新生儿呼吸窘迫综合征肺表面活性物质蛋白B不同表达水平分析

目的探讨肺表面活性物质蛋白B(SP-B)参与新生儿呼吸窘迫综合征(RDS)发病的可能机制。方法选择无血缘关系的60例因RDS死亡的新生儿为RDS组,其中≤31周亚组、32～36周亚组及≥37周亚组每组各纳入20例;选择无血缘关系的60例因其他疾病死亡的新生儿为对照组,胎龄与RDS组以1:1相匹配。所有研究对象均在死后30min内取肺组织,采用免疫印迹方法分析SP-B蛋白在肺部的表达,实时定量-聚合酶链反应(RT-PCR)方法分析肺部SP-B信使RNA(mRNA)表达。SP-BmRNA和SP-B蛋白缺陷的频率采用统计学分析。结果 RDS组8例肺组织SP-B蛋白表达减少或缺失,其中6例完全缺失;对照组1例肺组织SP-B蛋白表达减少;此9例均分布在≥37周亚组。RDS组SP-BmRNA相对表达量显著低于对照组[(2.55±1.90)比(3.74±1.12),t=4.145,P<0.001];≤31周亚组RDS组与对照组差异无统计学意义[(2.35±1.34)比(2.66±1.14),t=0.776,P>0.05];32～36周亚组和≥37周亚组中,RDS组均低于对照组[32～36周亚组:(2.23±1.22)比(3.80±0.25),t=5.661,P<0.001;≥37周亚组:(3.08±2.74)比(4.75±0.49),t=2.682,P<0.05]。SP-B蛋白和mRNA水平成同向表达减少。结论转录和翻译水平均介入了SP-B蛋白的最后表达,SP-BmRNA和SP-B蛋白减少参与了RDS发病。     

Surfactant protein A in the course of respiratory distress syndrome

Surfactant-associated protein (SP-A) was measured in tracheal aspirates of ventilated infants with (n = 51) and without (n = 21) respiratory distress syndrome (RDS). SP-A concentrations in samples collected after birth were significantly lower in RDS than in infants ventilated for other reasons than RDS (median 0.03 vs. 1.60 micrograms/ml). As a biochemical test to diagnose RDS early after birth, the sensitivity of measuring SP-A in tracheal aspirates was 87% and specificity 81%. SP-A content in tracheal aspirates of infants with RDS was monitored during the first 7 days of life. A significant (P less than 0.001) increase within the first 4 days was found in those infants who survived, whereas no such change was found in those infants who died.     

Surfactant protein (SP) B associations and interactions with SP-A in white and black subjects with respiratory distress syndrome

BACKGROUND: The etiology of respiratory distress syndrome (RDS) is multifactorial and/or multigenic. Surfactant protein A (SP-A) and/or SP-B genetic variants have been identified as risk or protection factors for RDS. METHODS: We genotyped subjects with and without RDS for the SP-B intron 4 size variants (invariant (inv), deletion (del), insertion (ins) and for four (-18 (A/C), 1013 (A/C), 1580 (C/T), 9306 (A/G)) SP-B single nucleotide polymorphisms (SNP), to study case-control associations in black and white subjects. We also determined whether specific SP-B variants interact with RDS susceptibility or protective SP-A variants to enhance or reduce risk for RDS. RESULTS: Based on odds ratio: (1) the SP-B intron 4 del variant in white subjects is more of an RDS risk factor for males and for subjects of 28 weeks 相似文献   

Surfactant treatment for acute respiratory distress syndrome

OBJECTIVE—To determine prospectively the efficacy of surfactant in acute respiratory distress syndrome.STUDY DESIGN—Twenty patients, 1 month to 16 years of age, diagnosed with an acute pulmonary disease with severe hypoxaemia (PaO₂/FiO₂ < 100) (13 with systemic or pulmonary disease and seven with cardiac disease) were treated with one to six doses of 50-200 mg/kg of porcine surfactant administered directly into the trachea. The surfactant was considered to be effective when the PaO₂/FiO₂ improved by > 20%.RESULTS—After initial surfactant administration the PaO₂/FiO₂ increased significantly in patients with systemic or pulmonary disease from 68 to 111, and the oxygenation index (OI) diminished significantly from 36.9 to 27.1. The PaO₂/FiO₂ and OI did not improve in children with cardiac disease. The improvement of the patients who survived was greater than that of those who died.CONCLUSIONS—Surfactant moderately improves oxygenation in some children with severe acute respiratory distress syndrome secondary to pulmonary or systemic disease.     

Surfactant replacement therapy for neonatal respiratory distress syndrome

Conclusions Surfactant treatment of RDS improves oxygcnation and ventilation whether given immediately after birth or after the onset of the disease. There is also a decrease in associated morbidity (air leak), and improved survival with no significant short term side effects. Information about long term follow-up is limited, but encouraging. The future should bring better surfactants (recombinant DNA human surfactant) and optimization of timing, multiplicity and size of dose, and technique of ventilation. This will allow for the survival of most of the premature infants beyond 25 weeks gestation with minimal morbidity. Surfactant treatment of RDS will go down as a true landmark in the history of neonatology.     

Surfactant treatment for acute respiratory distress syndrome.

OBJECTIVE: To determine prospectively the efficacy of surfactant in acute respiratory distress syndrome. STUDY DESIGN: Twenty patients, 1 month to 16 years of age, diagnosed with an acute pulmonary disease with severe hypoxaemia (PaO2/FiO2 < 100) (13 with systemic or pulmonary disease and seven with cardiac disease) were treated with one to six doses of 50-200 mg/kg of porcine surfactant administered directly into the trachea. The surfactant was considered to be effective when the PaO2/FiO2 improved by > 20%. RESULTS: After initial surfactant administration the PaO2/FiO2 increased significantly in patients with systemic or pulmonary disease from 68 to 111, and the oxygenation index (OI) diminished significantly from 36.9 to 27.1. The PaO2/FiO2 and OI did not improve in children with cardiac disease. The improvement of the patients who survived was greater than that of those who died. CONCLUSIONS: Surfactant moderately improves oxygenation in some children with severe acute respiratory distress syndrome secondary to pulmonary or systemic disease.     

Surfactant replacement therapy in neonatal respiratory distress syndrome

We conducted a prospective, randomized, controlled trial comparing the efficacy of two doses of a reconstituted bovine surfactant (Surfactant TA) in premature infants requiring mechanical ventilation shortly after birth for respiratory distress syndrome. Forty-six infants weighing 1000–1499 g were randomized into two groups: a low-dose group (23 infants given a single dose of 60 mg surfactant lipid/kg) and a high-dose group (23 infants given a single dose of 120 mg/kg). The mean (SD) age at which surfactant was given was 5.5 (±1.2) h in the low-dose group and 6.0 (±1.5) h in the high dose group. Both treatments improved oxygenation (increased arterial-alvcolar PO₂ ratio) with decreased mean airway pressure, the high-dose surfactant having a more beneficial effect in prolonging the response. Infants in the high-dose group had significantly less (P<0.05) incidence of both intraventricular haemorrhage and bronchopulmonary dysplasia. This prospective trial documents that a greater benefit can be obtained by increasing the dose of surfactant (120 mg/kg) beyond 60 mg/kg in the treatment of premature infants with severe respiratory distress syndrome (RDS).Abbreviations RDS respiratory distress syndrome - Surfactant TA Surfactant Tokyo-Akita - 5 kDa 5 kilodaltons - ELISA enzyme-linked immunosorbent assay - PDA patent ductus arteriosus - a/APO₂ arterial-alveolar oxygen tension ratio - MAP mean airway pressure - ^99mIc-DTPA 99m technetium diethylenetriamine pentacetate     

肺表面活性物质治疗新生儿呼吸窘迫综合征的临床对照研究

目的　探讨肺表面活性物质 (PS)治疗新生儿呼吸窘迫综合征 (NRDS)的有效性及临床价值。方法　采用气管内滴注单剂PS治疗NRDS患儿 2 5例 ,并与同期未用PS治疗的 2 5例NRDS患儿进行前瞻性临床对照研究。结果　治疗组在应用PS后 2～ 3h皮肤颜色转红 ,经皮血氧饱和度逐渐升高。 6h后动脉血氧分压 (PaO2 )、动脉 /肺泡血氧分压比值 (a/APO2 )及呼吸机有效指数 (VEI)分别由 ( 48± 14)mmHg( 1mmHg =0 .133kPa)、0 .14± 0 .0 6及 ( 0 .16± 0 .0 9)ml/ (mmHg·kg)上升到 ( 6 5±2 9)mmHg、0 .2 4± 0 .15及 ( 0 .2 9± 0 .16 )ml/ (mmHg·kg) ;而氧合指数 (OI)、吸入氧浓度 (FiO2 )及平均气道压 (MAP)由 11.6± 5 .7、0 .5 9± 0 .13及 ( 15 .6± 3.1)cmH2 O( 1cmH2 O =0 .0 98kPa)逐渐降低至 6 .3±3 .4、0 .47± 0 .10及 ( 13 .5± 2 .4)cmH2 O。经广义线性模型方差分析 ,主效应、分组因素及时间因素对两组PaO2 、a/APO2 、OI、FiO2 、MAP及VEI的值具有明显影响。而分组与时间因素的交互作用无显著影响。治疗组机械通气及氧疗时间较对照组明显缩短 ,二者差异有显著性。结论　PS能有效地改善NRDS患儿肺顺应性及氧合功能 ,缩短需要机械通气及氧疗时间。     

A genetic and statistical study of the respiratory distress syndrome

The hospital records of 197 infants with the respiratory distress syndrome (RDS) were reviewed and the families of 111 of them subsequently contacted to obtain a family history. After correcting for bias of ascertainment, the incidence of RDS among the full sibs was found to be between 12 and 19% depending on whether the individuals diagnosed as possible RDS were counted as affected. Among the low birth weight (LBW, 2.5 kg) and/or preterm (37 weeks gestation) infants in the sibships, the incidence of RDS was 32–50%. Considering only sibs born after the probands yielded the empiric recurrence risk of 17–27% for all younger sibs and of 39–67% for LBW/preterm younger sibs. The risk for maternal half-sibs was of about the same magnitude as that for full sibs, while the risk for paternal half-sibs was minimal. Among the LBW/preterm first cousins of probands, only the infants of maternal aunts showed an RDS incidence clearly higher than that in the general population. We think these data suggest a genetically determined maternal factor predisposing the infants of certain mothers to RDS.Other significant findings include: 1) an excess of males among the probands but a normal sex ratio among the sibs of the probands; 2) a decrease in mean birth weight and mean length of gestation for not only the probands but also their sibs; 3) a decrease in the mean parental ages at the birth of the probands; 4) a relative dearth of first-born and an excess of second-born infants among the probands; 5) an increased incidence of stillbirths in the sibships; 6) an increased number of probands born by cesarean section; and 7) a twin concordance of 75%.Supported by DHEW/USPH Grants GM20130 and GM00398 from the National Institute of General Medical Science. Paper No. 1963 from the University of Wisconsin Genetics Laboratory.     

新生儿呼吸窘迫综合征患儿肺表面活性物质蛋白B表达的研究

目的探讨肺表面活性物质蛋白B(SP-B)缺陷是否为新生儿呼吸窘迫综合征(RDS)发病的影响因素。方法选择无血缘关系的30例RDS死亡新生儿为RDS组,其中<34周、34~36周及≥37周每组各纳入10例;选择无血缘关系的30例其他疾病死亡新生儿为对照组,胎龄与RDS组以1∶1相匹配分成3个亚组(P>0.05)。所有研究对象均在死后半小时内取肺组织浸入4%多聚甲醛固定,石蜡包埋后5μm连续切片,采用免疫组织化学技术检测各组患儿SP-B在肺部的表达;计算两组SP-B缺陷的频率。结果 SP-B位于细胞胞浆中,部分分泌至气道及肺泡表面,着色深浅不一、范围不同,随组别、胎龄、疾病严重程度而变化;RDS组肺部SP-B蛋白未随胎龄增加而增加,对照组除2例26周患儿SP-B明显低于同组同胎龄外,肺部SP-B蛋白随胎龄增加而增加。RDS组SP-B阳性表达细胞明显低于对照组(t=10.205,P<0.001),RDS组SP-B缺陷13例,缺陷频率43.3%,对照组SP-B缺陷2例,缺陷频率6.7%,RDS组高于对照组(χ2=60.00,P<0.001)。结论 SP-B缺陷参与了新生儿RDS的发病。     

肺表面活性蛋白C基因突变相关性新生儿呼吸窘迫综合征2例并文献复习

目的 总结2例肺表面活性蛋白C基因（SFTPC）突变的新生儿呼吸窘迫综合征（NRDS）的临床特点和基因诊断,提高对该病的认识。方法 总结分析本文2例NRDS患儿的临床资料和基因检测结果,并进行文献复习。结果 2例患儿分别为38+3周足月儿和35+2周早产儿,均于生后即发生呼吸窘迫,X线胸片示NRDS,病原学检查均为阴性。均否认肺部疾病家族史。表面活性物质替代治疗和正压辅助通气支持有效。基因检测显示：1例为SFTPC基因c.68G>G/A,p.R23Q杂合错义突变,为首次报道;1例为SFTPC基因c.115G>G/T,p.V39L杂合错义突变,为已报道致病突变。共检索到临床资料完整的SFTPC突变NRDS 6篇文献7例,结合本文2例,9例均生后呼吸窘迫,影像学以弥漫性侵润和间质性改变为主,多予机械通气、PS对症支持治疗,2例死亡,1例间质性肺病,1例支气管肺发育不良,4例随访健康,1例失访。结论 中国NRDS病例中存在SFTPC基因突变,相关基因突变的识别,可为早期干预、预后判断以及遗传咨询提供依据。     

A protein that inhibits surfactant in respiratory distress syndrome

A protein that interferes with surfactant function is present in the airways and alveoli of infants with respiratory distress syndrome (RDS). This inhibitor is also found in serum and amniotic fluid and presumably appears in the alveoli because of the abnormal protein leak present in the lungs of infants with RDS. This protein has a molecular weight of about 110,000 and is resistant to boiling or lipid extraction. As measured by radioimmunoassay, the ratio of inhibitor to phosphatidylcholine decreased from 8.1 +/- 2.3 early in the course of RDS to 0.7 +/- 0.1 on the day of extubation. The value at extubation was the same as that measured for preterm infants without RDS. The inhibitor to phosphatidylcholine ratio in airway samples from infants with RDS correlated significantly with simultaneously recorded pO2/FiO2 ratios and the peak inspiratory pressures used to normalized pCO2 values. These results are consistent with the concept that the inhibitor contributes to surfactant dysfunction and thus the respiratory failure characteristic of RDS.     

Surfactant treatment for respiratory distress syndrome following prolonged rupture of membranes

Surfactant replacement for respiratory distress syndrome (RDS) following very prolonged rupture of the membranes (PROM) is of uncertain value. Seven preterm babies born after PROM (median 48 days, range 22–61 days) were compared with 14 babies without PROM. All had clinical and radiological evidence of severe RDS, requiring mechanical ventilation with inspired oxygen concentrations 60%. Indices of oxygenation and compliance were compared before and serially up to 4h after surfactant treatment. Before treatment the PROM babies had more severe lung disease, based upon higher inspired oxygen concentration and mean airway pressure, and lower arterial/alveolar oxygen tension ratio and ventilator efficiency index. These indices were significantly worse in the PROM group than the comparison group at all times after treatment. The poor response of the PROM group, perhaps because of pulmonary hypoplasia, suggests that surfactant replacement may not be beneficial for RDS in these babies.