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


CONCLUSIONS
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 Crsbefore 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.
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
SB
Drysdale
Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, SE5 9RS, UK.
Mireia
M
Alcazar
Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, SE5 9RS, UK.
Theresa
T
Wilson
South London Specialist Virology Centre, King's College Hospital, London, SE5 9RS, UK.
Melvyn
M
Smith
South London Specialist Virology Centre, King's College Hospital, London, SE5 9RS, UK.
Mark
M
Zuckerman
Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Hennie M
HM
Hodemaekers
Centre for Health Protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Riny
R
Janssen
Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands.
Louis
L
Bont
Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, W2 1PG, London, UK.
Sebastian L
SL
Johnston
Division of Asthma, Allergy and Lung Biology, MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, London, SE5 9RS, UK. anne.greenough@kcl.ac.uk.|NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK. anne.greenough@kcl.ac.uk.|Neonatal Intensive Care Centre, King's College Hospital, 4th Floor Golden Jubilee Wing Denmark Hill, London, SE5 9RS, UK. anne.greenough@kcl.ac.uk.
Anne
http://orcid.org/0000-0002-8672-5349
A
Greenough
D002675:Child, Preschool; D004247:DNA / Q000032:analysis*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases; D016753:Interleukin-10; D008168:Lung / Q000503:physiopathology*; D008297:Male; D015997:Neonatal Screening; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000821:virology; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000821:virology; D012229:Rhinovirus / Q000235:genetics*
D016753:Interleukin-10; D004247:DNA
Compliance and resistance of the respiratory system; Functional residual capacity; Human rhinovirus; Single nucleotide polymorphisms
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