Pressurized IntraPeritoneal Aerosol Chemotherapy with one minute of electrostatic precipitation (ePIPAC) is feasible,but the histological tumor response in peritoneal metastasis is insufficient

IntroductionElectrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC) has shown superior penetration depth and tissue uptake compared to standard PIPAC. We investigated the feasibility and objective tumor response to ePIPAC with 1 min of precipitation in patients with peritoneal metastasis (PM).Materials and methodsPatients with PM from various abdominal cancers were included in an amendment to the ongoing prospective PIPAC-OPC2 trial. Colorectal and appendiceal PM were treated with oxaliplatin, patients with PM from other primaries were treated with a combination of cisplatin and doxorubicin. Three ePIPAC procedures were planned in each patient including repeated peritoneal biopsies for response evaluation. After emission to the peritoneal cavity, the aerosolized chemotherapeutics were precipitated for 1 min followed by immediate exsufflation and abdominal closure. Histological regression from the first to the third ePIPAC was evaluated according to the Peritoneal Regression Grading Score (PRGS) and compared to data from the PIPAC-OPC1 trial. Complications and toxicities were recorded according to Dindo-Clavien and CTCAE.ResultsSixty-five ePIPAC procedures were performed in 33 patients (median 2, range 1–6). Ten patients were eligible for response evaluation based on biopsies from the first and third ePIPAC procedure. Four patients had disease progression, four patients had regressive disease, and two patients had stable disease according to PRGS. No life threatening adverse reactions and no mortality was observed following ePIPAC.ConclusionOne minute ePIPAC was feasible and safe, but the histological tumor response was insufficient compared to standard PIPAC directed therapy with 30 min passive diffusion time.     

宽胸气雾剂改善冠心病合并活动后胸闷胸痛患者运动耐量临床研究

目的探索宽胸气雾剂对冠心病合并活动后胸闷胸痛患者的临床疗效。方法14例冠心病患者予宽胸气雾剂3次/天,每次1揿,共使用10天。测量治疗前后最大公斤摄氧量(VO2 max)、运动过程最大心输出量(COmax)、运动心肺数据及动态血流动力学,并观察胸闷胸痛症状是否缓解。结果最终12例患者纳入分析,其中9例(75.0%)自觉症状改善。与治疗前比较,治疗后COmax、呼吸熵、心率、无氧阈代谢当量、最大值左心做功指数及运动中心输出量均值升高(P<0.05,P<0.01)。结论宽胸气雾剂可有效提高心输出量,促进血氧结合,改善心脏冠脉缺血情况,增强患者的心脏功能及运动储备能力。     

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

1,5-Iodonaphthyl azide-inactivated V3526 protects against aerosol challenge with virulent venezuelan equine encephalitis virus

Venezuelan equine encephalitis virus (VEEV) is a New World alphavirus. VEEV is highly infectious in aerosolized form and has been identified as a bio-terrorism agent. There is no licensed vaccine for prophylaxis against VEEV. The current IND vaccine is poorly immunogenic and does not protect against an aerosol challenge with virulent VEEV. We have previously shown that VEEV inactivated by 1,5-iodonaphthyl azide (INA) protects against footpad challenge with virulent VEEV. In this study, we inactivated an attenuated strain of VEEV, V3526, with INA and evaluated its protective efficacy against aerosol challenge with wild type VEEV. We demonstrated that among three routes of immunization, intramuscular immunization with INA-inactivate V3526 (INA-iV3526) provided complete protection against aerosol challenge with virulent VEEV. Our data suggests that INA-iV3526 can be explored further for development as an effective vaccine candidate against aerosol challenge of virulent VEEV.     

雾化吸入布地奈德混悬液治疗COPD急性加重期的效果观察

目的：探索雾化吸入布地奈德混悬液治疗慢性阻塞性肺疾病(COPD)急性加重期的临床效果。方法选取本院2012年1月~2013年11月收治入院的COPD急性加重期患者200例,将其随机分为两组,所有患者均给予化痰止咳抗炎等常规综合性治疗,观察组(100例)在常规综合性治疗基础上给予雾化吸入布地奈德混悬液,观察两组的临床疗效及不良反应。结果观察组的总有效率(100.0%)高于对照组(76.0%)(P<0.05);治疗后,两组的肺功能指标均有改善,但观察组的改善情况明显优于对照组,差异有统计学意义(P<0.05);观察组治疗后的血清IL-8、CRP水平与治疗前及对照组比较差异有统计学意义(P<0.05);用药期间,观察组有4例出现口干,加强漱口,并继续用药,症状消失。两组均未因不良反应而提前终止实验。结论雾化吸入布地奈德混悬液能够改善COPD急性加重期患者的肺功能,减轻其气道炎症反应,临床效果更优,可为临床治疗提供参考。     

辛芩雾化剂联合布地奈德雾化吸入治疗支气管哮喘30例

目的:观察辛芩雾化剂联合布地奈德雾化吸入治疗支气管哮喘的疗效。方法:选择支气管哮喘患者60例,采用随机数字表法随机分为对照组和研究组各30例。两组均给予呼吸科常规治疗,对照组另加用布地奈德治疗,研究组给予辛芩雾化剂联合布地奈德雾化吸入治疗。结果:治疗2周后,研究组FVC、FEV1和MMEF明显高于对照组(P<0.05);研究组有效率显著高于对照组(P<0.05)。结论:辛芩雾化剂联合布地奈德雾化吸入治疗支气管哮喘疗效显著,能有效改善支气管哮喘患者的肺功能。     

影响COPD患者正确吸入定量气雾剂因素的Logistic回归分析

目的探讨影响慢性阻塞性肺疾病(COPD)患者正确吸入定量气雾剂因素。方法回顾性分析2011年3月到2014年3月240例门诊及住院COPD患者,以定量气雾剂的临床应用目的和使用指征的认知度调查为评价要点,将患者性别、年龄、病程、文化程度、接受健康教育的情况以及病情与正确吸入定量气雾剂之间的关系做Logistic多元线性回归分析。结果 1多数患者对气雾剂的认知程度较低,在1~2分间;患者使用定量气雾剂过程中出现的错误频率最高的操作即为"屏气不足10 s"和"喷吸不同步",分别占总错误操作的36.99%和29.91%。2单因素分析显示,除性别以外,年龄、文化程度、病理程度、病程、接受健康教育均与定量气雾剂的正确吸入情况有一定的相关性(P0.05),以年龄(P=0.032)和文化程度(P=0.029)这两个因素对气雾剂正确吸入的影响程度最大;多因素分析显示,年龄、文化程度、病理程度这三个因素是影响气雾剂正确吸入的重要因素(P0.05)。结论年龄、文化程度、病理程度是影响COPD患者正确吸入定量气雾剂的重要因素,需要引起临床医生的足够重视,对患者进行针对性的健康干预。     

布地奈德沙丁胺醇联合异丙托溴铵雾化吸入治疗支气管哮喘急性发作临床效果观察

目的：探讨布地奈德、沙丁胺醇联合异丙托溴铵雾化吸入对支气管哮喘急性发作患者临床症状、体征及肺功能的影响。方法：选择符合标准的患者83例,采用入院先后顺序分为观察组42例和对照组41例,两组患者均给予基础治疗,对照组加用沙丁胺醇气雾剂,观察组加用布地奈德气雾剂、沙丁胺醇气雾剂及异丙托溴铵气雾剂,比较两组患者临床症状及体征、肺功能变化情况。结果：观察组患者气急、胸闷、咳嗽及哮鸣音缓解时间明显短于对照组,差异有统计学意义（ P＜0．05）。两组患者治疗前肺功能相似,差异无统计学意义（ P＞0．05）;治疗后患者肺功能较治疗前均明显改善,差异有统计学意义（ P＜0．05）;观察组较对照组改善幅度更大,差异有统计学意义（ P＜0．05）。治疗5d后观察组患者临床控制21例、显效12例、好转8例及无效1例;对照组患者临床控制14例、显效13例、好转9及无效5例,差异有统计学意义（ P＜0．05）。结论：布地奈德、沙丁胺醇联合异丙托溴铵雾化吸入能快速改善支气管哮喘急性发作患者的肺功能,缓解临床症状及体征,临床疗效确切。     

氧气驱动雾化吸入在支气管哮喘急性发作患者中的综合应用价值探讨

目的:分析氧气驱动雾化吸入在支气管哮喘急性发作中的综合应用价值.方法:将180例来本院接受雾化吸入治疗的支气管哮喘急性发作患者随机分为两组,随机分为两组,对照组和观察组各90例.雾化吸入的药物均为沙丁胺醇和布地奈德,其中对照组采用超声雾化吸入法,观察组则采用氧气驱动雾化吸入法.比较两组间疗效及临床症状缓解时间差异,比较治疗前后两组间肺功能及血清炎症因子水平差异.结果:观察组临床控制率和治疗总有效率明显高于对照组,观察组发热、咳嗽、气喘、哮鸣音及肺部啰音等临床症状缓解时间明显短于对照组,差异均具有统计学意义(P＜0.05);治疗后第3、7天,观察组最大呼气峰流速(PEF)、第1S用力呼气容量(FEV1)大于对照组,而肺泡-动脉氧分压差(PA-aDO2)和呼吸指数(RI)则明显高于对照组,差异具有统计学意义(P＜0.05);观察组血清炎症因子白介素-4(IL-4)、白介素-6(IL-6)、白介素-17(IL-17)、肿瘤坏死因子(TNF-a)水平均低于对照组,差均异具有统计学意义(P＜0.05).结论:氧气驱动雾化吸入能更有效的改善支气管哮喘急性发作者的炎症状态和肺功能,相比于超声雾化吸入能促进哮喘急性发作症状更快更好的缓解.