Roberts Katelyn, Stepanovich Gretchen, Bhatt-Mehta Varsha, Donn Steven M
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
College of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
J Exp Pharmacol. 2021 Mar 25;13:377-396. doi: 10.2147/JEP.S262350. eCollection 2021.
Bronchopulmonary Dysplasia is the most common long-term respiratory morbidity of preterm infants, with the risk of development proportional to the degree of prematurity. While its pathophysiologic and histologic features have changed over time as neonatal demographics and respiratory therapies have evolved, it is now thought to be characterized by impaired distal lung growth and abnormal pulmonary microvascular development. Though the exact sequence of events leading to the development of BPD has not been fully elucidated and likely varies among patients, it is thought to result from inflammatory and mechanical/oxidative injury from chronic ventilatory support in fragile, premature lungs susceptible to injury from surfactant deficiency, structural abnormalities, inadequate antioxidant defenses, and a chest wall that is more compliant than the lung. In addition, non-pulmonary issues may adversely affect lung development, including systemic infections and insufficient nutrition. Once BPD has developed, its management focuses on providing adequate gas exchange while promoting optimal lung growth. Pharmacologic strategies to ameliorate or prevent BPD continue to be investigated. A variety of agents, to be reviewed henceforth, have been developed or re-purposed to target different points in the pathways that lead to BPD, including anti-inflammatories, diuretics, steroids, pulmonary vasodilators, antioxidants, and a number of molecules involved in the cell signaling cascade thought to be involved in the pathogenesis of BPD.
支气管肺发育不良是早产儿最常见的长期呼吸系统疾病,其发生风险与早产程度成正比。随着新生儿人口统计学特征和呼吸治疗方法的演变,其病理生理和组织学特征也随时间发生了变化,目前认为其特征是远端肺生长受损和肺微血管发育异常。尽管导致支气管肺发育不良发生的确切事件顺序尚未完全阐明,且可能因患者而异,但一般认为它是由慢性通气支持对脆弱的早产肺造成的炎症性、机械性/氧化性损伤引起的,这些早产肺易受表面活性物质缺乏、结构异常、抗氧化防御不足以及比肺更顺应的胸壁等因素的损伤。此外,非肺部问题可能会对肺发育产生不利影响,包括全身感染和营养不足。一旦支气管肺发育不良形成,其治疗重点是在促进肺最佳生长的同时提供充足的气体交换。改善或预防支气管肺发育不良的药物策略仍在研究中。本文将对多种药物进行综述,这些药物已被开发或重新用于针对导致支气管肺发育不良的不同途径中的靶点,包括抗炎药、利尿剂、类固醇、肺血管扩张剂、抗氧化剂以及许多参与细胞信号级联反应且被认为与支气管肺发育不良发病机制有关的分子。