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The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants


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.

  • chronic lung disease of prematurity
  • apoptosis
  • neutrophils
  • respiratory distress syndrome
  • 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

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