Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

The expression and correlation of MMP-9 and NF-κB in obstructive sleep apnea syndrome patients with hypertension / 重庆医学

Objective To investigate the role of plasma matrix metalloproteinase-9 (MMP-9) and nuclear factor kappa B (NF-κB) in the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) complicated with hypertension.Methods The patients were selected in the respiratory medicine and neurology of our hospital from January 2014 to June 2014.Polysomnography(PSG) monitoring was employed to assess the patient.All patients were divided into 3 groups,including snoring group(23 cases),OSAHS group(32 cases),OSAHS with hypertension group(31 cases).And then according to the hypertension stage,OSAHS with hypertension group was divided into 3 groups,including OSAHS with stage 1 hypertension group(9 cases),OSAHS with stage 2 hypertension group(9 cases),OSAHS with stage 3 hypertension group(13 cases).The plasma MMP-9 was measured by ELISA.The mRNA expression levels of MMP-9 and NF-κB were detected by real-time quantitative PCR.Results The levels of MMP-9 and MMP-9 mRNA and NF-κB mRNA in OSAHS with hypertension group were significantly higher than those of snoring group and OSAHS group and the differences were statistically significant(P<0.05).The expression of MMP-9,the MMP-9 and NF-κB mRNA expression of monocytes in OSAHS with stage 3 hypertension group was significantly higher than those of OSAHS with stage 1 hypertension group and OSAHS with stage 2 hypertension group and the differences were statistically significant(P<0.05).The plasma MMP-9 was positively correlated with AHI and oxygen desaturation index and negatively correlated with LSaO2(P<0.05).The plasma MMP-9 was positively correlated with the MMP-9 mRNA expression(P<0.05).The MMP-9 mRNA expression was positively correlated with the NF-κB mRNA expression(P<0.05).Conclusion The plasma concentrations of MMP-9,the MMP-9 and NF-κB mRNA expression of monocytes in OSAHS with hypertension patients was significantly high,which is associated with disease severity and degree of hypoxia.The MMP-9 might play an important role in the pathogenesis of OSAHS with hypertension and be regulated by NF-κB pathway.

Study of the association between a disintegrin and metalloprotease 19 gene polymorphisms and chronic obstructive pulmonary disease susceptibility / 中华老年医学杂志

Objective To explore the association between genetic polymorphism of a disintegrin and metalloprotease 19 (ADAM19) and chronic obstructive pulmonary disease (COPD).Methods Totally 116 patients with COPD (the COPD group) and 82 healthy volunteers (the control group) were enrolled in this study.Fasting peripheral blood was taken and whole blood corpuscle genomic DNA was extracted.The genetic polymorphism of ADAM19 (rs1422795) was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).Results The difference in genotypes frequencies (GG,AG,AA) distribution of the ADAM19 between patients (73.3％,22.4％,and 4.3％) and controls (68.3％,28.0％,and 3.7％) showed no statistically significance (x2 =0.887,P=0.634).There were also no significant differences in the distribution of the different allele gene frequencies(A,G) between patients (84.5％,15.5％) and controls(82.3％,17.7％)(x2=0.582,P=0.446).No differences were found in the distribution of the genotypes between patients of different COPD severity classified according to FEV1 (％ pred),and healthy controls(x2=3.325,P=0.787).Conclusions ADAM19 (rs1422795) genetic polymorphism is not related to the development of COPD,which may not be the COPD-related gene.