Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: The COSMEX Study

PurposeThe goal of this study was to assess the long-term safety and efficacy of mepolizumab in patients with the most severe eosinophilic asthma.MethodsThis multicenter, open-label, long-term, Phase IIIb study (COSMEX [COSMOS Extension]; 201312/NCT02135692) enrolled patients from the 52-week, open-label extension study COSMOS (A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects) that previously enrolled patients from the double-blinded, placebo-controlled Phase III studies MENSA (Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma) and SIRIUS (Steroid Reduction with Mepolizumab Study). To enter COSMEX, patients had to have life-threatening/seriously debilitating asthma before entering MENSA or SIRIUS and to have completed these previous studies with demonstrated improvement while receiving mepolizumab. In COSMEX, patients received mepolizumab 100 mg subcutaneously every 4 weeks as add-on therapy for up to 172 weeks. Primary endpoints were adverse event frequency and exacerbation rate per year; also assessed were forced expiratory volume in 1 s, Asthma Control Questionnaire-5 score, and daily oral corticosteroid (OCS) use.FindingsOf the 340 patients enrolled, 339 received mepolizumab; median treatment duration within this extension study was 2.2 years, equating to 718 patient-years of additional exposure. No new safety signals were identified. Patients receiving mepolizumab throughout this study and previous studies had lasting reductions in exacerbation rate and daily OCS use and improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire-5 score. In COSMEX, the on-treatment exacerbation rate (95% CI) was 0.93 (0.81–1.06) event/year for clinically significant exacerbations, 0.13 (0.10–0.18) event/year for exacerbations requiring hospitalization/emergency department visit, and 0.07 (0.05–0.10) event/year for exacerbations requiring hospitalization. In patients requiring systemic/oral corticosteroids with ≥128 weeks of continuous enrollment across SIRIUS, COSMOS, and COSMEX, mepolizumab maintained the median daily OCS dose at 1.3–2.8 mg during COSMEX, with additional patients no longer requiring OCS after extended mepolizumab treatment.ImplicationsThis study indicates that long-term mepolizumab treatment is well tolerated and associated with sustained clinical benefits in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT02135692.     

危重型哮喘并发呼吸衰竭的治疗体会

目的 :探讨危重型哮喘并发呼吸衰竭的发病机理和治疗措施。方法 :选择危重型哮喘并发呼吸衰竭的患者5 6例 ,分析其发病原因 ,发病机理。并采取氧疗、肾上腺皮质激素、抗生素、机械通气等综合治疗。结果 :5 2例血气分析PH、PaO2 、PaCO2 、HCO3 治疗后较治疗前明显好转 (P <0 .0     

重症支气管哮喘无创正压通气的疗效评价

目的：无创通气在重症支气管哮喘患者的疗效评价。方法：观察20例应用无创通气治疗重症哮喘患者治疗前，治疗后4h，24h及72h的血气指标及部分生理指标变化；治疗前后肺功能PEF，FEV1％的变化。与20例使用常规方法治疗的重症哮喘患者作了对比。结果：无创通气组的血气指标（pH，PaO2，PaCO2），肺功能指标（呼吸频率，PEF，FEV1％）以及心率的改善均优于治疗前及对照组（P〈0．05）。结论：应用无创正压通气治疗危重症哮喘效果好，并发症少，患者易于接受，值得临床推广。     

Predicting the development of early skin test sensitization in offspring of parents with asthma

BACKGROUND: The direct causal relationship between skin sensitization and asthma are controversial until now and remains to be further researched. Our aim is to analyse the role of parental asthma in the development of skin sensitization in offspring. MATERIALS AND METHODS: This study was performed among nuclear families (determined by index of asthma patients), and subjects included parents and offspring. Parents were subdivided into four phenotypes on the basis of skin sensitization (SPT+ or SPT-) and asthma status (AST+ or AST-) and offspring were subdivided into three age groups: 3-8, 9-14 and 15-20 years. The main tests included a standard questionnaire and skin prick tests. RESULTS: Offspring's skin sensitization differed among parental phenotypes at all ages (P < 0.05). In the SPT+/AST-, SPT-/AST+ and SPT+/AST+ groups, offspring were significantly more likely to be allergic than the ones in SPT-/AST- group at 3-8 years. Offspring with at least one parent with asthma were significantly more likely to have positive skin prick test response than those with non-asthmatic parents at age 3-8 years and 9-14 years, but not at 15-20 years among offspring with allergic parents. Results were independent of asthma in the children and of the characteristics of atopy in the parents. CONCLUSION: Parent asthma history is an independent risk factor for allergic sensitization in their offspring in a Chinese population.     

Advances in the treatment of peanut allergy: a case report

Background: Peanut allergies affect 1.5% of children. The majority of reactions to peanuts are mild, but peanut allergy is also the most common cause of fatal anaphylactic reactions to food. Case Report: The purpose of this case report was to describe a 1-year old boy who developed difficulty breathing after eating a peanut food product. The boy was taken immediately by his mother to an Emergency Department, exhibiting severe respiratory distress. After speaking to the child's mother, the emergency physician (EP) realized that the wheezing was due to a peanut food allergy. The child's respiratory symptoms responded within 10 min to bronchodilatator inhalation. The EP gave the mother educational information regarding the management of asthma and the proper use of metered dose inhalers with spacer devices. The EP referred the child to a clinical allergist who specializes in the management of food allergies. The diagnosis was made by skin prick testing as well as in vitro measurement of peanut-specific immunoglobulin E. Conclusion: The allergist explained that the mainstay of management of peanut allergy is avoidance of the allergenic food. Patient education involved teaching the mother to avoid high-risk situations such as dinner with family members who are not informed about the child's allergy to peanuts, encouraging the child to wear a Medic Alert Bracelet, and teaching the family and child to recognize early symptoms of allergic reactions and to manage an anaphylactic reaction, including the use of self-injectable epinephrine, as well as activating emergency services.     

Comparison of oral montelukast and inhaled fluticasone in the treatment of asthma associated with chronic rhinopolyposis: a single-blind, randomized, pilot study

Background: Rhinopolyposis is considered to be a non-immunoglobulin E-mediated inflammatory condition of the nose and sinuses, often associated with chronic rhinitis and asthma. Inhaled corticosteroids are currently the most commonly used anti-inflammatory agents for the chronic treatment of asthma and rhinopolyposis. Recently, montelukast, a selective cysteinyl leukotriene receptor antagonist indicated for the prophylaxis and treatment of asthma, has been shown to be effective in controlling rhinopolyposis and related symptoms.Objective: The aim of this study was to compare the short-term clinical efficacy of montelukast with that of fluticasone propionate in patients with asthma associated with rhinopolyposis.Methods: In this prospective, single-blind, randomized, pilot study, 12 out-patients with asthma associated with rhinopolyposis were given oral montelukast (10 mg once daily) or inhaled fluticasone propionate (intranasal suspension 50 μg and spray 250 μg twice daily). At baseline and after 30 days of treatment, the patients completed an asthma and rhinitis questionnaire and underwent nasal endoscopy, pulmonary function tests, and bronchial provocation testing.Results: Of the 12 study patients (9 men, 3 women), 7 were randomized to the montelukast group and 5 to the fluticasone group. There were no significant differences in baseline characteristics between the 2 treatment groups. After treatment, improvements in nasal and respiratory symptoms and nasal endoscopy results were found in 6 patients, 3 in each treatment group. No significant differences in the peak expiratory flow rate, forced expiratory volume in 1 second, or bronchial hyperresponsiveness changes after treatment were observed between the 2 groups.Conclusions: Our preliminary data show a comparable effect on respiratory and nasal symptoms and pulmonary function test results between oral montelukast and inhaled fluticasone in this small patient population, suggesting that leukotriene-receptor antagonists might be considered an alternative to inhaled corticosteroids in the treatment of asthma associated with rhinopolyposis.     

Cough after inhalation of corticosteroids delivered from spacer devices in children with asthma

Children using a spacer device rather than another device for delivering inhaled corticosteroids (ICS) has been identified as a risk factor for cough immediately after inhalation. The aim of this study was to point out the different factors influencing the occurrence of such lateral side-effects. We studied this local side-effect in 402 asthmatic children (55.6 +/- 34.9 months; 65.6% boys) treated for at least 1 month with beclomethasone dipropionate (n = 331), budesonide (n = 47) or fluticasone propionate (n = 24) delivered from pressurized metered-dose inhalers and small (75.1%) or large volume (24.8%) spacer devices mainly used with face mask (90.7%). A total of 219 patients (54.5%), treated with either high doses of ICS or ICS and long-acting beta2-agonist, were considered as having severe asthma. Cough was reported after each inhalation of corticosteroids in 216 patients (53.7%). Among them, about 30% also complained of cough with beta2-agonists. Despite different propellants and dispersants, all corticosteroids induced cough similarly. Cough was not linked with asthma severity, but was significantly related to therapy duration and use of long-acting beta2-agonist. Type and volume of the spacer device, use of a face mask or mouthpiece were not influencing factors. Cough after inhalation of corticosteroids delivered from spacer devices is a frequent local side-effect in children with asthma. This side effect can greatly alter compliance. A practitioner must be sought at each visit.     

Real-world Clinical Characteristics,Treatment Patterns,and Exacerbations in US Patients With Asthma Newly Treated With Omalizumab

Purpose

The objective of this study was to examine patient characteristics, treatment patterns, and exacerbations among patients with asthma newly treated with omalizumab.

成都地区变应性鼻炎患者皮肤点刺结果分析

目的：调查成都地区变应性鼻炎患者主要变应原的分布特点。方法：采用标准化变应原对286例经四川大学华西医院耳鼻咽喉头颈外科医师检查怀疑患有变应性鼻炎的门诊患者进行皮肤点刺试验。结果：皮肤点刺试验阳性率80．8％,前5位的变应原分别为屋尘螨（66．4％）、粉尘螨（65．0％）、杂草（36．4％）、霉菌Ⅱ（25．2％）、霉菌Ⅰ（21．3％）。不同性别之间变应原分布无差异,儿童对粉尘螨和屋尘螨的敏感程度明显高于成人。绝大多数变应性鼻炎患者对多个变应原皮试反应阳性。结论：成都地区变应原的分布特点与气候的特殊性一致,尘螨是最重要的变应原,应重视对尘螨的特异性免疫治疗的开展。     

哮喘儿童变应原皮试临床分析

目的 :探讨儿童哮喘的常见变应原和哮喘儿童进行变应原皮肤试验的病例选择指征。方法 :随机选择 2 0 0例支气管哮喘儿童 ,按年龄、性别、既往过敏病史、家庭过敏病史分组进行变应原皮肤试验 ,并对结果进行总结分析。结果 :(1)屋尘、粉尘螨、多价昆虫皮肤试验阳性率 (5 6 %、49%     

不同气管内吸痰方式对应用机械通气重症哮喘患者呼吸功能的影响

目的研究不同的吸痰方式对应用机械通气危重症哮喘患者呼吸功能的影响。方法2007年1月至2008年4月收治的43例应用机械通气治疗的重症哮喘患者,应用前后自身对照的方法分别进行密闭式气管内吸痰（close endotracheal suction,CS）和开放式气管内吸痰（open endotracheal suction,OS）。观察患者在不同吸痰方式下,吸痰前后的pH、动脉氧分压（PaO2）、动脉二氧化碳分压（PaCO2）、血氧饱和度的（SaO2）、潮气量（Vt）、呼吸道峰压（Ppeak）、呼吸道平台压（Pplat）及呼吸频率（BF）的变化。结果应用OS后患者的PaO2、SaO2、Vt均较吸痰前显著降低（P〈0．05）,而PaCO2、Ppeak、Pplat及BF均较吸痰前明显升高（P〈0．05）;而应用CS后,患者的pH、PaO2、SaO2、Vt、PaCO2、Ppeak、Pplat及BF较吸痰前无明显变化（P〉0．05）。结论应用机械通气的重症哮喘患者使用CS能较好的维持机体氧合状态,保持呼吸参数及呼吸道压力的相对稳定,是重症哮喘患者机械通气治疗时的较为安全有效的气管内吸痰方式。     

重型颅脑损伤135例的急救及预后分析

目的　探讨重型颅脑损伤的急救与预后。方法　分析从 1993～ 2 0 0 0年的 135例重型颅脑损伤的入院急救和疗效。结果　 135例患者中 ,手术治疗 10 3例 ,非手术治疗 32例 ,恢复良好 6 0例 (4 4% ) ,中度残废 6例 (4 % ) ,重度残废 4例(3% ) ,植物生存 18例 (13% ) ,死亡 47例 (35 % )。结论　重型颅脑外伤患者的急救关键是及时降低颅内压 ,改善脑组织的微循环 ,手术后的其他综合治疗 ,有助于改善预后 ,减少残障及死亡率。     

抗返流治疗对胃-食管返流相关性哮喘患者的临床观察

目的：观察抗返流治疗对胃-食管返流（GER）相关性哮喘的影响。方法：32例GER相关性哮喘患者．在常规哮喘治疗基础上均给予抗返流治疗8周。结果：临床控制18例（56％），好转14例（44％）；28例需要长期服用支气管扩张剂的患者，18例完全停用（64％），10例用量减少一半以上（36％）；17例需要长期服用糖皮质激素的患者，11例停药（64％），6例减量（36％）。结论：抗返流治疗GER相关性哮喘，无论GER先于哮喘或哮喘先于GER．均能明显改善患者的症状。     

院前急救对重型颅脑损伤病人预后的影响

目的:评价院前急救对重型颅脑损伤病人预后的影响。方法:回顾性分析我科2001年7月～2006年10月诊治的190例重型颅脑损伤病人的临床资料,其中102例经过院前急救入院(院前急救组),88例未经任何处理由家属直接送入医院(对照组)。对比两组病人伤后至入院的时间和伤后6个月的GOS评分、预后。结果:院前急救组病人伤后至入院时间平均时间为(20.2±10.3)min,预后为良好28例(27.5%),中残34例(33.3%),重残22例(21.6%),植物状态4例(3.9%),死亡14例(13.7%);而对照组伤后至入院时间平均时间为(60.4±14.5)min,预后为良好12例(13.6%),中残19例(21.6%),重残28例(31.8%),植物状态7例(8.0%),死亡22例(25.0%),两组治疗效果比较有显著性差异(P<0.05)。结论:院前急救为重型颅脑病人患者抢救赢得了时间,对于提高生存率与生存质量,改善预后具有重大意义。     

生长抑素与奥美拉唑联合治疗重症急性胰腺炎30例临床分析

目的：探讨生长抑素与奥美拉唑联合治疗重症急性胰腺炎（SAP）的临床疗效。方法：回顾性分析2007~F4月到2012年10月收治的SAP患者30例的临床资料。结果：本组30例中,痊愈15例,有效10例,总有效率为83．3％（25／30）,自动出院3例,死亡2例。结论：生长抑素联合奥美拉唑治疗SAP的临床效果较好,病因治疗是影响其疗效的重要因素之一。     

屋尘螨脱敏治疗对哮喘患儿血清粉尘螨特异性IgG4的影响

[目的]探讨屋尘螨特异性免疫治疗对哮喘患儿血清屋尘螨和粉尘螨特异性IgG4（sIgG4）水平的影响.[方法]40例接受屋尘螨特异性免疫治疗12月的哮喘患儿,抽取其治疗前后血清,检测治疗前后血清屋尘螨及粉尘螨的特异性IgG（sIgE）和sIgG4.[结果]脱敏治疗后的患者血清中屋尘螨和粉尘螨特异性sIgE无明显变化,sIgG4抗体水平均有显著上升（P〈0.01）.[结论]使用屋尘螨脱敏疫苗治疗所产生的sIgG4抗体能同时识别屋尘螨和粉尘螨两种抗原,从而使机体产生对这两种致敏原的免疫保护作用.     

慢性重症肝炎膜式血浆置换治疗后肝脏生化功能的变化

目的观察慢性重症肝炎膜式血浆置换(PE)治疗后肝脏生化指标的变化,为评价PE治疗慢性重症肝炎疗效提供客观依据.方法将71例慢性重症肝炎随机分为对照组和治疗组,对照组(36例)为内科综合治疗的慢性重症肝炎患者,治疗组(35例)为内科综合治疗联合PE治疗的病情相同患者.检测PE治疗前后患者肝脏生化指标(ALT、AST、F-Bil、D-Bil、CHE、CHOL、ALB、PTA、ALP、NH3)的变化.结果 PE治疗后各项肝脏生化指标明显好转,ALT、AST、T-Bil、D-Bil、CHE、、ALB、PTA、ALP、NH3治疗前后相差非常显著(P<0.001),CHOL相差显著(P<0.05),治疗组治愈好转26例(74%),对照组治愈好转18例(50%).两组治愈好转率经卡方检验,相差显著(P<0.05).结论内科综合治疗联合血浆置换疗法,能显著改善慢性重症肝炎肝功能衰竭患者的临床症状及肝脏生化指标,提高治愈率.     

Feasibility of Exercise Testing in Patients Who Are Critically Ill: A Prospective,Observational Multicenter Study

Objective

To evaluate the feasibility and safety of exercise testing and to describe the physiological response to exercise of patients in the Intensive Care Unit (ICU).

消化道症状对重症肝病患者营养摄入的影响

目的了解恶心、腹胀、纳差等消化道症状对重症肝病患者营养摄入的影响。方法调查了解患者饮食及消化道症状情况,计算出每位患者的目标能量值和实际摄入量,将不同症状种类和不同症状个数患者的能量、蛋白质、脂肪、碳水化合物值进行比较。结果消化道症状可导致重症肝病患者能量摄入不足,不同消化道症状对重症肝病患者营养摄入影响不同,纳差对营养摄入影响最大。消化道症状越多,重症肝病患者营养摄入越差。结论减轻重症肝病患者消化道不适症状是改善其摄入不足的重要途径,护士应采取有针对性的护理措施改善其营养状况。