.039) and smoking history (OR: 5.01; 95% CI: 1.91 to 13.10; p < 0.001). There were no correlations between DLCO and other lung function parameters and hemodynamics. Compared with patients with DLCO≥45% , patients with DLCO<45% had a significantly worse outcome (survival rate at 3 years 36.5% vs. 87.8%, p < 0.001 by log-rank analysis). Cox proportional hazard analysis identified DLCO<45% as an independent predictor of death (hazard ratio: 6.6; 95% CI: 2.6 to 16.9; p < 0.001). Conclusions In patients with PH-HFpEF, a low DLCO is strongly associated with mortality.
Non-occlusive mesenteric ischemia (NOMI) is a life-threatening condition occurring in patients with shock and is characterized by vasoconstriction of the mesenteric arteries leading to intestinal ...ischemia and multi-organ failure. Although minimal invasive local intra-arterial infusion of vasodilators into the mesenteric circulation has been suggested as a therapeutic option in NOMI, current knowledge is based on retrospective case series and it remains unclear which patients might benefit. Here, we prospectively analyzed predictors of response to intra-arterial therapy in patients with NOMI.
This is a prospective single-center observational study to analyze improvement of ischemia (indicated by reduction of blood lactate > 2 mmol/l from baseline after 24 h, primary endpoint) and 28-day mortality (key secondary endpoint) in patients with NOMI undergoing intra-arterial vasodilatory therapy. Predictors of response to therapy concerning primary and key secondary endpoint were identified using a) clinical parameters as well as b) data from 2D-perfusion angiography and c) experimental biomarkers of intestinal injury.
A total of 42 patients were included into this study. At inclusion patients had severe shock, indicated by high doses of norepinephrine (NE) (median (interquartile range (IQR)) 0.37 (0.21-0.60) μg/kg/min), elevated lactate concentrations (9.2 (5.2-13) mmol/l) and multi-organ failure. Patients showed a continuous reduction of lactate following intra-arterial prostaglandin infusion (baseline: (9.2 (5.2-13) mmol/l vs. 24 h: 4.4 (2.5-9.1) mmol/l, p < 0.001) with 22 patients (52.4%) reaching a lactate reduction > 2 mmol/l at 24 h following intervention. Initial higher lactate concentrations and lower NE doses at baseline were independent predictors of an improvement of ischemia. 28-day mortality was 59% in patients with a reduction of lactate > 2 mmol/l 24 h after inclusion, while it was 85% in all other patients (hazard ratio 0.409; 95% CI, 0.14-0.631, p = 0.005).
A reduction of lactate concentrations was observed following implementation of intra-arterial therapy, and lactate reduction was associated with better survival. Our findings concerning outcome predictors in NOMI patients undergoing intra-arterial prostaglandin therapy might help designing a randomized controlled trial to further investigate this therapeutic approach. Trial registration Retrospectively registered on January 22, 2020, at clinicaltrials.gov (REPERFUSE, NCT04235634), https://clinicaltrials.gov/ct2/show/NCT04235634?cond=NOMI&draw=2&rank=1 .
Exercise limitation is frequently described among asthmatic patients and could be related to different mechanisms of the pulmonary, cardiovascular and muscular systems. Despite this, cardiopulmonary ...exercise testing (CPET) does not have an established role in the management of severe asthma. The aim of our study was to investigate the role of CPET and inspiratory pressure measurement in exercise capacity and muscle strength in severe asthmatic patients treated with anti-IL-5 therapy.
A monocentric observational study was conducted at Hanover Medical School, Germany, from April 2018 to June 2019. Patients affected by severe asthma treated with either mepolizumab or benralizumab were included. All patients underwent CPET before the initiation of antibody therapy and after 3 months, and follow-up visits were scheduled at 3, 6 and 12 months with plethysmography, inspiratory pressure measurement and blood gas analysis.
14 patients were enrolled: 10 (71.4%) females, median age 52 years (IQR 47-61). Seven patients were treated with benralizumab, seven with mepolizumab. Oxygen uptake (
'
peak) did not change significantly after 3 months of antibody treatment, while the mean value of the breathing reserve exhaustion reduced significantly from 78% to 60% (p=0.004). Whereas at baseline seven patients depleted the breathing reserve and two of them experienced oxygen desaturation during exercise, at 3 months no one presented any desaturation or breathing reserve exhaustion. The inspiratory pressure remained unchanged before and after the antibody therapy.
CPET could show hints of alveolar recruitment and ventilatory efficiency in severe asthma patients treated with antibody therapy.
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