珠海儿童支气管哮喘的药学服务模式效果研究

目的本研究旨在观察临床药学服务对于儿童支气管哮喘的改善情况。方法进行了一项随机双盲对照研究,比较传统发药模式和临床药学服务模式的影响。90例支气管哮喘患儿入组,年龄在2-12 a,经临床医生确诊为支气管哮喘后,随机分为传统发药模式组和临床药学服务模式组,主要观察2组患儿不同时间点用药依从性、就诊次数和例数以及哮喘控制情况。结果传统发药模式组中依从性评分量表中≥30分在1个月、3个月和6个月分别为31%、29%和33%;相比药学服务组达到了76%（P=0.002）、85%（P=0.000 1）和94%（P=0.000 2）。药物服务组患儿的就诊次数和例数都明显降低,特别是7-12个月,与传统发药模式比有明显的统计学差异（P=0.002;P=0.024）;在哮喘控制上,儿童哮喘控制测试量表显示,传统发药模式组中评分≥30分的患者比例在1-3个月内为27%,4-6个月为31%,7-12个月为30%;相比药学服务模式组达到了53%（P=0.028）、82%（P=0.001）和92%（P=0.0002）。临床医生和简易肺功能检测中,传统发药模式组中完全控制的患儿比例、1、3和6个月分别为53%、66%和65%,相比药学服务组分别为70%（P=0.020）,85%（P=0.026）和90%（P=0.005）。结论在儿童支气管哮喘中开展药学服务,有助于改善患儿的病情,使哮喘得到较好的控制,这一服务模式可以长期开展,以此降低和控制儿童支气管哮喘的发病。     

微囊蛋白-1蛋白参与哮喘气道平滑肌细胞增殖中ERK1／2调控以及罗红霉素的干预

目的：在细胞水平研究微囊蛋白-1（caveo-1in-1）对气道平滑肌细胞（ASMCs）的增殖作用以及对ERK1／2的通路调控,探讨caveolin-1抑制ASMCs增殖的可能机制。方法：复制哮喘大鼠模型,光镜观察肺组织病理变化,透射电镜观察ASMCs上微囊（caveolae）的结构及变化,用组织贴壁法体外培养气道平滑肌细胞,实验设正常对照组（A组）、哮喘组（B组）、ERKl／2信号通路阻断剂PD98059（C组）、罗红霉素组（D组）、caveo—lae结构破坏药物8-甲基环糊精组（E组）;用CCK-8法检测各组细胞的增殖情况,逆转录-聚合酶链测定（RT-PCR）和蛋白质印迹法（WesternBlot）检测ERKmRNA和p-ERK1／2蛋白的表达;WesternBlot法检测各组caveolin-1蛋白细胞表达。结果：CCK-8检测结果显示D组及C组ASMCs增殖反应低于B组,D组（0．59±0．15） vs B组（0．96±0．14）,P〈0．05,C组（0．63±0．11） vs （0．96±0．14）,P〈0．05;E组ASMCs增殖反应较B组进一步活跃（1．26±0．21） vs （0．96±0．14）,P〈0．05。D组及C组ASMCs上caveolin-1的表达较B组明显升高,P〈0．01,pERKl／2蛋白以及ERKInRNA表达较B组降低,E组相反。D组ASMCs的ERK mR-NA和p-ERK1／2蛋白表达水平均显著低于B组及E组（P〈0．01）。结论：caveolin-1可能是ASMCs内信号转导的负调控蛋白,这-作用可能是通过抑制ERK信号通路实现。罗红霉素可能上调caweolin-1蛋白的表达量,抑制ERK mR-NA表达和翻译,从而抑制哮喘大鼠ASMCs的增殖。     

噻托溴铵联合沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的改善

目的：探讨联合吸入噻托溴铵和沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的影响。方法：将本院呼吸内科100例确诊为支气管哮喘的患者随机分为吸入噻托溴铵和沙美特罗/氟替卡松治疗组43例,沙美特罗/氟替卡松组29例,噻托溴铵组28例。治疗6个月后,观察治疗疗效、治疗前后肺功能变化及治疗后肺功能改善率。结果：联合吸入噻托溴铵和沙美特罗/氟替卡松组的总有效率为88.4%,明显高于噻托溴铵组的67.9%和沙美特罗/氟替卡松组的72.4%,差异具有统计学意义,P〈0.05。同时联合吸入噻托溴铵和沙美特罗/氟替卡松组的肺功能改善率高于其他两组,改善更显著,差异具有统计学意义。结论：噻托溴铵联合沙美特罗/氟替卡松能明显改善支气管哮喘患者肺通气功能,疗效显著。     

布地奈德混悬液联用复方异丙托溴铵吸入治疗96例婴幼儿哮喘的疗效评价

目的：评价用布地奈德混悬液联合复方异丙托溴铵雾化吸入治疗婴幼儿哮喘的临床疗效。方法：采用随机分组方法,将2010年3月—2013年6月间萍乡市妇幼保健院儿科门诊内收治的确诊96例婴幼儿哮喘患者,分为观察组（48例）,给予布地奈德混悬液联合复方异丙托溴铵雾化吸入治疗,对照组（48例）,给予常规方法治疗;将治疗前后的临床症状消失时间、临床疗效及不良反应情况等做一比较,并回顾性分析两组患儿的临床资料。结果：治疗后,观察组总有效率91.67%与对照组总有效率79.17%比较,其差异有统计学意义（P〈0.05）,观察组咳嗽,憋喘及肺部哮鸣音等临床症状的缓解或消失时间皆短于对照组（P〈0.05）,两组患儿均未发生不良反应。结论：用布地奈德混悬液联合复方异丙托溴铵雾化吸入治疗婴幼儿哮喘,其疗效较显著,不良反应较少,安全性较高,值得临床使用。     

无创正压通气在重症支气管哮喘治疗中的应用

目的：分析研究无创正压通气在重症支气管哮喘疾病治疗中的应用效果。方法：从我院呼吸科室收治的重症支气管哮喘患者中选取其中43例,给患者采用无创正压通气治疗,观察患者的生理指标以及血气指标变化情况,并判定患者临床治疗效果。结果：对比治疗前后的血气分析变化情况,差异显著有统计学意义（P〈0.05）,治疗2h、24h、48h血气分析对比有显著差异,有统计学意义（P〈0.05）,治疗有效率为95.3%,均无严重并发症发生。结论：给予重症支气管哮喘患者采用无创正压通气治疗,可显著改善患者的临床症状,安全高效,应用效果显著,值得推广应用到临床治疗中。     

Cutaneous basal cell carcinoma with endobronchial metastasis

Although basal cell carcinoma is a very common malignancy, metastasis from this tumour is extremely rare. For this reason, many plastic surgeons, dermatologists and physicians dealing with skin malignancies consider this as a locally invasive malignancy. We present a rare case of metastatic basal cell carcinoma manifested as a bronchial tumour. This case highlights the fact that despite basal cell carcinoma’s local invasive potential, the possibility of distant metastasis still exists and clinicians should therefore be cautious about interpreting extracutaneous symptoms. Chest physicians should always consider the possibility of this rare tumour in the lungs in patients with a history of large basal cell carcinomas in the head and neck region.     

比较隐源性咯血和慢性肺结核咯血动脉造影表现及栓塞治疗效果

目的比较顽固性隐源性咯血(CH)和慢性肺结核(CTB)咯血的动脉造影表现特点及介入栓塞治疗效果。方法对17例顽固性CH患者(CH组)及20例CTB咯血患者(TB组)行责任血管栓塞,比较两组责任血管数目、非支气管体循环动脉(NBSA)参与供血血管数目、血管造影表现及栓塞后中远期效果。结果 TB组人均责任血管数目、NBSA参与供血血管数目多于CH组(t'=5.469,t=5.212,P0.01);TB组血管增粗、纡曲、富血管化、BP分流及动静脉瘘的发生率均高于CH组(P均0.05)。TB组术后2年复发率高于CH组(P0.01)。CH组和TB组并发症发生率分别为64.71%(11/17)、95.00%(19/20),差异无统计学意义(P0.05)。结论支气管动脉是CH的主要责任血管。CTB咯血因存在大量NBSA供血,责任血管复杂。CTB咯血复发率高,与栓塞不彻底有关。根据造影特点选择栓塞剂及决定栓塞程度可预防严重并发症。     

Emerging role of long acting muscarinic antagonists for asthma

Acetlycholine is involved in the control of airway smooth muscle constriction and in recruitment of inflammatory cells via neuronal and paracrine effects on muscarinic type 3 receptors. Long acting muscarinic antagonists (LAMA) are well established in guidelines for COPD but are not currently licensed for use in asthma. There are emerging data from key clinical trials to show that LAMA may confer bronchodilator effects and improved control when used in addition to inhaled corticosteroid (ICS) alone or in conjunction with long acting β-adrenoceptor agonists (LABA). Further studies in persistent asthmatic patients are required to evaluate ICS sparing effects of LAMA looking particularly at airway hyper-responsiveness and surrogate inflammatory markers, in addition to evaluation of possible synergy between LAMA and LABA when given together. Future possible development of combination inhalers comprising ICS/LAMA or ICS/LAMA/LABA will require long term studies looking at asthma control and exacerbations in both adult and paediatric patients.     

Adenosine dry powder inhalation for bronchial challenge testing,part 1: Inhaler and formulation development and in vitro performance testing

Dry powder administration of adenosine by use of an effective inhaler may be an interesting alternative to nebulisation of adenosine 5′-monophosphate in bronchial challenge testing, because of a shorter administration time and more consistent delivered fine particle dose over the entire dose range. In this study, we tested various powder formulations and classifier based dispersion principles and investigated the in vitro performance of the most promising formulation/classifier combination in a new test inhaler system. Spray-dried formulations of either pure adenosine (100%) or adenosine and lactose as diluent (1% and 10% adenosine) were prepared to cover the entire expected dose range for adenosine (0.01–20 mg). All three powders, in all 12 suggested doses, dispersed well with the newly developed test inhaler with a multiple air jet classifier disperser, into aerosols with an average volume median diameter of 3.1 μm (3.0–3.3 μm). For eleven out of 12 dose steps, the fine particle fractions < 5 μm as percent of the loaded dose varied within the range of 67–80% (mean: 74%). The new test concept allows for more consistent aerosol delivery over the entire dose range with narrower size distributions than nebulisation and thus may improve adenosine administration in bronchial challenge testing.     

Digoxin net secretory transport in bronchial epithelial cell layers is not exclusively mediated by P-glycoprotein/MDR1

The impact of P-glycoprotein (MDR1, ABCB1) on drug disposition in the lungs as well as its presence and activity in in vitro respiratory drug absorption models remain controversial to date. Hence, we characterised MDR1 expression and the bidirectional transport of the common MDR1 probe ³H-digoxin in air–liquid interfaced (ALI) layers of normal human bronchial epithelial (NHBE) cells and of the Calu-3 bronchial epithelial cell line at different passage numbers. Madin–Darby Canine Kidney (MDCKII) cells transfected with the human MDR1 were used as positive controls. ³H-digoxin efflux ratio (ER) was low and highly variable in NHBE layers. In contrast, ER = 11.4 or 3.0 were measured in Calu-3 layers at a low or high passage number, respectively. These were, however, in contradiction with increased MDR1 protein levels observed upon passaging. Furthermore, ATP depletion and the two MDR1 inhibitory antibodies MRK16 and UIC2 had no or only a marginal impact on ³H-digoxin net secretory transport in the cell line. Our data do not support an exclusive role of MDR1 in ³H-digoxin apparent efflux in ALI Calu-3 layers and suggest the participation of an ATP-independent carrier. Identification of this transporter might provide a better understanding of drug distribution in the lungs.