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01-12-2016 | Original Article

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

Authors: Simon B Drysdale, Mireia Alcazar, Theresa Wilson, Melvyn Smith, Mark Zuckerman, Hennie M Hodemaekers, Riny Janssen, Louis Bont, Sebastian L Johnston, Anne Greenough

Published in: European Journal of Pediatrics | Issue 12/2016

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 (C_rs), and resistance (R_rs) 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 C_rs (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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Belderbos ME, Houben ML, Wilbrink B, Lentjes E, Bloemen EM, Kimpen JL, Rovers M, Bont L (2011) Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics 127:e1513–e1520CrossRefPubMed

Broughton S, Bhat R, Roberts A, Zuckerman M, Rafferty GF, Greenough A (2006) Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants. Arch Dis Child 91:26–30CrossRefPubMed

Chidekel AS, Rosen CL, Bazzy AR (1997) Rhinovirus infection associated with serious lower respiratory illness in patients with bronchopulmonary dysplasia. Pediatr Infect Dis J 16:43–47CrossRefPubMed

Chun RF, Liu PT, Modlin RL, Adams JS, Hewison M (2014) Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol 5:151CrossRefPubMedPubMedCentral

Drysdale SB, Lo J, Prendergast M, Alcazar M, Wilson T, Zuckerman M, Smith M, Broughton S, Rafferty GF, Peacock JL, Johnston SL, Greenough A (2014) Lung function of preterm infants before and after viral infections. Eur J Pediatr 173:1497–1504CrossRefPubMed

Drysdale SB, Prendergast M, Alcazar M, Wilson T, Smith M, Zuckerman M, Broughton S, Rafferty GF, Johnston SL, Hodemaekers HM, Janssen R, Bont L, Greenough A (2014) Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants. Eur J Pediatr 173:905–912CrossRefPubMed

Drysdale SB, Wilson T, Alcazar M, Broughton S, Zuckerman M, Smith M, Rafferty GF, Johnston SL, Greenough A (2011) Lung function prior to viral lower respiratory tract infections in prematurely born infants. Thorax 66:468–473CrossRefPubMed

Hadchouel A, Decobert F, Franco-Montoya M-L, Halphen I, Jarreau PH, Boucherat O, Martin E, Benachi A, Amselem S, Bourbon J, Danan C, Delacourt C (2008) Matrix metalloproteinase gene polymorphisms and bronchopulmonary dysplasia: identification of MMP16 as a new player in lung development. PLoS One 3:e3188CrossRefPubMedPubMedCentral

Helminen M, Nuolivirta K, Virta M, Halkosalo A, Korppi M, Vesikari T, Hurme M (2008) IL-10 gene polymorphism at −1082 A/G is associated with severe rhinovirus bronchiolitis in infants. Pediatr Pulmonol 43:391–395CrossRefPubMed

10.

Lahti M, Marttila R, Hallman M (2004) Surfactant protein C gene variation in the Finnish population—association with perinatal respiratory disease. Eur J Hum Genet 12:312–320CrossRefPubMed

11.

Lemanske RF, Jackson DJ, Gangnon RE, Evans MD, Li Z, Shult PA, Kirk CJ, Reisdorf E, Roberg KA, Anderson EL, Carlson-Dakes KT, Adler KJ, Gilbertson-White S, Pappas TE, Dasilva DF, Tisler CJ, Gern JE (2005) Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol 116:571–577CrossRefPubMed

12.

McNally JD, Sampson M, Matheson L, McNally JD, Sampson M (2014) Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: a systematic review and meta-analysis. Pediatr Pulmonol 49:790–799CrossRefPubMed

13.

Miller EK, Bugna J, Libster R, Shepherd BE, Scalzo PM, Acosta PL, Hijano D, Reynoso N, Batalle JP, Coviello S, Klein MI, Bauer G, Benitez A, Kleeberger SR, Polack FP (2012) Human rhinoviruses in severe respiratory disease in very low birth weight infants. Pediatrics 129:e60–e67CrossRefPubMedPubMedCentral

14.

Müller L, Mack I, Tapparel C, Kaiser L, Alves MP, Kieninger E, Frey U, Regamey N, Latzin P (2015) Human rhinovirus types and association with respiratory symptoms during the first year of life. Pediatr Infect Dis J 34:907–909CrossRefPubMed

15.

Papi A, Contoli M, Adcock IM, Bellettato C, Padovani A, Casolari P, Stanciu LA, Barnes PJ, Johnston SL, Ito K, Caramori G (2013) Rhinovirus infection causes steroid resistance in airway epithelium through nuclear factor κb and c-Jun N-terminal kinase activation. J Allergy Clin Immunol 132:1075–1085 e6CrossRefPubMed

16.

Park J, Hwang S, Lee YS, Kim SC, Lee D (2007) SNP@ethnos: a database of ethnically variant single-nucleotide polymorphisms. Nucleic Acids Res 35:D711–D715CrossRefPubMed

17.

Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S (2008) Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood. J Infect Dis 197:676–680CrossRefPubMed

18.

Roth DE, Shah R, Black RE, Baqui H (2010) Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh. Acta Paediatr 99:389–393CrossRefPubMed

19.

Siezen CLE, Bont L, Hodemaekers HM, Ermers MJ, Doornbos G, Van’t Slot R, Wijmenga C, Houwelingen HC, Kimpen JL, Kimman TG, Hoebee B, Janssen R (2009) Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes. Pediatr Infect Dis J 28:333–335CrossRefPubMed

20.

Simpson A, Maniatis N, Jury F, Cakebread JA, Lowe LA, Holgate ST, Woodcock A, Ollier WE, Collins A, Custovic A, Holloway JW, John SL (2005) Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function. Am J Respir Crit Care Med 172:55–60CrossRefPubMed

21.

Tran DN, Trinh QD, Pham NTK, Pham TM, Ha MT, Nguyen TQ, Okitsu S, Shimizu H, Hayakawa S, Mizuguchi M, Ushijima H (2015) Human rhinovirus infections in hospitalized children: clinical, epidemiological and virological features. Epidemiol Infect:1–9

22.

van der Zalm MM, Uiterwaal CSPM, Wilbrink B, Koopman M, Verheij TJ, van der Ent CK (2011) The influence of neonatal lung function on rhinovirus-associated wheeze. Am J Respir Crit Care Med 183:262–267CrossRefPubMed

23.

van der Zalm MM, Wilbrink B, van Ewijk BE, van Ewijk BE, Overduin P, Wolfs TF, van der Ent CK (2011) Highly frequent infections with human rhinovirus in healthy young children: a longitudinal cohort study. J Clin Virol 52:317–320CrossRefPubMed

24.

van Piggelen RO, van Loon AM, Krediet TG, Verboon-Maciolek M (2010) Human rhinovirus causes severe infection in preterm infants. Pediatr Infect Dis J 29:364–365PubMed

25.

Zomer-Kooijker K, Uiterwaal CSPM, van der Gugten AC, van der Gugten AC, Wilbrink B, Bont LJ, van der Ent CK (2014) Decreased lung function precedes severe respiratory syncytial virus infection and post-respiratory syncytial virus wheeze in term infants. Eur Respir J 44:666–674

Title: Functional and genetic predisposition to rhinovirus lower respiratory tract infections in prematurely born infants
Authors: Simon B Drysdale
Mireia Alcazar
Theresa Wilson
Melvyn Smith
Mark Zuckerman
Hennie M Hodemaekers
Riny Janssen
Louis Bont
Sebastian L Johnston
Anne Greenough
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 12/2016
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-016-2780-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

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Springer Medicine

Abstract

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