The influence of dimethylfumarate and monomethylfumarate on endothelial antigen expression and dynamic lymphocyte-endothelial cell interactions

For years Fumaric acid esters (FAE) have been successfully used in the systemic treatment of severe psoriasis. However, their pleiotropic mode of action is not yet fully understood. To further elucidate the mode of action of FAE, the effect of dimethylfumarate (DMF) and monomethylfumarate (MMF) on human endothelial cells in vitro was investigated. As Psoriasis is associated with inflammatory lymphocytic infiltrates, it was focused on adhesion molecule expression and the interaction between endothelial cells and human peripheral blood mononuclear cells (PBMC) under conditions of shear flow. Dimethylfumarate concentration-dependently reduced the TNFα-induced expression of E-selectin (CD62E), ICAM-1 (CD54) and VCAM-1 (CD106) on human umbilical vein endothelial cells (HUVEC), both on mRNA and protein level. All three proteins are essential for the initial steps of lymphocyte recruitment to inflamed tissues. Treatment with dimethylfumarate concentrations ranging between 252013-11-3

Eosinophilic cationic protein as marker for response to antibody therapy in severe asthma

This study of the eosinophil cationic protein (ECP) as predictor of clinical response to biological therapy in severe asthma found that ECP is not useful in unselected patients but may have a role in those not exposed to oral corticosteroids. https://bit.ly/398RwE

Anti-IL-5 therapy in patients with severe eosinophilic asthma – clinical efficacy and possible criteria for treatment response

Abstract Background Interleukin-5 (IL-5) antibodies represent a promising therapeutic option for patients with severe eosinophilic asthma. To date, no official treatment response criteria exist. In this study, simple criteria for treatment response applicable to all asthma patients were used to evaluate clinical efficacy and predictors for treatment response in a real-life setting. Methods Data from 42 patients with severe eosinophilic asthma treated with mepolizumab for at least six months were analysed. Simple criteria to assess treatment response in clinical practice were used: increase of FEV1 ≥ 12% or ≥ 200 ml, reduction of blood eosinophils (< 150/μl or < 80% from baseline) and improvement of subjective condition (patient-judged subjective improvement or worsening following therapy). Patients were considered treatment responders if two criteria were fulfilled. Results Thirty-two out of 42 patients (76% [61–87%]) were classified as responders. Within the groups (responder vs non-responder), treatment with mepolizumab led to significant increase in FEV1 (+ 600 ml vs -100 ml, p = 0.003), oxygenation (+ 8 mmHg vs -3 mmHg, p = 0.001), quality of life (visual analogue scale; + 28% vs − 5%, p = 0.004) and Asthma Control Test (+ 8 vs + 1 points, p = 0.002). In the responder group a significant decrease in the exacerbation rate over 12 months (1.45 vs 0.45, p = 0.002) was observed. Baseline characteristics (sex, BMI, smoking history, allergies, baseline level of eosinophils) did not predict treatment response. Conclusion Using improvement of lung function, decrease of eosinophils and improvement of subjective condition as response criteria, 76% of treated patients could be classified as treatment responders, demonstrating the efficacy of anti-IL-5 therapy in clinical practice

Treatment with interleukin (IL)-5/IL-5 receptor antibodies in patients with severe eosinophilic asthma and COPD

Background Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies represents an established treatment for patients with severe eosinophilic asthma (SEA) but did not show clinical efficacy in patients with COPD. The objective of the present study was to evaluate treatment response to anti-eosinophilic antibody therapy in patients with asthma and COPD. Methods A retrospective comparison of pulmonary function testing, oral corticosteroid intake, quality of life and pulmonary symptom control in patients with SEA and COPD and 1:1 propensity score matched patients suffering from SEA alone was performed. All patients received treatment with either mepolizumab or benralizumab. Data were assessed prior to antibody treatment start and after 6 months of therapy. Results Data from 84 patients (42 patients with SEA and COPD and 42 patients with SEA) were analysed. After 6 months of treatment, patients in both groups showed improved forced expiratory volume in 1 s (improvement by 11% (IQR 5–18) in the SEA and COPD group versus 15% (IQR −3–23); p=0.637) and decreased oral corticosteroid dosages (median reduction by 3 mg in the SEA and COPD group versus 5 mg; p=0.070), without significant differences between groups. Pulmonary symptom control and quality of life improved in both groups. A significant decrease in eosinophils could be measured in both groups with similar cell numbers prior to treatment initiation (600 cells·µL−1 in the SEA and COPD group versus 500 cells·µL−1). Conclusion Anti-eosinophilic therapy with interleukin-5/interleukin-5-receptor antibodies shows clinical efficacy in patients with SEA and COPD comparable to treatment response in patients with SEA alone

The impact of anti-eosinophilic therapy on exercise capacity and inspiratory muscle strength in patients with severe asthma

Introduction Exercise limitation is frequently described among asthmatic patients and could be related to different mechanisms of the pulmonary, cardiovascular and muscular systems. Despite this, cardiopulmonary exercise testing (CPET) does not have an established role in the management of severe asthma. The aim of our study was to investigate the role of CPET and inspiratory pressure measurement in exercise capacity and muscle strength in severe asthmatic patients treated with anti-IL-5 therapy. Methods A monocentric observational study was conducted at Hanover Medical School, Germany, from April 2018 to June 2019. Patients affected by severe asthma treated with either mepolizumab or benralizumab were included. All patients underwent CPET before the initiation of antibody therapy and after 3 months, and follow-up visits were scheduled at 3, 6 and 12 months with plethysmography, inspiratory pressure measurement and blood gas analysis. Results 14 patients were enrolled: 10 (71.4%) females, median age 52 years (IQR 47–61). Seven patients were treated with benralizumab, seven with mepolizumab. Oxygen uptake (V′O2 peak) did not change significantly after 3 months of antibody treatment, while the mean value of the breathing reserve exhaustion reduced significantly from 78% to 60% (p=0.004). Whereas at baseline seven patients depleted the breathing reserve and two of them experienced oxygen desaturation during exercise, at 3 months no one presented any desaturation or breathing reserve exhaustion. The inspiratory pressure remained unchanged before and after the antibody therapy. Conclusion CPET could show hints of alveolar recruitment and ventilatory efficiency in severe asthma patients treated with antibody therapy

Switch from IL-5 to IL-5-Receptor alpha Antibody Treatment in Severe Eosinophilic Asthma

Background: Anti-IL-5 antibodies represent an established therapy for severe eosinophilic asthma (SEA), but some patients show inadequate response. The objective of this study was to assess the effects of a switch to anti-IL-5R alpha therapy in patients with inadequate response to anti-IL-5 therapy. Methods: In this retrospective multi-centre, real-life study, we analysed all SEA patients switched from anti-IL-5 to anti-IL-5R alpha therapy due to inadequate response or intolerability. Pulmonary function tests, blood gas analyses, asthma control tests (ACT) and oral corticosteroid (OCS) usage were analysed and compared at three timepoints: baseline (BL, before anti-IL-5 therapy), timepoint 1 (T1, under anti-IL-5 therapy) and timepoint 2 (T2, under anti-IL-5R alpha therapy). Results: Of 665 patients treated with anti-IL-5 antibodies, 70 were switched to anti-IL-5R alpha and 60 were included in the analysis. Median treatment duration was 8 months [IQR 5;15] for anti-IL-5 and 5 months [IQR 4;6] for anti-IL-5R alpha therapy. FEV1 was 61% of predicted at BL [IQR 41;74], 61% [IQR 43;79] at T1 and 68% [IQR 49;87] at T2 (P-T1-(T2)=0.011). ACT score was 10 [IQR 8;13], 16 [IQR 10;19] and 19 [IQR 14;22], respectively (both p<0.001). The number of patients requiring OCS was reduced from 41 (BL) to 32 (T1) and 19 (T2) (both p<0.001). Ten patients discontinued anti-IL-5Ra therapy due to insufficient efficacy (n=7) and adverse events (n=3). Conclusion: Switching from anti-IL-5 to anti-IL-5R alpha therapy in patients with inadequate response was associated with significantly improved FEV1, asthma control and OCS reduction

Effects of a randomized-controlled and online-supported physical activity intervention on exercise capacity, fatigue and health related quality of life in patients with post-COVID-19 syndrome

Abstract Background The Post-COVID-19 syndrome (PCS), which can occur after acute respiratory syndrome coronavirus 2 infection, leads to restrictions in everyday activity. Our study assessed the impact of an online-guided intervention which intended to facilitate physical activity on the mental and physical capability of PCS patients. Methods We randomized 62 patients with PCS (20 male/ 42 female; age: 46 ± 12 years; body mass index: 28.7 ± 6.7 kg/m2) with a score ≥ 22 in the fatigue assessment scale (FAS) to a 3-month exercise-focused intervention (IG n = 30) or control period (CG n = 32). We assessed changes in exercise capacity (bicycle exercise test with measurements of gas exchange), fatigue, markers of health-related quality of life (HrQoL) and mental health. Results The FAS score decreased significantly in both study groups (IG: 35.1 ± 7.4 to 31.8 ± 8.5 points; CG: 35.6 ± 7.4 to 32.6 ± 7.5 points, both p < 0.01). Exercise capacity did not increase in the CG or IG (within-group changes for IG: peak oxygen uptake: 0.9 ± 2.6 ml/min/kg, p = 0.098; peak power output: 6.1 ± 17.8 W, p = 0.076) with no significant changes in HrQoL and work ability. Patients with a FAS score at baseline ≥ 35 (severe fatigue) showed no change in exercise capacity with the 3-month intervention whereas the sub-group of patients with FAS < 35 points (moderate fatigue) showed improvements, independent of the study group. Conclusions Our 3-month intervention seems appropriate for patients with moderate fatigue, whereas those with more severe fatigue appear to be too restricted with respect to their mental or physical health status to perform exercise at a level which is sufficient to improve markers of physical performance. Trial registration German Clinical Trials Register (registration trial number: DRKS00026245) on September 2 2021