支气管肺发育不良的研究进展

支气管肺发育不良(BPD)是早产儿最常见的严重呼吸系统疾病。随着产前糖皮质激素的应用、呼吸支持的改善、肺表面活性物质(PS)的应用,经典型BPD发病率有所降低,新型BPD发生率有所增多,其发病机制主要是在基因易感性的基础上,宫内和出生后的多重打击引起促炎、抗炎因子的级联反应,对发育不成熟的肺引起损伤,以及损伤后血管化失调和肺组织异常修复。在治疗上无满意的治疗策略,目前常采用的方法包括保持适当的血氧含量,允许性高碳酸血症,早期使用无创呼吸支持,使用气管内插管-PS使用-尽早拔管改用无创呼吸支持模式,常用药物为咖啡因、类固醇、外源性PS等,但具体效果仍存在争议。     

Expression of Laminin and Fibronectin in Renal Dysplasia

The pathogenesis of renal dysplasia is a matter of debate. Recent theories have conceptualized the role of extracellular matrix proteins in the genesis of renal dysplasia. During normal nephrogenesis, collagen type I and III and fibronectins are lost and laminin and syndecan appear once proper induction has occurred. Any deviation from the normal pattern is said to lead to dysplasia. In this study, the expressions of adhesive glycoproteins, laminin, and fibronectin were studied immunohistochemically in 25 autopsy cases of renal dysplasia and normal age-matched control cases. These cases of renal dysplasia were categorized into 3 groups based on the period of gestation: 20 to 26 weeks, 27 to 33 weeks, and 34 to 40 weeks. The immunohistochemical findings were graded from 0 to 4+ based on the visual intensity. Chi-square analysis was used to calculate the difference in expressions of laminin and fibronectin in cases and controls as a whole and within and between age groups. Immunostaining for laminin in all age groups showed a significant difference in expression between dysplastic kidneys (less expression) and normal controls (greater expression). In the case of fibronectin expression, all but 1 group showed a significant difference, with dysplastic kidneys showing more and normal controls showing less expression. The inference derived is that laminin expression decreases and fibronectin expression increases in renal dysplasia compared with normal nephrogenesis.     

胰岛素样生长因子结合蛋白5在高体积分数氧致新生鼠慢性肺疾病的表达及其作用机制

目的研究胰岛素样生长因子结合蛋白5（IGFBP-5）在高体积分数氧致新生大鼠慢性肺疾病（CLD）中的表达及作用机制。方法将足月新生大鼠96只随机分为高体积分数氧组（高氧组）和空气组，分别于实验1、3、7、10、14、21d应用免疫组织化学和RT—PCR技术检测IGFBP-5的动态表达及阳性表达部位。结果CLD时IGFBP-5呈动态变化。高氧组和空气组比较，在实验3～10d IGFBP-5表达明显增强，14051121d表达明显降低。阳性部位在支气管上皮细胞、肺泡上皮细胞、成纤维细胞、血管周围和间隔的间质细胞。结论IGFBP-5参与CLD发生，作为胰岛素样生长因子-I的抑制因子发挥作用。     

Bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is the most common sequelae of preterm birth. It has proven a difficult condition to define as improving early management of the premature infant has led to a changing clinical picture over time. However, despite the advances in neonatal care, rates of BPD are at best unchanged and may even have risen. As BPD has significant long-term consequences, particularly from respiratory, cardiovascular and neurodevelopmentary perspectives, effective early management is key to improving long term outcomes. In this review the various definitions of BPD, and their limitations, are discussed alongside the evidence behind effective management of preterm infants, including the long-term management needed after discharge from hospital.     

支气管肺发育不良的研究进展

支气管肺发育不良是由于发育不成熟等多种因素共同作用下致肺泡和肺内血管发育受阻的一种慢性肺疾患,是由于早产、治疗损伤、感染和炎症等多种因素共同作用的结果。该病需采用综合的方法来预防和治疗,包括产前糖皮质激素的应用、合适的呼吸及营养支持、防治感染、抗炎及抗氧化治疗等。要想找到更有效的防治方法,需加强基础和临床研究,特别是对肺发育和该病发生机制的研究。     

Bronchopulmonary dysplasia in very low birth weight infants

Objective  The developments in newborn care have enabled many more very low birth weight premature infants to live. The aim of our study was to determine the risk factors for bronchopulmonary dysplasia (BPD) development by evaluating mild and moderate/severe BPD in extramural neonates with a birth weight <1501 g. Methods  A case-control study was conducted between January 1, 2004- December 31, 2006 at the Dr. Sami Ulus Children’s Hospital Neonatal Intensive Care Unit. Patients with BPD and without BPD were compared. Bronchopulmonary dysplasia was diagnosed and classified according to the Bancalari criteria. One-hundred and six (106) extramural premature infants with a birth weight <1501 g and admitted to the Neonatal Unit in the first three days of life and survived for more than 28 postnatal days were included. Patients with multiple congenital anomalies and complex cardiac pathologies were excluded. The maternal and neonatal risk factors, clinical features, mechanical ventilation treatment were compared. The principal risk factors for BPD development were analyzed and followed by logistic regression test. Results  The diagnosis was mild BPD in 27 of the 106 patients and moderate/severe BPD in 29. The incidence of BPD was 52.8%. Fifty of 106 patients had no BPD. Analysis of risk factors revealed that gestational age ≤28 weeks (p=0.019), birth weight ≤1000 g (p=0.007), hypothermia (p=0.003), acidosis (p=0.003) and hypotension (p=0.005) at admission, respiratory distress syndrome (RDS) ( p<0.001), mechanical ventilation therapy (p<0.001), surfactant therapy (p=0.005), higher amount of mean fluid therapy on 7^th days (p=0.008), nosocomial infection (p<0.001), higher amount of mean packed red cell transfusions (p<0.001) and more than two packed red cell transfusions (p=0.033) were risk factors associated with the development of BPD. Multivariant logistic regression analysis showed acidosis at admission (OR 5.12, 95%CI 1.17–22.27, p=0.029), surfactant treatment (OR 7.53, 95%CI 2.14–26.45, p=0.002), nosocomial infections (OR 4.66, 95%CI 1.27–17.12, p=0.02) and PDA (OR 9.60, 95%CI 2.23–41.22, p=0.002) were risk factors increasing the severity of BPD. Conclusion  The most important risk factors for BPD development in our study were RDS and nosocomial infections while the presence of acidosis at admission, surfactant administration, nosocomial infections and the presence of PDA were the most important risk factors regarding BPD severity. Presence of acidosis at admission as a risk factor emphasized the importance of suitable transport conditions for premature infants.     

新生儿支气管肺发育不良诊治进展

支气管肺发育不良（bronchopulmonarydy splasia,BPD）是一种慢性肺部疾病,常见于长期氧疗和机械通气的早产儿。BPD由Northway于1967年首次报道,近年来其发生率有逐年增加的趋势,并成为NICU最为棘手的问题之一以及婴儿期慢性肺疾病（CLD）的主要病因。产前糖皮质激素和出生后外源性表面活性物质的应用,以及保护性通气策略实施,使BPD表现形式发生了很大变化,更为常见的是一种轻型BPD（又称为“neWBPD”）,这种“newBPD”与40年前的“oldBPD”从病因、病理改变及临床表现等方面均有很大区别。文章对BPD最新定义、诊断标准及治疗进展作一介绍。     

Bronchopulmonary dysplasia: An update

Bronchopulmonary dysplasia (BPD) is a chronic lung disease associated with premature birth and characterized by early lung injury. Over the past 4 decades, there have been significant changes in its definition, pathology and radiological findings as well as management of BPD. Management of the acute phase and later stages of this lung disease continue to evolve. Use of non-invasive ventilatory techniques, recombinant human SOD and CC10 and inhaled NO are some novel approaches that are being studied. Adequate nutrition is vital to optimize lung growth and repair. The widely accepted practice of prophylaxis against viral infections has markedly decreased the rates of rehospitalization. Infants with BPD, however, continue to have significant pulmonary and neurodevelopmental sequelae. Unraveling the genetic contribution to BPD will potentially pave the way to improved preventive and therapeutic approaches.     

Dexamethasone in the Treatment of Bronchopulmonary Dysplasia

Benini, F., Rubaltelli, F. F., Griffith, P., Sala, M. and Zorzi, C. (Department of Paediatrics, University of Padova, Italy). Dexamethasone in the treatment of bronchopulmonary dysplasia. Acta Paediatr Scand Suppl 360: 108, 1989.
Sixteen chronically ventilator-dependent newborns with BPD were treated with one or more cycles of dexamethasone (0.5 mg/kg/day). In 11 cases extubation was possible during the therapy period. Ventilatory parameters were lowered in 3 other newborns. FIO₂, respiratory rate, PIP, and PEEP, assessed before and after dexamethasone administration, decreased in a statistically significant way. Our data confirm the utility of dexamethasone in the extubation in chronically ventilated infants with BPD.     

支气管肺发育不良分子遗传学研究进展

支气管肺发育不良(BPD)的发病率在我国呈逐年上升趋势,但其病因及发病机制尚不十分清楚,研究表明,BPD的发生不仅与早产及氧体积分数等外源性因素有关,且有较大的遗传易感性。现就肺表面活性物质、基质金属蛋白酶、血管内皮生长因子、TNF、转化生长因子-β和结缔组织生长因子等在BPD发生发展中的调节作用的研究进展进行综述。     

Composition of the Pulmonary Interstitium during Normal Development of the Human Fetus

Normal lung development is dependent on epithelial–mesenchymal interactions. This study was undertaken to examine the structure of the interstitium of the developing human fetal lung, concentrating particularly on the first and second trimesters. Lung tissue was obtained at autopsy from nonmalformed, nonmacerated cases of spontaneous abortion (n = 15), stillbirth (n = 9), and very early neonatal death (n = 5) (range of gestations, 10–42 weeks). Paraffin-embedded tissue sections were examined using immunohistochemical methods to determine expression of collagens I, III, IV, V, and VI; the glycoproteins fibronectin and laminin; and the intermediate filaments vimentin, α-smooth muscle actin (αSMA), and desmin. Collagens III and VI and cells expressing αSMA were present consistently at points of airway branching and secondary crest formation, indicating a role for these components in the initiation and stabilization of airway branches in the developing lung. Desmin expression by stromal cells succeeded αSMA temporally, and may represent a marker of terminal smooth muscle differentiation within the airway; it was not detected in the vascular tree. Other components were widely expressed throughout the extracellular matrix, including basement membranes, at all gestations. The spatial and temporal patterns of expression of components of the lung interstitium provide clues to the mechanisms underlying normal human lung development and possible insights into the pathogenesis of fetal and neonatal lung disease. Received March 2, 1998; accepted October 13, 1998.     

Disodium Cromoglycate in the Treatment of Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) has become the most common form of chronic lung disease in the neonate. Recently, we have experienced a severe case of BPD and examined the effect of disodium cromoglycate (DSCG) on BPD. The gestational age and birth weight of the patient were 27 weeks and 1,000 g, respectively. Although RDS subsided after surfactant replacement therapy, the arterial-alveolar oxygen tension ratio (a/AP_O2) gradually decreased and Fi_O2 increased with age, respectively, and pure oxygen supplementation was eventually required after 67 days of life. The DSCG treatment was commenced at 80 days of life. After 6 days of the inhalation therapy, a/AP_O2 gradually increased. After 10 days of the treatment, the baby was extubated. While the baby was intubated, intratracheal lavage fluid samples were obtained. Eosinophilic cationic protein (ECP) and polymorphonuclear (PMN) elastase concentrations were determined. ECP and PMN elastase concentrations of intratracheal lavage fluids gradually decreased with the DSCG treatment. These results may indicate that DSCG has led to an improvement of pulmonary function and facilitated weaning from mechanical ventilation in an infant with BPD.