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Pia Maria Plank,1,* Christopher Alexander Hinze,2,* Victoria Campbell,3 Stefanie Konwert,4 Tobias Welte,1,4 Nora Drick,1 Moritz Z Kayser,1 Hendrik Suhling,1,4,* Jan Fuge1,4,* 1Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany; 2Department of Respiratory Medicine and Infectious Disease, Hannover Medical School, Hannover, Germany; 3Department of Paediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; 4Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany*These authors contributed equally to this workCorrespondence: Christopher Alexander Hinze, Department of Respiratory Medicine and Infectious Disease, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany, Tel +49 511-5323531, Email hinze.christopher@mh-hannover.dePurpose: Asthma is associated with a high prevalence of psychopathological disorders, especially depressive disorders or anxiety. In patients with uncontrolled severe asthma, monoclonal antibody (mAb)-therapy positively influenced control of mental disorders. Therefore, we evaluated the impact of antibody therapy on the burden of these mental diseases depending on responder status.Patients and Methods: Data were collected retrospectively in patients with uncontrolled severe asthma (n = 82) prior to mAb-therapy (“baseline”) (omalizumab, dupilumab, benralizumab or mepolizumab). Symptoms of Major Depressive Disorder (MDD) or General Anxiety Disorder (GAD) were detected at baseline using the Hospital Anxiety and Depression Scale (HADS), as well as general sociodemographic data and lung function parameters. At 6-month (± 3 month) follow-up, the burden of psychopathological symptoms under mAb-therapy was assessed using the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder Scale-2 (GAD-2). Response status was classified using the Biologics Asthma Response Score (BARS), assessing exacerbations, oral corticosteroid usage and asthma control test (ACT) score. Predictors for non-response to mAb-therapy were identified using linear regression analysis.Results: Patients with severe asthma suffered from symptoms of MDD/GAD more often compared to the general population, with a higher prevalence among mAb therapy non-responders. mAb-responders exhibited a declining burden of MDD, better quality of life (QoL), less exacerbations, better lung function and better disease control compared to non-responders. A history of symptoms of depression was identified as a predictor for non-response to mAb-therapy.Conclusion: Asthma symptoms and psychological problems are linked and more prevalent in our cohort of severe asthma patients than in the general population. Patients with signs of MDD/GAD before mAb-therapy show less mAb therapy response suggesting a negative impact of prior psychological problems on treatment response. In some patients, the score on MDD/GAD was caused by severe asthma – here symptoms decreased after effective treatment.Keywords: severe asthma, monoclonal antibody therapy, depression, anxiety, therapy response

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

Background: Severe asthma affects the working life of millions of people worldwide. Interleukin (IL)-5/anti-interleukin-5 receptor α (IL-5Rα) antibodies are highly effective in reducing symptoms in patients with severe eosinophilic asthma. We analysed effects of anti-IL-5/anti-IL-5Rα treatment on self-reported productivity and absenteeism at work in patients with severe eosinophilic asthma., Methods: In this prospective single-centre study, patients with severe eosinophilic asthma received a questionnaire assessing their actual occupational status and the influence asthma has on their work life, productivity and missed days at work prior to initiation of antibody treatment and after 6 and 12 months of therapy. Among others, the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) was used., Results: Out of 54 patients with a median age of 60 years, 27 (50%) were employed. In addition to an increase in asthma control and lung function, self-reported productivity increased significantly with a decrease on the WPAI:SHP from 30% (interquartile range (IQR) 20-50%) to 10% (IQR 0-27.5%) under treatment (p=0.001). Furthermore, self-reported missed days at work were reduced from 2 days·month -1 (IQR 1.75-6 days·month -1 ) to 0 days·month -1 (IQR 0-2 days·month -1 ; p=0.067). At baseline 22 employed patients (81%) stated they were affected at work by their asthma. After 12 months of treatment, this number decreased to eight patients (30%; p=0.038)., Conclusions: This prospective analysis could prove the substantial impact severe asthma has on patients' working life. Anti-IL-5/anti-IL-5Rα treatment in patients with severe eosinophilic asthma leads to a significant increase in self-reported productivity at work, and after 12 months of treatment patients state substantially fewer negative effects on their working situation., Competing Interests: Conflict of interest: L. Brinkmann has no relevant conflicts of interest. J. Fuge reports speaker fees from AstraZeneca. T. Welte reported personal fees from AstraZeneca, GSK and Sanofi Aventis, and his institution received research grants from the German Ministry of Research and Education. H. Suhling reports speaker fees from AstraZeneca, GSK and Novartis. N. Drick reports speaker fees for AstraZeneca., (Copyright ©The authors 2024.)

Background: Non-contrast-enhanced 1 H magnetic resonance imaging (MRI) with full lung coverage shows promise for assessment of regional lung ventilation but a comparison with direct ventilation measurement using 19 F MRI is lacking., Purpose: To compare ventilation parameters calculated using 3D phase-resolved functional lung (PREFUL) MRI with 19 F MRI., Study Type: Prospective., Population: Fifteen patients with asthma, 14 patients with chronic obstructive lung disease, and 13 healthy volunteers., Field Strength/sequence: A 3D gradient-echo pulse sequence with golden-angle increment and stack-of-stars encoding at 1.5 T., Assessment: All participants underwent 3D PREFUL MRI and 19 F MRI. For 3D PREFUL, static regional ventilation (RVent) and dynamic flow-volume cross-correlation metric (FVL-CM) were calculated. For both parameters, ventilation defect percentage (VDP) values and ventilation defect (VD) maps (including a combination of both parameters [VDP Combined ]) were determined. For 19 F MRI, images from eight consecutive breaths under volume-controlled inhalation of perfluoropropane were acquired. Time-to-fill (TTF) and wash-in (WI) parameters were extracted. For all 19 F parameters, a VD map was generated and the corresponding VDP values were calculated., Statistical Tests: For all parameters, the relationship between the two techniques was assessed using a Spearman correlation (r). Differences between VDP values were compared using Bland-Altman analysis. For regional comparison of VD maps, spatial overlap and Sørensen-Dice coefficients were computed., Results: 3D PREFUL VDP values were significantly correlated to VDP measures by 19 F (r range: 0.59-0.70). For VDP RVent , no significant bias was observed with VDP of the third and fourth breath (bias range = -6.8:7.7%, P range = 0.25:0.30). For VDP FVL-CM , no significant bias was found with VDP values of fourth-eighth breaths (bias range = -2.0:12.5%, P range = 0.12:0.75). The overall spatial overlap of all VD maps increased with each breath, ranging from 61% to 81%, stabilizing at the fourth breath., Data Conclusion: 3D PREFUL MRI parameters showed moderate to strong correlation with 19 F MRI. Depending on the 3D PREFUL VD map, the best regional agreement was found to 19 F VD maps of third-fifth breath., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 2., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Tezepelumab is a novel biologic blocking thymic stromal lymphopoetin, approved for severe asthma irrespective of biomarker levels or phenotype., Objective: To characterize a real-world tezepelumab patient cohort and the efficacy among various asthma phenotypes., Methods: We performed a retrospective, multicenter study on patients with severe asthma initiating tezepelumab. Clinical response was evaluated at 3 and 6 months., Results: We included 129 patients with an average age of 52.5 ± 13.1 years, 59.7% were female. The majority (86.0%) had increased type 2 (T2) biomarkers, 68.2% an allergic and 31.8% an eosinophilic phenotype. 23.3% of patients were biologic-naive. 22 (18.2%) patients discontinued tezepelumab therapy owing to suspected side effects or insufficient efficacy. At 6 months' follow-up, median reduction in annualized exacerbation rate was-1 [25th percentile; 75% percentile {-2.9; 0.0}], the reduction of oral corticosteroid dose among patients with long-term oral corticosteroid therapy was -5 mg [-10; 0] and the Asthma Control Test (ACT) improved by 2 [0; 5] points. A treatment response according to Biologic Asthma Response Score of 80.8% was demonstrated. There were no significant differences in treatment response between T2-high versus T2-low, early- versus adult-onset and eosinophilic versus non-eosinophilic asthma. Prior treatment with other biologics was associated with inferior treatment response., Conclusions: In this real-life cohort, including a large proportion of patients with history of previous biologic use and encompassing various subgroups, the majority responded to tezepelumab. Our data further suggest a steroid-sparing effect of tezepelumab., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Inhalation of crack and freebase results in alveolar hemorrhage. In severe courses of the disease, progressive respiratory insufficiency may lead to respiratory failure and acute respiratory distress syndrome (ARDS). Computed tomography of the thorax reveals bilateral consolidation and ground-glass pattern leaving a subpleural gap. This case report of a 48-year-old male patient highlights the importance of a thorough medical history while ruling out infectious causes., (© 2024. The Author(s).)

After the GINA update in 2019, the proportion of SMART therapy increased with evidence for better disease control in SMART patients compared to SABA alone https://bit.ly/3SSPX1C., Competing Interests: Conflict of interest: C.A. Hinze has nothing to disclose. Conflict of interest: R. Ehmann has nothing to disclose. Conflict of interest: M. Jandl has nothing to disclose. Conflict of interest: K. Milger reports fees for lectures or consultation from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis and Sanofi, all outside the submitted work. Conflict of interest: O. Schmidt reports fees for lectures or consultations from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis and Sanofi, all outside the submitted work. Conflict of interest: C. Schulz reports fees for lectures or consultations from AstraZeneca, Novartis and Sanofi, all outside the submitted work. Conflict of interest: D. Skowasch reports fees for lectures or consultation from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Janssen, MSD and Sanofi, all outside the submitted work. Conflict of interest: T. Welte and/or his institution received grants advisory/lecture/clinical trial fees and non-financial support from BMBF (German Ministry of Research and Education), AstraZeneca, GSK, Sanofi Aventis and Biotest, outside the submitted work. Conflict of interest: R. Buhl reports grants to Mainz University from Boehringer Ingelheim, GSK, Novartis, and Roche, as well as personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GSK, Novartis, Roche, Sanofi and Teva, all outside the submitted work. Conflict of interest: E. Hamelmann is funded by the BMBF (CHAMP, project number 01GL1742D) for characterisation of children and adolescents with severe asthma; he reports personal fees from ALK, Boehringer Ingelheim, GSK, Leti Pharma, Novartis, Nutricia, Sanofi and Stallergenes, all outside the submitted work. Conflict of interest: M. Idzko has received fees for lectures and/or advisory board meetings from Alk Pharma, AstraZeneca, Berlin-Chemie, Chiesi, CSL-Behring, Jansen & Jansen, Menarini, Novartis, Roche, Sanofi Aventis and Teva, all outside the submitted work. Conflict of interest: C. Taube has nothing to disclose. Conflict of interest: S. Korn has received fees for lectures and/or advisory board meetings from AstraZeneca, Chiesi, GSK, Novartis, Roche, Sanofi Aventis and Teva, all outside the submitted work. Conflict of interest: H. Suhling reports fees for lectures or consultation from AstraZeneca, GSK, Novartis and Sanofi, all outside the submitted work., (Copyright ©The authors 2024.)

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., (© 2024. The Author(s).)

Background: For therapy of severe asthma 5 monoclonal antibodies have been available in Germany up to November 2022, but no clear rules exist on choice of initial therapy, assessment of response, and switch., Objective: To assess current practice on all aspects of biologic therapy by specialists in Germany., Methods: A questionnaire was created by specialists for severe asthma, which was tested and modified by further experts. We invited 119 pulmonologists of the German Asthma Net (GAN) to complete the survey and used SoSci Survey and SPSS for data collection and analysis., Results: Forty-seven pulmonologists took part in the survey with a median annual number of patients treated with biologics of 35, 55% worked in an outpatient practice, and 40% in a hospital. Exacerbations and oral steroid use were the most important factors for the decision to start a biologic therapy. Accordingly, these parameters were also the most relevant for assessment of response. Most participants considered type-2 inflammation biomarkers and comorbidities (foremost CRSwNP and AD) for choosing initial biologic. Asthma Control Test (ACT) was the most common instrument for assessing status of disease control. There was no consensus on thresholds for response of pulmonary function tests including FEV1, FVC, and RV. Eighty-five percent of participants distinguished between "responders", "partial responders" and "non-responders". Comorbidities played an important role for the decision to switch to another biologic, eg, when initial therapy had insufficient effectiveness on CRSwNP., Conclusion: This study provides a detailed insight into current opinions and practice of biologic use in severe asthma in Germany., Competing Interests: HS reports fees for lectures or consultations from Astrazeneca, GSK, Novartis, Sanofi all outside the submitted work. DS reports fees for lectures or consultations from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, GSK, Janssen, MSD, Sanofi, all outside the submitted work. KCB reports speaker fees from AstraZeneca, GSK, Novartis, Sanofi all outside the submitted work. CM no conflicts of interest. RB reports consulting fees or honoraria for lectures from ALK, AstraZeneca, Berlin-Chemie, Boehringer-Ingelheim, Chiesi, Cipla, GSK, Novartis, Roche, Sanofi, and TEVA, and grants to Mainz University Hospital for research or clinical trials, or both from Boehringer Ingelheim, GSK, Novartis, and Roche. RE no conflicts of interest. EH is funded by the German Ministry of Education and Research (BMBF) (CHAMP, Project Number: 01GL1742D) for characterisation of children and adolescents with severe asthma. He reports personal fees from ALK, Boehringer Ingelheim, GSK, Leti Pharma, Novartis, Nutricia, Sanofi, and Stallergenes all outside the submitted work. MI reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, Menarini, MSD, Novartis, Roche, Sanofi, all outside the submitted work. MJ no conflicts of interest. CS received personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, and Sanofi, all outside the submitted work. OS reports speaker fees from AstraZeneca, Novartis, Sanofi and Boehringer Ingelheim, all outside the submitted work. CT no conflicts of interest. KM reports speaker fees from AstraZeneca, GSK, Novartis, Sanofi, all outside the submitted work. SK reports speaker fees from AstraZeneca, GSK, Novartis, Sanofi, all outside the submitted work., (© 2023 The Authors.)

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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)