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Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants

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Abstract

The aim of this study was to assess whether prematurely born infants have a genetic predisposition to respiratory syncytial virus (RSV) infection-related respiratory morbidity. One hundred and forty-six infants born at less than 36 weeks of gestation were prospectively followed. Nasopharygeal aspirates were obtained on every occasion the infants had a lower respiratory tract infection (LRTI) regardless of need for admission. DNA was tested for 11 single-nucleotide polymorphisms (SNPs). Chronic respiratory morbidity was assessed using respiratory health-related questionnaires, parent-completed diary cards at a corrected age of 1 year and review of hospital notes. Lung function was measured at a post menstrual age (PMA) of 36 weeks and corrected age of 1 year. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36-week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (interleukin 10 (IL10), nitric oxide synthase 2A (NOS2A), surfactant protein C (SFTPC), matrix metalloproteinase 16 (MMP16) and vitamin D receptor (VDR)) and reduced lung function at 1 year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs. Conclusions: Our results suggest that prematurely born infants may have a genetic predisposition to RSV LRTIs and subsequent respiratory morbidity which is independent of premorbid lung function.

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Acknowledgments

This research was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The research nurses (MA, TW) were supported by Abbott Laboratories. SLJ is supported by the Asthma UK Clinical Chair CH11SJ and the ERC FP7 Advanced Grant 233015. SLJ and AG are MRC and Asthma UK Centre in Allergic Mechanisms of Asthma Investigators and supported by the MRC Centre Grant G1000758. AG and SLJ are NIHR Senior Investigators.

Conflict of interest

Abbott Laboratories, who supported Mrs Wilson and Mrs Alcazar, market palivizumab, a monoclonal antibody against RSV.

Author information

Authors and Affiliations

  1. Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, King’s College London, London, UK

    Simon B. Drysdale, Michael Prendergast, Mireia Alcazar, Theresa Wilson, Simon Broughton, Gerrard F. Rafferty & Anne Greenough

  2. South London Specialist Virology Centre, King’s College Hospital, London, UK

    Melvyn Smith & Mark Zuckerman

  3. Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, London, UK

    Sebastian L. Johnston

  4. Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

    Hennie M. Hodemaekers & Riny Janssen

  5. University Medical Centre, Wilhelmina Children’s Hospital, Utrecht, The Netherlands

    Louis Bont

  6. Neonatal Intensive Care Centre, King’s College Hospital, Denmark Hill, London, SE5 9RS, UK

    Anne Greenough

Authors
  1. Simon B. Drysdale
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  2. Michael Prendergast
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  3. Mireia Alcazar
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  4. Theresa Wilson
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  7. Simon Broughton
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  9. Sebastian L. Johnston
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  10. Hennie M. Hodemaekers
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  11. Riny Janssen
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  12. Louis Bont
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  13. Anne Greenough
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Corresponding author

Correspondence to Anne Greenough.

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Communicated by Willem Proesman

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Drysdale, S.B., Prendergast, M., Alcazar, M. et al. Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants. Eur J Pediatr 173, 905–912 (2014). https://doi.org/10.1007/s00431-014-2263-0

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  • DOI: https://doi.org/10.1007/s00431-014-2263-0

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