Sheikh S, Null D, Gentile D, Bimle C, Skoner D, McCoy K, Guthrie R
Division of Pulmonary Medicine, Department of Pediatrics, Columbus Children's Hospital, Ohio State University, Columbus, OH 43205, USA.
Chest. 2001 Jun;119(6):1749-54. doi: 10.1378/chest.119.6.1749.
Inflammation plays an important role in the pathogenesis of bronchopulmonary dysplasia (BPD), but the exact nature of this inflammatory process is incompletely understood. Older infants with established BPD have higher levels of urinary leukotriene E(4) (LTE(4)) compared to healthy infants of the same age. This suggests that cysteinyl leukotrienes may play a role in the abnormalities seen in BPD.
To measure urinary LTE(4) levels during the first month of life in premature infants, and to determine whether there are significant differences in premature infants who develop BPD, as compared to those who do not develop BPD.
Prospective, blinded, controlled study.
Neonatal ICUs of a tertiary-care university hospital.
Thirty-seven premature infants (< 33 weeks of gestational age) were enrolled prospectively at birth. Urinary LTE(4) levels were measured blinded, using a standard radioimmunoassay technique at 2 days, 7 days, and 28 days of life. At 1 month of age, infants were classified as with or without BPD, based on need for supplemental oxygen, and characteristic chest radiographs. Clinical features and urinary LTE(4) were compared between the two groups.
Mean +/- SD gestational age was 29 +/- 2.6 weeks. None of the infants had a family history of asthma. Thirteen of 37 infants were classified as having BPD at 28 days after birth. Mean gestational age in infants who developed BPD was 27 +/- 2.4 weeks, compared to 30 +/- 2 weeks in infants who did not develop BPD (p < 0.05). In infants with BPD, mean urinary LTE(4) levels of urinary creatinine were 1,762 +/- 2,003 pg/mg, 1,236 +/- 992 pg/mg, and 5,541 +/- 5,146 pg/mg at days 2, 7, and 28, respectively, compared to 1,304 +/- 1,195 pg/mg, 1,158 +/- 1,133 pg/mg, and 2,800 +/- 2,080 pg/mg in infants without BPD. LTE(4) levels at 2 days, 7 days, and 28 days did not correlate with the subsequent development of BPD. LTE(4) levels at day 28 were significantly higher than LTE(4) levels at day 2 and day 7 in both groups, even after correcting for gestational age or birth weight (p < 0.05). There was significant inverse correlation between LTE(4) levels at day 2 with gestational age and birth weight (p < 0.05). All 13 infants with BPD received steroid pulses, compared to 3 of 26 infants without BPD. Gestational age and use of postnatal steroid pulses, diuretics, and theophylline (for apnea of prematurity) were significantly associated with each other and with the subsequent development of BPD.
Urinary LTE(4) levels measured on the second day of life in very-low-birth-weight infants inversely correlate with gestational age and birth weight. Urinary LTE(4) levels may reflect lung injury and/or inflammation in premature infants, not necessarily related to BPD as it is presently defined.
炎症在支气管肺发育不良（BPD）的发病机制中起重要作用，但这种炎症过程的确切性质尚未完全明确。与同龄健康婴儿相比，患有BPD的大龄婴儿尿白三烯E4（LTE4）水平更高。这表明半胱氨酰白三烯可能在BPD所见异常中起作用。
测量早产儿出生后第一个月的尿LTE4水平，并确定与未发生BPD的早产儿相比，发生BPD的早产儿是否存在显著差异。
前瞻性、盲法、对照研究。
一所三级医疗大学医院的新生儿重症监护病房。
37例胎龄小于33周的早产儿在出生时前瞻性入组。采用标准放射免疫分析技术，在出生后第2天、第7天和第28天对尿LTE4水平进行盲法测量。在1月龄时，根据是否需要补充氧气以及特征性胸部X线片，将婴儿分为有或无BPD两组。比较两组的临床特征和尿LTE4水平。
平均胎龄为29±2.6周。所有婴儿均无哮喘家族史。37例婴儿中有13例在出生后28天被诊断为BPD。发生BPD的婴儿平均胎龄为27±2.4周，未发生BPD的婴儿平均胎龄为30±2周（p<0.05）。患有BPD的婴儿在第2天、第7天和第28天尿肌酐中的平均尿LTE4水平分别为1762±2003 pg/mg、1236±992 pg/mg和5541±5146 pg/mg，而未患BPD的婴儿分别为1304±1195 pg/mg、1158±1133 pg/mg和2800±2080 pg/mg。第2天、第7天和第28天的LTE4水平与随后BPD的发生无关。两组在第28天的LTE4水平均显著高于第2天和第7天，即使校正胎龄或出生体重后也是如此（p<0.05）。第2天的LTE4水平与胎龄和出生体重呈显著负相关（p<0.05）。13例患有BPD的婴儿均接受了类固醇冲击治疗，而26例未患BPD的婴儿中只有3例接受了该治疗。胎龄以及出生后类固醇冲击治疗、利尿剂和茶碱（用于早产儿呼吸暂停）的使用彼此之间以及与随后BPD的发生均显著相关。
极低出生体重儿出生后第二天测量的尿LTE4水平与胎龄和出生体重呈负相关。尿LTE4水平可能反映早产儿的肺损伤和/或炎症，不一定与目前定义的BPD相关。
