The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants
- 1Department of Child Health, University of Leicester, Leicester, UK
- 2Heartlink ECMO Centre, Glenfield Hospital, Leicester
- 3Respiratory Medicine Unit, Division of Genomic Medicine, University of Sheffield, Sheffield, UK
- Correspondence to:
Dr Sailesh Kotecha, Department of Child Health, University of Leicester, Leicester LE2 7LX, UK;
- Received 25 October 2002
- Accepted 29 July 2003
Background: The persistent airway neutrophilia observed in chronic lung disease of prematurity (CLD) may reflect inappropriate suppression of neutrophil apoptosis.
Methods: 134 bronchoalveolar lavage (BAL) samples were obtained from 32 infants requiring mechanical ventilation for respiratory distress syndrome (RDS): 13 infants (median gestation 26 weeks, range 23 to 28) subsequently developed CLD (CLD group), and 19 infants (gestation 31 weeks, range 25 to 39) recovered fully (RDS group). A further 73 BAL samples were obtained from 20 infants (median age 2 days, range 1 to 402) receiving extracorporeal membrane oxygenation (ECMO) for severe respiratory failure.
Results: Neutrophil apoptosis was increased in the RDS group (mean (SEM) neutrophil apoptosis on day 7 BAL: RDS 17.0 (8.6)% v CLD 0.7 (0.2)% (p<0.05)). BAL fluid obtained from RDS but not CLD patients was proapoptotic to neutrophils (apoptosis ratio BAL fluid/saline control: day 1, RDS 9.8 (5.5) v CLD 1.2 (0.1) (p<0.05); day 2, RDS 4.32 (2.8) v CLD 0.5 (0.4) (p<0.05)). There were similar findings in the ECMO group: survivors had proapoptotic BAL fluid compared with non-survivors (apoptosis ratio day 1, survivors 7.9 (2.1) v non-survivors 2.1 (0.7) (p<0.05)).
Conclusions: Inappropriate suppression of neutrophil apoptosis may be associated with a poor outcome in newborn infants with respiratory failure.
- ARDS, acute respiratory distress syndrome
- BAL, bronchoalveolar lavage
- CLD, chronic lung disease of prematurity
- ECMO, extracorporeal membrane oxygenation
- GM-CSF, granulocyte-macrophage colony stimulating factor
- IL, interleukin
- RDS, respiratory distress syndrome
- TNFα, tumour necrosis factor α
- TRAIL, tumour necrosis factor related apoptosis inducing ligand
- TUNEL, TdT mediated dUTP-biotin 3′-OH nick-end labelling