奥马珠单抗治疗哮喘的临床应用进展

奥马珠单抗是第一个抗IgE人源化单克隆抗体,已作为重度哮喘患者的附加治疗药物写入GINA和我国的哮喘指南中.奥马珠单抗可减轻哮喘患者气道炎症和气道重塑,经大剂量吸入性糖皮质激素和长效β受体激动剂后仍未控制的成人和6岁以上儿童,附加该药治疗可以获得较好的临床疗效和安全性.奥马珠单抗已完成在我国的注册临床研究,其疗效和安全性与国外研究相仿.该药即将在我国上市,它将给重度哮喘患者提供新的治疗方式.     

奥马珠单抗治疗中重度哮喘的初步临床观察

目的:探讨奥马珠单抗在中国真实世界临床实践中治疗中重度哮喘的疗效、安全性及管理特点。方法:回顾性分析2018年3月至2020年4月在广州医科大学附属第一医院接受奥马珠单抗治疗至少4个月的中重度哮喘患者79例,男30例,女49例,年龄14~76岁,中位年龄50岁。比较患者治疗前后的临床表现、血嗜酸性粒细胞计数、呼出气一氧...     

奥马珠单抗对过敏性哮喘患者血清细胞因子谱的影响

目的 ：探讨奥马珠单抗对过敏性哮喘患者血清细胞因子谱的影响。方法 ：纳入2019年1月至2021年1月在上海交通大学医学院附属瑞金医院呼吸与危重症医学科就诊并接受奥马珠单抗治疗的过敏性哮喘患者20例。收集奥马珠单抗治疗前及治疗4个月后患者肺功能数据,评估肺功能改善状况;采用电化学发光免疫分析法测定奥马珠单抗治疗前后患者血清中29个细胞因子水平,并比较其治疗前后的变化;采用哮喘控制测试（asthma control test,ACT）问卷评估哮喘控制改善状况;采用全球治疗有效性评估（global evaluation of treatment effectiveness,GETE）评分评估治疗有效性。结果：20例患者接受奥马珠单抗治疗4个月后,肺功能中平均用力呼出50%肺活量呼气流速（maximal expiratory flow at 50%of forced vital capacity,MEF50%）显著改善（P<0.05）;血清中辅助性T17细胞（helper T17 cell, Th17细胞）相关因子白细胞介素（interleukin,IL）-17A及IL-23水平显著上...     

呼吸道过敏原特异性IgE累积水平与重度哮喘奥马珠单抗治疗反应性的关系

目的 分析呼吸道过敏原特异性免疫球蛋白E(sIgE)累积水平与重度哮喘奥马珠单抗治疗反应性的关系。方法 选择2020年10月至2022年6月我院收治的经奥马珠单抗治疗重度哮喘患者106例,根据国际疾病分类,过敏性哮喘57例,非过敏性哮喘40例和混合型哮喘9例。采用标准经验过敏诊断(过敏记忆、皮肤点刺试验、传统途径的总IgE和过敏原sIgE测定)、血液嗜酸性粒细胞计数、Phadiatop^TM测试对呼吸道过敏原sIgE累积水平。34例过敏性哮喘患者经奥马珠单抗治疗12个月,评估临床疗效。结果 在过敏性和混合性严重哮喘患者中,通过Phadiatop^TM测试确定的呼吸道过敏原sIgE累积水平高于非过敏性哮喘患者(P<0.001)。区分过敏性哮喘和非过敏性哮喘的受试者工作特征曲线下面积为0.891±0.038,最佳临界值0.24 kAU/L。Phadiatop^TM测试≥0.24 kAU/L为阳性,过敏记忆+Phadiatop^TM测试阳性诊断过敏性哮喘的患病率为84.21%(48/57),高于过敏记忆+s...     

奥马珠单抗优化冲击脱敏治疗方案的疗效及安全性研究

目的 评价单次奥马珠单抗注射后行冲击脱敏治疗轻中度过敏性哮喘的疗效及安全性。方法 67例轻中度过敏性哮喘患者,27例单次奥马珠单抗注射后行冲击脱敏治疗(联合组),40例仅行冲击脱敏治疗(对照组),之后行每4周1次的维持脱敏。记录冲击脱敏阶段不良反应的发生情况,维持脱敏至第16周时患者的症状、药物评分及肺功能指标等。结果 联合组冲击脱敏峰值浓度完成率100%,冲击阶段全身不良反应发生率2.38%(9/378);对照组冲击脱敏峰值浓度完成率80%,冲击阶段全身反应发生率5.18%(29/560)。联合组冲击脱敏峰值浓度完成率高于对照组,冲击阶段不良反应发生率低于对照组,差异均有统计学意义(P<0.05)。维持脱敏至第16周时,对比两组的症状ACT评分、药物用量评分、FEV₁%、FEV₁/FVC、FeNO,均无显著差异(P>0.05),但较治疗前均有明显改善(P<0.05)。结论 单次奥马珠单抗注射后行冲击脱敏,可显著降低冲击阶段的不良反应,提高冲击脱敏的完成率,同时保障了冲击脱敏后续的临床疗效。     

评估FeNO水平对奥马珠单抗在重度过敏性哮喘患者早期治疗疗效的预测能力

目的 评估呼出气一氧化氮(FeNO)水平对奥马珠单抗(Omalizumab)在重度过敏性哮喘患者早期治疗疗效的预测能力。方法 收集从2019年3月1日至2021年7月31日期间自厦门长庚医院呼吸与危重症医学科接受Omalizumab治疗的重度过敏性哮喘患者44例,行FeNO及肺功能检查,采用Omalizumab 300mg每4周皮下注射的方案,治疗12周后,观察控制情况并评估影响疗效的因素。结果 经过单因素卡方检验以及独立样本非参数检验分析,影响治疗早期(12周)疗效的因素为FeNO水平(P<0.001)、FEV₁%(P=0.008)、FEV₁/FVC(P=0.035)、PEF_25%-75%(P=0.032);而性别、年龄、是否多重过敏并不影响治疗的早期疗效。经过多因素二元Logistic回归分析,治疗前基线FeNO水平是影响Omalizumab在重度过敏性哮喘患者早期治疗有效的独立影响因子(OR:1.052; 95%CI:1.008～1.098)。结论 患者治疗前基线FeNO水平是作为影响Omalizumab在重...     

曲妥珠单抗联合帕妥珠单抗对HER2阳性乳腺癌的治疗研究进展

曲妥珠单抗联合帕妥珠单抗能够显著提高HER2阳性乳腺癌患者的无复发生存期(RFS)、总体生存期(OS)及病理完全缓解率(pCR),并且曲妥珠单抗联合帕妥珠单抗对HER2阳性乳腺癌具有良好的耐受性和有效性.本文总结曲妥珠单抗联合帕妥珠单抗对HER2阳性乳腺癌靶向治疗研究的相关文献并对此做一综述.     

奥玛珠单抗在支气管哮喘中的应用现状

大多数支气管哮喘(哮喘)患者根据国内外哮喘防治指南推荐的标准疗法可以达到临床控制,但仍有5%～10%的患者在此基础上口服或静脉使用糖皮质激素仍不能控制病情。奥玛珠单抗是哮喘的第一个靶向治疗药物,临床研究证实其能有效减少哮喘急性发作频率、减少糖皮质激素使用剂量、改善哮喘症状,该药于2018年3月进入中国市场,因价格较为昂...     

真实世界奥马珠单抗治疗中重度过敏性哮喘的疗效及安全性

目的探讨奥马珠单抗治疗中重度过敏性哮喘的临床疗效及安全性。方法分析复旦大学附属中山医院呼吸科门诊49例奥马珠单抗治疗的中重度过敏性哮喘患者临床特征,比较治疗前后哮喘控制评分(ACT)、哮喘生活质量评分(AQLQ)、第一秒用力呼气容积(FEV1)、FEV1占预计值(FEV1%pred)、呼出气一氧化氮(Fe NO)、急性发作次数及口服激素用量变化。结果纳入49例中重度过敏性哮喘患者,其中25例经奥马珠单抗治疗16周后,ACT从(18. 3±0. 9)升至(20. 8±0. 6)分(P0. 05),AQLQ从(184. 8±8. 1)升至(206. 8±5. 4)(P0. 05)。FEV1从(2. 2±0. 2) L升至(2. 3±0. 2) L; FEV1%pred从(70. 4±5. 3)%升至(77. 1±4. 6)%; Fe NO从(56. 0±12. 6) ppb降至(29. 0±4. 6) ppb (P0. 05)。10例重度激素依赖型哮喘患者急性发作次数从(1. 2±0. 1)次/3个月减至(0. 5±0. 1)次/3个月(P0. 01),口服泼尼松从(17. 0±2. 4) mg/d减至(4. 5±1. 6) mg/d(P0. 001)。治疗期间2例有轻度乏力、嗜睡; 1例有双下肢水肿; 1例出现明显头晕、恶心,后继发性高血压。结论奥马珠单抗能够控制哮喘及过敏症状,减少急性发作次数及口服激素用量,同时可改善肺功能,使哮喘患者获益。     

Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma.

The ability of omalizumab, an anti-immnoglobulin-E agent, to maintain long-term disease control in patients with moderate-to-severe allergic asthma was investigated in a 24-week double-blind extension to a 28-week core trial. During the extension, 483 of the initial 546 patients were maintained on randomised treatment and the lowest sustainable dose of beclomethasone dipropionate (BDP) as established during the steroid-reduction phase of the core trial. The use of concomitant asthma medication was permitted and investigators were allowed to adjust the BDP dose or switch patients from BDP to other asthma medications if deemed necessary. More omalizumab-treated patients (33.5%) than placebo-treated patients (13.5%) were able to complete the extension period without requiring inhaled corticosteroid treatment. The mean BDP equivalent dose throughout the extension was lower in the omalizumab group (25 microg x day(-1)) than in the placebo group (43 microg x day(-1)). Disease control was sustained in 76% of omalizumab patients compared with 59.4% of placebo patients free from an asthma exacerbation during the extension period. Compared with placebo, fewer patients in the omalizumab group used other concomitant asthma medication during the extension. Treatment with omalizumab was well tolerated and the incidence of adverse events was similar between groups. In conclusion, these results suggest that omalizumab is a promising new agent for the long-term control of allergic asthma.     

Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany

Omalizumab is a humanized monoclonal anti-immunoglobulin E (IgE) antibody indicated in Europe for the treatment of uncontrolled severe persistent allergic (IgE-mediated) asthma despite optimal therapy with inhaled corticosteroids and long-acting β₂ agonists.Between 2005 and 2007 280 patients (58% female, mean age 44 ± 16 yrs., 46% on oral corticosteroids, median serum IgE level 235 IU/ml) who met the EU criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab by 134 physicians as part of a post-marketing surveillance trial and were followed-up for 6 months.The median follow-up time was 195 days, the patients were treated with a median dose of 450 mg omalizumab every 4 weeks. After 6 months there was a marked effect of omalizumab treatment on daily (−76%) and nocturnal symptoms (−84%), exacerbations (−82%), unscheduled health care contacts (−81%), hospitalizations (−78%) and quality of life (Mini-AQLQ: score increase from 2.9 to 4.5). Overall, efficacy of omalizumab was rated as excellent or good by the majority of physicians (82%) and patients (86%). In 19 patients (7%) omalizumab-related adverse events were recorded.This post-marketing surveillance trial confirms the marked and clinically relevant effect of omalizumab on asthma symptoms and level of asthma control in the majority of patients with severe persistent allergic (IgE-mediated) asthma in a real-life situation.     

Omalizumab and asthma control in patients with moderate-to-severe allergic asthma: a 6-year pragmatic data review

Controlled clinical trials have shown the recombinant humanized monoclonal anti-IgE antibody omalizumab to improve asthma control and reduce symptom exacerbations in patients with moderate-to-severe allergic asthma who remain clinically unstable despite optimal medical therapy. An objective retrospective review compared clinical experience with the data reported in the controlled studies. Data tracking for 167 patients progressively enrolled between 2003 and 2010 treated with omalizumab included symptoms, forced expiratory volume at 1 second (FEV(1)), systemic steroid bursts, and need for short-acting bronchodilator rescue measured at the start of therapy; 3, 6, and 12 months after starting treatment, and yearly thereafter. Exacerbations were compared for the 12 months before and the 12 months after starting treatment in a subgroup of patients. Asthma control improved with omalizumab over time (up to 6 years) as indicated by fewer symptoms and less need for rescue medication (p < 0.001 for both). FEV(1) remained stable. The number of patients reporting asthma exacerbations requiring urgent care decreased by 49% during the first 12 months of treatment (p ≤ 0.01), and significant reductions in exacerbations were also evident when measured by hospitalizations or systemic corticosteroid bursts (p < 0.001 for both). This is the first long-term pragmatic review of omalizumab. Our clinical experience (up to 6 years in some patients) supports the results of earlier controlled studies, confirming the usefulness of adding omalizumab to the long-term management of patients with difficult-to-treat disease who suffer from persistent symptoms despite optimal therapy with medications.     

难治性哮喘治疗策略新进展

难治性哮喘是一种高度异质性呼吸道慢性炎症性疾病,在实际临床工作中,我们对它并不陌生,但对其发病机制、临床特征却知之甚少,并且处理起来相当棘手,其在支气管哮喘患者中发病率约为5％～10％,然而却占用了重大比例的医疗卫生资源,造成了患者更高的病死率.难治性哮喘需要高剂量吸人性糖皮质激素(inhaled corticosteroid,ICS),甚至需要全身应用糖皮质激素,它包括多个临床或病理生理学表型,在很大程度上,其异质性制约着疾病的特征,从而阻碍了合适治疗方案的选择.因此,这就特别要求我们要有对难治性哮喘表型的正确理解与认识.ICS联合长效β.受体激动剂目前是治疗哮喘的一线药物,但有相当一部分难治性哮喘患者,对此治疗并不敏感.随着对哮喘发病机制、炎性标志物、病理生理学及炎症表型的不断深入研究,免疫抑制剂、抗IgE抗体、支气管热成形术、几种新型炎性介质拮抗剂、干细胞治疗、支气管镜灌洗等成为难治性哮喘治疗的新热点.     

Phadiatop,Phadiatop Infant and total IgE evaluated in allergic Brazilian children and adolescents

The clinical history is of importance in the investigation of allergic diseases but does have limitations. Many allergic conditions will be over-diagnosed if anamnesis alone is used for diagnostic criteria. Serum total immunoglobulin E (TIgE) quantification, as well as panels containing allergens prevalent in the studied population, may serve as screening tests and facilitate the diagnosis of allergic disease or its exclusion. We assessed the positivity of two versions of these tests, Phadiatop Europe® (PhEU) and Phadiatop Infant® (PhInf), as well as total IgE (TigE) values in patients with a medical diagnosis of allergic disease and non-allergic individuals.MethodsA cross-sectional study performed in eleven Brazilian pediatric allergy centers with patients divided into groups according to the primary condition and a group of assessed control subjects. They were submitted to TIgE measurement and screening tests (PhEu and PhInf).ResultsTIgE mean serum levels were significantly higher among allergic patients, especially those with asthma/rhinitis or atopic dermatitis. The positivity of the screening tests, considering the total population, was 63.8% for PhEU and 72.6% for PhInf. These increased when we evaluated only the allergic subjects. The concordance index of the two tests was Kappa = 0.7 and higher among those of greater age.ConclusionsIn the assessed population, there were significantly higher levels among those with positive screening tests and PhInf showed better performance in the identification of sensitized individuals, regardless of age. This is the first study to evaluate Phadiatop and Phadiatop Infant in the same population.     

EOS、总IgE与儿童哮喘严重程度和肺功能的相关性

目的 分析血嗜酸性粒细胞(EOS)、总IgE与儿童哮喘严重程度和肺功能的相关性。方法 选择2018年1月至2021年1月我院收治并确诊的55例支气管哮喘患儿,根据病情严重程度分为轻度组18例、中度组22例、重度组15例。对比不同病情严重程度组儿童血清EOS、总IgE、FeNO及肺功能第1秒用力呼气容积占预测值百分比(FEV₁%pred)、呼气峰值流速(PEF)和用力肺活量(FVC)水平变化;观察给予吸入性糖皮质激素(ICS)治疗前后,哮喘组儿童上述指标变化情况;采用Spearman秩相关和Pearson相关性分析血清EOS、总IgE与儿童哮喘FeNO、病情严重程度及肺功能的相关性。结果 哮喘组儿童FeNO及血EOS%、总IgE水平升高,肺功能指标FEV₁%pred、PEF、FVC明显降低(P<0.05);重度哮喘组上述指标高于/低于中度组,中度组高于/低于轻度组(P<0.05)。ICS治疗后,哮喘组儿童FeNO及血EOS%、总IgE水平较治疗前降低,肺功能指标升高,治疗前后差异有统计学意义(P<0.05)。儿童哮喘血EOS%...     

难治性哮喘患者血浆中miR-21和miR-126的表达及意义

目的 探讨miR-21和miR-126在难治性哮喘及完全控制性哮喘患者血浆中的表达水平和意义.方法 采用实时荧光定量PCR法检测miR-21和miR-126在28例难治性哮喘及完全控制性哮喘患者血浆中的表达水平.结果 难治性哮喘患者血浆中miR-21和miR-126的表达水平均显著高于完全控制性哮喘患者,差异均有统计学意义(t=29.300、3.667,P值均＜0.01).结论 miR-21和miR-126在难治性哮喘患者血浆中的表达均高于完全控制性哮喘患者,miR-21和miR-126的表达水平可能与难治性哮喘有关,且调控可能参与了支气管哮喘发生过程.