High-mobility group box-1 protein in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia and steroid therapy.

OBJECTIVE: High-mobility group box-1 (HMGB1) is a potent inflammatory mediator and contributes to acute lung injury in adults. The role of HMGB1 in neonatal lung injury and the development of bronchopulmonary dysplasia (BPD) is unknown. We studied the association between HMGB1 levels in tracheal aspirates (TAs) and adverse outcomes (BPD/death) in ventilated premature infants (VPIs) and modulation of HMGB1 levels with dexamethasone (Dex) use. STUDY DESIGN: Infants born before 32 weeks gestation and requiring mechanical ventilation were enrolled. Serial TA samples were collected on days 1, 3, 5 and 7 and HMGB1 levels were measured. HMGB1 levels in TA samples were compared between infants with no BPD and infants who developed BPD or died. HMGB1 TA levels were also compared before and after using Dex. RESULT: In all, 24 infants (gestational age 26.4+/-1.9 weeks, birth weight 859+/-200 g) had no BPD, 60 infants (gestational age 25.4+/-1.8 weeks, birth weight 749+/-156 g) developed BPD or died before 36 weeks postmenstrual age. Mean HMGB1 level in first week of life was significantly lower in infants with no BPD (27.3+/-16.5 ng mg(-1)) compared with those who developed BPD or died (45.1+/-30.9 ng mg(-1), P=0.004). In total, 29 VPIs received Dex. There was no significant change in HMGB1 levels with steroid therapy (before 47.0+/-43.9, after 60.1.5+/-58.8, P=0.3). CONCLUSION: Our data suggest that higher HMGB1 levels in TA are associated with the development of BPD or death in VPI. Dex use had no effect on HMGB1 levels.

Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone.

OBJECTIVES: To study the association between angiopoietin 2 (Ang2) concentrations in tracheal aspirates (TAs) and adverse outcome (bronchopulmonary dysplasia (BPD)/death) in ventilated premature infants (VPIs) and modulation of Ang2 concentrations with dexamethasone (Dex) use. STUDY DESIGN: Serial TA samples were collected on days 1, 3, 5 and 7, and Ang2 concentrations were measured. Ang2 TA concentrations were compared prior to and after 48 to 72 h of using Dex. RESULT: A total of 151 TA samples were collected from 60 VPIs. BPD was defined as the oxygen requirement at 36 weeks postmenstrual age (PMA). Twelve infants (mean+/-s.d.) (gestational age (GA) 26.5+/-2.1 weeks, birth weight (BW) 913+/-230 g) had no BPD, 32 infants (GA 25.8+/-1.4 weeks, BW 768+/-157 g) developed BPD and 16 infants (GA 24.5+/-1.1 weeks, BW 710+/-143 g) died before 36 weeks PMA. Ang2 concentrations were significantly lower in infants with no BPD (median, 25th and 75th percentile) (157, 16 and 218 pg mg(-1)) compared with those who developed BPD (234, 138 and 338 pg mg(-1), P=0.03) or BPD and/or death (234, 157 and 347 pg mg(-1), P=0.017), in the first week of life. Twenty-six VPIs (BW 719+/-136 g, GA 25.1+/-1.3 weeks) received 27 courses of Dex. Ang2 concentrations before starting Dex were 202, 137 and 278 pg mg(-1) and significantly decreased to 144, 0 and 224 pg mg(-1) after therapy (P=0.007). CONCLUSIONS: Higher Ang2 concentrations in TAs are associated with the development of BPD or death in VPIs. Dex use suppressed Ang2 concentrations.