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Abstract Background Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. Methods We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. Results 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. Conclusion We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.

Background Air trapping and lung hyperinflation are major determinants of prognosis and response to therapy in chronic obstructive pulmonary disease (COPD). They are often determined by body plethysmography, which has limited availability, and so the question arises as to what extent they can be estimated via spirometry. Methods We used data from visits 1–5 of the COPD cohort COSYCONET. Predictive parameters were derived from visit 1 data, while visit 2–5 data was used to assess reproducibility. Pooled data then yielded prediction models including sex, age, height, and body mass index as covariates. Hyperinflation was defined as ratio of residual volume (RV) to total lung capacity (TLC) above the upper limit of normal. (ClinicalTrials.gov identifier: NCT01245933). Results Visit 1 data from 1988 patients (Global Initiative for Chronic Obstructive Lung Disease grades 1–4, n=187, 847, 766, 188, respectively) were available for analysis (n=1231 males, 757 females; mean±sd age 65.1±8.4 years; forced expiratory volume in 1 s (FEV1) 53.1±18.4 % predicted (% pred); forced vital capacity (FVC) 78.8±18.8 % pred; RV/TLC 0.547±0.107). In total, 7157 datasets were analysed. Among measures of hyperinflation, RV/TLC showed the closest relationship to FEV1 % pred and FVC % pred, which were sufficient for prediction. Their relationship to RV/TLC could be depicted in nomograms. Even when neglecting covariates, hyperinflation was predicted by FEV1 % pred, FVC % pred or their combination with an area under the curve of 0.870, 0.864 and 0.889, respectively. Conclusions The degree of air trapping/hyperinflation in terms of RV/TLC can be estimated in a simple manner from forced spirometry, with an accuracy sufficient for inferring the presence of hyperinflation. This may be useful for clinical settings, where body plethysmography is not available.

Background: The Asthma Impairment and Risk Questionnaire (AIRQ), a 10-item, equally weighted, yes/no tool assessing symptom impairment and risk of exacerbations in patients with asthma aged ≥12 years, was developed and validated in a US patient population to evaluate varying levels of asthma control. This study aimed to validate the German language version of the AIRQ in patients aged ≥12 years with different levels of asthma control., Methods: A cross-sectional, observational, multi-centre study comprising a single visit was conducted in multiple specialised asthma centres and general practices in Germany. A total of 300 patients completed the following measures: 1) Patient Sociodemographic and Clinical Questionnaire, 2) AIRQ, 3) Asthma Control Test (ACT), and 4) Asthma Control Questionnaire (ACQ-6). Logistic regression analyses were conducted to assess the AIRQ score cut points with the greatest predictive validity in discriminating between different control levels relative to a standard of ACT plus prior-year exacerbations or ACQ-6 plus prior-year exacerbations., Results: The German version of the AIRQ demonstrated a robust capability to correctly identify well-controlled versus not well- or very poorly controlled (AUC values of 0.90 or higher) and well- or not well-controlled versus very poorly controlled asthma (AUC values of 0.89 or higher)., Conclusions: The German version of the AIRQ is a suitable tool to identify adults with varying levels of asthma control, which in turn can help to accurately identify patients with uncontrolled asthma in clinical practice., Competing Interests: F. Kanniess has served as a speaker and on advisory boards from AstraZeneca, Mundipharma, Novartis, GSK and Teva. M. Lommatzsch has served as a speaker and on advisory boards for ALK, Allergopharma, AstraZeneca, Bencard Allergie, Berlin-Chemie, Boehringer Ingelheim, Bosch, Chiesi, Circassia, GSK, HAL Allergy, Janssen-Cilag, MSD, Mundipharma, Novartis, Nycomed/Takeda, Sanofi, Teva, and UCB. T. Schultz has served as a speaker and on advisory boards and has received research support from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Esanum, GSK, Meda, Mundipharma, Novartis, Omniamed, TEVA, UCB and various professional associations. H. Timmermann has served as a speaker and lecturer and received consultant fees and/or research grants from AstraZeneca, Almirall, Astellas Pharma, Bayer, Boehringer Ingelheim, Berlin-Chemie, GSK, Leti Pharma, Meda, Mundipharma, Novartis, Nycomed, Pfizer, Sanofi, Takeda, and TEVA. O. Schmidt received fees for lectures or consulting from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis, and Sanofi. S. Heindl has served as speaker and received consultation fees from AstraZeneca, GSK, Sanofi and Klosterfrau Melissengeist. H.J. Baumann has served as a speaker and lecturer and received consultant fees and/or research grants from AstraZeneca, Boehringer Ingelheim, Berlin-Chemie, Chiesi, GSK, Novartis, Orion Pharma and Pfizer. R. Buhl has received grants from Boehringer Ingelheim, GSK, Novartis, and Roche, as well as personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GSK, Novartis, Sanofi, Roche and Teva. S. Korn has served as a speaker received consultation fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, and Sanofi. K. Defosse and F. Höing are employees of AstraZeneca. C. Taube has no competing interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Dupilumab is approved for the treatment of severe type 2 (T2) asthma; however, the characteristics of patients receiving dupilumab in routine clinical practice are incompletely understood. This study describes the characteristics of patients with severe asthma before dupilumab treatment in a real-world setting., Methods: This interim analysis of an ongoing real-life study of dupilumab assessed baseline characteristics of the first patient cohort enrolled in the ProVENT study., Results: A total of 99 patients (59% females) were analyzed (17% received another biologic before dupilumab treatment and 15% were on maintenance oral corticosteroid treatment). Adult-onset asthma (>18 years) and an allergic phenotype were documented in 58% and 48% of patients, respectively. Median (interquartile range) age was 54 (40-61) years; the median number of exacerbations in the last 24 months was 1 (0-3); median fractional exhaled nitric oxide (FeNO) value was 38 (23-64) ppb; and median blood eosinophils (bEOS) count was 184 (8-505) cells/µL. According to the United Kingdom Severe Asthma Registry classification, 53% of patients had T2 intermediate asthma (bEOS ≥150 cells/µL or FeNO ≥25 ppb), 17% had T2 high asthma (bEOS ≥150 cells/µL and FeNO ≥25 ppb), and 4% had T2 low asthma (bEOS <150 cells/µL and FeNO <25 ppb). At least one GINA criterion for T2 airway inflammation was documented in 70% of patients. T2 comorbidities were observed in 64% of patients., Conclusions: This analysis suggests that patients eligible for dupilumab treatment display various clinical and biochemical characteristics rather than one clear-cut phenotype., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background and Objective: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit a negative BDR response. Aim: To describe the frequency of positive and Negative BDR response in patients with severe asthma and study associations with phenotypic characteristics., Methods: A positive BDR response was defined as an increase in FEV1 >200 mL and >12% upon testing with a short-acting ß-agonist., Results: BDR data were available for 793 of the 2013 patients included in the German Asthma Net (GAN) severe asthma registry. Of these, 250 (31.5%) had a positive BDR response and 543 (68.5%) a egative BDR response. Comorbidities significantly associated with a negative response were gastroesophageal reflux disease (GERD) (28.0% vs 40.0%, P<.01) and eosinophilic granulomatosis with polyangiitis (0.4% vs 3.0%; P<.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and comorbid chronic obstructive pulmonary disease (COPD) (5.2% vs 7.2%) were similar in both groups. Patients with a positive BDR response had worse asthma control (median Asthma Control Questionnaire 5 score, 3.4 vs 3.0, P<.05), more frequently reported dyspnea at rest (26.8% vs 16.4%, P<.001) and chest tightness (36.4% vs 26.2%, P<.001), and had more severe airway obstruction at baseline (FEV1% predicted, 56 vs 64, P<.001) and higher fractional exhaled nitric oxide (FeNO) levels (41 vs 33 ppb, P<0.05). There were no differences in diffusion capacity of the lung for carbon monoxide, single breath (% pred, 70% vs 71%). Multivariate linear regression analysis identified an association between positive BDR response and lower baseline FEV1% (P<.001) and chest tightness (P<.05) and a negative association between BDR and GERD (P<.05)., Conclusion: In this real-life setting, most patients with severe asthma had a negative BDR response. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: In Germany, psychotherapy in outpatient statutory health care is regulated by the Psychotherapy Guideline (PT-GL). A discussion on waiting times and inadequate care for patients resulted in a structural reform of the PT-GL in 2017. The reform aims to improve access to psychotherapy and the entire course of care and treatment. The purpose of the present study was the evaluation of the new elements and identification of obstacles and barriers in their implementation., Methods: Quantitative and qualitative methods were used to evaluate the reform of the PT-GL. In a retrospective cohort-based analysis of anonymized administrative claim data from the statutory health insurances BARMER and AOK, the health care situation before and after the reform were compared. In addition, a cross-sectional questionnaire survey evaluated the implementation of the new care elements from the perspective of psychotherapists, general practitioners and patients. The questionnaires were developed based on focus groups with stakeholders and a literature search. The survey results provided the data basis for the cross-sectional analysis together with the routine data on the care situation after the reform of the PT-GL as well as aggregated, anonymized data from the National Association of Statutory Health Insurance Physicians on statutory health insurance care and on the use of the appointment service centers., Conclusion: By combining quantitative and qualitative data, the effects of the structural reform of the PT-GL of 2016 can be analyzed at the individual and structural level as well as in relation to the entire care and treatment process. Based on this, proposals for a needs-oriented further development of the PT-GL will be prepared, considering the perspectives of various interest groups., Competing Interests: Dieter Best: Mitgliedschaft Deutsche Psychotherapeuten Vereinigung (DPtV), Christa Schaff: Mitgliedschaft Berufsverband für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie in Deutschland e. V. (bkjpp); Helene Timmermann: Mitgliedschaft Vereinigung Analytischer Kinder- und Jugendlichen-Psychotherapeuten in Deutschland e.V. (VAKJP), Kathrin Klipker: Bis Ende März 2023 Beschäftigungsverhältnis beim AOK Bundesverband, Ursula Marschall: Beschäftigungsverhältnis bei der Barmer., (Thieme. All rights reserved.)

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.)

Background:  The introduction of monoclonal antibodies (biologics) has revolutionized the therapy of severe asthma. Even though there is a response in the majority of patients, the degree of response varies. To date criteria for assessment of response to biologics are not consistently defined., Aim:  To define criteria for evaluation of response to biologics that are precise, simple and suitable for daily use in order to guide decision-making regarding continuation, switching or stopping of biological therapy., Methods:  8 physicians with large experience in this indication, supported by a data-scientist, developed a consensus on criteria to evaluate response to biologics in patients with severe asthma., Result:  We developed a combined score based on current literature, own experience and practicability. It uses the main criteria exacerbations, oral corticosteroid (OCS) therapy and asthma control (asthma control test, ACT). We defined thresholds for "good response", "response" and "insufficient response" rated with a score of "2", "1" and "0" respectively: annual exacerbations ("0 or reduction ≥ 75 %", "reduction 50-74 %", "reductio < 50 %"), daily OCS dose ("stopping or reduction ≥ 75 %", "reduction 50-74 %", "reduction < 50 %"), asthma control ("ACT increase ≥ 6 or ≥ 3 with result ≥ 20", "ACT increase 3-5 with result < 20", "ACT increase < 3"). Additional individual criteria like lung function and comorbidities may be important for evaluation of response. We propose 3, 6 and 12 months timepoint for assessment of tolerability and response. Using the combined score, we developed a scheme to guide the decision whether switching the biologic should be considered., Conclusion:  The Biologic Asthma Response Score (BARS) serves as objective and simple tool to evaluate response to biologic therapy using the three main criteria exacerbations, OCS use and asthma control. A validation of the score was initiated., Competing Interests: KM: Lecture and consultancy fees for AstraZeneca, GSK, Janssen, Novartis, Sanofi.SK: Lecture and consultancy fees for AstraZeneca, GSK, Chiesi, GSK, Novartis, Sanofi.CF: Lecture and consultancy fees for AstraZeneca, GSK, Sanofi, ALK.JF: Fees for lecturing and consulting for AstraZeneca.AM: Nothing to disclose.WS: Nothing to disclose.DS: Lecture and consultancy fees for AstraZeneca, Bayer, Boehringer-Ingelheim, Chiesi, GSK, Janssen, Novartis.HT: Speaker fees and lecturing, consulting activities and/or research grants from: AstraZeneca, Almirall, Astellas Pharma, Bayer, Boehringer Ingelheim, Berlin-Chemie, GSK, Leti Pharma, Meda, Mundipharma, Novartis, Nycomed, Pfizer, Sanofi, Takeda, Teva.HS: Lecture and consultancy fees for AstraZeneca, GSK, Novartis, Sanofi., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: 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 IQVIA TM 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 β2-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., Competing Interests: C.N. received honoraria and advisory board fees from GSK, Sanofi, AstraZeneca and Novartis. D.K. reports speaker and/or advisory fees from AstraZeneca, Boehringer, Chiesi, Berlin-Chemie, GSK, Novartis, and Sanofi. K.C.B. and O.S. have no relevant competing interests to disclose. S.H. is a GSK employee and shareholder. K.M. reports speaker and/or advisory fees from Astrazeneca, GSK, Novartis, Sanofi. D.S. received honoraria for lectures and/or consultancy from AstraZeneca, Bayer, Berlin-Chemie, BMBF, Boehringer, Chiesi, DFG, GSK, Janssen, MSD, Novartis, Sanofi, Pfizer. F.S. is affiliated with IQVIA Commercial GmbH & Co and reports grants from GSK. J.C.V. has lectured for and received honoraria from AstraZeneca, Avontec, Bayer, Bencard, Bionorica, Boehringer-Ingelheim, Chiesi, Essex/Schering-Plough, GSK, Janssen-Cilag, Leti, MEDA, Merck, MSD, Mundipharma, Novartis, Nycomed/Altana, Pfizer, Revotar, Sandoz-Hexal, Stallergens, TEVA, UCB/Schwarz-Pharma, and Zydus/Cadila, and has participated in advisory boards for Avontec, Boehringer-Ingelheim, Chiesi, Essex/Schering-Plough, GSK, Janssen-Cilag, MEDA, MSD, Mundipharma, Novartis, Regeneron, Revotar, Roche, Sanofi-Aventis, Sandoz-Hexal, TEVA, and UCB/Schwarz-Pharma, and has received research grants from Deutsche Forschungsgesellschaft, Land Mecklenburg-Vorpommern, GSK, and MSD, and is a full-time employee of the Universitätsmedizin Rostock. The authors report no other conflicts of interest in this work., (© 2023 Timmermann et al.)

Background: Asthma causes various clinical symptoms, including unpredictable severe exacerbations, and even though most patients can achieve a reasonable disease control due to adequate treatment, some patients do not. This study seeks to describe healthcare resource utilization (HCRU) and treatment of asthma and severe asthma patients in Germany., Method: A retrospective claims data analysis has been conducted on adult asthma patients and a subset of patients with severe asthma, identified during July 2017 - June 2018. A proxy was used to identify severe asthma patients based on therapy options recommended within the German treatment guideline for treating these patients. These include (i) biologics, (ii) medium/high-dose inhaled corticosteroids (ICS) in conjunction with LABA/montelukast and antibiotics/oral corticosteroids (OCS), and (iii) long-term OCS therapy. HCRU and treatment of patients were observed during a 1-year follow-up period (July 2018 - June 2019)., Results: The study included 388 932 adult asthma patients (prevalence: 7.90%), with 2.51%-12.88% affected by severe asthma (depending on the definition). 22.60% of all asthma patients experienced hospitalizations (severe asthma: 36.11%). Furthermore, 13.59% received OCS (severe asthma: 39.91%), but only 0.18% (severe asthma: 1.25%) received biologics. Only 23.95% (severe asthma: 41.17%) visited a pulmonologist., Conclusions: A considerable proportion of severe asthma patients receive long-term OCS therapy. However, less than 50% have seen a pulmonologist who would typically seek a change in treatment to avoid the long-term consequences of OCS. To optimize the treatment of severe asthma in Germany, better referral of these patients to specialists is needed and considering potential treatment alternatives.

Background : This study aimed to evaluate differences in healthcare resource utilization and cost among patients with controlled and uncontrolled asthma. Methods : Claims data from a German sickness fund was linked to patient survey data. Outpatient physicians enrolled patients and assessed asthma control using the ACT TM questionnaire. All-cause and asthma-specific healthcare resource use (HCRU)/costs were compared descriptively and based on multivariable models using a continuous ACT TM score. Results : Overall, 492 asthma patients were included (mean age: 53.8, 73.8% female). The mean/median ACT TM score was 19.9/20.7, with 183 patients (37.2%) classified as having uncontrolled asthma (mean ACT TM score<20) Patients with uncontrolled asthma had significantly more hospitalizations ( p = .035) and medication prescriptions ( p < .001), which resulted in higher total healthcare costs for asthma-related (€1785 vs. €1615; p = .004) and all-cause care (€4695 vs. €4117; p = .009). While controlling for baseline characteristics, multivariable models confirmed a negative association between asthma control and total all-cause healthcare costs ( p = .008), total asthma-related costs ( p = .008), and costs of medication prescriptions ( p = .001). However, no significant association was found for all-cause ( p = .062) and asthma-related hospitalization costs ( p = .576). Conclusion : Considering continuous patient care, improving asthma control is not only desirable from a clinical perspective, but could also be an effective approach to reduce asthma-related HCRU and cost burden.

Background: Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome of suspected SARS-CoV-2 vaccine hypersensitivity., Methods: Totally, 334 individuals underwent an allergy work up regarding SARS-CoV-2 vaccination (group A: 115 individuals suspected to be at increased risk for vaccine-related reactions before vaccination and group B: 219 patients with reactions after COVID vaccination). The large majority of the SPT/IDT with the vaccines were negative; however, we identified in 14.1% (n = 47) a possible sensitization to the SARS-CoV-2 vaccine and/or its ingredients defined as one positive skin test. Of the 219 individuals (group B) who experienced symptoms suspicious for a hypersensitivity reaction after vaccination, 214 were reported after the first vaccination with a mRNA vaccine (157 mRNA (Comirnaty®, 38 Spikevax®) and 18 with a vector vaccine (Vaxzevria®), 5 cases were after the second vaccination., Results: The symptom profile in group B was as follows: skin symptoms occurred in 115 cases (n = 59 angioedema, n = 50 generalized urticaria and n = 23 erythema/flush. Seventy individuals had cardiovascular, 53 respiratory and 17 gastrointestinal symptoms. Of the overall 334 individuals, 78 patients tolerated (re)-vaccination (out of skin test positive/negative 7/19 from group A and 17/35 from group B)., Conclusion: Proven IgE-mediated hypersensitivity to SARS-CoV-2 vaccines is extremely rare and not increased in comparison with reported hypersensitivity to other vaccines. The value of skin tests is unclear and nonspecific reactions, in particular when intradermal testing is applied, should be considered., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: 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., Competing Interests: KCB and OS have no relevant competing interests to disclose. SH is a GSK employee and shareholder. KM reports speaker and/ or advisory fees from AstraZeneca, GSK, Novartis, Sanofi. CN received honoraria and advisory board fees from GSK, Sanofi, AstraZeneca and Novartis. DS received honoraria for lectures and/or consultancy from AstraZeneca, Bayer, Berlin-Chemie, Boehringer, Chiesi, GSK, Janssen, Novartis, Pfizer. RL is an employee of IQVIA. IQVIA is a technology service provider that carried out the database studies within the scope of a commercial engagement with GSK. DK reports personal fees from GSK. JCV has lectured for and received honoraria from AstraZeneca, Avontec, Bayer, Bencard, Bionorica, Boehringer-Ingelheim, Chiesi, Essex/Schering-Plough, GSK, Janssen-Cilag, Leti, MEDA, Merck, MSD, Mundipharma, Novartis, Nycomed/Altana, Pfizer, Revotar, Sandoz-Hexal, Stallergens, TEVA, UCB/Schwarz-Pharma, Zydus/Cadila and has participated in advisory boards for Avontec, Boehringer-Ingelheim, Chiesi, Essex/Schering-Plough, GSK, Janssen-Cilag, MEDA, MSD, Mundipharma, Novartis, Regeneron, Revotar, Roche, Sanofi-Aventis, Sandoz-Hexal, TEVA, UCB/Schwarz-Pharma and has received research grants from Deutsche Forschungsgesellschaft, Land Mecklenburg-Vorpommern, GSK, MSD and is a full time employee of the Universitätsmedizin Rostock. The authors report no other conflicts of interest in this work., (© 2022 Bergmann et al.)

Background: Asthma is one of the most common chronic diseases in Germany. While many patients achieve asthma control under standard therapies, some patients still experience exacerbations and persistent airway obstructions. Thus, further pharmacological treatment is needed, and biologics could fill this gap, as they have shown clinical benefit in patients with severe asthma. Therefore, this real-world study aimed to compare healthcare resource utilization (HCRU) and associated costs before and after biologic therapy initiation., Methods: A retrospective claims data analysis has been conducted on adult asthma patients who initiated a long-term biologic therapy between January 2015 and June 2018. Patients were therapy-naïve to biologics for at least 12 months. HCRU and cost incurred by patients during 12 months before and after therapy initiation were compared., Results: Overall, 571 asthma patients initiated a biologic therapy during the observational period (316 omalizumab, 232 mepolizumab, 16 benralizumab, and 7 reslizumab). Patients had a mean age of 54.86 (62.70% female), and the majority (93.70%) received at least one follow-up prescription of their index-biologic agent within one year. During baseline, patients received on average 2.75 OCS prescriptions compared to 2.17 during follow-up. Most patients received less or the same amount of OCS after therapy initiation. Moreover, hospitalizations and asthma-related sick leave days decreased significantly. The average total costs per patient were €6618.90 during baseline and €22,832.33 during follow-up. Biologics mainly drove the increase; however, hospitalization costs were reduced significantly (€2443.37 vs €1941.93; p<0.001)., Conclusion: Our study demonstrates an improved asthma control due to the initiation of a biologic therapy in terms of decreased hospitalization frequency, OCS consumption, and sick leave days. However, biologics are associated with high costs for healthcare providers during the first year after initiation. Therefore, short- and long-term clinical benefits and financial burden must be considered in the overall context of healthcare., Competing Interests: Fränce Hardtstock and Julia Krieger participated in this study as staff members of IPAM; the work of IPAM in this study was financed by GlaxoSmithKline GmbH & Co. KG. Thomas Wilke is the founder of IPAM e.V., and has received honoraria from various pharmaceutical companies, including Novo Nordisk, Janssen Pharmaceutica, Boehringer Ingelheim Pharma, Bayer Health Care, Novartis, Sanofi, Pfizer and GlaxoSmithKline. Marco Lukas, Bernhard Ultsch and Robert Welte are GlaxoSmithKline employees and shareholders. Renate Quinzler is an employee of AOK Baden-Württemberg. Ulf Maywald is an employee of AOK PLUS. Hartmut Timmermann is affiliated with Schwerpunktpraxis Colonnaden and has received consultancy fees and grants from several pharmaceutical companies, including AstraZenica, Takeda, Bayer Health Care, Almirall, Astrellas Pharma, Novartis, Sanofi, Leti Pharma, Boehringer Ingelheim Pharma, Meda Pharmaceuticals, Mundipharma, Pfizer, Nycomed, Berlin-Chemie, Teva and GlaxoSmithKline. The authors report no other conflicts of interest in this work., (© 2022 Hardtstock et al.)

Objective: The objective of this study was to assess non-adherence (NA) and non-persistence (NP) to long-acting asthma medications in Germany by differentiating between measurement of NA in periods of therapy continuation and measurement of NP in therapy-naïve patients., Methods: We analyzed treatment adherence to long-acting asthma medication using German claims data for periods of treatment continuation based on the medication possession ratio (MPR) and the proportion of days covered. Persistence was assessed in treatment-naïve patients. Outcomes were observed from the date of the first to the last prescription within a 12-month period. Both NA and NP analyses considered prescription supply, using either defined daily dosages, or prescribed daily dosages derived from a medical chart review., Results: We identified 52,508 asthma patients (mean age: 40.1, 58.4% female) who received at least two long-acting asthma prescriptions within 12 months; 50,660 treatment-naïve patients were included in the NP analysis (mean age: 39.7, 58.8% female). The mean 12-month MPR was 38.5% (89.4% NA according to MPR ≤ 80%) and the average proportion of days covered was 40.4% (85.9% NA). Agent-specific MPR and NA rates varied between 31.8% (91.8% NA) and 56.2% (71.6% NA). The average weighted-MPR increased to 53.1% when using the prescribed daily dosage. Based on a  > 90-day gap definition, 86.7% of patients were considered non-persistent after 12 months (>180: 72.3%). When using prescribed daily dosages, NP rates ranged from 66.7 to 78.5%., Conclusion: High levels of treatment NA and NP indicate a substantial need to improve adherence and persistence to long-acting asthma medication in Germany.

Introduction: The German Asthma Net Severe Asthma Registry is collecting long-term data from a large cohort of patients aged ≥6 years with severe asthma. This manuscript presents their baseline characteristics, and identifies relationships with exacerbations and/or poor asthma control., Methods: The registry is collecting routine clinical parameters including: demographics and medical history; disease characteristics (Asthma Control Questionnaire [ACQ]-5, forced expiratory volume in 1 s [FEV 1 ]); exacerbations; and biomarkers (eosinophils, immunoglobulin E [IgE], fractional exhaled nitric oxide [FeNO])., Results: These analyses include data from 2011 patients at 72 sites (91.9% adult). Children (6-17 years) were more likely to be male, whereas more adults were female (males: children/adults 62%/41%). Most were receiving inhaled corticosteroid/long-acting β 2 -agonist combinations (78%/81%); 38.0% of adults were receiving systemic steroids. Asthma control was suboptimal in both groups: 21.5%/13.3% were controlled; 10.4%/49.1% were symptomatic; 33.1%/37.2% received emergency asthma treatment in the previous year. Median blood eosinophil (400/238 cells/μL) and IgE levels (494/186 IU/mL) were higher in children; FeNO was lower (19/35 ppb). Patients with ≥2 exacerbations in the previous year had lower FEV 1 (absolute and % predicted) and IgE, and higher ACQ-5, FeNO and blood eosinophil levels (all p < 0.05). There was a weak, negative correlation between ACQ-5 and FEV 1 % predicted in adults (p < 0.001)., Conclusions: These analyses characterise the typical German patient with severe asthma, and provide information on their overall care. Their planned long-term follow-up will assess whether asthma control can be optimised, how best to do so, and most importantly how such optimisation can benefit patients., (Copyright © 2022. Published by Elsevier Ltd.)

In Germany, cognitive-behavioral therapy, psychodynamic therapy, and systemic therapy are scientifically and legally approved as suitable procedures for treating mental disorders. While all methods have provided empirical evidence of their effectiveness in adults according to defined criteria of the "Scientific Advisory Board for Psychotherapy" (in German: "Wissenschaftlicher Beirat Psychotherapie"), i. e., the official board which decides upon the formal scientific approval of psychotherapeutic approaches in Germany, an evaluation is lacking for the psychodynamic methods in children and adolescents. Against this background, we evaluated the available empirical data for psychodynamic therapy in children and adolescents based on the methods paper of the "Scientific Advisory Board for Psychotherapy" (2019; version 2.9). Published reviews served as the basis for identifying relevant studies, supplemented by a systematic literature search. We identified 91 potentially relevant studies but could not consider the majority of these due to formal exclusion criteria (mainly not disorder-specific, no control group). Up to 26 of the remaining studies provide evidence of efficacy as defined by the "Scientific Advisory Board for Psychotherapy". These cover 10 of the 18 areas of application as defined by the "Scientific Advisory Board for Psychotherapy". According to our evaluation, the reviewed studies provide empirical evidence for the three most relevant areas of application (i. e., affective disorders; anxiety disorders and obsessive-compulsive disorders; hyperkinetic disorders and conduct disorders). Thus, the available evidence supports the suitability of psychodynamic therapy as a method for the treatment of children and adolescents.

Background: There exists a range of treatments in the management of asthma. Non-adherence to these medications has been identified as a factor negatively impacting the effects of treatment., Objective: The objective of this study was to identify the potential barriers to medication adherence among adult patients with asthma in Germany., Patients and Methods: A multi-center observational study was conducted addressing adult patients with asthma who were prescribed regular maintenance medication between 2014 and 2016. Data were derived from physicians' documentation as well as claims data, which were linked to the above primary observational data, and patient survey data. Adherence barriers were assessed by the validated Adherence Barriers Questionnaire, both descriptively and in a logistic regression framework. Cluster analysis identified distinct patient groups with respect to the relevance of specific adherence barriers., Results: We included 524 patients with asthma (mean age 53.1 years, 74.6% female, 43.1% allergic asthma, 37.6% nonallergic, 19.3% mixed). Most of the participants reported to face at least three barriers (61.1%). Frequently reported barriers were the perception that medications are all harmful (53.6% of the participants), the burden of medication co-payment (44.1%), positive perception about current health status (39.9%), feeling of depression (30.9%), and the fear of side effects (27.5%). Four distinct patient clusters could be identified: cluster 1 with a low number of barriers (28.6% of participants), cluster 2 (11.6%) with a comparably high number of existing barriers, cluster 3 with high importance of depression as a barrier (27.3% of participants), and cluster 4 that was dominated by the perception that medications are all harmful (32.5% of participants)., Conclusions: Results of this study provide important insights for further development of adherence programs, which should focus on distinct patients' clusters that differ substantially in the relevance of specific adherence barriers.

In the EU, five biologics have been approved as add-on therapy for patients with severe asthma. Until recently, none of the biologics was approved for home use and had to be administered under medical supervision, a time-consuming schedule for both patients and physicians, accompanied by greater expenditure. However, over the last year, four out of the five biologics have been granted approval for patient self-administration at home. The objective of this multiple-choice survey was to understand how patients with severe asthma treated with omalizumab and their treating physicians view the potential home use of biologics exemplified by omalizumab. The questionnaires were answered by 120 physicians and 432 patients (response rate: 51.7 % and 20.6 %, respectively). Overall, 44.7 % of patients were in favour of self-administration at home while 30.6 % opposed this method of administration and 23.8 % of patients were neutral. Especially teenagers and young adults had a positive attitude towards self-administration. 76.7 % of the questioned physicians were in favour of home use for certain patients. Time saving was the main advantage for self-administration mentioned by patients (53.2 %) as well as by physicians (72.5 %). The main concern for patients was 'making a mistake while injecting' (43.8 %) while 'forgetting to inject omalizumab' (73.3 %) was the main concern for physicians. 44.4 % of patients expressed a wish for individual training and 70.8 % of physicians agreed with this statement. The latter group also considered a starter kit including several information materials (54.2 %) as well as an electronic reminder system (50.8 %) as useful. In conclusion, self-administration of biologics has the potential to be timesaving for both patients and physicians., Competing Interests: Claudia Mailänder is an employee of Novartis Pharma GmbH.Hartmut Timmermann has received consultancy fees from several pharmaceutical companies (Astra-Zeneca, Almirall, Astellas, Bayer, Boehringer, Berlin Chemie AG, GSK, Leti, Meda, Mundipharma, Novartis, Nycomed, Pfizer, Sanofi, Takeda und Teva).Financial support: The study was sponsored by Novartis Pharma GmbH, Germany. Novartis Pharma GmbH, Germany, provided financial support for the preparation of the manuscript, including all article-processing charges., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects., Methods: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters., Results: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV 1 , 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same., Conclusion: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.