孟鲁司特联合丙酸氟替卡松对变应性鼻炎患儿的临床疗效及免疫功能评价

目的 评价孟鲁司特联合丙酸氟替卡松对变应性鼻炎患儿的临床疗效及免疫调节作用。方法 收集2014年1月－2016年12月惠州市中心人民医院第一分院收治的变应性鼻炎患儿140例,使用数字法随机分为丙酸氟替卡松单药治疗对照组和孟鲁司特联合丙酸氟替卡松治疗观察组,每组70人。ELISA法检测免疫球蛋白IgE、白介素（IL）-17、IL-10因子表达。比较两组的临床疗效和临床不良反应。结果 治疗前两组症状体征评分无显著差异,治疗后均较治疗前有显著降低（P<0.01）,且观察组评分降低作用显著优于对照组（P<0.05）;对照组临床有效率为80.0%,显著低于观察组的94.3%（P<0.05）;治疗前两组IgE、IL-17和IL-10表达无显著差异,治疗后两组IgE和IL-17表达显著降低、IL-10表达显著升高（P<0.01）,且观察组对IgE和IL-17的减低作用以及对IL-10的升高作用优于对照组（P<0.05）。IgE表达与IL-17呈显著正相关（r=0.392,P<0.05）,与IL-10呈显著负相关（r=-0.364,P<0.05）。观察组不良反应发生率为14.3%,对照组的为11.4%,治疗期间两组临床不良反应发生率无显著差异。结论 孟鲁司特钠联合丙酸氟替卡松治疗小儿变应性鼻炎临床疗效显著,使用安全,调节IL-17/IL-10因子失衡可能是其起效的作用机制。     

羧甲司坦联合沙美特罗替卡松气雾剂治疗稳定期D组慢性阻塞性肺疾病的疗效观察

目的：探讨羧甲司坦联合沙美特罗替卡松气雾剂治疗稳定期D组慢性阻塞性肺疾病（COPD）患者的临床疗效。方法选取2011年8月—2013年6月就诊于天津市第四中心医院处于稳定期D组COPD患者96例,随机分为治疗组（50例）和对照组（46例）。对照组在常规治疗基础上吸入沙美特罗替卡松气雾剂,1揿/次,2次/d。治疗组在对照组治疗的基础上口服羧甲司坦口服溶液10 mL/次,3次/d。两组均连续治疗48周。观察两组患者治疗前,治疗8、24、48周运动耐量、呼吸困难指数（mMRC）及肺功能的变化,同时观察两组患者治疗过程中急性加重次数。结果两组患者6 min 步行距离（6MWD）在治疗8、24、48周后均较治疗前显著增加,mMRC均较治疗前有所降低,治疗前后差异有统计学意义（P＜0.05）;治疗24、48周治疗组6MWD显著长于对照组,mMRC显著低于对照组,两组比较差异有统计学意义（P＜0.05）。两组患者在治疗24、48周第1秒用力呼气容积（FEV1）、FEV1占预计值百分比（FEV1/pred%）均较治疗前有所增加,治疗前后差异有统计学意义（P＜0.05）;治疗24、48周治疗组患者FEV1、FEV1/pred%显著高于对照组,两组比较差异有统计学意义（P＜0.05）。结论羧甲司坦联合沙美特罗替卡松气雾剂治疗稳定期D组COPD患者具有较好的临床疗效,可增加患者的运动耐力,改善呼吸困难症状和肺功能,值得临床推广应用。     

A One-Week Dose-Ranging Study of Inhaled Salmeterol in Children with Asthma

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 μg and 42 μg administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral β-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vita signs, electrocardiogram (ECC), and 24-hr ECG (Holter) monitoring. Both the 21 -μg and 42-μg doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV₁) (p ≤ 0.02) and PEFR (p ≤ 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-μg dosage producing consistently higher serial FEV₁and PEFR than did the 21 -μg dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p ≤ 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECCs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 μg or 42 μg twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 μg twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 μg.     

沙美特罗／丙酸氟替卡松对支气管哮喘患者转化生长因子β1／Smad通路的影响

目的观察沙美特罗／N酸氟替卡松对中重度持续支气管哮喘（简称哮喘）患者转化生长因子p1（transforminggrowthfactor—β1,TGF-β1）／Smad通路的影响。方法中重度持续哮喘患者30例,对照组20例。哮喘组给予规律吸入沙美特罗／N酸氟替卡松50／250／xg,2次／d,持续6个月。酶联免疫吸附试验（ELISA法）定量测血清TGF-β1、Smad2表达,宝石能谱高分辨率CT（HRCT）扫描测量气道壁厚度／气道外径（T／D）、气道壁面积占气道总面积百分比（WA％）评估气道重塑程度。结果哮喘组（治疗前）血清TGF-β1（301．5±27．3）ng／L、Smad2（1182．1±50．6）ng／L与对照组TGF—β1（55．2±12．8）ng／L、Smad2（796．4±56．2）ng／L比较差异有统计学意义（t=8．52,t=5．90,P值均〈0.05）,哮喘组（治疗后）TGF-β1,（96．1±25．6）ng／L、Smad2（853．4±49．7）ng／L与哮喘组（治疗前）比较差异具有统计学意义（t=7．21,t=3．13,P值均〈O．05）,哮喘组（治疗后）血清Smad2与对照组比较差异无统计学意义（t=0．24,P〉o．05）;哮喘组（治疗前）T／D（23．66士4．06）％较对照组（19．79士3．37）％增加,差异有统计学意义（t=3．45,P〈O．05）,哮喘组（治疗前）wA％（69．24±6．03）‰值与对照组（51．67±4．55）％比较差异有统计学意义（t=3．77,P〈O．05）。规律吸入沙美特罗／丙酸氟替卡松6个月后,哮喘组（治疗后）T／D（20,43±3．00）％、WA％（58．40±3．85）％下降,与哮喘组（冶疗前）比较差异有统计学意义（t=2．96,t=3．05．P值均〈0．05）,哮喘组（治疗后）T／D与对照组比较差异无统计学意义（t=0．95,P〉0．05）,气道重塑减轻。结论哮喘患者气道重塑伴随血TGF-β1、Smad2蛋白的表达增加,规律吸入沙美特罗j丙酸氟替卡松可以通过减少血清TGF-β1、Smad2蛋白的表达,从而减轻哮喘患者气道重塑。调节TGF-β1／Smad通路可能是治疗哮喘气道重塑的新策略。     

沙美特罗替卡松粉联合噻托溴铵治疗慢性阻塞性肺病稳定期C组患者的临床疗效观察

目的 观察吸入不同剂量沙美特罗替卡松粉（舒利迭）联合噻托溴铵治疗慢性阻塞性肺病（COPD）稳定期C组患者的疗效.方法 门诊选取72例COPD稳定期C组患者,随机分成3组,Ⅰ组单独吸入舒利迭（50μg沙美特罗/500 μg丙酸氟替卡松,2次/日）、Ⅱ组单独吸入噻托溴铵（18μg,1次/日）和Ⅲ组吸入舒利迭（50μg沙美特罗/250 μg丙酸氟替卡松,2次/日）＋噻托溴铵（18μg,1次/日）,共治疗12周.用药前后分别检测患者肺功能,应用改良的英国医学研究委员会呼吸困难量表（mMRC）进行评分、COPD评估测试（CAT）及6分钟步行试验（6MWT）.结果 Ⅰ、Ⅲ组患者肺功能指标、mMRC及CAT评分、6分钟步行距离均较治疗前明显改善（P＜0.05）;Ⅱ组患者肺功能指标改善不明显,6分钟步行距离、mMRC及CAT评分均较前改善（P＜0.05）.结论 沙美特罗替卡松粉（50 μg/250 μg,2次/日）联合噻托溴铵治疗COPD稳定期C组患者疗效确切,治疗风险未增加,值得临床推广.     

噻托溴铵联合沙美特罗替卡松治疗慢性阻塞性肺疾病稳定期患者的疗效观察

目的 观察噻托溴铵联合沙美特罗替卡松对慢性阻塞性肺疾病(COPD)稳定期的治疗效果.方法 采用随机、双盲的方法将62例COPD患者分为观察组和对照组,观察组给予噻托溴铵和沙美特罗替卡松治疗,对照组给予沙美特罗替卡松治疗,分别对两组患者治疗前后呼吸困难评分和肺功能检测进行比较.结果 治疗两个月后,与对照组比较观察组肺功能FEV1、FVC、FEV1/FVC%,呼吸困难评分改善差异有统计学意义(P＜0.05).结论 噻托溴铵与沙美特罗替卡松联合吸入治疗COPD,疗效优于沙美特罗替卡松单药治疗.     

沙美特罗替卡松粉剂在慢性阻塞性肺疾病稳定期应用的临床观察

目的观察长期吸入沙美特罗替卡松粉剂对于稳定期中重度慢性阻塞性肺疾病（COPD）患者肺功能及生活质量的影响。方法将50例COPD稳定期患者随机分为两组。治疗组长期给予沙美特罗替卡松粉剂2次/d,每次1吸;对照组仅在急性发作期吸入沙美特罗替卡松粉剂1,年后比较两组肺功能、呼吸困难指数、急性发作次数及平均入院天数。结果①治疗组一年后FEV1及FVC较对照组有明显改善;②治疗组呼吸困难明显改善;③治疗组急性发作次数及住院天数均少于对照组。结论对于稳定期中重度COPD患者长期吸入沙美特罗替卡松粉剂可改善肺功能及生活质量。     

沙美特罗替卡松在哮喘治疗中的控制作用

目的研究沙美特罗替卡松粉吸入剂治疗支气管哮喘的临床安全性及疗效。方法选择2009年2～10月笔者所在医院110例支气管哮喘患者,随机分成治疗组和对照组,每组各55例。治疗组患者选择沙美特罗替卡松粉吸入剂治疗;对照组患者只选择丙酸氟替卡松进行治疗,观察两组患者药物反应和症状改善情况,比较两组患者咳嗽、喘息及呼吸困难消失时间。结果治疗组患者咳嗽、喘息及呼吸困难消失时间都比对照组患者短,差异有统计学意义（P〈0.05）;治疗组用药后各项肺功能改变率与对照组比较,差异有统计学意义（P〈0.05）。结论应用沙美特罗替卡松粉吸入剂治疗哮喘,不但治疗效果好而且使用安全,值得临床上推广应用。     

The Effects of Inhaled Albuterol and Salmeterol in 2- to 5-Year-Old Asthmatic Children as Measured by Impulse Oscillometry*

The functional assessment of the response to bronchodilators in 2- to 5-year-old asthmatic children is technically difficult. For this reason, there have been no reports on the effects of long-acting bronchodilators, such as salmeterol, in this age group. Of the several techniques available for measuring resistance to airflow, forced oscillation remains the most adaptable to young children and the most practical for research and clinical use. In this study we used the Jaeger MasterScreen Impulse Oscillometry System to assess the response of 2 to 5 year-old asthmatic children to an inhaled long-acting bronchodilator, salmeterol, by comparing it to the effect of a standard dose of the short-acting bronchodilator, albuterol. We performed a placebo-controlled, randomized, crossover study in 10 children aged 2 to 5 years who had a history of physician-diagnosed asthma and who were not on regular controller therapy. At weekly intervals after baseline measurements of reversibility, each child received two inhalations from an albuterol metered-dose inhaler (MDI) with a spacer (200 µg), or placebo MDI with spacer, or two inhalations from a salmeterol MDI (50 µg), or 50 µg from a salmeterol Diskus®. Measurements were obtained at 5, 30, 60, 360, and 540 min, the last time interval only on the salmeterol days. Based on previous studies, total respiratory system reactance at 5 Hz (X₅), calculated by the MasterScreen computer from mouth pressure and flow data, was used as the primary efficacy variable. The mean intra-individual variability in X₅ was 10.5% (range 3.6% to 17.9%). The mean (SE) changes from baseline X₅ at each time point were as follows: for placebo, 9.6 (3.0), 10.1 (2.6), 5.1 (2.9), 6.1 (3.5), p=0.36 vs. baseline; after treatment with albuterol, 32.7 (3.8), 53.9 (1.2), 47.3 (5.4), 18.1 (5.8), p<0.01 vs. baseline at all time points; after salmeterol MDI, 16 (6.4), 28.9 (5.2), 32.7 (3.9), 34.6 (4.4), 31.2 (4.8), p<0.05 at 60, 360, and 540 min; and after salmeterol Diskus®, 16.4 (4.0), 16.9 (6.6), 27.8 (5.9), 28.6 (5.6), 33.8 (4.0), p<0.05 at 540 min. No significant adverse events or electrocardiographic changes were noted at any time. Impulse oscillometry is an acceptable method of assessing airway responses to bronchoactive drugs in this age group. Compared to albuterol and to its effect in older children and adults, the response to salmeterol Diskus® appears to be somewhat blunted in this age group. The MasterScreen system is well suited for pharmacodynamic studies and clinical investigations in pre-school-aged children.     

The effect of fixed combination of fluticasone and salmeterol on asthma drug utilization,asthma drug cost,and episodes of asthma exacerbations

ABSTRACT

Objective: This study evaluated the use and drug costs of inhaled corticosteroids (ICSs), long-acting β₂-agonists (LABAs), and fluticasone propionate and salmeterol in a fixed-dose combination (FSC) and their relationship to asthma exacerbations before and after the market introduction of FSC in April 2001.

Methods: This is a retrospective analysis of employer-sponsored health insurance claims filed between January 1, 1998, and December 31, 2003 to detect impact of introduction of FSC (approved by the US Food and Drug Administration in August 2000) on utilization and cost of FSC, any ICS (excluding FSC), and any LABA (excluding FSC) along with utilization of medical services related to asthma exacerbations. Asthma medications were identified using National Drug Codes and Redbook, whereas asthma exacerbations were identified using ICD?9?CM primary diagnosis code 493.x. These medical and pharmacy claims were converted to rates per 100 asthma office visits.

Results: For all ICSs, the average pharmacy claims per 100 office visits increased from 383 in the year before FSC was introduced to 407 (120 [29.5%] were for FSC and 287 [70.5%] were for single-entity ICSs) in 2003. LABA prescribing increased from 72 in the year before FSC to 147 (120 from FSC, 27 single-entity LABA) in 2003 (?p < 0.001). An additional $13?511 per 100 asthma office visits was spent on the FSC product (?p < 0.001). After the introduction of FSC, there was no significant difference in asthma admissions (?p = 0.17), whereas emergency department (ED) visits increased by 0.92 visits per 100 office visits (?p = 0.03). The diagnosis and severity of asthma was inferred from the pharmacy claims and patients with chronic obstructive pulmonary disease could not be excluded. In addition, the study was not designed to assess the impact of other asthma medications on the disease and/or associated costs, and patient adherence to claimed medication could not be monitored.

Conclusions: The introduction of FSC was associated with increased LABAs/FSC patient exposure and expenditure with no change in asthma hospitalizations and an increase in ED visits.