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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

Zusammenfassung Einleitung Sauerstoff (O2) ist eines der am häufigsten angewendeten Arzneimittel in deutschen Krankenhäusern und im Rettungswesen. Sowohl eine Hypoxämie als auch eine Hyperoxämie sind mit Komplikationen vergesellschaftet. In Deutschland fehlen bislang belastbare Daten zur Anwendung, Dokumentation und Überwachung der O2-Therapie. Methoden Eine Querschnittsstudie zur Sauerstoff-Anwendung wurde in 3 Krankenhäusern der maximalen bzw. supramaximalen Versorgung in Hannover im Herbst 2020 durchgeführt. Ergebnisse Von 343 erfassten Patienten erhielten 20 % eine O2-Therapie. Bei 29 % der Patienten mit O2-Therapie bestand ein Hyperkapnie-Risiko. Lediglich bei 68 % Patienten mit einer O2-Therapie lag eine SOP zur O2-Anwendung auf den jeweiligen Stationen vor und nur bei 22 % entsprach die gegebene O2-Therapie dem tatsächlichen Bedarf des Patienten. Nur bei 30 % des Gesamtkollektivs und 41 % der Patienten mit O2-Therapie erfolgte eine vollständige Dokumentation der Vitalparameter. Eine Überwachung der O2-Therapie mittels arterieller oder kapillärer Blutgasanalyse (BGA) erfolgte bei 76 % der O2-Patienten. Hier zeigte sich bei 64 % der Patienten eine Normoxämie, bei 17 % eine Hyperoxämie und bei 19 % eine Hypoxämie. Der einzige identifizierbare Prediktor für eine adäquate O2-Therapie war eine vorangegangene Beatmungstherapie. Diskussion Insgesamt zeigt sich eine suboptimale Indikationsstellung, Anwendung und Kontrolle der Sauerstofftherapie. Schulungen des pflegerischen und ärztlichen Personals zur Verbesserung der Anwendung der O2-Therapie und resultierend auch der Patientensicherheit sind dringend notwendig.

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

Background Serology testing is explored for epidemiological research and to inform individuals after suspected infection. During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. Methods In a large German university hospital, we performed weekly questionnaire assessments and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements with various commercial tests, a novel surrogate virus neutralisation test, and a neutralisation assay using live SARS-CoV-2. Results From baseline to week 6, 1080 screening measurements for anti-SARS CoV-2 (S1) IgG from 217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12.4% in week 6, p

Background: The coronavirus disease 2019 (COVID-19) pandemic has disrupted health care systems worldwide. This is due to both to the reallocation of resources toward COVID-19 patients as well as concern for the risk of nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. The interruption of routine care is especially problematic for patients with chronic conditions requiring regular follow-up, such as lung transplant (LTx) recipients. Introduction: New methods such as telemedicine are needed to bridge the gap in follow-up care caused by the pandemic. Materials and Methods: A retrospective analysis of video consultations (VCs) in comparison with on-site visits (OSVs) was performed during a 6-week period in an LTx center in Germany. VC included a structured work-up questionnaire and vital sign documentation. Results: During the 6-week study period, 75 VCs were performed for 53 patients and 75 OSVs by 51 patients occurred. By the end of our study period, 77% of physician-patient contacts occurred through VC. Physician-patient consultations were reduced by 47% compared with the equivalent time frame in 2019. In 62% of cases, VC resulted in a concrete clinical decision. One COVID-19 patient in home quarantine was admitted due to respiratory failure detected by VC. Patient satisfaction with VC was high. Discussion: Implementation of VC helped to reduce the need for OSV and thus the risk of SARS-CoV-2 exposure in our patient cohort. This technology can be adopted to provide care for a wide range of chronic illnesses. Conclusions: VC can preserve access to specialist care while reducing SARS-CoV-2 exposure for patients with chronic illnesses during the pandemic.

Despite advances in lung transplantation (LTx), morbidity, and mortality are high. We hypothesized that pleural effusions requiring thoracocentesis lead to poor outcomes after LTx. We performed a single-center retrospective analysis of thoracocenteses after initial hospital discharge in LTx patients between March 2008 and September 2020 to identify risk factors, etiologies, and outcomes. Of the 1223 patients included, 113 patients (9.2%) required a total of 195 thoracocenteses. The cumulative incidence of thoracocentesis was 10.6% at 1 year and 14.2% at 5 years after transplantation. We observed a bimodal distribution of pleural effusion onset with a threshold at 6 months. Late-onset effusions were mostly of malignant or cardiac origin. We observed a high rate of nonspecific effusions (41.5%) irrespective of the timepoint post-transplantation. Patients with late-onset effusions had significantly lower survival compared to a matched controlled group (HR 2.43; 95% CI (1.27-4.62). All pulmonary function parameters were significantly decreased in patients requiring thoracocentesis compared to matched controls. Male sex and re-transplantation were risk factors for pleural effusions. In conclusion, pleural effusions requiring thoracocentesis occur frequently in LTx patients and lead to a reduced long-term allograft function. Late-onset effusions are associated with a lower survival.

BackgroundSerology testing is explored for epidemiological research and to inform individuals after suspected infection. During the COVID-19 pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist.MethodsIn a large German university hospital, we performed weekly questionnaire assessments and anti-SARS-CoV-2 IgG measurements with various commercial tests, a novel surrogate virus neutralization test, and a neutralization assay using live SARS-CoV-2.ResultsFrom baseline to week six, n=1,080 screening measurements for anti-SARS CoV-2 (S1) IgG from n=217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12·4 % in week six, pConclusionWhen assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates.

Background: The COVID-19 pandemic has disrupted health care systems worldwide. This is due to the demand for medical resources in other areas as well as concern for the risk of nosocomial SARS-CoV-2 exposure. The interruption of routine care is especially problematic for patients with chronic conditions requiring regular follow-up, such as lung transplant recipients. New methods like telemedicine are needed to provide care to these patients. Methods: A retrospective analysis of video consultations (VC) in comparison to on-site visits (OSV) was performed during a six-week period in a lung transplant center in Germany. VC included a structured work-up questionnaire and vital sign documentation. Results: During the 6-week study period, 75 VC were performed for 53 patients and 75 OSV by 51 patients occurred. By the end of our study period, 77% of physician-patient contacts occurred via VC. Overall, physician-patient consultations were reduced by 47% in comparison to an equivalent time frame in 2019. In 62% of cases, VC resulted in a concrete clinical decision. For two VC patients, the indication for inpatient admission was established during the consultation. One COVID-19 patient in home quarantine was admitted due to respiratory failure detected by VC. Patient satisfaction with VC was high. Conclusions: By transitioning to VC, OSV for lung transplant patients during the COVID-19 pandemic was reduced. VC was well received by the majority of patients. This technology can be adopted to provide care for a wide range of chronic illnesses.

Paracoccidioidomycosis (PCM) is a fungal infection caused by Paracoccidioides brasiliensis and P. lutzii. It is endemic to South and Central America. While PCM frequently remains latent, the disease can reactivate years after the initial infection. As the disease is rare outside the endemic area, and symptoms can mimic other pulmonary diseases, correct diagnosis can be challenging for clinicians in developed countries. In this report, we present the case of a 57-year-old female Venezuelan immigrant with PCM. She was initially misdiagnosed with sarcoidosis and treated with corticosteroids, leading to an exacerbation of the infection requiring intensive care. Because cultivation of Paracoccidioides sp. is slow and unsensitive, we opted for microscopic observation of fungal elements and molecular testing on a tissue biopsy and bronchoalveolar lavage (BAL) together with antibody detection. This allowed the diagnosis of PCM, enabling specific management. PCM and other imported mycoses should be considered as a differential diagnosis in patients originating from South and Central America displaying symptoms suggestive of sarcoidosis. The reviews of this paper are available via the supplemental material section.