支气管哮喘的药物基因组学研究

哮喘治疗的主要药物包括支气管扩张的β2受体激动剂、抗炎的吸入性糖皮质激素、白三烯调节剂和茶碱.然而每个哮喘患者对治疗药物的疗效均有差异,70％的差异可能是由患者的基因变异造成的.药物基因组学用基因信息提供了提高有效性或避免不良反应的个体化药物选择的可能.支气管扩张剂的可逆性和连续服用β2激动剂者病情恶化与肾上腺素β2受体的Gly16Arg基因型相关;β2肾上腺受体上的基因突变(Arg16Gly)可预测抗胆碱能类哮喘治疗的疗效.使用传统单核苷酸多态性方法发现了糖皮质激素释放激素受体1(CRHR1)上一个疗效相关的可能标记基因;CRHR1、TBX21和FCER2的变异体与肺功能、气道反应性和吸入糖皮质激素患者病情恶化的差异性有关.另一个主要通路是对半胱氨酸白三烯受体激动剂的可能有效途径;ALOX5、LTA4H、LTC4S、ABCC1、CYSLTR2和SLCO2B1的变异体与白三烯调节剂疗效差异性相关.个体基因信息为基础的药物基因组学方法将为患者提供最好的个体化治疗.     

哮喘发病机制和治疗新进展

哮喘是儿童常见病,其发病机制复杂,多种环境冈素可以作用于哮喘候选基因,对哮喘表犁产生影响.气道重建是哮喘的特征之一,而且气道平滑肌细胞重建和微血管重建在哮喘呼吸道巾相当普遍,在哮喘发病中起着晕要作用.解聚素和金属蛋白酶33是哮喘的易患基因,同时也是哮喘病情加重的牛物标记物.对β2肾上腺素受体基因多态性分析使长效β受体激动剂风险机制更复杂化.吸人性糖皮质激素预防性应用并不能防止哮喘发病,吸人性糖皮质激素.长效β受体激动剂联合治疗方案和肿瘤坏死因子免疫调节剂治疗在临床上取得了较好疗效,对临床工作意义重大.     

β肾上腺素受体与哮喘

β肾上腺素受体与哮喘殷凯生，杨明，吴剑卿自从１９６８年Ｓｚｅｎｔｉｖａｎｙｉ首次提出支气管哮喘患者存在β肾上腺素受体（β－ａｄｒｅｎｅｒｇｉｃｒｅｃｅｐｔｏｒ，β－ＡＲ）功能低下现象（即所谓β－ＡＲ阻断学说）以来，β－ＡＲ与哮喘的关系、β受体激动剂在...     

硫酸羟甲叔丁肾上腺素治疗新生儿百日咳2例

百日咳是儿科常见的传染病,新生儿百日咳也时有发生,且病情重,并发症多。如何及早有效消除痉挛性咳嗽是治疗的关键。从70年代起开始用β受体激动剂治疗痉咳,取得良好效果,我科应用羟甲叔丁肾上腺素(Salbutamol)治疗2例重症新生儿百日咳患儿取得满意疗效。例1.女婴,14日龄。以痉咳伴青紫入院。咽拭子培养出百日咳杆菌。入院后予红霉素治疗,同时给     

沙美特罗替卡松治疗儿童哮喘96例

新型联合制剂沙美特罗替卡松干粉吸入剂是将糖皮质激素丙酸沙美特罗替卡松和β受体激动剂沙美特混入同一装置的新型复合吸入型抗哮喘药物,既含有糖皮质激素又含有长效肾上腺素β2受体激动剂,兼具抗炎解痉双重功效。我们观察了96例中、重度哮喘病儿吸入沙美特罗替卡松干粉剂治疗前后肺功能的变化及疗效,现报道如下。[第一段]     

哮喘吸入治疗药物新进展

吸入治疗是目前支气管哮喘治疗的首选方法。该文依据作用机制的不同分别对抗炎药（糖皮质激素、肥大细胞膜稳定剂、奈多罗米钠、肝素、利多卡因等），支气管扩张剂（肾上腺素能β受体激动剂、胆碱能受体拮抗剂、速尿），复合用药及中药等在吸入治疗支气管哮喘中的应用进展作一阐述，并简单介绍吸入药物的副作用和应用注意事项。     

婴幼儿喘息诊治进展

婴幼儿喘息是一种异质性疾病,可分为婴幼儿暂时性喘息、非过敏性持续性喘息和过敏性喘息(即哮喘).婴幼儿暂时性喘息主要与先天性支气管肺发育不良等因素有关,非过敏性持续性喘息主要与病毒感染引起的炎症有关,这一炎症参与的细胞主要是嗜中性粒细胞和淋巴细胞,而哮喘参与的细胞主要是嗜酸性粒细胞.婴幼儿期喘息的发作次数不是诊断哮喘的理想指标,婴幼儿期哮喘的诊断应重视过敏性疾病的遗传背景、个人过敏性疾病史、实验室过敏指标的检查及对支气管扩张剂治疗的反应.在不能明确婴幼儿喘息类型的情况下,联合应用激素、β2肾上腺素能受体激动剂、白三烯受体调节剂和组织胺H1受体阻断剂治疗是一个有效的选择.     

盐酸班布特罗治疗儿童咳嗽变异型哮喘72例临床分析

咳嗽变异型哮喘是儿科常见的呼吸系统疾病，β2受体激动剂是治疗本病的有效药物，以往倾向于应用短效β2受体激动剂，近年来长效β2受体激动剂相继问世，使临床疗效大大提高，盐酸班布特罗(帮备)作为长效β2受体激动剂就是一种非常有效的治疗咳嗽变异型哮喘的药物，特别能改善夜间咳嗽症状，从而改善睡眠。自2001年4月至2002年4月间我院门诊就诊的咳嗽变异型哮喘儿童共144例，应用帮备治疗72例，现总结如下。     

静脉用特布他林治疗儿童严重哮喘的心脏毒性

严重哮喘病人首选吸入肾上腺素能β２受体激动剂和全身应用皮质类固醇,无有效应答者持续吸入短效β２受体激动剂是安全有效的疗法,如病情持续加重,就需静脉应用β２受体激动剂治疗,但有报道静脉应用β２受体激动剂有明显的心脏毒性。该研究在静脉应用特布他林（ＩＶＤ）治疗儿童严重哮喘期间通过测定血肌钙蛋白（ｃＴｎＴ）来检查其心脏毒性并与肌酸激酶（ＣＫ）及同工酶（ＣＫ－ＭＢ）、心电图（ＥＣＧ）改变进行比较。 方法 研究对象为１９９７年１～１２月间在波士顿儿童医院用ＩＶＴ治疗急性严重哮喘的患儿,仅在对持续雾化吸入沙丁…     

注意缺陷多动障碍的非中枢兴奋治疗药物

中枢兴奋剂是目前临床治疗注意缺陷多动障(ADHD)的首选药物,临床有效率达80%左右,但仍有相当一部分患者对中枢兴奋剂治疗无效,或不能耐受其不良反应,开发应用非中枢兴奋剂药物成为近年来研究的热点.托莫西汀是唯一获美国FDA批准的非中枢兴奋药物,对儿童和成人患者的各种ADHD核心症状均有显著疗效,在国外已成为ADHD的一线治疗药物;抗抑郁药(丙米嗪、去甲丙米嗪、安非他酮、瑞波西汀、文拉法辛等)和α2肾上腺素能受体激动剂(可乐定和胍法辛)证明对ADHD治疗有效,但其短期和长期安全性和疗效仍有待进一步的对照研究;其他非中枢兴奋剂司来吉兰、莫达非尼等作为潜在治疗儿童ADHD安全有效的新药,正受到研究人员的关注.     

新生儿急性肺损伤的诊断与治疗策略

急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)是新生儿临床的常见危重症,随着对ALI/ARDS实验与临床研究的不断深入,人们对新生儿ALI/ARDS的认识明显提高,文章提出了新生儿ALI/ARDS诊断依据与治疗策略,在控制原发疾病基础上,应用肺保护性通气策略、加强液体管理、降低肺动脉压力和给予抗炎治疗等,对提高新生儿ALI/ARDS抢救成功率具有重要意义.     

Blood aspiration syndrome as a cause of respiratory distress in the newborn infant

Early-onset respiratory distress and a radiographic appearance of an aspiration syndrome occurred in three neonates who had not passed meconium before delivery. In each case there was evidence of inhalation of blood, associated with very high plasma protein concentration in lung fluid. Blood aspiration syndrome is a distinct diagnostic entity that can result in significant respiratory distress in the neonate.     

Aerosolized surfactants

PURPOSE OF REVIEW: To present existing data on the potential use of aerosolized surfactants for treatment of neonatal respiratory distress syndrome in the era of noninvasive ventilatory support. RECENT FINDINGS: Current surfactant therapy requires endotracheal intubation and application of positive pressure ventilation. Instillation of the drug itself can be complicated by 'peridosing adverse events' including, but not limited to, desaturations, bradycardias, changes in blood pressure, drug reflux and even the need for reintubations. Increasing use of noninvasive ventilatory support for neonatal respiratory distress syndrome has motivated clinicians and researchers to look for alternate ways of introducing surfactants to patients. Aerosolized surfactants have been tested in animal models of respiratory distress syndrome. In addition, four small clinical studies have been performed to date. The effectiveness of this form of treatment requires further study, however, which will need to include optimizing the dose of aerosolized surfactant, choosing particle size, developing the best delivery system, and using a surfactant formulation that maintains its activity once aerosolized. SUMMARY: Aerosolized surfactants for neonatal respiratory distress syndrome may prevent the need for endotracheal intubation. Appropriately designed randomized controlled studies are required to determine if this form of surfactant administration is as effective and safe as tracheal instillation.     

For or against the early use of nasal continuous positive pressure and exogenous surfactant in hyaline membrane disease. Physiopathologic arguments]

The use of nasal CPAP in the treatment of respiratory distress syndrome in very premature newborns follows pathophysiological basis. The authors emphasize the usefulness of nasal CPAP and surfactant in the treatment of respiratory distress syndrome. The aim of this strategy is to reduce alveolar atelectasis, thus reducing the incidence and the severity of respiratory distress syndrome, together with a possible reduction of the incidence of bronchopulmonary dysplasia.     

小儿急性呼吸窘迫综合征诊疗技术规范--南京医科大学附属南京儿童医院急诊医学科/重症医学科诊疗技术规范

本文介绍一家三级儿童医院重症医学科的小儿急性呼吸窘迫综合征的技术诊疗规范,包括其病因判断、诊断标准、诊断时注意事项、诊断流程图、辅助检查及治疗等。在治疗中强调了病因治疗、保守补液、肺保护性通气策略、俯卧位通气及镇痛镇静肌松等。     

New interpretation and management of dry lung syndrome: A case report

A premature female infant with life-threatening respiratory distress which was diagnosed as ‘dry lung syndrome’ is reported. The mother had 4 weeks of large volume leakage of the amniotic fluid due to premature rupture of the fetal membranes (PROM) at 23 weeks' gestation. The infant was bom after 27 weeks' gestation (birthweight, 1016 g) and was suffering severe respiratory distress. Although a chest radiogram and gastric juice microbubble test did not prove the possibility of respiratory distress syndrome (RDS), very high ventilator settings did not improve her respiratory disorders. Considering the infant's deteriorating respiratory status and the prolonged leakage of the amniotic fluid, we suspected the presence of pulmonary hypoplasia. Although an attempt at high frequency oscillation (HFO) to rescue this infant had no effect, intratracheal instillation of epinephrine (EP) showed dramatic improvement of her respiratory status. This clinical course showed that the patient did not have pulmonary hypoplasia but might have severe airway obstruction and this airway obstruction may be the major cause of ‘dry lung syndrome’. We postulate that when a newborn with suspected pulmonary hypoplasia is unresponsive to respiratory support, HFO should be administered. If HFO is ineffective in relieving the respiratory distress, one should suspect the presence of airway collapse and administer a bronchodilator such as EP. If the infant improves, a diagnosis of ‘dry lung syndrome’ may be assumed.     

Treatment of acute (Adult) respiratory distress syndrome. The holy grail of surfactant therapy

The treatment of neonatal respiratory distress syndrome with surfactant represents a successful culmination of decades of basic and clinical research. In many babies, respiratory distress syndrome is a relatively pure expression of surfactant deficiency. Acute respiratory distress syndrome (ARDS) is a more common disease that is most frequently seen in adults, but the processes are common to lung injuries in newborns and children as well. While some impairment of production and secretion of surfactant constituents may be present in ARDS, surfactant inactivation is probably a more important factor in this disease. Until recently, surfactants available for human use have been easily susceptible to inactivation and this may explain why they have been less successful for treatment of ARDS than for neonatal respiratory distress syndrome. This review outlines recent information on surfactant inactivation and describes initiatives that may result in 'inactivation-proof' surfactants that may be of increased benefit in ARDS.     

Secondary surfactant deficiencies.]

Preterm babies born before the 33rd week of gestation often exhibit primary surfactant deficiency responsible for the respiratory distress syndrome or hyaline membrane disease. In that situation, there is a limited and insufficient production of surfactant by type II alveolar cells of the lung due to immaturity. Secondary surfactant deficiencies occur in patients with prior normal surfactant synthesis and can be related to sepsis, hypoxia, ventilator induced lung injury or surfactant inhibition by a variety of substances reaching the alveolar spaces. They occur in full-term newborns with meconium aspiration syndrome, acute respiratory distress syndrome and congenital diaphragmatic hernia. In children and adults, acute respiratory distress syndrome and respiratory syncytial virus bronchiolitis can be responsible. In prematures they occur after the initial primary deficiency during pulmonary hemorrhage, pneumonia and bronchopulmonary dysplasia. Treatment with exogenous surfactant may be beneficial. There is a need for randomized controlled studies for evaluation of this treatment. Next generation of surfactants containing recombinant surfactant protein or synthetic peptides appear as promising agents in these situations of secondary surfactant deficiencies.     

Bronchopulmonary dysplasia: possible relationship to pulmonary edema

The pathogenesis of bronchopulmonary dysplasia is controversial. Oxygen toxicity, mechanical trauma to the lung secondary to respirator therapy, and congestive heart failure with a left to right shunt through a patent ductus arteriosus have all been implicated. Our data suggest that in addition to these three conditions, all of which are edemagenic, infants with bronchopulmonary dysplasia have a significantly greater mean fluid intake in the first five days of life when compared with infants with respiratory distress syndrome or patent ductus arteriosus alone. We suggest that the addition of a fluid load may potentiate the effects of other factors and increase the risk of bronchopulmonary dysplasia in infants with respiratory distress syndrome who require respiratory support.     

Neonatal aspiration syndrome due to vernix caseosa

Fetal aspiration of meconium in amniotic fluid is a well-known cause of respiratory distress in newborn infants. It causes an irregular, coarse, nodular pattern on chest radiographs. Less known is that aspiration of vernix caseosa causes a similar syndrome. We present a post-mature infant in whom aspiration of vernix caseosa caused respiratory distress, ventilatory difficulty, and radiographic changes essentially the same as in aspiration of meconium.