TY - JOUR
T1 - Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants
AU - Drysdale, Simon B.
AU - Prendergast, Michael
AU - Alcazar, Mireia
AU - Wilson, Theresa
AU - Smith, Melvyn
AU - Zuckerman, Mark
AU - Broughton, Simon
AU - Rafferty, Gerrard F.
AU - Johnston, Sebastian L.
AU - Hodemaekers, Hennie M.
AU - Janssen, Riny
AU - Bont, Louis
AU - Greenough, Anne
N1 - Funding Information:
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.
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
KW - Health-care utilisation
KW - Lung function
KW - Polymorphisms
KW - RSV
UR - http://www.scopus.com/inward/record.url?scp=84903818871&partnerID=8YFLogxK
U2 - 10.1007/s00431-014-2263-0
DO - 10.1007/s00431-014-2263-0
M3 - Article
C2 - 24487983
AN - SCOPUS:84903818871
SN - 0340-6199
VL - 173
SP - 905
EP - 912
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
IS - 7
ER -