Management of bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a common and important complication of prematurity and is associated with significant mortality, morbidity and healthcare resource utilization. Despite advances in both perinatal and neonatal care the incidence of the condition continues to rise. The management of BPD and its related problems remains a major challenge to neonatologists and paediatricians. There is unlikely to be a single intervention which will dramatically alter the management of BPD and thus multiple interventions have been proposed to prevent and treat the disease. Many of these interventions are still not evidence based and some of those that are have been shown to have unacceptable long-term effects. It is useful to conceptualize BPD in three stages, namely (i) prevention, (ii) treatment of evolving BPD and (iii) treatment of established BPD. In this review current and potential future management approaches to BPD and the relevant evidence for these are discussed within the framework of these three stages.     

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。     

Review of use of postnatal corticosteroids in evolving or established bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a condition that affects a significant proportion of infants born prematurely. Whilst there have been advances in many aspects of neonatal respiratory care the rates of BPD remain relatively static. Much effort has been put into exploring the role of corticosteroids in potentially reducing inflammation in the developing lung; however, research has been hindered by concerns regarding adverse side–effect profiles and difficulties recruiting adequate numbers to power the results. Currently, two strategies are gaining popularity: low-dose dexamethasone after 7 days of age to facilitate ventilator weaning and prophylactic physiological hydrocortisone use from the first day of life. However, use in practice is limited whilst awaiting full-powered randomised trials. This article briefly discusses the evidence for each approach.     

Bronchopulmonary dysplasia and very low birthweight: Lung function at 11 years of age

Objective : To determine the relationship between lung function at 11 years of age and bronchopulmonary dysplasia (BPD) in very low birthweight (VLBW) children.
Methodology : This study comprised 154 consecutive surviving VLBW children, divided into three groups with respect to their neonatal respiratory morbidity: group I developed BPD; group II required assisted ventilation but did not develop BPD; and group III required no assisted ventilation. Lung function tests were measured on 120/154 (77.9%) children at 11 years of age. The relationship between various lung function variables and neonatal lung disease was analysed by multiple linear regression.
Results : Several lung function variables reflecting airflow were significantly diminished in the BPD group ( n = 15), and residual volume was significantly higher. Despite poorer lung function overall, few children in the BPD group had lung function abnormalities in the clinically significant range ( n = 2 [13.3%] with a forced expired volume in 1 s <75% predicted; n = 2 [13.3%] with a forced vital capacity <75% predicted; n = 1 [6.7%] with a residual volume/total lung capacity >35%). There were no significant differences in lung function variables between group II ( n = 41) and group III ( n = 64). Changes in lung function tests between 8 and 11 years did not vary significantly between the three groups.
Conclusions : VLBW children with BPD in the newborn period have poorer lung function at 11 years of age than other surviving VLBW children without BPD, although few have lung function abnormalities in the clinically significant range.     

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 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.     

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.     

Long-term effects of postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia: Balancing the risks and benefits

Postnatal corticosteroids are effective in preventing or treating bronchopulmonary dysplasia (BPD) in preterm newborns, but their benefits need to exceed their risks. Several types of corticosteroids, and different timing and administration modes have been trialed. Systemic corticosteroids, given either early or late, have proven efficacy for reducing BPD and the combined outcome of death or BPD. Inhaled corticosteroids are less effective. However, systemic dexamethasone given early is associated with more neurosensory disability and cerebral palsy in survivors. The risk of adverse neurodevelopment is highest if dexamethasone is given to preterm infants at low risk of BPD. Current trials focus on corticosteroids, mixed with surfactant, delivered intratracheally directly to the lung, which may avoid some systemic adverse effects of corticosteroids. Early trials of intratracheal corticosteroids are encouraging, but more data are needed to determine whether this method of administration is preferable to systemic corticosteroids for preventing or treating BPD.     

Minimising ventilator induced lung injury in preterm infants

Ventilator induced lung injury continues to occur at an unacceptably high rate, which is inversely related to gestational age. Although the "new BPD" may not be entirely avoidable in the extremely premature infant, recognition of risk factors and adoption of an appropriate ventilatory strategy, along with continuous real time monitoring, may help to minimise lung damage. This paper will review the pathogenesis of ventilator induced lung injury and strategies that may mitigate it.     

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??There are still problems??including difficulty in feeding baby?? apnea?? stunting on infants with bronchopulmonary dysplasia??BPD?? after being discharged from hospital. The risk of sudden infant death syndrome also increases. Healthcare after discharge from hospital is a continuation after treatment in hospital?? which is important for BPD treatment. Healthcare includes home oxygen after discharge from hospital?? continuing to strengthen infant’s nutrition and feeding guidance?? regular follow-up and prevention of sudden infant death syndrome.     

Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia

OBJECTIVE: To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use. METHODS: Infants included in the study were those delivered at less than 30 completed weeks gestation from January 1996 to July 2001, identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen required were collected. Bronchopulmonary dysplasia was defined as death due to respiratory failure or any oxygen requirement at 36 weeks postmenstrual age. RESULTS: Two hundred and forty-one infants were included in the study. The mean gestational age was 27.7 weeks and mean birthweight 1089 g. One hundred and sixty-one infants were not exposed to any in utero inflammation, 40 showed chorioamnionitis and 40 showed chorioamnionitis and funisitis. There was no significant difference between antenatal steroid and surfactant treatment between the three groups. There was no significant difference between the three groups in the development of bronchopulmonary dysplasia. Low gestational age was the most significant predictor of developing bronchopulmonary dysplasia. CONCLUSION: The risk of developing bronchopulmonary dysplasia is not increased following exposure to chorioamnionitis or funisitis in the context of current antenatal steroid and surfactant use. The most significant predictor for developing bronchopulmonary dysplasia is gestational age at the time of delivery.     

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.