早产儿支气管肺发育不良的研究进展

doi:10.3877/cma.j.issn.1673-5250.2016.03.016

随着新生儿重症监护技术的迅速发展，早产儿，尤其是极低出生体重儿的存活率得到较大提高。早产是导致支气管肺发育不良(BPD)的重要因素之一，加之早产儿可能合并低出生体重、围生期感染和动脉导管未闭等，以及进行机械通气与给氧治疗所致并发症，而使早产儿BPD的发生率呈逐年上升趋势。BPD早产儿的初次住院时间及BPD导致的病死率，均明显高于非BPD早产儿，因此早产儿BPD已成为临床最棘手的问题之一。笔者拟就目前早产儿BPD的研究进展，包括相关危险因素、早期预测生物学标志物及防治等进行综述。

关键词: 支气管肺发育不良, 危险因素, 生物学标记, 防治, 婴儿，早产

With the rapid development of neonatal intensive care technology, the survival rate of premature infants, especially the very low birth weight infants, increases greatly. Premature birth is one of the most important factors of bronchopulmonary dysplasia (BPD). The incidence of BPD increases year by year due to different risk factors, such as low birth weight, perinatal infection, patent ductus arteriosus, complications lead by mechanical ventilation and oxygen supplement therapy etc.. Overall, BPD prolongs neonatal initial hospitalization time and increases the mortality. Therefore, BPD has become one of the most difficult problems in clinical practice. In this article, we will review the current research progress of preterm infants with BPD, including related risk factors, early biomarkers and methods of prevention and therapy.

Key words: Bronchopulmonary dysplasia, Risk factors, Biological markers, Prevention and therapy, Infant, premature

表1 受试者工作特征曲线下面积分析BPD相关生物学标志物的预测能力

生物学标志物		敏感度(%)	特异度(%)	ROC_AUC^a
血液
	KL-6^[13]	91.7	89.8	0.952
	NGAL^[14]	94.0	85.0	0.910
	CC16^[13]	75.5	87.5	0.855
	IL-6^[15]	100.0	59.0	0.849
	BNP^[16]	85.7	76.1	0.800
	PlGF^[17]	53.0	95.0	－
	E-选择素^[18]	83.3	75.0	－
	sgp130^[15]	82.0	60.0	－
尿液
	NT-proBNP/肌酐^[19]	－	－	0.830
TA与BALF
	IL-8^[20]	88.0	74.0	－
	VEGF＋TGF-α^[21]	－	－	0.920
	VEGF^[21]	－	－	0.870

表1 受试者工作特征曲线下面积分析BPD相关生物学标志物的预测能力

生物学标志物		敏感度(%)	特异度(%)	ROC_AUC^a
血液
	KL-6^[13]	91.7	89.8	0.952
	NGAL^[14]	94.0	85.0	0.910
	CC16^[13]	75.5	87.5	0.855
	IL-6^[15]	100.0	59.0	0.849
	BNP^[16]	85.7	76.1	0.800
	PlGF^[17]	53.0	95.0	－
	E-选择素^[18]	83.3	75.0	－
	sgp130^[15]	82.0	60.0	－
尿液
	NT-proBNP/肌酐^[19]	－	－	0.830
TA与BALF
	IL-8^[20]	88.0	74.0	－
	VEGF＋TGF-α^[21]	－	－	0.920
	VEGF^[21]	－	－	0.870

1	薛辛东，杨海萍．早产儿支气管肺发育不良防治及管理的新认识[J/CD]．中华妇幼临床医学杂志：电子版，2014，10(1)：5-8.
2	Jensen EA, Schmidt B. Epidemiology of bronchopulmonary dysplasia[J]. Birth Defects Res A Clin Mol Teratol, 2014, 100(3):145-157.
3	早产儿支气管肺发育不良调查协作组．早产儿支气管肺发育不良发生率及高危因素的多中心回顾调查分析[J]．中华儿科杂志，2011，49(9)：655-662.
4	彭磊，乐功芳，陈绪萍，等．早产儿支气管肺发育不良的高危因素及防治对策[J]．临床肺科杂志，2015，20(1)：92-95.
5	Check J, Gotteiner N, Liu X, et al. Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia[J]. J Perinatol, 2013, 33(7):553-557.
6	Chen C, Yuan L. Etiology and risk factors of bronchopulmonary dysplasia in preterm infants [J]. Chin J Pract Pediatr, 2014, 29(1):5-7.
7	Shaw GM, O'Brodovich HM. Progress in understanding the genetics of bronchopulmonary dysplasia[J]. Semin in Perinatol, 2013, 37(2):85-93.
8	Parker RA, Lindstrom DP, Cotton RB. Evidence from twin study implies possible genetic susceptibility to bronchopulmonary dysplasia[J]. Semin Perinatol, 1996, 20(3):206-209.
9	潘睿，常立文，李文斌，等．支气管肺发育不良与遗传因素的相关分析[J]．实用儿科临床杂志，2012，27(16)：1230-1232.
10	Hadchouel A, Durrmeyer X, Bouzigon E, et al. Identification of SPOCK2 as a susceptibility gene for bronchopulmonary dysplasia[J]. Am J Respir Crit Care Med, 2011, 184(10):1164-1170.
11	郑雁芮，韦红．支气管肺发育不良研究进展[J]．现代医药卫生，2015，31(14)：2141-2143.
12	Jobe AH. What is BPD in 2012 and what will BPD become？[J]. Early Hum Dev, 2012, 88(Suppl 2):S27-S28.
13	Wang K, Huang X, Lu H, et al. A comparison of KL-6 and Clara cell protein as markers for predicting bronchopulmonary dysplasia in preterm infants[J]. Dis Markers, 2014: 736536.
14	Inoue H, Ohga S, Kusuda T, et al. Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants [J]. Early Hum Dev, 2013, 89(6):425-429.
15	Zhang ZQ, Huang XM, Lu H. Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review[J]. Eur J Pediatr, 2014, 173(1):15-23.
16	Kalra VK, Aggarwal S, Arora P, et al. B-type natriuretic peptide levels in preterm neonates with bronchopulmonary dysplasia: a marker of severity？[J]. Pediatr Pulmonol, 2014, 49(11):1106-1111.
17	Tsao PN, Wei SC, Su YN, et al. Placenta growth factor elevation in the cord blood of premature neonates predicts poor pulmonary outcome[J]. Pediatrics, 2004, 113(5):1348-1351.
18	杜悦新．血液中与支气管肺发育不良相关的生物标记研究进展[J]．广东医学，2015，36(12)：1945-1948.
19	Czernik C, Metze B, Müller C, et al. Urinary N-terminal B-type natriuretic peptide predicts severe retinopathy of prematurity[J]. Pediatrics, 2011, 128(3):e545-e549.
20	Bhandari A, Bhandari V. Biomarkers in bronchopulmonary dysplasia[J]. Paediatr Respir Rev, 2013, 14(3):173-179.
21	Been JV, Debeer A, van Iwaarden JF, et al. Early alterations of growth factor patterns in bronchoalveolar lavage fluid from preterm infants developing bronchopulmonary dysplasia[J]. Pediatr Res, 2010, 67(67):83-89.
22	Mohamed WA, Niyazy WH, Mahfouz AA. Angiopoietin-1 and endostatin levels in cord plasma predict the development of bronchopulmonary dysplasia in preterm infants[J]. J Trop Pediatr, 2011, 57(5):385-388.
23	Procianoy RS, Hentges CR, Silveira RC. Vascular endothelial growth factor/placental growth factor heterodimer levels in preterm infants with bronchopulmonary dysplasia[J]. Am J Perinatol, 2016, 33(5):480-485.
24	王晓燕，张新日，曹大伟．Clara细胞分泌蛋白CC16在急性肺损伤中的作用[J]．中外医疗，2013，32(2)：186-187.
25	薛辛东，刘子云．高危早产儿支气管肺发育不良早期监测及其临床意义[J]．中国实用儿科杂志，2014，29(1)：7-11.
26	Kim SB, Lee JH, Lee J, et al. The efficacy and safety of Montelukast sodium in the prevention of bronchopulmonary dysplasia[J]. Korean J Pediatr, 2015, 58(9):347-353.
27	黄勇，郑青．支气管肺发育不良患儿血浆及支气管肺泡灌洗液中TGF-β1和KL-6水平变化的意义[J]．广东医学，2014，35(12)：1867-1871.
28	Ghanta S, Leeman KT, Christou H. An update on pharmacologic approaches to bronchopulmonary dysplasia[J]. Semin Perinatol, 2013, 37(2):115-123.
29	Schulzke SM, Kaempfen S, Patole SK. Pentoxifylline for the prevention of bronchopulmonary dysplasia in preterm infants[J]. Cochrane Database Syst Rev, 2014, 11:CD010018.
30	Gadhia MM, Cutter GR, Abman SH, et al. Effects of early inhaled nitric oxide therapy and vitamin A supplementation on the risk for bronchopulmonary dysplasia in premature newborns with respiratory failure[J]. J Pediatr, 2014, 164(4):744-748.
31	Meyer S, Gortner L, NeoVitaA Trial Investigators. Early postnatal additional high-dose oral vitamin A supplementation versus placebo for 28 days for preventing bronchopulmonary dysplasia or death in extremely low birth weight infants[J]. Neonatology, 2014, 105(3):182-188.
32	Shah SS, Ohlsson A, Halliday HL, et al. Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates[J]. Cochrane Database Syst Rev, 2012, 5:CD002058.
33	Iyengar A, Davis JM. Drug therapy for the prevention and treatment of bronchopulmonary dysplasia[J]. Front Pharmacol, 2015, 6:12.
34	Hascoët JM, Picaud JC, Ligi I, et al. Late surfactant administration in very preterm neonates with prolonged respiratory distress and pulmonary outcome at 1 year of age: a randomized clinical trial[J/OL]. JAMA Pediatr, 2016, 170(4):365-372.
35	Kinsella JP, Cutter GR, Steinhorn RH, et al. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns[J]. J Pediatr, 2014, 165(6):1104-1108. e1.
36	Gadhia MM, Cutter GR, Abman SH, et al. Effects of early inhaled nitric oxide therapy and vitamin A supplementation on the risk for bronchopulmonary dysplasia in premature newborns with respiratory failure[J]. J Pediatr, 2014, 164(4):744-748.
37	Trottier-Boucher MN, Lapointe A, Malo J, et al. Sildenafil for the treatment of pulmonary arterial hypertension in infants with bronchopulmonary dysplasia[J]. Pediatr Cardiol, 2015, 36(6):1255-1260.
38	Nair V, Loganathan P, Soraisham AS. Azithromycin and other macrolides for prevention of bronchopulmonary dysplasia: a systematic review and meta-analysis[J]. Neonatology, 2014, 106(4):337-347.
39	岳嗣凤，张华．重组人促红细胞生成素对新型支气管肺发育不良模型肺发育及肺Bcl-2、Caspase-9表达的影响[J]．广东医学，2014，35(23)：3632-3636.
40	Keszler M, Sant'Anna G. Mechanical ventilation and bronchopulmonary dysplasia[J]. Clin Perinatol, 2015, 42(4):781-796.
41	陈洪，潘家华．常频机械通气和鼻塞式持续气道正压通气致早产儿支气管肺发育不良的临床比较[J]．安徽医药，2014，18(12)：2294-2296.
42	Bhandari V. The potential of non-invasive ventilation to decrease BPD[J]. Semin Perinatol, 2013, 37(2):108-114.

[1]	刘欢颜, 华扬, 贾凌云, 赵新宇, 刘蓓蓓. 颈内动脉闭塞病变管腔结构和血流动力学特征分析[J]. 中华医学超声杂志（电子版）, 2023, 20(08): 809-815.
[2]	马艳波, 华扬, 刘桂梅, 孟秀峰, 崔立平. 中青年人颈动脉粥样硬化病变的相关危险因素分析[J]. 中华医学超声杂志（电子版）, 2023, 20(08): 822-826.
[3]	唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[4]	吴方园, 孙霞, 林昌锋, 张震生. HBV相关肝硬化合并急性上消化道出血的危险因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 45-47.
[5]	陈旭渊, 罗仕云, 李文忠, 李毅. 腺源性肛瘘经手术治疗后创面愈合困难的危险因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 82-85.
[6]	晏晴艳, 雍晓梅, 罗洪, 杜敏. 成都地区老年转移性乳腺癌的预后及生存因素研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 636-638.
[7]	莫闲, 杨闯. 肝硬化患者并发门静脉血栓危险因素的Meta分析[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 678-683.
[8]	毛永欢, 仝瀚文, 缪骥, 王行舟, 沈晓菲, 喻春钊. 造口旁疝危险因素预测模型构建[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 682-687.
[9]	侯超, 潘美辰, 吴文明, 黄兴广, 李翔, 程凌雪, 朱玉轩, 李文波. 早期食管癌及上皮内瘤变内镜黏膜下剥离术后食管狭窄的危险因素[J]. 中华消化病与影像杂志(电子版), 2023, 13(06): 383-387.
[10]	陆猛桂, 黄斌, 李秋林, 何媛梅. 蜂蛰伤患者发生多器官功能障碍综合征的危险因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(9): 1010-1015.
[11]	李达, 张大涯, 陈润祥, 张晓冬, 黄士美, 陈晨, 曾凡, 陈世锔, 白飞虎. 海南省东方市幽门螺杆菌感染现状的调查与相关危险因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(08): 858-864.
[12]	李琪, 黄钟莹, 袁平, 关振鹏. 基于某三级医院的ICU多重耐药菌医院感染影响因素的分析[J]. 中华临床医师杂志(电子版), 2023, 17(07): 777-782.
[13]	孟科, 李燕, 闫婧爽, 闫斌. 胶囊内镜胃通过时间的影响因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 671-675.
[14]	杨艳丽, 陈昱, 赵若辰, 杜伟, 马海娟, 许珂, 张莉芸. 系统性红斑狼疮合并血流感染的危险因素及细菌学分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 694-699.
[15]	孙培培, 张二明, 时延伟, 赵春燕, 宋萍萍, 张硕, 张克, 周玉娇, 赵璨, 闫维, 吴蓉菊, 宋丽萍, 郭伟安, 马石头, 安欣华, 包曹歆, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病患病情况及相关危险因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 711-719.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Research progress of preterm infants with bronchopulmonary dysplasia

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Research progress of preterm infants with bronchopulmonary dysplasia