INTRODUCTIONOnly little is known about COVID-19 in patients with asthma. There is no data on COVID-19 in patients with severe asthma or patients with asthma who are treated with monoclonal ...antibodies. CASE STUDYHere, we present the case of a severe eosinophilic asthmatic in whom benralizumab treatment, an anti-IL-5R monoclonal antibody, was initiated 2 years ago. Prior to benralizumab treatment, every viral infection had resulted in a prolonged course of oral corticosteroids (OCS). Since initiation of benralizumab, the patient has had good asthma control. Mid-March 2020, the patient developed high fever. RESULTSA SARS-CoV-2-PCR (nasopharyngeal swab) was positive. The patient's symptoms subsided after few days. No OCS was needed. The asthma control questionnaire 6-item scale worsened moderately in the week of the infection and returned to normal levels thereafter. The asthma control test, measuring longer term asthma control, showed no decline. CONCLUSIONThe course of COVID-19 was very mild in this particular patient with severe eosinophilic asthma. So far, there is no evidence that would suggest a more severe course of COVID-19 in patients with asthma. It is worth noting, that prior to the initiation of benralizumab this patient had multiple exacerbations per year triggered by viral infections (4/year), which all required OCS. Whilst only anecdotal, this case study provides the first evidence to support the current recommendation of continuing monoclonal antibodies in patients with severe asthma during the COVID-19 pandemic.
Summary
This statement was written by a group of pulmonologists and pediatric pulmonologists belonging to the corresponding professional associations ÖGP (Austrian Society for Pulmonology) and ÖGKJ ...(Austrian Society for pediatric and adolescent medicine) to provide a concise overview of the latest updates in the 2015 GINA Guidelines and to include aspects that are specific to Austria.
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
Many patients with allergic rhinitis (AR) have moderate-to-severe persistent AR. Meda Pharma’s AzeFlu (MP-AzeFlu
®
) is an intranasal AR treatment comprising a novel formulation of ...azelastine hydrochloride and fluticasone propionate in a single device.
Methods
This prospective observational study of 214 adults and adolescents in Austria with moderate-to-severe persistent AR assessed the effectiveness of MP-AzeFlu (one spray/nostril twice daily; daily doses: azelastine hydrochloride 548 μg; and fluticasone propionate 200 μg) for AR control in clinical practice using the visual analog scale. Symptom severity was reported on days 0, 1, 3, 7, 14, 21, 28, 35, and 42. Patient demographics, AR phenotype, allergen sensitization, symptomatology, AR treatments in the previous year, and the reason for the MP-AzeFlu prescription were recorded.
Results
MP-AzeFlu treatment was associated with a rapid and statistically significant reduction in the visual analog scale score from baseline to each timepoint measured, including day 1 (all
p
< 0.0001). Mean (standard deviation) visual analog scale score was 53.5 mm (26.3) at baseline, 25.3 mm (21.0) on day 28, and 19.6 mm (17.4) on day 42, a mean overall reduction from baseline of 41.4 (23.9) mm for completers. Results were consistent irrespective of patient age, gender, severity, or traditional AR phenotype. Prior to MP-AzeFlu prescription, congestion was considered the most bothersome symptom. The majority of patients reported using at least two AR therapies in the past year, including oral antihistamines, intranasal corticosteroids, and intranasal antihistamines.
Conclusions
Many patients in Austria live with uncontrolled persistent AR despite treatment. MP-AzeFlu provides effective and rapid control of persistent AR in a real-world Austrian setting.
Long-lasting symptoms following SARS-CoV2-infection have been described in several studies. However, there is only limited knowledge about the ongoing pathophysiology and the association with ...pathological findings in medical examinations.
In this post hoc analysis of a prospective trial, 135 patients following COVID-19 were enrolled and grouped with respect to the presence or absence of respiratory ongoing symptoms following COVID-19. Pulmonary function test (PFT), diffusion capacity measurement (TLCO SB and TLCO/VA), blood gas analysis (BGA), laboratory tests and high-resolution computed tomography (HRCT) of patients with persistent respiratory symptoms were compared to those of asymptomatic patients.
In this analysis, 71% (96/135) of all patients (mean age 49 years; range 20-91 years) reported long-lasting symptoms after a median (IQR) of 85 days (60-116) following COVID-19 whereby 57.8% (78/135) complained about persistent pulmonary symptoms. Pathological findings in blood test, PFT, TLCO, BGA and/or HRCT were found in 71.8% and 64.1% of patients with and without long-lasting respiratory symptoms respectively. Patients with persistent respiratory symptoms were significantly younger and presented a significant lower FVC (%), TLC (L), and TLCO SB compared to asymptomatic patients (p < 0.05). The multiple logistic regression results in a significant effect of age (p = 0.004) and TLCO SB (p = 0.042).
Following COVID-19, a large proportion of patients experience ongoing symptoms, whereby the respiratory symptoms are the predominant complaints. Compared to asymptomatic patients, patients with ongoing symptoms were younger and presented a significant lower FVC, TLC and TLCO SB. The multiple logistic regression demonstrated only a significant association between the TLCO SB as the only PFT parameter and the perceived symptoms.
The subject of this article is my personal path from the near-field optical (NFO) microscope to the optical antenna and its potential for modern optics.
Abstract
Background
Despite the fast establishment of new therapeutic agents in the management of COVID-19 and large-scale vaccination campaigns since the beginning of the SARS-CoV-2 pandemic in ...early 2020, severe disease courses still represent a threat, especially to patients with risk factors. This indicates the need for alternative strategies to prevent respiratory complications like acute respiratory distress syndrome (ARDS) associated with COVID-19. Aviptadil, a synthetic form of human vasoactive intestinal peptide, might be beneficial for COVID-19 patients at high risk of developing ARDS because of its ability to influence the regulation of exaggerated pro-inflammatory proteins and orchestrate the lung homeostasis. Aviptadil has recently been shown to considerably improve the prognosis of ARDS in COVID-19 when applied intravenously. An inhaled application of aviptadil has the advantages of achieving a higher concentration in the lung tissue, fast onset of activity, avoiding the hepatic first-pass metabolism, and the reduction of adverse effects. The overall objective of this project is to assess the efficacy and safety of inhaled aviptadil in patients hospitalized for COVID-19 at high risk of developing ARDS.
Methods
This multicenter, placebo-controlled, double-blinded, randomized trial with 132 adult patients hospitalized for COVID-19 and at high risk for ARDS (adapted early acute lung injury score ≥ 2 points) is conducted in five public hospitals in Europe. Key exclusion criteria are mechanical ventilation at baseline, need for intensive care at baseline, and severe hemodynamic instability. Patients are randomly allocated to either inhale 67 μg aviptadil or normal saline (three times a day for 10 days), in addition to standard care, stratified by center. The primary endpoint is time from hospitalization to clinical improvement, defined as either hospital discharge, or improvement of at least two levels on the nine-level scale for clinical status suggested by the World Health Organization.
Discussion
Treatment strategies for COVID-19 are still limited. In the context of upcoming new variants of SARS-CoV-2 and possible inefficacy of the available vaccines and antibody therapies, the investigation of alternative therapy options plays a crucial role in decreasing associated mortality and improving prognosis. Due to its unique immunomodulating properties also targeting the SARS-CoV-2 pathways, inhaled aviptadil may have the potential to prevent ARDS in COVID-19.
Trial registration
ClinicalTrials.gov,
NCT04536350
. Registered 02 September 2020.
Asthma affects up to nearly 40% of patients with allergic rhinitis (AR). Poor control of AR symptoms is associated with poor asthma control. The goal of this study was to evaluate the effect of AR ...treatment with MP-AzeFlu on symptoms of AR as well as symptoms of asthma.
This prospective study used a visual analog scale (VAS) to assess symptoms of AR and asthma before and after treatment with MP-AzeFlu (Dymista
; azelastine hydrochloride plus fluticasone propionate; 1 spray in each nostril twice daily for 2 weeks). Participants suffered from moderate-to-severe AR according to Allergic Rhinitis and its Impact on Asthma criteria, with acute AR symptoms (AR-VAS scores ≥ 50 mm) on inclusion day. In addition to symptom assessment, patients recorded the impact of AR symptoms on quality-of-life measures before, during, and at the conclusion of the treatment period (approximately 14 days). Patients self-reported change in frequency of their usage of asthma reliever medication on the last day of treatment.
Of 1103 study participants, 267 (24.2%) had comorbid asthma. These participants reported using a mean of 5.1 puffs of asthma reliever medication in the week before treatment with MP-AzeFlu. A total of 81.8% of patients with comorbid asthma responded to AR therapy (AR-VAS < 50 mm on at least 1 study day). Among patients with AR and comorbid asthma, MP-AzeFlu was associated with improved VAS scores across all study parameters, including AR symptom severity, asthma symptom severity, sleep quality, daily work or school activities, daily social activities, and daily outdoor activities. Asthma symptom severity decreased from a mean of 48.9 mm to 24.1 mm on the VAS. Self-reported frequency of asthma reliever medication use was reduced for 57.6% of participants (n = 139/241).
MP-AzeFlu used to relieve AR symptoms was associated with reduced asthma symptom VAS scores and frequency of asthma reliever medication usage. Changes in overall symptoms of AR and asthma were correlated.
Introduction
A significant number of patients with moderate asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS). These patients do not yet meet the criteria for oral ...corticosteroids (OCS) and monoclonal antibodies. The new anti-chemokine oral drug XC8 could represent an alternative treatment option for these patients. The objective of this trial was to evaluate the effect of different doses of the XC8 in patients with partly controlled asthma in a phase 2a clinical trial.
Methods
A double-blind, parallel-group, randomized, multicenter, phase 2a trial was conducted at 12 sites in Russia. Patients with asthma were randomized into four groups (
n
= 30 each) to receive XC8 at 2 mg, 10 mg, 100 mg or placebo once-daily for 12 weeks in addition to low-dose ICS with or without LABA. Efficacy and safety parameters were evaluated at weeks 0, 2, 6, and 12.
Results
No statistically significant difference between the treatment arms in the number of patients with adverse events was observed. The primary endpoint, improvement of forced expiratory volume in 1 s (FEV
1
) % predicted over 12 weeks compared to placebo, was not statistically significant. The treatment of patients with XC8 (100 mg) resulted in statistically and clinically significant improvements in FEV
1
compared to baseline (7.40% predicted,
p
< 0.001). Patients with elevated peripheral blood eosinophil count (PBEC, > 300 cells/μl) or serum interferon-γ (IFN-γ) level (> 100 pg/mL) treated with XC8 (100 mg) achieved a statistically significant improvement in FEV
1
(11.33% predicted or 8.69% predicted, respectively,
p
< 0.05) as compared to the baseline versus the placebo. The strongest effect was observed in patients with both high PBEC and IFN-γ level. Pharmacodynamic engagement was demonstrated through the reduction of serum levels of C–C motif ligand 2 (CCL2) and C–X–C motif chemokine 10 (CXCL10). Treatment with XC8 (100 mg) alleviated resistance to maintenance ICS therapy in patients with elevated IFN-γ level.
Conclusions
Given the high safety, oral route of administration, and efficacy, XC8 may provide a promising treatment option for patients with mild-to-moderate asthma.
Trial Registration
795–30/12/2015 (Ministry of Health Russian Federation), NCT03450434 (ClinicalTrials.gov).
PDF
