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Katrin Milger,1 Dirk Koschel,2 Dirk Skowasch,3 Hartmut Timmermann,4 Olaf Schmidt,5 Karl-Christian Bergmann,6 Claus Neurohr,7 Robert Lindner,8 Sebastian Heck,9 Johann Christian Virchow10 1Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; 2Division of Pneumonology, Medical Department I, University Hospital Carl Gustav Carus, Dresden and Fachkrankenhaus Coswig, Lung Centre, Coswig, Germany; 3Department of Internal Medicine II – Pneumology, University Hospital Bonn, Bonn, Germany; 4Schwerpunktpraxis Colonnaden, Hamburg, Germany; 5Pneumologische Gemeinschaftspraxis und Studienzentrum KPPK, Koblenz, Germany; 6Institute for Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; 7Abteilung für Pneumologie und Beatmungsmedizin, Robert-Bosch-Krankenhaus Lungenzentrum, Stuttgart, Germany; 8IQVIA Commercial GmbH & Co. OHG, Frankfurt Am Main, Germany; 9GlaxoSmithKline GmbH & Co. KG, Munich, Germany; 10Abteilung Pneumologie & Interdisziplinäre Internistische Intensivmedizin, Universitätsmedizin Rostock - Zentrum für Innere Medizin, Medizinische Klinik I, Rostock, GermanyCorrespondence: Katrin Milger, Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, 8036, Austria, Email katrin.milger-kneidinger@medunigraz.atPurpose: Asthma is affecting 4– 5% of all adults (10% of children) in Germany, ≥ half are inadequately controlled. In 2019 up to 54 thousand patients suffered from severe uncontrolled asthma, 52% were treated/co-treated by pneumonologists. 45% of them had continuous oral corticosteroid (OCS)- and short-acting β 2-agonist (SABA) overuse for ≥ 2 years. The aim of the current study was to analyze the main treatments, escalation schemes and the adherence to the GINA recommendations.Patients and Methods: Retrospective analysis in 2021 based on data from January to December 2019 in Germany, using the IQVIA™ LRx prescription database and the IQVIA™ Disease Analyzer database containing anonymized electronic medical records as the main data sources.Results: In 2019 25,200 patients with severe, uncontrolled asthma treated in a pneumonologist´s practice in Germany received GINA 3 (0,4%), GINA 4 (76%) or GINA 5 therapy (24%) during the study year compared to 59% GINA 5 therapy in the 5– 10% (1,500– 3,000) co-treated in a specialized outpatient department. In Pneumonologists` practices the most frequent choice in GINA 5 was OCS in 69% of patients (biologicals 37%, long-acting muscarinic antagonist (LAMA) 20%) compared to 66% biologicals, 55% OCS, and 25% LAMA in the outpatient department. 54,958 of 613,000 GINA 4/5 patients were treated with OCS, 9,725 even with doses above the so called “Cushing threshold” for prednisolone of 2700 mg/year. After introduction of a biological treatment, patients reduced their SABA prescriptions by 28%, OCS by 55%, and OCS overall exposure by 40%, one-third did not need OCS anymore.Conclusion: In 75% of patients with uncontrolled asthma for ≥ 2 years therapy was not escalated beyond GINA 4 or low dose OCS was used as the most frequent add-on treatment in GINA 5 contradictory to treatment recommendations. Use of biologics reduced on demand rescue medication and OCS use.Keywords: prescription database, disease analyzer, uncontrolled asthma, biological treatment, OCS use, Germany, guideline adherence

Hartmut Timmermann,1 Katrin Milger,2 Johann Christian Virchow,3 Olaf Schmidt,4 Karl-Christian Bergmann,5 Dirk Koschel,6 Claus Neurohr,7 Florian Scholz,8 Sebastian Heck,9 Dirk Skowasch10 1Schwerpunktpraxis Colonnaden, Hamburg, Germany; 2Medicine V, Ludwig-Maximilians-University (LMU) Munich, Member of the German Center for Lung Research (DZL), Comprehensive Pneumology Center Munich (CPC-M), Munich, Germany; 3Abteilungen für Pneumologie / Intensivmedizin, Universitätmedizin Rostock, Rostock, Germany; 4Studienzentrum KPPK, Pneumologische Gemeinschaftspraxis, Koblenz, Germany; 5Institute of Allergology, Charité–Universitätsmedizin, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, Berlin, Germany; 6Fachkrankenhaus Coswig, Lung Centre, Coswig, and Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus, Dresden, Germany; 7Abteilung für Pneumologie und Beatmungsmedizin, Robert-Bosch-Krankenhaus Lungenzentrum Stuttgart, Stuttgart, Germany; 8IQVIA Commercial GmbH & Co. OHG, Frankfurt am Main, Germany; 9GlaxoSmithKline GmbH & Co. KG, Munich, Germany; 10Department of Internal Medicine II – Pneumology, University Hospital Bonn, Bonn, GermanyCorrespondence: Hartmut Timmermann, Schwerpunktpraxis Colonnaden 72, Hamburg, 20354, Germany, Tel +49 4086648880, Fax +49 40866488824, Email timmermann@allergopraxis.dePurpose: It has been estimated that, in 2019, 54,000 patients in Germany had uncontrolled GINA step 4/5 asthma. In the current study we analyzed which health care providers were involved in the management of these patients and their role in disease phenotyping.Patients and Methods: The year 2019 was retrospectively analyzed using the IQVIATM LRx, a longitudinal anonymized prescription database, and the electronic, anonymized medical records database, the IQVIA Disease Analyzer.Results: Of 54,000 uncontrolled GINA step 4/5 asthma patients in Germany, 52% had consulted both general practitioners (GPs) and pulmonologists, and 48% were seen exclusively by a GP. Of these 54,000 patients, 45% were being prescribed and were thus overusing short-acting β 2-agonists (SABAs) and oral corticosteroids (OCS) for ≥ 2 years, 26% for ≥ 3 years, and 16% for ≥ 4 years. In most regions, pulmonologists saw one of their uncontrolled GINA step 4/5 asthma patients per week. Laboratory tests from consultations with a GP were available for only 10% of patients referred to a pulmonologist. In 50% of uncontrolled asthma patients treated according to GINA step 4/5, these were initiated by the pulmonologist, and 34% received laboratory testing within the first year (in GINA step 4/5 asthma, the numbers are 20% and 18%, respectively).Conclusion: Fifty percent of uncontrolled asthma patients treated according to GINA step 4/5 were regularly seen by pulmonologists, who performed most of the phenotyping confirming their importance in the management of severe, uncontrolled asthma in Germany. To understand treatment pathways for these patients, further studies are needed.Keywords: prescription database, biological treatment, laboratory test, uncontrolled GINA step 4/5 asthma, Germany

Karl-Christian Bergmann,1 Dirk Skowasch,2 Hartmut Timmermann,3 Robert Lindner,4 Johann Christian Virchow,5 Olaf Schmidt,6 Dirk Koschel,7 Claus Neurohr,8 Sebastian Heck,9 Katrin Milger10 1Institute for Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, and Berlin Institute of Health, Berlin, Germany; 2Department of Internal Medicine II – Pneumology, University Hospital Bonn, Bonn, Germany; 3Schwerpunktpraxis Colonnaden, Hamburg, Germany; 4IQVIA Commercial GmbH & Co. OHG, Frankfurt Am Main, Germany; 5Universitätsmedizin Rostock - Zentrum für Innere Medizin, Medizinische Klinik I, Abteilung Pneumologie & Interdisziplinäre Internistische Intensivmedizin, Rostock, Germany; 6Pneumologische Gemeinschaftspraxis und Studienzentrum KPPK, Koblenz, Germany; 7Fachkrankenhaus Coswig, Lung Centre, Coswig, and Division of Pulmonology, Medical Department I, University Hospital Carl Gustav Carus, Dresden, Germany; 8Abteilung für Pneumologie und Beatmungsmedizin, Robert-Bosch-Krankenhaus Lungenzentrum, Stuttgart, Germany; 9GlaxoSmithKline GmbH & Co. KG, Munich, Germany; 10Department of Medicine V, University Hospital, Ludwig-Maximilians-University (LMU) Munich, Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, GermanyCorrespondence: Karl-Christian Bergmann, Institute for Allergology-Charité, Luisenstraße 2, Berlin, 10117, Germany, Tel +491711934508, Fax +49 30 549090609, Email karlchristianbergmann@gmail.comPurpose: Asthma is one of the most prevalent chronic diseases in Germany affecting 4– 5% of all adults and 10% of children. Despite the availability of biologicals in recent years, studies show patients with inadequately controlled severe asthma in real life. The aim of the current study was to characterize and estimate the number of patients with NVL/GINA level 4 or 5 asthma and signs of poor control in Germany.Patients and Methods: In 2021, we retrospectively analyzed data collected during 2019 using the IQVIA™ LRx and IQVIA™ Disease Analyzer databases which contain anonymized longitudinal data covering approximately 80% of statutory health insurance (GKV) prescriptions in Germany with most relevant information about prescriptions, basic patient demographics or location of the prescriber; the IQVIA™ Disease Analyzer anonymized electronic medical records from a representative sample of office-based GPs and specialists. An expert committee of pulmonologists from different hospitals and expert practices supported the study. Asthma patients treated according to NVL/GINA 4/5 who used SABAs frequently (≥ 3 on days with no ICS-containing prescriptions/year) and/or received prescriptions for oral corticosteroids (OCS) (score of ≥ 2/year, a pulmonologist prescription scored 1.0, GP 0.75) were classified as severe, uncontrolled asthma.Results: In 2019, 3.4 million patients received at least two prescriptions of respiratory medications and 2.4 million patients on maintenance respiratory treatment have asthma. A total of 625,000 asthma patients were treated according to NVL/GINA step 4 or 5. Among these, 54,000 were uncontrolled according to the pre-defined OCS and/or SABA use, which corresponds to approximately 15% of patients in certain regions.Conclusion: In 2019, approximately 54,000 patients in Germany treated according to NVL/GINA step 4/5 had evidence suggestive for poor asthma control, up to 15% of patients in certain regions. Yet, only 12,000 patients overall were being treated with biologicals suggesting a possible treatment gap that requires further investigation.Keywords: prescription database, disease analyzer, uncontrolled asthma, oral corticosteroid, OCS, short-acting β 2-agonist, SABA

We present state-selective measurements on the NH2+ + H+ and NH+ + H+ + H dissociation channels following single-photon double ionization at 61.5 eV of neutral NH3, where the two photoelectrons and two cations are measured in coincidence using 3D momentum imaging. Three dication electronic states are identified to contribute to the NH2+ + H+ dissociation channel, where the excitation in one of the three states undergoes intersystem crossing prior to dissociation, producing a cold NH2+ fragment. In contrast, the other two states directly dissociate, producing a ro-vibrationally excited NH2+ fragment with roughly 1 eV of internal energy. The NH+ + H+ + H channel is fed by direct dissociation from three intermediate dication states, one of which is shared with the NH2+ + H+ channel. We find evidence of autoionization contributing to each of the double ionization channels. The distributions of the relative emission angle between the two photoelectrons, as well as the relative angle between the recoil axis of the molecular breakup and the polarization vector of the ionizing field, are also presented to provide insight on both the photoionization and photodissociation mechanisms for the different dication states.

We report measurements on the H++H+ fragmentation channel following direct single-photon double ionization of neutral NH3 at 61.5 eV, where the two photoelectrons and two protons are measured in coincidence using three-dimensional (3D) momentum imaging. We identify four dication electronic states that contribute to H++H+ dissociation, based on our multireference configuration-interaction calculations of the dication potential energy surfaces. The extracted branching ratios between these four dication electronic states are presented. Of the four dication electronic states, three dissociate in a concerted process, while the fourth undergoes a sequential fragmentation mechanism. We find evidence that the neutral NH fragment or intermediate NH+ ion is markedly rovibrationally excited. We also identify differences in the relative emission angle between the two photoelectrons as a function of their energy sharing for the four different dication states, which bare some similarities to previous observations made on atomic targets.

We present an experimental investigation of symmetry breaking of H2 and D2 molecules after single photoionization due to the Coulomb field of the emitted slow electron interacting with the parent cation during dissociation. The experiments were carried out by measuring the three-dimensional momentum vectors of the photoelectron and recoiling ion in coincidence using a reaction microscope. For photon energies close to threshold, the low-energy photoelectron influences the dissociation process, which results in an asymmetric molecular frame photoelectron angular distribution. This can be explained by the retroaction of the Coulomb field of the photoelectron on its parent ion and has been recently experimentally demonstrated by M. Waitz et al. [Phys. Rev. Lett. 116, 043001 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.043001], confirming theoretical predictions by V. V. Serov and A. S. Kheifets [Phys. Rev. A 89, 031402(R) (2014)PLRAAN1050-294710.1103/PhysRevA.89.031402]. High-momentum resolution and a new series of photon energies just above the dissociation threshold enable the observation of a strong influence of the electron energy and nuclear kinetic energy on the electron localization process for energies below ∼100 meV, which so far has neither been observed nor discussed by theory. Exploring the limitations of the retroaction mechanism at our lowest photon energy, we are able to single out a sensitive testbed and present data of non-Born-Oppenheimer dynamics of the simplest molecular system for future benchmark computational treatments.

We present a combined experimental and theoretical investigation of the electron dynamics and body-frame angular dependence of valence photo-single ionization of CF4 and subsequent dissociation into CF3+ and F. Ionization from a valence t2 orbital shows overlapping shape resonances close to threshold that couple to the same total symmetry, leading to striking changes in the photoelectron angular distributions when viewed in the body-frame.