Benralizumab Reduces Respiratory Exacerbations and Oral Glucocorticosteroid Dose in Patients with Severe Asthma and Eosinophilic Granulomatosis with Polyangiitis

Carlo Mümmler,1 Pontus Mertsch,1 Michaela Barnikel,1 Frank Haubner,2 Ulf Schönermarck,3 Ulrich Grabmaier,4 Hendrik Schulze-Koops,5 Jürgen Behr,1 Nikolaus Kneidinger,1,6 Katrin Milger1 1Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center of Lung Research (DZL), Munich, Germany; 2Department of Otorhinolaryngology, LMU University Hospital, LMU Munich, Munich, Germany; 3Division of Nephrology, Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; 4Department of Medicine I, LMU University Hospital, LMU Munich, Munich, Germany; 5Division of Rheumatology and Clinical Immunology, Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany; 6Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, AustriaCorrespondence: Katrin Milger, Department of Medicine V, LMU University Hospital, Marchioninistr, 15, LMU Munich, Munich, 81377, Germany, Tel +49-89-4400-73071, Email [email protected]: Benralizumab reduces exacerbations and long-term oral glucocorticosteroid (OCS) exposure in patients with severe eosinophilic asthma. In patients with eosinophilic granulomatosis with polyangiitis (EGPA), uncontrolled symptoms and exacerbations of asthma and chronic rhinosinusitis (CRS) are important reasons for continued OCS therapies. We aimed to describe outcomes of patients with severe asthma and EGPA treated with benralizumab in real-life.Methods: We retrospectively analyzed adult patients from the Severe Asthma Unit at LMU Munich diagnosed with severe asthma and EGPA treated with benralizumab, differentiating two groups: Group A, patients with a stable daily OCS dose and diagnosis of EGPA > 6 months ago; and Group B, patients treated with high-dose daily OCS due to recent diagnosis of EGPA < 6 months ago. We compared outcome parameters at baseline and 12 months after initiation of benralizumab, including respiratory exacerbations, daily OCS dose, and lung function.Results: Group A included 17 patients, all receiving OCS therapy and additional immunosuppressants; 15 patients (88%) continued benralizumab for more than 12 months, demonstrating a significant reduction in daily OCS dose and exacerbations while FEV1 increased. Group B included 9 patients, all with high-dose daily OCS and some receiving cyclophosphamide pulse therapy for life-threatening disease. Benralizumab addition during induction was well tolerated. A total of 7/9 (78%) continued benralizumab for more than 12 months and preserved EGPA remission at the 12-month timepoint.Conclusion: In this real-life cohort of patients with severe asthma and EGPA, benralizumab initiation during remission maintenance reduced respiratory exacerbations and daily OCS dose. Benralizumab initiation during remission induction was associated with a high rate of clinical EGPA remission.Keywords: EGPA, asthma, CRS, vasculitis, glucocorticoid, OCS, anti-IL5R, biologics, benralizuma

The value of historical documents for hazard zone mapping

The assessment of historical data of small mountain torrents in Alpine catchment areas has shown a significant difference between the results of a regular hazard zone mapping and a thorough historical analysis. The Gemsbach in the Ostrach valley near Hinterstein (Municipality of Hindelang, southern Bavaria/Germany) serves, among others, as an example. A 'traditional' hazard zone for the Gemsbach has been mapped in the 1990s. The oldest event included in the analysis was the flood of 1954. But historical data collected and analysed by the HANG-project shows flood-prone areas around the Gemsbach differing greatly in size and location from the one shown in the hazard zone maps. The inclusion of all data available for the Gemsbach area (15 events between 1671 and 1960 collected from four different archives) leads to a completely new picture of the regional hazardous activity and demands a re-structuring of the traditional way of hazard zone mapping

Oxidation Behaviour and Microstructural Stability of Alloy 625 During Long-Term Exposure in Steam

Nickel-based alloys are being considered as construction materials for various components in high-efficiency steam turbines with envisaged operating temperatures around 700 °C. In the present study, the steam oxidation behaviour of the nickel-based alloy 625 in the temperature range of 700–800 °C was investigated whereby exposures up to 10000 h were carried out. Gravimetric data in combination with results from a variety of post exposure analysis techniques showed in all cases the formation of protective oxide scales mainly consisting of chromia with minor amounts of outer Cr/Mn spinel and internal silica. The phases found in the bulk alloy after long-term exposure were mainly needle-shaped δ-Ni3(Nb,Mo) phase, μ-phase and Si-rich η-M6C carbide. Microstructural features and phase formation were found to be related to minor variations in the alloy composition, especially iron and silicon content. The oxidation-induced chromium depletion caused a number of microstructural changes in the subsurface depletion layer. Most important was an enrichment of the intermetallic δ-phase at the scale–alloy interface. DICTRA modelling revealed this effect to be caused by uphill diffusion as a result of a negative niobium activity gradient in the subscale chromium depletion zone. Although the available kinetic and thermodynamic data allowed qualitative explanation of the δ-phase enrichment, the databases do not correctly describe the high molybdenum solubility in the δ-phase

Real-life effectiveness of biological therapies on symptoms in severe asthma with comorbid CRSwNP.

BACKGROUND: We aimed to evaluate the effectiveness of different antibody therapies on nasal polyp symptoms in patients treated for severe asthma. METHODS: We performed a retrospective analysis of patients with severe asthma&nbsp;and comorbid CRSwNP who were treated with anti-IgE, anti-IL-5/R or anti-IL-4R. CRSwNP symptom burden was evaluated before and after 6&nbsp;months of therapy. RESULTS: Fifty patients were included hereof treated with anti-IgE: 9, anti-IL-5/R: 26 and anti-IL-4R: 15 patients. At baseline median SNOT-20 was similar among groups (anti-IgE: 55, anti-IL-5/R: 52 and anti-IL-4R: 56, p&nbsp;=&nbsp;0.76), median visual analogue scale (VAS) for nasal symptoms was 4, 7 and 8 (p&nbsp;=&nbsp;0.14) and VAS for total symptoms was higher in the anti-IL-4R group (4, 5 and 8, p&nbsp;=&nbsp;0.002). After 6&nbsp;months SNOT-20 improved significantly in all patient groups with median improvement of anti-IgE: -8 (p&nbsp;&lt;&nbsp;0.01), anti-IL-5/R: -13 (p&nbsp;&lt;&nbsp;0.001) and anti-IL-4R: -18 (p&nbsp;&lt;&nbsp;0.001), with larger improvement in the anti-IL-4R group than in anti-IgE (p&nbsp;&lt;&nbsp;0.001) and anti-IL-5/R (p&nbsp;&lt;&nbsp;0.001) groups. VAS nasal symptoms improved by median anti-IgE: 0 (n.s.), anti-IL-5/R: -1 (p&nbsp;&lt;&nbsp;0.01) and anti-IL-4R: -3 (p&nbsp;&lt;&nbsp;0.001), VAS total symptoms by anti-IgE: -1 (n.s.), anti-IL-5/R: -2 (p&nbsp;&lt;&nbsp;0.001) and anti-IL-4R: -2 (p&nbsp;&lt;&nbsp;0.001). CONCLUSIONS: Treatment by all antibodies showed effectiveness in reducing symptoms of CRSwNP in patients with severe asthma, with the largest reduction observed in anti-IL-4R-treated patients

Variability of forced vital capacity in progressive interstitial lung disease: A prospective observational study.

BackgroundFibrotic interstitial lung disease (ILD) is often associated with poor outcomes, but has few predictors of progression. Daily home spirometry has been proposed to provide important information about the clinical course of idiopathic pulmonary disease (IPF). However, experience is limited, and home spirometry is not a routine component of patient care in ILD. Using home spirometry, we aimed to investigate the predictive potential of daily measurements of forced vital capacity (FVC) in fibrotic ILD.MethodsIn this prospective observational study, patients with fibrotic ILD and clinical progression were provided with home spirometers for daily measurements over 6 months. Hospital based spirometry was performed after three and 6 months. Disease progression, defined as death, lung transplantation, acute exacerbation or FVC decline &gt;10% relative was assessed in the cohort.ResultsFrom May 2017 until August 2018, we included 47 patients (IPF n=20; non-IPF n=27). Sufficient daily measurements were performed by 85.1% of the study cohort. Among these 40 patients (IPF n=17; non-IPF n=23), who had a meanSD age of 60.7 +/- 11.3years and FVC 64.7 +/- 21.7% predicted (2.4 +/- 0.8L), 12 patients experienced disease progression (death: n= 2; lung transplantation: n=3; acute exacerbation: n=1; FVC decline &gt;10%: n=6). Within the first 28days, a group of patients had high daily variability in FVC, with 60.0% having a variation &gt;= 5%. Patients with disease progression had significantly higher FVC variability than those in the stable group (median variability 8.6% vs. 4.8%; p=0.002). Cox regression identified FVC variability as independently associated with disease progression when controlling for multiple confounding variables (hazard ratio: 1.203; 95% CI:1.050-1.378; p=0.0076).Conclusions Daily home spirometry is feasible in IPF and non-IPF ILD and facilitates the identification of FVC variability, which was associated with disease progression