Clinical decision making is improved by BioFire Pneumonia Plus in suspected lower respiratory tract infection after lung transplantation: Results of the prospective DBATE‐IT * study

Background: Lower respiratory tract infections (LRTIs) are a significant cause of morbidity and mortality in lung transplant (LTx) recipients. Timely and precise pathogen detection is vital to successful treatment. Multiplex PCR kits with short turnover times like the BioFire Pneumonia Plus (BFPPp) (manufactured by bioMérieux) may be a valuable addition to conventional tests. Methods: We performed a prospective observational cohort study in 60 LTx recipients with suspected LRTI. All patients received BFPPp testing of bronchoalveolar lavage fluid in addition to conventional tests including microbiological cultures and conventional diagnostics for respiratory viruses. Primary outcome was time‐to‐test‐result; secondary outcomes included time‐to‐clinical‐decision and BFPPp test accuracy compared to conventional tests. Results: BFPPp provided results faster than conventional tests (2.3 h [2–2.8] vs. 23.4 h [21–62], p < 0.001), allowing for faster clinical decisions (2.8 [2.2–44] vs. virology 28.1 h [23.1–70.6] and microbiology 32.6 h [4.6–70.9], both p < 0.001). Based on all available diagnostic modalities, 26 (43%) patients were diagnosed with viral LRTI, nine (15 %) with non‐viral LRTI, and five (8 %) with combined viral and non‐viral LRTI. These diagnoses were established by BFPPp in 92%, 78%, and 100%, respectively. The remaining 20 patients (33 %) received a diagnosis other than LRTI. Preliminary therapies based on BFPPp results were upheld in 90% of cases. There were six treatment modifications based on pathogen‐isolation by conventional testing missed by BFPPp, including three due to fungal pathogens not covered by the BFPPp. Conclusion: BFPPp offered faster test results compared to conventional tests with good concordance. The absence of fungal pathogens from the panel is a potential weakness in a severely immunosuppressed population

Changes in serum metabolomics in idiopathic pulmonary fibrosis and effect of approved antifibrotic medication

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

Qualitative and quantitative evaluation of computed tomography changes in adults with cystic fibrosis treated with elexacaftor-tezacaftor-ivacaftor: a retrospective observational study

Introduction: The availability of highly effective triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination therapy with elexacaftor–tezacaftor–ivacaftor (ETI) has improved pulmonary outcomes and quality of life of people with cystic fibrosis (pwCF). The aim of this study was to assess computed tomography (CT) changes under ETI visually with the Brody score and quantitatively with dedicated software, and to correlate CT measures with parameters of clinical response.Methods: Twenty two adult pwCF with two consecutive CT scans before and after ETI treatment initiation were retrospectively included. CT was assessed visually employing the Brody score and quantitatively by YACTA, a well-evaluated scientific software computing airway dimensions and lung parenchyma with wall percentage (WP), wall thickness (WT), lumen area (LA), bronchiectasis index (BI), lung volume and mean lung density (MLD) as parameters. Changes in CT metrics were evaluated and the visual and quantitative parameters were correlated with each other and with clinical changes in sweat chloride concentration, spirometry [percent predicted of forced expiratory volume in one second (ppFEV1)] and body mass index (BMI).Results: The mean (SD) Brody score improved with ETI [55 (12) vs. 38 (15); p &lt; 0.001], incl. sub-scores for mucus plugging, peribronchial thickening, and parenchymal changes (all p &lt; 0.001), but not for bronchiectasis (p = 0.281). Quantitatve WP (p &lt; 0.001) and WT (p = 0.004) were reduced, conversely LA increased (p = 0.003), and BI improved (p = 0.012). Lung volume increased (p &lt; 0.001), and MLD decreased (p &lt; 0.001) through a reduction of ground glass opacity areas (p &lt; 0.001). Changes of the Brody score correlated with those of quantitative parameters, exemplarily WT with the sub-score for mucus plugging (r = 0.730, p &lt; 0.001) and peribronchial thickening (r = 0.552, p = 0.008). Changes of CT parameters correlated with those of clinical response parameters, in particular ppFEV1 with the Brody score (r = −0.606, p = 0.003) and with WT (r = −0.538, p = 0.010).Discussion: Morphological treatment response to ETI can be assessed using the Brody score as well as quantitative CT parameters. Changes in CT correlated with clinical improvements. The quantitative analysis with YACTA proved to be an objective, reproducible and simple method for monitoring lung disease, particularly with regard to future interventional clinical trials

Predictors of response to intra-arterial vasodilatory therapy of non-occlusive mesenteric ischemia in patients with severe shock: results from a prospective observational study

Background: 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. Methods: 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. Results: 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 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). Conclusions: 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 . Keywords: Intestinal failure; Non-occlusive mesenteric ischemia; Sepsis; Shoc

Anti-IL-5 therapy in patients with severe eosinophilic asthma – clinical efficacy and possible criteria for treatment response

Abstract Background 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. Methods 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 FEV1 ≥ 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. Results 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 FEV1 (+ 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. Conclusion 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

Eosinophilic cationic protein as marker for response to antibody therapy in severe asthma

This study of the eosinophil cationic protein (ECP) as predictor of clinical response to biological therapy in severe asthma found that ECP is not useful in unselected patients but may have a role in those not exposed to oral corticosteroids. https://bit.ly/398RwE

Periprocedural safety and outcome after pump implantation for intravenous treprostinil administration in patients with pulmonary arterial hypertension

Methods!#!In this retrospective observational study, we analyzed all patients with pulmonary arterial hypertension undergoing LenusPro® pump implantation between November 2013 and October 2019 at our center. Periprocedural safety was assessed by describing all complications that occurred within 28 days after surgery; complications that occurred later were described to assess long-term safety. Clinical outcomes were measured by comparison of clinical parameters and echocardiographic measurements of right ventricular function from baseline to 6-months-follow-up.!##!Results!#!Fifty-four patients underwent LenusPro® pump implantation for intravenous treprostinil treatment during the investigation period. Periprocedural complications occurred in 5 patients; the only anesthesia-related complication (right heart failure with recovery after prolonged intensive care and death in the further course) occurred in the only patient who underwent general anesthesia. All other patients underwent local anesthesia with or without short-acting (analgo-) sedation. Eighteen long-term complications occurred in 15 patients, most notably pump pocket or catheter related problems. Transplant-free survival rates at 1, 2, and 3 years were 77 %, 56 %, and 48 %, respectively.!##!Conclusions!#!Subcutaneous pump implantation under local anesthesia and conscious analgosedation while avoiding intubation and mechanical ventilation is feasible in patients with advanced PAH. Controlled studies are needed to determine the safest anesthetic approach for this procedure.!##!Background/objectives!#!Intravenous treprostinil treatment via a fully implantable pump is a treatment option for patients with advanced pulmonary arterial hypertension. However, there is no consensus on the preferred anesthetic approach for the implantation procedure. Primary objective was to assess periprocedural safety with particular attention to feasibility of local anesthesia and conscious analgosedation instead of general anesthesia. Long-term safety and clinical outcomes were secondary endpoints

Adherence is associated with a favorable outcome after lung transplantation.

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

Treatment with interleukin (IL)-5/IL-5 receptor antibodies in patients with severe eosinophilic asthma and COPD

Background Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies represents an established treatment for patients with severe eosinophilic asthma (SEA) but did not show clinical efficacy in patients with COPD. The objective of the present study was to evaluate treatment response to anti-eosinophilic antibody therapy in patients with asthma and COPD. Methods A retrospective comparison of pulmonary function testing, oral corticosteroid intake, quality of life and pulmonary symptom control in patients with SEA and COPD and 1:1 propensity score matched patients suffering from SEA alone was performed. All patients received treatment with either mepolizumab or benralizumab. Data were assessed prior to antibody treatment start and after 6 months of therapy. Results Data from 84 patients (42 patients with SEA and COPD and 42 patients with SEA) were analysed. After 6 months of treatment, patients in both groups showed improved forced expiratory volume in 1 s (improvement by 11% (IQR 5–18) in the SEA and COPD group versus 15% (IQR −3–23); p=0.637) and decreased oral corticosteroid dosages (median reduction by 3 mg in the SEA and COPD group versus 5 mg; p=0.070), without significant differences between groups. Pulmonary symptom control and quality of life improved in both groups. A significant decrease in eosinophils could be measured in both groups with similar cell numbers prior to treatment initiation (600 cells·µL−1 in the SEA and COPD group versus 500 cells·µL−1). Conclusion Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies shows clinical efficacy in patients with SEA and COPD comparable to treatment response in patients with SEA alone