Efficacy and Safety of Benralizumab for Severe Eosinophilic Asthma ：A Meta-analysis / 中国药房

OBJECTIVE：To systematic ally ev aluate the efficacy and safety of benralizumab in the treatment of severe eosinophilic asthma ，and to provide evidenced-based reference for clinical treatment. METHODS ：Retrieved from PubMed ， Embase，Cochrane Library ，ClinicalTrials.gov，CNKI，VIP and Wanfang database ，randomized controlled trials （RCTs）about benralizumab+routine treatment （trial group ）versus placebo+routine treatment （control group ）were collected during the inception to Dec. 2020. The relevant references were also retrieved manually. After data extraction ，the quality of included literatures was evaluated with bias risk evaluation tool 2.0 recommended by Cochrane systematic evaluator manual 6.1. Meta-analysis was conducted by using Rev Man 5.4 software. RESULTS ：Totally 5 studies involving 2 646 patients were included. Results of Meta-analysis showed that acute exacerbation rate of asthma [RR ＝0.67，95％ CI（0.61，0.74），P＜0.000 01]，asthma control questionnaire score [MD ＝－0.29，95％CI（－0.37，－0.21），P＜0.000 01] and the incidence of severe adverse event [RR ＝0.67，95％CI （0.53，0.84），P＝0.000 6] in trial group were significantly lower than control group. FEV 1[MD＝0.13，95％CI（0.09，0.17），P＜0.000 01] and asthma quality of life questionnaire score [MD ＝0.23，95％CI（0.13，0.33），P＜0.000 01] in trial group were significantly higher than control group. There was no statistical significance in the incidence of adverse event between 2 groups [RR ＝0.97，95％CI （0.92，1.02），P＝0.28]. CONCLUSIONS ：Benralizumab is effective and safe in the treatment of severe eosinophilic asthma. Due to the relatively limited data ，this conclusion needs to be confirmed by more studies.

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma / 生物医学与环境科学（英文）

OBJECTIVE@#To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis.@*METHODS@#Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis.@*RESULTS@#The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%.@*CONCLUSION@#Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

Efficacy and safety of benralizumab in patients with eosinophilic asthma: a meta-analysis of randomized placebo-controlled trials / 医学前沿

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1 s (FEV1), Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 (ACQ-6) scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg (every eight weeks) dosage can improve the health-related quality of life and appear to be more effective than 30 mg (every four weeks) dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg (every eight weeks).

Kv1.3 channel current changes in neutrophilic asthma and eosinophilic asthma / 国际儿科学杂志

Objective Allergic asthma is a chronic inflammatory disease of the airways.T lymphocytes play important roles in the pathogenesis of asthma.The voltage-gated Kvl.3 potassium channel may be a key factor in the activation of T lymphocytes.This research aims to detect the function of Kvl.3 channel in the neutrophlial asthma(NA) model and eosinophilic asthma(EA) model.Methods A total of 24 mice were randomly assigned into three groups:control,neutrophilic asthma model and eosinophilic asthma group.Neutrophilic asthma model was established with ovalbumin (OVA)and lipopolysaccharide(LPS);eosinophilic asthma was established with OVA and Al(OH)3;airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument;lung inflammation changes were observed by pathological HE staining;IL-17A and IL-4 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA;Kvl.3 channel protein level in lung was evaluated by western blot;the change of current density in CD4 +.T lymphocytes were tested by whole-cell patch clamp technique.Results Levels of IL-17A and IL-4 in bronchoalveolar lavage fluid increased in both NA and EA model (P ＜ 0.05).Compare with EA model,the IL-17A level was significantly higer in NA model,while the IL-4 level was significantly lower.In NA and EA model,kv1.3 protein expression in lung tissue was significantly higher than that in the control group(P ＜ 0.05),and kv1.3 protein expression in NA model was significantly higer than that in the EA model (P ＜ 0.05).Current intensity and current density of kv1.3 channel increased in both NA and EA model.While the current intensity and current density of kv1.3 channel were significantly higher in NA model than that in EA model.Conclusion Kv1.3 protein level,Kv1.3 channel current intensity and kv1.3 channel current density increased in both NA and EA model,especially in NA group,providing a new way for treatment of bronchial asthma.

Avanços recentes no emprego de imunobiológicos nas doenças alérgicas / Recent advances in the use of biologicals in allergic diseases

O uso de imunobiológicos, já consagrados como importantes avanços terapêuticos na Reumatologia, para o tratamento de pacientes com doenças autoimunes do tecido conjuntivo, e na Gastroenterologia, no manejo de pacientes com doenças intestinais inflamatórias, inicia uma trajetória também muito promissora no controle mais eficaz de várias condições em Alergia-Imunologia, incluindo asma grave eosinofílica, urticária crônica espontânea, dermatite atópica, e esofagite eosinofílica. É possível que futuramente, tal como na Oncologia, possam ser empregadas várias combinações de drogas visando um melhor controle da alergia, baseado sempre que possível na caracterização dos diversos endótipos e fenótipos estabelecidos. No presente artigo, é feita uma revisão objetiva e atualizada de vários agentes imunobiológicos em Alergia: omalizumabe (anti-IgE), anti-IL-5 (mepolizumabe, reslizumabe e benralizumabe), dupilumabe (anti-subunidade alfa do receptor de IL-4), quilizumabe (anti-receptor M1 prime de membrana da IgE nas células-alvo), anti-TSLP (AMG 157), e lebrikizumabe (anti-IL-13). Futuramente, novos agentes imunoterapêuticos poderão surgir, com potencial de melhorar as atuais estratégias para tratamento das doenças alérgicas mais complexas e graves, de difícil controle...

The use of biologicals, currently recognized as an important therapeutic advance in the fields of rheumatology – in the treatment of patients with autoimmune connective tissue disorders – and gastroenterology – in the management of patients with inflammatory bowel disease – has also shown promising results in terms of a more effective control of different conditions in the field of allergy and immunology, including severe eosinophilic asthma, chronic spontaneous urticaria, atopic dermatitis and eosinophilic esophagitis. Similarly to what has been seen in oncology, it is possible that, in the future, several drug combinations can be used with the aim of better controlling atopic conditions, whenever possible based on the characterization of established endotypes and phenotypes. This article presents an objective, up-to-date review of the use of different biologicals in allergy, namely, omalizumab (anti-IgE), anti-IL-5 (mepolizumab, reslizumab,and benralizumab), dupilumab (anti-alpha subunit of the IL-4 receptor), quilizumab (anti-M1 prime membrane receptor of IgE in target cells), anti-TSLP (AMG 157), and lebrikizumab (anti-IL-13). In the future, other biological agents may be developed, with the potential to improve the treatment strategies currently available for more severe, complex, difficult-to-control allergic diseases...