早产儿支气管肺发育不良的诊治新进展

支气管肺发育不良(BPD)是目前早产儿最常见的并发症之一,已经成为新生儿重症监护病房最棘手的问题之一。BPD的发病机制极其复杂,目前尚无有效的治疗方法。现主要介绍国内外有关早产儿BPD的最新定义、发病机制、诊断及治疗新进展。     

上皮间充质转化的信号传导在支气管肺发育不良中的研究进展

随着围生期医疗技术的迅速发展, 早产儿的存活率明显提高, 但支气管肺发育不良(bronchopulmonary dysplasia, BPD)发病率仍处于高水平。BPD是早产儿常见的慢性呼吸道疾病, BPD早产儿合并其他并发症的发生率和病死率显著增高。目前以肺损伤为特征的"经典BPD"已经转换为"新型BPD", 然而BPD的病理生理机制尚未阐明。近年来, 一些体外和体内实验研究已经证实, 肺泡Ⅱ型上皮细胞能以转化生长因子-β为枢纽, Wnt、SPHK1/S1P等多重信号通路诱导上皮间充质转化从而促进肺纤维化的发生, 为防治BPD提供了新的思路。该文综述EMT中的多种信号传导途径在BPD中的作用机制, 以期为临床治疗BPD提供参考。     

支气管肺发育不良的动物模型造模方法及其评价

随着新生儿救治水平的提高,早产儿尤其是极早早产儿和超低出生体重儿的存活率明显提高,导致支气管肺发育不良(BPD)的发病率逐年增加,BPD已成为早产儿,尤其是小早产儿最常见的呼吸系统疾病之一。肺泡发育受阻是导致BPD发生的重要原因,研究肺泡发育受阻机理及促进肺泡发育的干预措施是BPD研究的热点,选择合适的BPD动物模型是BPD基础研究获得有意义的研究结果的关键。基于此,本文总结及评价了几种常见的BPD动物模型造模方法及其产生的相应病理生理学改变,以期对BPD的发病机制、病理生理和防治对策的研究选择动物模型提供依据。     

极低与超低出生体重儿动脉导管未闭管理与支气管肺发育不良发生的关系

早产儿支气管肺发育不良( bronchopulmonary dysplasia,BPD)是早产儿特别是极低和超低出生体重儿常见的并发症之一。 BPD在其发生发展过程中受到多种因素的影响,其中动脉导管未闭( patent ductus arteriosus,PDA)及其临床管理,特别是PDA不同的治疗方案和治疗时机的选择对BPD发生的影响受到广泛关注。本文总结了早产儿PDA管理与BPD发生关系的研究进展,并在此基础上提出可能有利于降低早产儿BPD发生率的PDA管理建议。     

早产儿支气管肺发育不良预测生物标志物的研究进展

支气管肺发育不良症(bronchopulmonary dysplasia,BPD)是早产儿、尤其是小早产儿呼吸系统常见疾病,具有独特的临床、影像学及组织学特征.目前其确切的病因和发病机制尚不明确,无特效治疗方法.现有的研究主要以筛选出高危儿及预防为主,其中预测BPD的可能生物标志物是研究重点.该文就近年来国内外对血液中BPD预测的生物标志物作一综述.     

新生儿呼吸窘迫综合征及支气管肺发育不良防治进展

新生儿呼吸窘迫综合征(NRDS)和支气管肺发育不良(BPD)常见于早产儿。近年来,随着围生期医疗技术水平的提高,NRDS早产儿的存活率也得以提升,但随着机械通气及高浓度氧疗的应用,BPD的发病率也逐渐升高。NRDS与BPD有着相同的基因因素,SP-B缺失与NRDS及BPD的发生发展均相关。两者在发病机制上也有所联系,规范防治NRDS可在一定程度上有效预防BPD。文章对NRDS与BPD防治的最新进展作一综述。     

早产儿气管分泌物中血管内皮生长因子的表达

目的 探讨早产儿气管内分泌物中血管内皮生长因子(VEGF)表达以及在支气管肺发育不良(BPD)中的作用.方法 选取我院2007年至2009年住院的需要机械通气治疗的早产儿50例,收集其气管内分泌物,采用酶联免疫吸附法检测VEGF表达.结果 早产儿治疗4周后,42.6%(20/47)有BPD,其气管内分泌物中VEGF表达水平明显低于无BPD的患儿.结论 早产儿VEGF表达降低可能是BPD发病原因之一.     

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支气管肺发育不良(bronchopulmonary dysplasia,BPD)是早产儿、尤其是小早产儿呼吸系统常见疾病。近年来,由于早产儿存活率提高,BPD发生率也有逐年增加的趋势,并成为新生儿重症监护病房(neonatal intensive care unit,NICU)最为棘手的问题之一,也是婴儿期慢性呼吸系统疾病的主要病因,严重影响早产儿存活率及生活质量。因此是目前国内外新生儿学科热门课题。1BPD的定义经典型BPD由Northway[1]于1967年首次报道,其主要特点为:(1)均为早产儿,但胎龄和出生体重相对较大(平均胎龄34周、出生体重2.2kg);(2)原发疾病为严重呼吸窘迫综合征(re…     

呼吸道微生态与早产儿支气管肺发育不良

早产儿支气管肺发育不良(bronchopulmonary dysplasia,BPD)是早产儿呼吸系统严重的合并症,其病因及发病机制复杂,目前尚未明确。近年来,有研究表明呼吸道微生态的改变与BPD的发生发展存在一定关联,在早产儿发展为BPD之前,其呼吸道微生态已经发生了改变,包括微生物多样性和演变方式的异常。因此,研究新生儿呼吸道微生态的定植和演变以及与BPD的关系,可为其防治提供新的思路。     

新生儿支气管肺发育不良危险因素研究进展

新生儿支气管肺发育不良( bronchopulmonary dysplasia,BPD)随早产儿存活率提高,患病人数逐年增加[1],防治BPD已成为早产儿治疗的重要目标.早期研究的BPD主要发生于胎龄32周、出生体重1900 G的早产儿,以严重的呼吸窘迫综合征为原发疾病,有长期接受高浓度氧、高气道压力机械通气的病史,且持续用氧超过28天,并存在典型的胸部X线改变.     

间充质干细胞移植治疗新生儿支气管肺发育不良:机遇与挑战

支气管肺发育不良（BPD）是新生儿尤其是早产儿最常见的慢性肺部疾病，是导致早产儿预后不良的重要原因，目前临床使用的治疗手段仍然难以很好改善其预后。近年来，实验及临床研究发现间充质干细胞移植对BPD有一定疗效，可能成为未来最有希望的治疗手段。该文就间充质干细胞的特点、间充质干细胞移植治疗BPD的可能机制及临床试验的安全性和可行性，以及进一步相关临床研究面临的挑战进行阐述。     

Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants who have been treated with supplemental oxygen and mechanical ventilation. Despite major advances in perinatal and neonatal medicine, limited progress has been made in reducing BPD rates. The use of mesenchymal stem cells (MSC) is a promising and innovative therapy for several diseases because they are easy to extract and they have low immunogenicity, anti‐inflammatory properties, and regenerative ability. According to several pre‐clinical studies that have used BPD animal models, one mechanism of action for MSC in BPD is mainly due to the paracrine effects of MSC‐derived humoral factors, such as interleukin (IL)‐6, IL‐8, vascular endothelial growth factor, collagen, and elastin, rather than the multilineage and regenerative capacities of MSC. Cell‐free preparations derived from MSC, including conditioned media and exosomes, remain a pre‐clinical technology despite their great clinical potential. A first‐in‐human clinical trial of MSC treatment for BPD was performed as a phase I dose‐escalation trial using umbilical cord blood‐derived MSC. That trial demonstrated the short‐ and long‐term safety and feasibility of MSC, given that significantly reduced inflammatory marker expression was observed in tracheal aspirates. As of recently, several clinical trials of MSC use for BPD are ongoing or are planned in some countries to investigate the efficacy of MSC in the prevention or treatment of BPD in premature infants. Many clinicians are currently awaiting the results from these trials so that MSC can be used clinically for human BPD.     

Bronchopulmonary dysplasia and surfactant

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants who survive prolonged mechanical ventilation. Exogenous surfactant administration clearly reduces the severity of respiratory distress syndrome (RDS) and consequently the need for aggressive ventilation and prolonged oxygen therapy. However, the overall incidence of BPD has not decreased but in fact may even have increased after the introduction of surfactant therapy. There are several reasons for the lack of effect on the incidence of BPD. First, surfactant therapy and antenatal steroids have markedly increased survival of the smallest infants, i.e. those at higher risk of BPD. Second, there has been a change in the pathogenesis and the presentation of BPD. While the classic BPD was mainly the consequence of barotrauma and oxygen toxicity, the new BPD seen in the surfactant era results from the interaction of many factors that lead to prolonged mechanical ventilation and colonization of the airway with pathogens that may trigger an inflammatory cascade. While the overall incidence of BPD has not been substantially modified by surfactant therapy, the more severe cases of BPD have become less common. The data regarding the effect of surfactant administration on the incidence and severity of BPD is conflicting. There is substantial evidence that the administration of exogenous surfactant, either as prophylaxis or as a treatment in infants with established RDS, can reduce neonatal mortality and the occurrence of BPD or death. The data also suggest that prophylactic or early administration is more effective than late treatment in reducing mortality and BPD or death. No clear difference has been documented between natural or synthetic surfactant treatment in terms of their effect on incidence of BPD or mortality. The lack of consistency in the results with surfactant replacement may reflect the changing pathogenesis of BPD and the multiplicity of factors involved among which surfactant deficiency is only one.     

Nasal CPAP and surfactant for treatment of respiratory distress syndrome and prevention of bronchopulmonary dysplasia

The Scandinavian approach is an effective combined treatment for respiratory distress syndrome (RDS) and prevention of bronchopulmonary dysplasia (BPD). It is composed of many individual parts. Of significant importance is the early treatment with nasal continuous positive airway pressure (nCPAP) and surfactant treatment. The approach may be supplemented with caffeine citrate and non-invasive positive pressure ventilation for apnoea. The low incidence of BPD seen as a consequence of the treatment strategy is mainly due to a reduced need for mechanical ventilation (MV).
Conclusion:  Early-postnatal treatment with nCPAP and surfactant decreases the severity and mortality of RDS and BPD. This is mainly due to a diminished use of MV in the first days of life.     

支气管肺发育不良诊断标准的研究进展

支气管肺发育不良(BPD)是早产儿,特别是极早产儿及超早产儿中常见的呼吸系统疾病,发病率有逐年增高趋势,且伴随多种并发症,远期预后不良。BPD诊断标准是其临床研究及诊断和治疗发展的基础。文章总结20世纪60年代以来BPD诊断标准的变迁,着重分析并比较21世纪初以来BPD诊断及分级标准的发展,包括2001年美国国家儿童和人类发展研究所的BPD共识,及在此基础上进行衍生的,分别于2018和2019年提出的改善后的新标准,讨论其分别的优势及不足。总体综述BPD诊断标准的发展,以期为制定符合我国临床的BPD诊断标准提供依据。     

血管内皮生长因子在支气管肺发育不良方面的研究进展

支气管肺发育不良(BPD)是早产儿中常见的慢性呼吸系统疾病,以肺泡发育受损和血管生长异常为特征的"新型BPD"的发生率呈逐年增高趋势。肺血管生长是影响肺发育的关键,血管内皮生长因子(VEGF),作为血管发生的核心因子,与BPD发生存在一定的相关性。研究表明,BPD的早产儿及高氧BPD模型动物,体内血管内皮生长因子表达水平在不同时间点可有不同程度的下降;抑制动物血管发育,可导致肺血管数目减少,辐射状肺泡计数下降,出现BPD样结构改变。通过病毒介导基因干预或肌肉注射等方式,将适量外源性VEGF带入BPD模型动物体内,则可改善肺血管发育,增加辐射状肺泡计数;但VEGF过表达也可导致肺水肿、肺出血等不良反应。文章综述了临床BPD及BPD模型动物VEGF蛋白表达,及VEDF在BPD动物模型治疗方面的研究进展。     

咖啡因对早产儿支气管肺发育不良的预防作用

随着危重早产儿及极早早产儿的抢救成功率不断增高,新生儿支气管肺发育不良（BPD）的发生率呈逐年增加的趋势。该病病死率高、遗留后遗症可能性大,严重影响存活早产儿的生存质量,并给患儿家庭带来严重负担,因此BPD的治疗至关重要。国内外学者对BPD治疗措施的意见尚不统一,但在近年来的研究中已证实咖啡因的早期使用具有预防BPD的作用。笔者查阅国内外对咖啡因预防BPD的最新研究,就咖啡因减少肺部炎症、改善肺损伤的形态学异常、减少氧化应激损伤、改善肺功能等方面,对咖啡因预防BPD的机制进行综述。     

糖皮质激素防治早产儿支气管肺发育不良的进展及争议

摘要: 支气管肺发育不良(BPD)是早产儿最严重的并发症之一,在诸多防治方法中,糖皮质激素的应用目前仍最具争议性。糖皮质激素治疗早产儿呼吸系统疾病早在1957年就有报道。在上世纪90年代糖皮质激素成为BPD预防与治疗的常规用药。因全身糖皮质激素治疗的并发症,自1999年糖皮质激素的使用开始减少。近年来,亦有很多文献对糖皮质激素治疗BPD进行了综述及报道,但结果参差不齐,正负面结果并存。建议临床医师应慎重使用糖皮质激素,并使用可能最低的剂量和最短的疗程。     

Progress in discovery and evaluation of treatments to prevent bronchopulmonary dysplasia

BACKGROUND: Recent improvements in the survival of extremely preterm infants have been accompanied by evolution in the pathogenesis and histopathology of bronchopulmonary dysplasia (BPD). Although oxygen and barotrauma-induced injury remain important contributing factors, pulmonary developmental arrest appears to play an equally important causal role in prolonged respiratory illness, especially among the most immature surviving preterm newborns. To date, clinical trials have failed to demonstrate a substantial benefit of a single treatment or preventive strategy for BPD. OBJECTIVES: To evaluate the current evidence in favor of treatments that might prevent BPD. METHODS: Review of clinical studies of preventive treatment strategies for BPD. RESULTS: High frequency oscillatory ventilation, permissive hypercapnea, and inhaled nitric oxide might offer benefit to infants at risk of BPD. These and other potential preventive therapies for BPD, such as superoxide dismutase, inositol, and alpha(1)-proteinase inhibitor, deserve further study. CONCLUSIONS: Although some current treatments offer promise, no preventive therapy for BPD has proven safe and effective, except for intramuscular vitamin A. Additional studies of respiratory technologies, management strategies, and protective molecules are needed.     

间充质干细胞治疗支气管肺发育不良作用机制的研究进展

支气管肺发育不良（bronchopulmonary dysplasia,BPD）是一种因早产儿肺发育受阻和损伤而导致的慢性肺疾病,是造成早产儿呼吸衰竭的主要病因之一。合并BPD的早产儿其他并发症发生率和病死率显著高于一般早产儿。目前主要通过综合管理对BPD进行干预,包括合理的呼吸循环支持,恰当的肠内、外营养,咖啡因、糖皮质激素及肺表面活性物质等药物的应用和出院后的院外管理。近年来干细胞医学的不断进展为治疗BPD提供了新的思路。多项临床前试验已证实干细胞治疗在有效避免肺损伤的同时促进肺的生长和损伤修复。因此,该文对间充质干细胞治疗BPD的作用机制进行全面分析,以期为临床应用提供依据。