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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 Katrin.Milger@med.uni-muenchen.deBackground: 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, benralizumab

Michaela Barnikel,1,2 Ulrich Grabmaier,3 Pontus Mertsch,1,2 Felix Ceelen,4 Christian Janke,5 Jürgen Behr,1,2 Nikolaus Kneidinger,1,2 Katrin Milger1,2 1Department of Medicine V, LMU University Hospital, Munich, Germany; 2Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Munich, Germany; 3Department of Medicine I, LMU University Hospital, Munich, Germany; 4Department of Pneumology, Asklepios-Fachkliniken Munich-Gauting, Gauting, Germany; 5Department of Infectious Diseases and Tropical Medicine, LMU University Hospital, Munich, GermanyCorrespondence: Katrin Milger, Department of Medicine V, LMU University Hospital, Marchioninistraße 15, Munich, 81377, Germany, Tel +49 89 4400 73071, Email Katrin.Milger@med.uni-muenchen.deAbstract: 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.Keywords: asthma, eosinophilia, parasitic infections, biologic, anti-IL5 treatment

Moritz Z Kayser,1 Nora Drick,1 Katrin Milger,2,3 Jan Fuge,1,4 Nikolaus Kneidinger,2,3 Stephanie Korn,5 Roland Buhl,6 Jürgen Behr,2,3 Tobias Welte,1,4 Hendrik Suhling1 1Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 2Department of Medicine V, University Hospital, LMU, Munich, Germany; 3Comprehensive Pneumology Center-Munich (CPC‐M), Member of the German Center for Lung Research (DZL), Munich, Germany; 4Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover, Germany; 5Clinical Research Centre for Respiratory Medicine, Mainz, Germany; 6Pulmonary Department, Mainz University Hospital, Mainz, GermanyCorrespondence: Moritz Z KayserDepartment of Respiratory Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Lower Saxony, GermanyTel +49 0511-532-3531Fax +49 511-532-161108Email kayser.moritz@mh-hannover.dePurpose: Treatment of severe eosinophilic asthma (SEA) has been revolutionized by the development of monoclonal antibodies targeting underlying immunological pathways of eosinophilic asthma. Two of the most frequently used antibodies in clinical practice are mepolizumab, targeting interleukin (IL) 5 and benralizumab, targeting the IL5 receptor alpha. The comparative treatment efficacy of these antibodies remains unclear, particularly regarding long-term outcomes.Patients and Methods: In this multicenter, retrospective study, we included 123 patients treated with mepolizumab and 64 patients treated with benralizumab for 12 months at one of three study sites in Germany. Data were collected at baseline and after 6 and 12 months of therapy. Endpoints were changes in pulmonary function (PF), exacerbation rate, oral corticosteroid (OCS) use and dose, asthma control test (ACT) score and fractional exhaled nitric oxide (FeNO) levels.Results: Both mepolizumab and benralizumab led to significant improvements in PF with an increase in median forced expiratory volume (FEV1) after 12 months from 59% to 74% for mepolizumab and 63% to 72% for benralizumab. Treatment also led to significant improvements in ACT scores after 12 months (mepolizumab: 13 [interquartile range (IQR) 9– 17] to 19 [IQR 15– 23]; benralizumab: 12 [IQR 9– 16] to 22 [IQR 16– 25]) as well as a reduction of mean OCS dose (mepolizumab 8 mg [IQR 5– 12.5 mg] median prednisolone equivalent at baseline to 5 mg [IQR 3– 7.5 mg]; benralizumab 7.5 mg [IQR 5– 15 mg] to 5 mg [IQR 2– 10 mg]). The exacerbation rates were reduced significantly, irrespective of the treatment. Overall, changes were similar after 6 and 12 months of therapy.Conclusion: Both mepolizumab and benralizumab are highly effective in the long-term treatment of SEA, with no clinically relevant differences in outcomes after 12 months of therapy. In both groups, improvements were similar after 6 and 12 months of therapy, underlining the feasibility of early treatment evaluation.Keywords: severe eosinophilic asthma, asthma control, lung, treatment response, interleukin-5, interleukin-5-receptor

Nora Drick,1,* Katrin Milger,2,* Benjamin Seeliger,1 Jan Fuge,1 Stephanie Korn,3 Roland Buhl,3 Maren Schuhmann,4 Felix Herth,4 Benjamin Kendziora,5 Juergen Behr,2 Nikolaus Kneidinger,2 Karl-Christian Bergmann,5 Christian Taube,6 Tobias Welte,1 Hendrik Suhling1 1Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 2Department of Internal Medicine V, Ludwig-Maximilians University of Munich (LMU), Munich, Germany; 3Pulmonary Department, Mainz University Hospital, Mainz, Germany; 4Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Heidelberg, Germany; 5Allergy-Centre-Charité, Charité – Universitätsmedizin Berlin, Berlin, Germany; 6Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Essen, Germany*These authors contributed equally to this workCorrespondence: Hendrik Suhling Email suhling.hendrik@mh-hannover.deBackground: Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5Rα therapy in patients with inadequate response to anti-IL-5 therapy.Methods: In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5Rα therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under anti-IL-5 therapy) and timepoint 2 (T2, under anti-IL-5Rα therapy).Results: Of 665 patients treated with anti-IL-5 antibodies, 70 were switched to anti-IL-5Rα and 60 were included in the analysis. Median treatment duration was 8 months [IQR 5; 15] for anti-IL-5 and 5 months [IQR 4; 6] for anti-IL-5Rα therapy. FEV1 was 61% of predicted at BL [IQR 41; 74], 61% [IQR 43; 79] at T1 and 68% [IQR 49; 87] at T2 (pT1-T2=0.011). ACT score was 10 [IQR 8; 13], 16 [IQR 10; 19] and 19 [IQR 14; 22], respectively (both p< 0.001). The number of patients requiring OCS was reduced from 41 (BL) to 32 (T1) and 19 (T2) (both p< 0.001). Ten patients discontinued anti-IL-5Rα therapy due to insufficient efficacy (n=7) and adverse events (n=3).Conclusion: Switching from anti-IL-5 to anti-IL-5Rα therapy in patients with inadequate response was associated with significantly improved FEV1, asthma control and OCS reduction.Keywords: benralizumab, eosinophils, mepolizumab, reslizumab, severe asthma

Katrin Milger,1 Lesca Miriam Holdt,2 Daniel Teupser,2 Rudolf Maria Huber,1 Jürgen Behr,1 Nikolaus Kneidinger1 1Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, 2Institute of Laboratory Medicine, University of Munich, Munich, Germany Abstract: Deficiency in the serine protease inhibitor, alpha-1 antitrypsin (AAT), is known to cause emphysema and liver disease. Other manifestations, including airway disease or skin disorders, have also been described. A 44-year-old woman presented to our emergency department with dyspnea and respiratory insufficiency. She had never smoked, and had been diagnosed with COPD 9 years earlier. Three months previously, she had suffered a pulmonary embolism. Chest computed tomography scan revealed severe cystic bronchiectasis with destruction of the lung parenchyma. The sweat test was normal and there was no evidence of the cystic fibrosis transmembrane conductance regulator (CFTR) mutation. Capillary zone electrophoresis showed a decrease of alpha-1 globin band and AAT levels were below the quantification limit (