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Dupilumab is a monoclonal antibody against the IL‐4 receptor alpha which has shown efficacy in T2 high severe asthmatics in phase 3 randomized controlled trials. The purpose of this real‐life study is to demonstrate the real‐life effectiveness of dupilumab in Austrian severe asthma patients. We retrospectively analyzed all patients receiving dupilumab at our severe asthma clinic. Thirteen patients have so far received dupilumab at our center. The primary outcome, asthma control questionnaire 6‐item scale at 2 weeks, improved by 0.57 points (p = .014), which is statistically and clinically significant. Similarly, the asthma control test at 4 weeks improved by 3.91 points (p = .024), also statistically and clinically significant. Improvements in forced expiratory volume in 1 s at 2 weeks were neither statistically, nor clinically significant. Improvements at 4 weeks (+220 ml, p = .041), and 3 months (+229 ml, p = .006), were statistically significant and clinically borderline significant. No severe adverse events or hypereosinophilia were observed. No adverse events led to treatment discontinuation. Most patients (85%) had previously received monoclonal antibody treatment for severe asthma. Previous monoclonal antibody treatment had been discontinued in these patients due to a lack of clinical response. Dupilumab is effective and safe in Austrian real‐life severe asthmatics. It provides a possible treatment strategy for T2 high severe asthmatics who do not qualify for anti‐immunoglobulin E or anti‐IL5/IL5R monoclonal antibody treatments or do not adequately respond to these., This is a real‐life study that shows that dupilumab is effective and safe in Austrian real‐life severe asthmatics. It rapidly improved asthma control. These improvements are comparable to previous randomized controlled trials.

Background: Efficacy of mepolizumab in severe eosinophilic asthma has been demonstrated in large randomized controlled trials (RCTs) but patients included in RCTs poorly reflect real-life patients. Objectives: The objective was to investigate whether mepolizumab is effective in a real-life setting. The primary outcome was patient reported asthma control (asthma control test, ACT) Methods: In this single-centre, single-arm, real-life study patients received 100 mg mepolizumab by subcutaneous injection every four weeks for treatment of severe eosinophilic asthma. ACT, FEV1 and OCS dose were collected at baseline and every four weeks for up to 24 weeks. Results: Thirty-five patients with a mean age of 57 years (60% female) were included. The median ACT at baseline was 14.5 and almost two-thirds of patients were on OCS (median dose 9.3 mg). Already at the first follow-up visit, four weeks after the first treatment, median ACT increased to 18 (+3.5, p Conclusion: Mepolizumab is effective and safe in severe eosinophilic asthmatics. This effectiveness is comparable to the efficacy seen in large RCTs.

Amidst the current pandemic there is only little clinical evidence regarding COVID-19 infections in asthma patients. Chinese data [1, 2] suggests that asthma patients might not be of an elevated risk of severe infections. A recent article by Carli et al. [3] hypothesises that asthma might even have a protective effect in COVID-19 infections. It is important to point out, that this is purely theoretical. Eosinophils from healthy probands have an antiviral activity against respiratory syncytial virus and influenza virus, but not eosinophils collected from asthma patients [4]. Eosinopenia, alongside lymphopenia has been seen in COVID-19 patients [2]. Both eosinopenia and lymphopenia are more common in in patients with COVID-19 pneumonitis compared to patients with non-COVID-19 viral pneumonitis [5]. Azkur et al. attribute this to an overwhelming type 1 response [6].

Mepolizumab was effective in several randomized clinical trials (RCTs) in patients with severe eosinophilic asthma, but evidence for symptom control in a real-world population is scarce.To assess asthma symptom control, lung function, use of oral corticosteroids, and biomarkers after mepolizumab initiation in real-world clinical practice.Thirty-five adult patients with severe eosinophilic asthma and inadequate asthma symptom control, including former smokers and patients with cardiac disease, were enrolled in a prospective single-arm real-world study. Asthma control tests (ACT), exacerbations, spirometry (pre-bronchodilator forced expiratory volume in 1 s [FEV1]), and oral corticosteroid doses were documented. Further assessments included peripheral blood eosinophil counts and adverse events.After mepolizumab initiation asthma symptom control was significantly improved with the median ACT score of 12.5 at baseline (interquartile range [IQR ]10.5-19.5) rising to 19 (15-22.5) after 4 weeks. The improvement was maintained throughout the observation period of 20 weeks. Likewise, exacerbations were reduced. After 8 weeks of mepolizumab daily OCS doses were reduced from 6.25 mg daily (0-20) at baseline to 2.5 mg daily (0-11.9) at week 8 (P 0.001). FEV1 remained generally unchanged during the course of the study. Eosinophil counts rapidly declined and remained at a low level during the observation period. No new safety signals were observed in this study.Mepolizumab improved asthma symptom control and had a steroid-sparing effect. Efficacy in this real-world study was comparable to RCTs, despite a history of smoking and comorbidities in many of the patients included.

Introduction XC8 (histamine glutarimide) is a novel agent which targets eosinophilic migration and mast cell degranulation and has shown anti-asthmatic effects in animal studies. Objective The objective of this placebo-controlled phase 1 study was to assess the safety of oral XC8 and to evaluate its pharmacokinetic and pharmacodynamic properties. Methods 32 healthy volunteers in three dose-escalation treatment groups (10 mg [n = 8], 50 mg [n = 8] and 200 mg [n = 16]) were randomized in a 3:1 ratio to XC8 or placebo respectively. The subjects received a single dose of the drug at Day 1 and then once-daily for 14 days (Days 8–21). Results No severe adverse events occurred. The number of adverse events was similar in the treatment arms compared to placebo and all subjects completed the study as planned. No clinically significant changes occurred in hematologic and biochemical blood tests in subjects receiving XC8. The pharmacokinetic data showed similar dose and time dependent mean plasma XC8 concentrations after single (Day 1) and multiple (Day 21) dosing. The mean maximum concentrations were 114–1993 ng/mL after single and 115–2089 ng/mL after multiple dosing. The mean times to maximum concentration were 0.68–1.01 and 0.67–0.98 h, respectively. There was no evidence for accumulation of XC8 after multiple dosing. Conclusion XC8 was safe and well tolerated. A phase 2 study is being performed to further evaluate the potential role of XC8 in asthma treatment. Trial registration ClinicalTrials.gov, NCT02882217.

Objective Evidence of the efficacy of single-inhaler triple therapy in COPD patients inferred from RCTs has not been assessed in a real-world setting in Austria. In this non-interventional study (NIS) tolerability and effectiveness of extrafine beclometasone-dipropionate, formoterol-fumarate and glycopyrronium (Trimbow® 87/5/9 μg) was evaluated in COPD patients. Methods A prospective NIS was conducted over 52 weeks in 24 sites in Austria. Eligible COPD patients had an indication for treatment with single-inhaler BDP/FF/G. In this study tolerability, lung function, exacerbation rate, symptom scores and CAT scores were recorded. Results 265 patients with moderate to very severe airflow limitation (GOLD Grade 2–4: 96.2%) and persistent symptoms (GOLD B: 62.3%, GOLD D: 34%) according to the 2018 GOLD Report were included. After 52 weeks, a significant improvement was detected in lung function (FEV1, FEV1% predicted and FVC; p Conclusions The present results support the tolerability and effectiveness of extrafine BDP/FF/G in COPD patients in a real-world setting, showing an improvement in lung function, symptom control and a significant reduction in exacerbations.

XC8 (histamine glutarimide) is a non-steroidal anti-inflammatory anti-bronchoconstriction agent which targets eosinophilic migration and mast cell degranulation by inhibition of chemokines (CCL2, CCL7, CCL8, CCL13). Previous animal studies have shown beneficial effects of XC8 on airway inflammation. The primary objective of this double-blind placebo-controlled multi-center dose-escalating phase-1 study was to assess the safety of oral XC8. The secondary objective was evaluating the pharmacokinetics (PK). The study population consisted of 32 healthy female (47%) and male adults. Three dose-escalation cohorts (10 mg [n=8], 50 mg [n=8] and 200 mg [n=16]) in two centers were randomized in a 3:1 ratio. The subjects received a single dose at Day 1 and then once-daily for 14 days (Days 8-21). Safety data was collected until Day 36. PK data were collected before (Days 1 and 8-21) and 20 min, 30 min, 1, 2, 4, 8 and 24h after (Days 1 and 21) the administration of the investigational product, respectively. No severe adverse events (AE) occurred. No AEs led to study discontinuation, all subjects completed the study as planned. AEs were not increased in the treatment arms compared to placebo. No clinically significant changes occurred in the safety laboratory in subjects receiving XC8. The PK data showed similar dose and time dependent mean plasma XC8 concentrations both after single (Day 1) and multiple (Day 21) dosing. The median time to maximum plasma concentration was 0.68-1.01 hours after single and 0.67-0.98 hours after multiple dosing. There was no evidence for accumulation of XC8 and it showed linear PK. XC8 was safe and well tolerated. A phase 2 study will be performed to further evaluate the potential role of XC8 in asthma treatment.

The inhaled long-acting muscarinic antagonist aclidinium bromide has been shown to significantly improve lung function parameters and symptom severity in patients with COPD in randomised placebo- and active-controlled clinical studies. To obtain a comprehensive view of the treatment effects, patient-reported outcomes were investigated in a real-life COPD population in routine clinical practice in Austria.Multicentre, prospective, non-interventional study in patients with COPD who were newly initiated on treatment with Eklira® Genuair® (aclidinium bromide; recommended dose 400 μg twice daily) as first-line or add-on therapy. Patients were either treatment naïve or switched from other COPD medications. Health-related quality of life by means of the COPD Assessment Test™ (CAT) and symptom-related variables were evaluated at the first visit (baseline) and after approximately 12 weeks of treatment. Features of the inhaler were assessed by patients and physicians at the follow-up visit.A total of 795 COPD patients (56% male; median age: 64 years) were enrolled and treated. During the observational period, the proportion of patients with at least moderate nighttime symptoms, early-morning symptoms, and limitations in morning activities decreased from 45.0% to 21.4%, from 57.7% to 26.0%, and from 49.9% to 25.3%, respectively. All improvements from baseline in symptom severity and activity limitation were statistically significant (p0.0001, all tests). The mean (±SD) frequency of nocturnal awakenings decreased from 1.2 (±1.4) to 0.7 (±1.2) times per night (p0.0001). Quality of life improved significantly in patients treated with aclidinium bromide over 3 months compared to baseline (p0.0001; mean CAT total score: 18.5 ± 7.5 vs. 13.8 ± 7.3). Up to 90% of the patients and up to 91% of the physicians assessed individual features of the inhaler as 'very good' or 'good'. Aclidinium bromide was well tolerated; 6.9% of the patients reported adverse drug reactions, none of which were serious.This non-interventional study indicated beneficial effects of Eklira® Genuair® in the treatment of COPD with regard to nighttime and early-morning symptoms, limitation of morning activities, and quality of life under routine conditions. The acceptance of the inhaler device was high, which is a prerequisite to ensure adherence in long-term therapy.

Background Increasing evidence suggests that the low-affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen-specific T cells through IgE-facilitated allergen presentation. Objective We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen-presenting cells is associated with IgE levels and influences allergen uptake and allergen-specific T-cell activation. Methods Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen-specific IgE levels, as well as with allergen-induced immediate skin reactivity. Allergen uptake and allergen-specific T-cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T-cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE-allergen immune complexes were formed with human monoclonal allergen-specific IgE and Bet v 1. Results In allergic patients the vast majority of CD23 molecules were expressed on naive IgD + B cells. The density of CD23 molecules on B cells but not the number of CD23 + cells correlated with total IgE levels ( R S = 0.53, P = .03) and allergen-induced skin reactions ( R S = 0.63, P = .008). Uptake of allergen-IgE complexes into B cells and activation of allergen-specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly ( P = .04) increased CD23 expression on B cells. Conclusion CD23 surface density on B cells of allergic patients is correlated with allergen-specific IgE levels and determines allergen uptake and subsequent activation of T cells.