Sildenafil therapy for bronchopulmonary dysplasia: not quite yet.
Sildenafil therapy for bronchopulmonary dysplasia: not quite yet.
复制标题
西地那非治疗支气管肺发育不良：尚未完成。
DOI：
10.1038/jp.2011.158
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Steinhorn,RH
中科院分区：
文献类型：
--
作者：
Farrow,KN;Steinhorn,RH
支气管肺发育不良（BPD）是婴儿期最常见的慢性肺部疾病，使多达三分之一的极早产儿的病程复杂化。BPD导致长期肺部预后不良，并增加神经发育延迟的风险。因此，大量的研究工作力求更好地界定风险最大的人群，并制定预防战略。1，2我们现在了解到BPD的风险随着胎龄的降低、宫内生长受限、绒毛膜炎的存在和完全肠内喂养时间的延迟而增加。然而，识别高危婴儿群体的能力并没有提高我们预防BPD的能力。虽然产前类固醇和出生后表面活性剂减少了呼吸窘迫综合征的影响，但它们并没有减少极低出生体重人群中BPD的频率或严重程度。近年来，各种策略，如氢化可的松，重组人超氧化物歧化酶，维生素A，咖啡因，最近，吸入一氧化氮都被测试为BPD预防策略，但成功程度不同。5-12到目前为止，除了预防早产外，还没有绝对的治疗方法来预防BPD。随着更小和更年轻的婴儿存活与BPD，并发症的BPD相关的肺动脉高压（PH）已获得承认。BPD相关的PH发生在30%至45%的中度至重度BPD婴儿中（根据NIH共识标准定义）。13-16这种PH的确切病因尚不清楚，尽管最近来自动物和人类研究的证据表明宫内生长限制增加了BPD相关PH的风险。14，17，18发育中的肺的早期损伤损害肺泡形成和血管生成，并且新出现的证据表明，在肺发育的早期阶段的早产导致肺血管形成的发育停滞。19其他因素，如暴露于超生理氧气水平，导致剩余小肺血管的重塑和修剪，产生血管功能障碍和PH。随着时间的推移，这种PH有助于持续的低氧血症，这诱导进一步的血管重塑，并最终导致右心室肥大。20在最严重的情况下，右心室肥大发展为右心室衰竭、肺心病和死亡。21尽管我们仍然需要更多地了解流行病学和结局，但一些病例系列表明，患有BPD相关PH的婴儿在2岁时的死亡率接近50%，并且对存活婴儿成年的能力以及这种新生儿疾病是否会产生持久的残留缺陷存在极大的担忧。15，22尽管预防仍然是一个主要的重点，我们也需要安全有效的治疗方法来治疗已经发展为BPD和BPD相关PH的婴儿。多年来，许多治疗方法，包括利尿剂，吸入性支气管扩张剂和类固醇，已被尝试改善显著BPD婴儿的肺功能。然而，没有明显有效的治疗方法出现，改善肺力学没有重要的副作用。4，23关于BPD相关PH的适当治疗，我们知道的甚至更少。
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy and complicates the course of up to onethird of extremely preterm babies. BPD results in poor long-term pulmonary outcomes and increases the risk of neurodevelopmental delay. As a result, a significant amount of research has sought to better define the population most at risk, as well as to develop prevention strategies. 1, 2 We now understand that the risk for BPD increases with younger gestational age, intrauterine growth restriction, presence of chorioamnionitis and delay in time to full enteral feeds. 2, 3 However, the ability to identify populations of at risk infants has not improved our ability to prevent BPD. Although prenatal steroids and postnatal surfactant have diminished the impact of respiratory distress syndrome, they have not diminished the frequency or severity of BPD in the extremely low birthweight population. 2, 4 In recent years, various strategies such as hydrocortisone, recombinant human superoxide dismutase, vitamin A, caffeine and, most recently, inhaled nitric oxide have all been tested as BPD-prevention strategies, but with a variable degree of success. 5–12 To date, there is no absolute therapy to prevent BPD other than to prevent preterm birth. As smaller and younger babies survive with BPD, the complication of BPD-associated pulmonary hypertension (PH) has gained recognition. BPD-associated PH occurs in 30 to 45% of infants with moderate to severe BPD (as defined by the NIH consensus criteria). 13–16 The exact etiology of this PH is poorly understood, although recent evidence from both animal and human studies suggests that intrauterine growth restriction increases risk for BPD-associated PH. 14, 17, 18 Early injury to the developing lung impairs both alveolarization and angiogenesis, and emerging evidence indicates that preterm birth at an early stage of lung development produces a developmental arrest of pulmonary vessel formation. 19 Other factors, such as exposure to supraphysiological oxygen levels, lead to remodeling and pruning of the remaining small pulmonary vessels, producing vascular dysfunction and PH. Over time, this PH contributes to ongoing hypoxemia, which induces further vascular remodeling and eventually leads to right ventricular hypertrophy. 20 In the most severe cases, right ventricular hypertrophy progresses to right ventricular failure, cor pulmonale and death. 21 Although we still need to learn more about the epidemiology and outcomes, several case series suggest that the mortality in infants with BPD-associated PH approaches 50% by 2 years of life, and there is tremendous concern about the ability of surviving infants to reach adulthood and whether this neonatal illness will create lasting residual deficits. 15, 22Although there continues to be a major focus on prevention, we also need safe and effective therapies to treat infants who have already developed BPD and BPD-associated PH. Over the years, many therapies including diuretics, inhaled bronchodilators and steroids have been attempted to improve the pulmonary function in infants with significant BPD. However, no clearly effective therapy has emerged that improves pulmonary mechanics without important side effects. 4, 23 Even less is known about appropriate therapy for BPD-associated PH.