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Functional and genetic predisposition to rhinovirus lower respiratory tract infections in prematurely born infants

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Abstract

Term born infants are predisposed to human rhinovirus (HRV) lower respiratory tract infections (LRTI) by reduced neonatal lung function and genetic susceptibility. Our aim was to investigate whether prematurely born infants were similarly predisposed to HRV LRTIs or any other viral LRTIs. Infants born less than 36 weeks of gestational age were recruited. Prior to neonatal/maternity unit discharge, lung function (functional residual capacity by helium gas dilution and multiple breath washout, lung clearance index and compliance (Crs), and resistance (Rrs) of the respiratory system) was assessed and DNA samples assessed for eight single nucleotide polymorphisms (SNPs) in seven genes: ADAM33, IL10, MMP16 NFκB1A,SFTPC, VDR, and NOS2A. Infants were prospectively followed until 1 year corrected age. Nasopharyngeal aspirates (NPAs) were sent whenever an infant developed a LRTI and tested for 13 viruses. One hundred and thirty-nine infants were included in the analysis. Infants who developed HRV LRTIs had reduced Crs (1.6 versus 1.2 mL/cmH2O/kg, p = 0.044) at 36 weeks postmenstrual age. A SNP in the gene coding for the vitamin D receptor was associated with the development of HRV LRTIs and any viral LRTIs (p = 0.02).

Conclusion: Prematurely born infants may have both a functional and genetic predisposition to HRV LRTIs.

What is Known:

• Term born infants are predisposed to rhinovirus lower respiratory tract (HRV LRTIs) infection by reduced neonatal lung function.

• Term born infants requiring hospitalisation due to HRV bronchiolitis were more likely to have single nucleotide polymorphism (SNP) in the IL-10 gene.

What is New:

• Prematurely born infants who developed a HRV LRTI had lower C rs before maternity unit discharge.

• A SNP in the gene coding for the vitamin D receptor was associated with the development of HRV LRTIs and overall respiratory viral LRTIs in prematurely born infants.

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Abbreviations

BPD:

Bronchopulmonary dysplasia

Crs :

Compliance of the respiratory system

FRCHE :

Functional residual capacity (by helium gas)

HRV:

Rhinovirus

LCI:

Lung clearance index

LRTI:

Lower respiratory tract infection

NPA:

Nasopharyngeal aspirates

PCR:

Polymerase chain reaction

PMA:

Postmenstrual age

Rrs :

Resistance of the respiratory system

RSV:

Respiratory syncytial virus

SNP:

Single nucleotide polymorphisms

VDR:

Vitamin D receptor

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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, SE5 9RS, UK

    Simon B Drysdale, Mireia Alcazar, Theresa Wilson & Anne Greenough

  2. South London Specialist Virology Centre, King’s College Hospital, London, SE5 9RS, UK

    Melvyn Smith & Mark Zuckerman

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

    Hennie M Hodemaekers & Riny Janssen

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

    Louis Bont

  5. Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, W2 1PG, London, UK

    Sebastian L Johnston

  6. NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, London, UK

    Anne Greenough

  7. Neonatal Intensive Care Centre, King’s College Hospital, 4th Floor Golden Jubilee Wing Denmark Hill, London, SE5 9RS, UK

    Anne Greenough

Authors
  1. Simon B Drysdale
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  2. Mireia Alcazar
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  3. Theresa Wilson
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  4. Melvyn Smith
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  5. Mark Zuckerman
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  6. Hennie M Hodemaekers
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  7. Riny Janssen
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  8. Louis Bont
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  9. Sebastian L Johnston
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  10. Anne Greenough
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Corresponding author

Correspondence to Anne Greenough.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

SBD was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust/King’s College London. The research nurses (MA and TW) were supported by Abbott Laboratories. SLJ is supported by the Asthma UK Clinical Chair CH11SJ, and ERC FP7 Advanced grant 233015. SLJ and AG are MRC and Asthma UK Centre in Allergic Mechanisms of Asthma Investigators, supported by MRC Centre Grant G1000758. SLJ is an NIHR Senior Investigator.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Infants whose parents gave informed written consent were recruited.

Additional information

Communicated by Patrick Van Reempts

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Drysdale, S.B., Alcazar, M., Wilson, T. et al. Functional and genetic predisposition to rhinovirus lower respiratory tract infections in prematurely born infants. Eur J Pediatr 175, 1943–1949 (2016). https://doi.org/10.1007/s00431-016-2780-0

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  • DOI: https://doi.org/10.1007/s00431-016-2780-0

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