对支气管肺发育不良从“经典型”向“新型”转变的思考北大核心CSCD

支气管肺发育不良（bronchopulmonary dysplasia,BPD）是新生儿期常见的慢性肺部疾病,肺发育水平不仅影响BPD患儿的生存,也决定了幸存儿成年后的肺功能状况.随着新生儿救治水平的提高,早产儿尤其是极早早产儿和极低出生体重儿存活率明显上升,与高氧及气压伤相关的“经典型”BPD已不常见,代之出现与肺泡发育及肺血管发育受阻相关的“新型”BPD.     

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。     

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。     

早产儿支气管肺发育不良防治新理念

尽管新生儿医学在呼吸领域已取得显著进展,但支气管肺发育不良（BPD）在早产儿的发病率仍相当高。文章重点探讨近期研究对于无创通气技术作为极早早产儿的一种治疗模式的重要性的评估和对BPD发生率的影响。同时也探讨了与早产儿肺转归相关的其他治疗策略包括允许性高碳酸血症及糖皮质激素、支气管扩张剂、咖啡因、吸入一氧化氮的应用。     

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。     

大环内酯类抗生素防治早产儿支气管肺发育不良的研究进展

<正>支气管肺发育不良(bronchopulmonary dysplasia,BPD)是极低和超低出生体重早产儿常见的慢性呼吸系统疾病,严重影响早产儿的存活率及远期生活质量。2000年,美国国家儿童健康和人类发展研究院(NICHD)规范了BPD的诊断及分级标准~([1])。2019年,NICHD的报道显示,极早产儿(胎龄32周)BPD的     

高氧致细胞衰老在支气管肺发育不良中的作用

支气管肺发育不良(bronchopulmonary dysplasia,BPD)是一种可造成早产儿呼吸衰竭及死亡的慢性呼吸系统疾病,高氧暴露是其发生的主要危险因素。细胞衰老描述了一种细胞周期阻滞的状态,近年来有研究证实高氧暴露可以引起细胞衰老。细胞衰老在肺上皮、肺间质、肺血管以及气道发育过程中起着至关重要的作用,且这些组织的异常发育与BPD的发生相关。因此,该文以细胞衰老和BPD为切入点进行综述,探讨高氧致细胞衰老在BPD发生发展中的作用机制以及目前应用于临床的抗衰老药物,以期为BPD的防治提供新方向。     

高氧致细胞衰老在支气管肺发育不良中的作用

支气管肺发育不良(bronchopulmonary dysplasia, BPD)是一种可造成早产儿呼吸衰竭及死亡的慢性呼吸系统疾病, 高氧暴露是其发生的主要危险因素。细胞衰老描述了一种细胞周期阻滞的状态, 近年来有研究证实高氧暴露可以引起细胞衰老。细胞衰老在肺上皮、肺间质、肺血管以及气道发育过程中起着至关重要的作用, 且这些组织的异常发育与BPD的发生相关。因此, 该文以细胞衰老和BPD为切入点进行综述, 探讨高氧致细胞衰老在BPD发生发展中的作用机制以及目前应用于临床的抗衰老药物, 以期为BPD的防治提供新方向。     

支气管肺发育不良早产儿婴儿期预后研究

目的 探讨支气管肺发育不良（BPD）患儿婴儿期体格发育、呼吸系统常见疾病发生情况以及运动发育情况。方法 回顾性分析2012年1月至2015年12月入住新生儿重症监护室的BPD早产儿的临床特征和婴儿期结局，并与同期住院胎龄及出生体重相近但未发生BPD的早产儿进行比较，比较两组早产儿婴儿期生长发育和运动发育情况、住院次数以及肺炎、喘息等疾病的发生情况。结果 与非BPD组患儿相比，BPD组患儿出院时更容易发生宫外发育迟缓（48% vs 41%），且生后更容易发生肺炎、喘息、湿疹、鼻炎，因呼吸道感染再次住院次数增加，差异均具有统计学意义（P < 0.05）。矫正3月龄、6月龄及12月龄时BPD组患儿头围小于非BPD组（P < 0.05）。矫正6月龄及9月龄时BPD组患儿粗大运动、精细运动以及总发育商均落后于非BPD组患儿（P < 0.05）。结论 BPD患儿出院时容易发生宫外发育迟缓，头围增长相对缓慢，婴儿期易发生肺炎及喘息，而且矫正6月龄及9月龄运动发育落后于非BPD早产儿。     

早产儿支气管肺发育不良相关肺动脉高压诊治研究进展

支气管肺发育不良(BPD)相关肺动脉高压(PH)是早产儿BPD最严重的并发症,是BPD患儿后期死亡的重要原因,近年日益受到关注。肺血管发育异常和重构是PH发生的病理基础。对中重度BPD患儿进行监测和筛查肺动脉压力,可早期诊断BPD相关PH,对BPD相关PH早期防治、改善预后具有重要意义。由于BPD相关PH为慢性过程,持续时间长,治疗仍然比较困难,主要药物是肺血管扩张剂,尚缺乏足够的证据支持,有待更多的研究进一步验证其有效性和安全性。     

Chronic lung disease in newborns

Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) occurs in preterm infants who require respiratory support in the first few days of birth. Apart from prematurity, oxygen therapy and assisted ventilation, factors like intrauterine/postnatal infections, patent ductus arteriosus, and genetic polymorphisms also contribute to its pathogenesis. The severe form of BPD with extensive inflammatory changes is rarely seen nowadays; instead, a milder form characterized by decreased alveolar septation due to arrest in lung development is more common. A multitude of strategies, mainly pharmacological and ventilatory, have been employed for prevention and treatment of BPD. Unfortunately, most of them have not been proved to be beneficial. A comprehensive protocol for management of BPD based on the current evidence is discussed here.     

Prevention of bronchopulmonary dysplasia

The clinical syndrome of bronchopulmonary dysplasia (BPD) in preterm infants results primarily from an arrest of lung vascular and alveolar development. The most likely mediators are proinflammatory cytokines that are induced by antenatal exposure to infection, postnatal ventilation, and oxygen exposure. New epidemiologic data suggest that attempts to avoid intubation and ventilation are the best ways to avoid severe BPD. The claim that one ventilation technique is better than another remains unconvincing, and any strategy that maintains the lung open and minimizes tidal volumes probably will be helpful. More adverse effects of postnatal steroids are being recognized. New insights into the pathophysiology of BPD and a new emphasis on minimizing ventilation and ventilator-mediated injury should improve outcomes for very preterm infants.     

早产儿机械通气治疗的研究进展

机械通气在治疗早产儿严重并发症尤其是呼吸系统疾病中起着非常重要的作用.随着产前及新生儿期护理技术和治疗策略的改进,早产儿生存率逐年增加,支气管肺发育不良的发生率也在持续增加,严重影响早产儿的预后.近年新生儿学者在非侵袭性呼吸支持技术对减轻肺损伤、降低早产儿并发症方面进行了许多有益的探索.本文就不同机械通气模式在治疗早产儿呼吸衰竭中的作用及肺保护策略在降低早产儿肺损伤中的应用现状进行综述.     

The use of inhaled glucocorticosteroids and recovery from adrenal suppression after systemic steroid use in a VLBW premature infant with BPD: case report and literature discussion

Despite development of many prevention and treatment modalities for bronchopulmonary dysplasia (BPD), a form of chronic respiratory insufficiency in premature infants recovering from respiratory distress syndrome, BPD remains a treatment challenge and a significant cause of long-term morbidity. A ventilator-dependent very low birth weight infant in our newborn special care unit was receiving multiple courses of systemic dexamethasone for severe respiratory failure. The infant demonstrated adrenal suppression manifested by a baseline cortisol concentration below reported levels in infants of similar birth weight and postnatal age. We hypothesized that he had developed adrenal insufficiency as a result of the prolonged systemic steroid administration used to treat his respiratory problems. We further hypothesized that inhaled beclomethasone therapy would aid in the infant's recovery phase during relative adrenal insufficiency--and so substituted inhaled for systemic steroids. Inhaled corticosteroid treatment improved the clinical respiratory course and postnatal growth of this premature infant with BPD without inhibiting his recovery from adrenal insufficiency.     

Mechanisms initiating lung injury in the preterm

Bronchopulmonary dysplasia (BPD)/chronic lung disease occurs primarily in very low birth weight infants (VLBW) often without antecedent severe respiratory distress syndrome. The BPD in these VLBW infants results in less fibrosis than the traditional BPD but the normal process of alveolarization seems to be disrupted. This review develops the thesis that BPD in VLBW infants results from inflammatory mediators interfering with the signaling required for normal late gestational lung development. Proinflammatory mediators may be elevated because of fetal exposure, postnatal infection or by release from preterm lungs ventilated at either low or high lung volumes. The preterm lung is highly susceptible to injury during resuscitation or more chronic mechanical ventilation because the gas volumes/kg body weight of the lungs are small. An understanding of what causes cytokine release and how cytokines influence lung development is necessary to develop targeted therapies to minimize BPD. However, care strategies that minimize inflammation and ventilator-induced lung injury should help decrease BPD.     

What is bronchopulmonary dysplasia and does caffeine prevent it?

Bronchopulmonary dysplasia (BPD) is among the most severe complications of very premature birth. Clinical and laboratory studies indicate that lung immaturity, inflammatory lung injury, and disordered lung repair are the primary mechanisms responsible for the development of BPD. Caffeine, initiated within the first 10 days after birth, is one of few drug therapies shown to significantly decrease the risk of BPD in very low birth weight infants. This benefit is likely derived, at least in part, from reduced exposure to positive airway pressure and supplemental oxygen with caffeine therapy. Additional cardiorespiratory benefits of caffeine that may contribute to the lower risk of BPD include less frequent treatment for a PDA, improved pulmonary mechanics, and direct effects on pulmonary inflammation, alveolarization, and angiogenesis. Routine administration of caffeine is indicated in the vast majority of very low birth weight infants. However, current preventative strategies including widespread use of caffeine do not avert BPD in all cases. As such, there is continued need for novel methods to further reduce the risk of BPD in very low birth weight infants.     

Prenatal inflammation and lung development

Prenatal exposure of very low birth weight infants to chronic indolent chorioamnionitis with organisms such as mycoplasma and ureaplasma is frequent. Chorioamnionitis is inconsistently associated with changed risks of respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD), probably because the diagnosis of chorioamnionitis does not quantify the extent or duration of the fetal exposures to infection and inflammation. The correlations between prenatal exposures and postnatal lung disease also are confounded by the imprecision of the diagnoses of RDS and BPD. In animal models, chorioamnionitis caused by pro-inflammatory mediators or live ureaplasma induces lung maturation, but also causes alveolar simplification and vascular injury. Intra-amniotic endotoxin administration also modulates the fetal innate immune system, resulting in maturation of monocytes to alveolar macrophages and the induction or paralysis of inflammatory responses depending on exposure history. Prenatal inflammation can have profound effects on the fetal lung and subsequent immune responses.     

Plasma 3-nitrotyrosine is elevated in premature infants who develop bronchopulmonary dysplasia

OBJECTIVE: Premature infants are susceptible to bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy that appears to be caused in part by oxidative stress from hyperoxia. To investigate the possible role of nitric oxide-derived oxidants such as peroxynitrite in the etiology of BPD, we measured levels of plasma 3-nitrotyrosine, which is produced by the reaction of peroxynitrite with proteins. PATIENTS AND METHODS: Ten premature infants who developed BPD, defined as requiring supplemental oxygen beyond 36 weeks' postmenstrual age, were identified retrospectively from a group of subjects enrolled in a clinical trial of antenatal therapy. Serial plasma samples had been collected on these infants during the first month of life as part of the trial. Sixteen comparison premature infants were identified from the same population: 5 had no lung disease, 6 had respiratory distress syndrome that resolved, and 5 had residual lung disease at 28 days of life that resolved by 36 weeks' postmenstrual age. Plasma 3-nitrotyrosine levels were measured using a solid phase immunoradiochemical method. RESULTS: All 3-nitrotyrosine values in infants without BPD were <0.25 ng/mg protein, and levels did not change with postnatal age. Plasma 3-nitrotyrosine concentrations were significantly higher in infants with BPD, increasing approximately fourfold during the first month of life. For the 20 infants who had blood samples available at 28 days of life, plasma 3-nitrotyrosine levels correlated with the fraction of inspired oxygen that the infant was receiving (r = 0.7). CONCLUSION: Plasma 3-nitrotyrosine content is increased during the first month of life in infants who develop BPD. This suggests that peroxynitrite-mediated oxidant stress may contribute to the development of this disease in premature infants and that 3-nitrotyrosine may be useful as an early plasma indicator of infants at risk for developing BPD.