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Paediatric lung disease
The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants
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  1. S Kotecha1,
  2. R J Mildner2,
  3. L R Prince3,
  4. J R Vyas1,
  5. A E Currie1,
  6. R A Lawson3,
  7. M K B Whyte3
  1. 1Department of Child Health, University of Leicester, Leicester, UK
  2. 2Heartlink ECMO Centre, Glenfield Hospital, Leicester
  3. 3Respiratory Medicine Unit, Division of Genomic Medicine, University of Sheffield, Sheffield, UK
  1. Correspondence to:
    Dr Sailesh Kotecha, Department of Child Health, University of Leicester, Leicester LE2 7LX, UK;
    sk43le.ac.uk

Abstract

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

https://doi.org/10.1136/thorax.58.11.961

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