合并内脏异位的先心病患者术后死亡率和呼吸道并发症及其与呼吸道纤毛功能障碍关系的研究

发布时间：2018-03-24 14:51

本文选题：内脏异位　切入点：先天性心脏病　出处：《复旦大学》2013年博士论文

【摘要】：先天性心脏病(以下简称先心病)是常见的出生缺陷之一,在新生婴儿中发病率约7.5‰～-9‰,是1岁以内婴儿死亡的主要原因。世界卫生组织资料显示,全球每年约有150万先心病患儿出生,其中,我国每年约有15万到20万先心病患儿出生。内脏异位常合并复杂先心病,研究提示,合并内脏异位先心病患者的术后呼吸道并发症和死亡率较高,一直以来都被归于心脏畸形的复杂和手术难度高。但是,近年的研究证实,内脏的左右模式发育和气道粘液清除机制都需要动力纤毛；内脏异位、先心病和原发性纤毛运动障碍(Primary Ciliary Dyskinesis,PCD)之间存在密切关系。我们推测,气道纤毛功能障碍(Ciliary Dysfunction, CD)可能是导致先心病合并内脏异位患者术后呼吸道并发症高发的重要原因。本研究内容包括：1.通过临床病例对照研究,观察先心病合并内脏异位患者呼吸道并发症和预后情况；2.测定先心病合并内脏异位患者鼻窦一氧化氮浓度(Nasal Nitric Oxide, nNO)、气道纤毛运动,观察CD的发生率；3.探讨先心病家系成员和内脏异位核心家庭成员的CD。本研究旨在阐明纤毛功能障碍对先心病合并内脏异位患者呼吸道并发症的影响,揭示纤毛功能障碍在内脏异位中的作用机制,将有助于改善先心病的临床预后。第一部分合并内脏异位的先心病患者术后死亡率和呼吸道并发症的回顾性研究目的以合并先心病的内脏异位患者为研究对象,将不合并内脏异位的先心病患儿作为对照组,探究内脏异位患者的术后死亡率和呼吸道并发症发生率。方法对从2000年1月1日到2011年12月31日期间,在我院心血管中心接受心脏外科手术的患儿,进行一项回顾性病例对照分析；一共纳入了107例合并内脏异位的先心病患者作为研究组。同时纳入了876例仅患有先心病,而未患有内脏异位的患儿作为对照组。采用先天性心脏病手术风险校正评分(Risk Adjustment in Congenital Heart Surgery-1, RACHS-1)评分系统来确保两个组的手术复杂程度是相当的,两组的RACHS-1评分的中位数均为3.0。结果相比于不合并内脏异位的先心病患儿,内脏异位的患儿的术后病死率明显升高(16.8%相比于4.7%；OR：3.0)。平均住院时间(12.7天对比9.1天),机械通气时间(57小时对比42小时)和ICU时间(93小时对比71小时)要明显延长。此外,研究组的延长的机械通气(6.5%对比2.1%；OR：3.1),病危通知书(13.1%对比5.8%；OR：2.4),抢救(11.2%对比5.1%；OR：2.3),发热(66.4%对比34.9%；OR：37)和Up音(30.0%对比18.9%；OR：1.8)的发生率都高于对照组。小结在中国人群中,与具有RACHS-1评分相当的对照组患儿相比,合并内脏异位的先心病患儿的术后病死率和呼吸道并发症的发生率显著增高,提示内脏异位患者可能存在的呼吸道缺陷如纤毛活动障碍。第二部分合并内脏异位的先心病患者的呼吸道纤毛功能障碍研究目的研究CD对内脏异位患者术后高死亡率和呼吸道并发症的影响。方法招募共计32例合并内脏异位的先心病患者,同时纳入51例不合并内脏异位的先心病患者作为先心病对照组,100例健康受试者作为健康对照组。利用配有微分干涉差(Differential Interference Contrast, DIC)系统和高频摄像头的显微镜,对取自鼻粘膜的呼吸道表皮细胞的纤毛运动进行评估,并测量这些患者的nNO；并进行观察内和观察者间一致性检验。最后,对所有怀疑异常的鼻粘膜样本进行体外细胞培养,排查继发性CD。结果 1、32例内脏异位患者中有13例(40.6%)出现了CD,并且CD患者的nNO显著降低,其中有8例患者(61.5%)的nNO低于或接近PCD的临界值。 2、观察内和观察者间的一致性检验证实了利用显微摄像评估纤毛运动方法的可靠性。 3、共计9例CD的鼻粘膜样本培养成功,其中2例样本(22.2%)在培养后证实为继发性CD。小结 1、内脏异位患者的CD发生率高,CD伴有nNO值的降低。 2、利用显微摄像动态评估纤毛运动的方法是可靠的。 3、鼻粘膜细胞培养有助于CD病因的分析。第三部分先心病家系成员和内脏异位核心家庭成员的呼吸道纤毛功能障碍研究目的评估先心病家系成员和内脏异位核心家庭成员的CD分布情况,探讨CD的遗传特点方法招募了5个完整的先心病家系,评估家系成员的纤毛运动和nNO值；统计33个已知先心家系中的内脏异位患者数量；调查53个已知内脏异位患者的先心病家族史；分析CD在22个内脏异位核心家庭成员中的分布。结果 1、5个先心病家系中共计招募了35例先心病家系成员,CD共有13例(37.1%)其中有5例成员(38.5%)的nNO值低于或接近PCD的临界值。 2、在已取得联系的33个家系共计78例的先心病患者中,内脏异位患者7例(9.0%)。 3、53例已取得联系的内脏异位患者中,有7例(13.2%)患者具有先心病家族史。 4、22例内脏异位核心家庭成员共计有49人,其中11人为CD,分布在7个核心家庭中,其中有3例成员(27.2%)的nNO值低于或接近PCD的临界值。小结 1、先心病家系成员中CD的发生率显著增高,且部分CD成员nNO低于或接近PCD的临界值。 2、具有先心病家族史的先心病患者人群中,内脏异位发病率高,而内脏异位患者中先心病家族史多见。 3、内脏异位核心家庭成员CD的发生率显著增高,且部分CD成员nNO低于或接近PCD的临界值,提示CD具有明显的遗传倾向。
[Abstract]:Congenital heart disease (CHD) is one of common birth defects in newborn babies, the incidence rate of about 7.5 per 1000 ~ -9%, is a major cause of infant death within 1 years. The WHO data shows that about 1 million 500 thousand of children with congenital heart disease was born, which is about 150 thousand per year worldwide, 200 thousand children with congenital heart disease born in China every year. Heterotaxy is often associated with complex congenital heart disease in patients with congenital heart disease, research suggests that patients with visceral ectopic postoperative respiratory complications and high mortality rate, has been attributed to the complex heart malformation and operation difficulty is high. However, recent studies confirmed that the mode of development and visceral about airway mucus clearance mechanism need to dynamic cilia; visceral ectopic, congenital heart disease and primary ciliary dyskinesia (Primary Ciliary, Dyskinesis, PCD) there is a close relationship between. We speculate that airway cilia dysfunction (Ciliary Dysfunction, CD) may be the cause of congenital heart disease with high incidence of ectopic important causes of respiratory complications in postoperative patients with visceral. The research contents include: 1. through the clinical case-control study, observation of congenital heart disease with respiratory tract in patients with ectopic visceral complications and prognosis; 2. measured CHD patients with heterotopic sinus (Nasal Nitric Oxide, the concentration of nitric oxide nNO), airway ciliary movement, the incidence of CD was observed; 3. of CHD pedigrees and Heterotaxis core family members CD. the present study aimed to elucidate the effect on ciliary dysfunction in congenital heart disease complicated with visceral complications in patients with respiratory tract ectopic, mechanism of ciliary dysfunction in visceral ectopic, will help to improve the clinical prognosis congenital heart disease.
A retrospective study of postoperative mortality and respiratory complications in patients with congenital heart disease with visceral heterotopic heart disease
objective
The patients with congenital heart disease with heterotopic heart disease were selected as the control group.
Method
From January 1, 2000 to December 31, 2011 period, undergoing cardiac surgery in the cardiovascular center of our hospital were conducted a retrospective case-control analysis; a total of 107 cases with congenital heart disease in patients with heterotaxy. At the same time as the study group included 876 cases with congenital heart disease, without visceral endometriosis patients as control group the risk of congenital heart disease. Surgical correction score (Risk Adjustment in Congenital Heart Surgery-1, RACHS-1) scoring system to ensure that the two group is the complexity of the surgery, the median RACHS-1 score of two groups were 3.0.
Result
Compared to the patients without heterotaxy in children with congenital heart disease heterotaxic children postoperative mortality rate was significantly increased (16.8% compared to 4.7%; OR:3.0). The average hospitalization time (12.7 days vs. 9.1 days), mechanical ventilation time (57 hours compared to 42 hours) and ICU time (93 hours to 71 hours) to obviously prolonged. In addition, prolonged mechanical ventilation group (6.5% vs. 2.1%; OR:3.1), notice (13.1% vs. 5.8%; OR:2.4), rescue (11.2% vs. 5.1%; OR:2.3), fever (66.4% vs. 34.9%; OR:37) and Up (30% vs. 18.9%; OR:1.8.) the incidence is higher than that of control group.
Summary
In Chinese population, the incidence of postoperative mortality and respiratory complications of children with congenital heart disease with heterotopic heterotopic heart disease is significantly higher than that of children with RACHS-1 score. This suggests that there may be respiratory defects such as ciliary dyskinesia in patients with heterotopic viscera.
The study of respiratory cilium dysfunction in the second part of patients with congenital heart disease with visceral heterotopic heart disease
objective
The effect of CD on postoperative high mortality and respiratory complications in patients with visceral heterotopic surgery was studied.
Method
Recruit a total of 32 cases of patients with visceral ectopia in patients with congenital heart disease, also included 51 cases of congenital heart disease with heterotaxy patients with congenital heart disease as control group, 100 cases of healthy subjects as healthy control group. The use of a differential interference contrast (Differential Interference, Contrast, DIC) system and the high frequency camera microscope, ciliary movement of epidermis the cells of the respiratory tract from the nasal mucosa was assessed and measured in these patients were observed in nNO; and the inter observer consistency test. Finally, all suspected of nasal mucosa samples were abnormal in vitro, the investigation of secondary CD.
Result
In 13 cases (40.6%) of 1,32 heterotopic patients, CD appeared, and nNO in CD patients decreased significantly, of which 8 patients (61.5%) had nNO below or near the critical value of PCD.
2, the consistency test between observation and observer confirmed the reliability of using microphotography to evaluate ciliary movement.
3, a total of 9 cases of CD's nasal mucosa samples were cultured successfully, of which 2 cases (22.2%) were identified as secondary CD. after culture.
Summary
1, the incidence of CD in patients with visceral ectopia was high, and CD was accompanied by a decrease in the nNO value.
2, the method of dynamic evaluation of cilium motion by microphotography is reliable.
3, the cell culture of the nasal mucosa is helpful to the analysis of the cause of CD.
The study of respiratory cilium dysfunction in third part of the family members of congenital heart disease and the members of the visceral heterotopic core family
objective
The CD distribution of members of the family members of congenital heart disease and the members of the visceral heterotopic core family was evaluated and the genetic characteristics of CD were discussed.
Method
The recruitment of 5 complete congenital heart disease pedigrees, assessment of family members of ciliary movement and nNO value; counting the number of 33 known congenital heart disease in a family with congenital heart disease in patients with heterotaxy; investigation of 53 known Heterotaxis with family history; analysis of CD distribution in the 22 Heterotaxis core in the family members.
Result
A total of 35 cases of congenital heart disease family members were recruited in the 1,5 family of congenital heart disease, and CD had 13 cases (37.1%). Among them, 5 patients (38.5%) had nNO value below or near the critical value of PCD.
2, of the 33 families with a total of 78 cases of congenital heart disease, 7 cases of visceral ectopia (9%).
Of the 3,53 cases, 7 (13.2%) had a family history of congenital heart disease (13.2%).
The total number of visceral ectopic family members in 4,22 was 49, of which 11 were CD and distributed in 7 core families. 3 of the 3 members (27.2%) had nNO value below or near the critical value of PCD.
Summary
1, the incidence of CD in the members of the CHD family was significantly higher, and some of the CD members nNO were lower or close to the critical value of PCD.
2, among the patients with a family history of congenital heart disease, the incidence of ectopic ectopic disease is high, and the family history of congenital heart disease is common in the patients with visceral ectopia.
3, the incidence of CD in the family members of the visceral heterotopic family was significantly higher, and some of the CD members nNO were lower or close to the critical value of PCD, suggesting that CD has an obvious genetic tendency.

【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R725.4

【共引文献】