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Paediatric lung disease
Relationship of proteinases and proteinase inhibitors with microbial presence in chronic lung disease of prematurity
  1. Philip L Davies1,
  2. O Brad Spiller1,
  3. Michael L Beeton1,
  4. Nicola C Maxwell1,
  5. Eileen Remold-O'Donnell2,
  6. Sailesh Kotecha1
  1. 1Department of Child Health, Cardiff University, School of Medicine, Cardiff, UK
  2. 2Immune Disease Institute and Program in Cellular and Molecular Medicine, Children's Hospital Boston and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Brad Spiller, Department of Child Health, Cardiff University, 5th Floor, University Hospital, Heath Park, Cardiff CF14 4XN, UK; SpillerB{at}cardiff.ac.uk

Abstract

Background A proteolytic imbalance has been implicated in the development of “classical” chronic lung disease of prematurity (CLD). However, in “new” CLD this pattern has changed. This study examines the longitudinal relationship between neutrophil proteinases and their inhibitors in ventilated preterm infants and their relationship to microbial colonisation.

Methods Serial bronchoalveolar lavage fluid was obtained from ventilated newborn preterm infants. Neutrophil elastase (NE) activity, cell counts, metalloproteinase (MMP)-9, MMP-9/TIMP-1 complex, SerpinB1 concentration and percentage of SerpinB1 and α1-antitrypsin (AAT) in complex with elastase were measured. The presence of microbial genes was examined using PCR for 16S rRNA genes.

Results Statistically more infants who developed CLD had NE activity in at least one sample (10/20) compared with infants with resolved respiratory distress syndrome (RDS) (2/17). However, NE activity was present in a minority of samples, occurring as episodic peaks. Peak levels of MMP-9, MMP-9/TIMP-1 complex, percentage of AAT and SerpinB1 in complex and cell counts were all statistically greater in infants developing CLD than in infants with resolved RDS. Peak values frequently occurred as episodic spikes and strong temporal relationships were noted between all markers. The peak values for all variables were significantly correlated to each other. The presence of bacterial 16S rRNA genes was associated with the development of CLD and with elevated elastase and MMP-9.

Conclusion NE activity and MMP-9 appear to be important in the development of “new” CLD with both proteinase and inhibitor concentrations increasing episodically, possibly in response to postnatal infection.

  • Chronic lung disease of prematurity
  • elastase
  • alpha-1-antitrypsin
  • metalloproteinases
  • serpinB1
  • proteinases
  • bronchopulmonary dysplasia

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/thx.2009.116061

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    Footnotes

    • Funding Arriva Pharmaceuticals Inc, 1010 Atlantic Avenue, Alameda, CA 94501, USA. Other funders: NIH (HL066548) to ERO and Wellcome Trust.

    • Competing interests None.

    • Ethics approval This study was conducted with the approval of the South Wales local research ethics committee and written informed consent was obtained from the parents of study subjects.

    • Provenance and peer review Not commissioned; externally peer reviewed.