Sweet D G, Halliday H L
Royal Maternity Hospital, and Department of Child Health, The Queen's University of Belfast, Northern Ireland.
Drug Saf. 2000 May;22(5):389-404. doi: 10.2165/00002018-200022050-00006.
Improvements in neonatal intensive care have resulted in more extremely low birthweight babies surviving who are at risk of developing chronic lung disease. The preterm lung is vulnerable as it is both structurally immature and deficient in surfactant and antioxidant defences. Mechanical ventilation and high inspired oxygen concentrations are often necessary for preterm babies to survive but they can cause pulmonary inflammation which leads to lung damage. Abnormal healing in the presence of ongoing inflammation leads to airways remodelling which can result in protracted respiratory problems in these babies. A commonly used definition for chronic lung disease is the requirement for supplemental oxygen beyond 36 weeks' postconception. Many drugs that are commonly used for chronic lung disease have not been subjected to proper randomised controlled trials but are widely used on the basis of small studies showing short term benefits. They can be broadly divided into 2 groups. First, there are preventative drugs that are administered early to reduce oxygen toxicity and pulmonary inflammation. Secondly, there are those administered in established chronic lung disease, designed to reduce respiratory morbidity. Pulmonary inflammation in the neonate is reduced by systemic corticosteroids. Corticosteroid therapy within the first 2 weeks of life enables earlier extubation of preterm babies with subsequent reduced chronic lung disease and improved neonatal survival when given between 7 and 14 days. However, there is an increased risk of gastrointestinal haemorrhage, metabolic derangement, ventricular hypertrophy and potential effects on long term growth and brain development. Diuretics and inhaled bronchodilators improve pulmonary compliance and reduce oxygen requirements in established chronic lung disease but probably have little effect in reducing the incidence. In babies with established chronic lung disease, home oxygen therapy enables earlier discharge and prophylaxis against respiratory syncytial virus can reduce morbidity from bronchiolitis. All of the above therapies have adverse effects that need to be considered before initiating treatment. Recently, new drugs have become available which may be beneficial. These include inhaled nitric oxide for reduction of ventilation-perfusion mismatching, recombinant human superoxide dismutase for protection against oxidative stress and alpha-1 proteinase inhibitor which may reduce airways remodelling. At present these therapies are undergoing clinical trials. Exogenous surfactant is beneficial in respiratory distress syndrome and may reduce the risk of chronic lung disease but there have been no randomised controlled trials of its use in established chronic lung disease. Drugs which have been tried unsuccessfully include erythromycin, ambroxol and mast cell stabilisers.
新生儿重症监护的改善使得更多极低出生体重儿存活下来，但这些婴儿有患慢性肺病的风险。早产肺很脆弱，因为其结构不成熟，且表面活性剂和抗氧化防御能力不足。机械通气和高吸入氧浓度对于早产儿存活往往是必要的，但它们会引发肺部炎症，进而导致肺损伤。在持续炎症存在的情况下异常愈合会导致气道重塑，这可能会使这些婴儿出现长期的呼吸问题。慢性肺病的一个常用定义是孕龄36周后仍需要补充氧气。许多常用于治疗慢性肺病的药物尚未经过适当的随机对照试验，但基于显示短期益处的小型研究而被广泛使用。它们大致可分为两类。第一类是预防性药物，早期给药以降低氧毒性和肺部炎症。第二类是用于已确诊慢性肺病的药物，旨在降低呼吸疾病的发病率。全身用皮质类固醇可减轻新生儿的肺部炎症。在出生后2周内进行皮质类固醇治疗，能使早产儿更早拔管，在7至14天给药时，随后慢性肺病减少，新生儿存活率提高。然而，胃肠道出血、代谢紊乱、心室肥大的风险增加，以及对长期生长和脑发育可能产生影响。利尿剂和吸入性支气管扩张剂可改善已确诊慢性肺病患者的肺顺应性并降低氧需求，但可能对降低发病率作用不大。对于已确诊慢性肺病的婴儿，家庭氧疗可使其更早出院，预防呼吸道合胞病毒可降低细支气管炎发病率。上述所有疗法都有不良反应，在开始治疗前需要加以考虑。最近，有一些新药可供使用，可能有益。这些药物包括吸入一氧化氮以减少通气-灌注不匹配、重组人超氧化物歧化酶以抵御氧化应激，以及α-1蛋白酶抑制剂，其可能减少气道重塑。目前这些疗法正在进行临床试验。外源性表面活性剂对呼吸窘迫综合征有益，可能降低慢性肺病风险，但尚无关于其用于已确诊慢性肺病的随机对照试验。曾尝试但未成功的药物包括红霉素、氨溴索和肥大细胞稳定剂。
