Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria

Nadja Hawwa Vissing; Jeppe Madura Larsen; Morten Arendt Rasmussen; Bo Lund Krogsgaard Chawes; Anna Hammerich Thysen; Klaus Bønnelykke; Susanne Brix Pedersen; Hans Bisgaard

doi:10.1097/INF.0000000000001092

Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria

Nadja Hawwa Vissing, Jeppe Madura Larsen, Morten Arendt Rasmussen, Bo Lund Krogsgaard Chawes, Anna Hammerich Thysen, Klaus Bønnelykke, Susanne Brix Pedersen, Hans Bisgaard

9 Citations (Scopus)

Abstract

BACKGROUND: Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy. The objective was to characterize in vitro the early life systemic immune response to pathogenic bacteria and study the possible association with incidence of LRI during the first 3 years of life.

METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) is a clinical birth cohort study of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2, IL-5, IL-10, IL-13 and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy.

RESULTS: A multivariable model including all cytokine responses from the 3 different bacterial stimulations significantly identified children at risk of LRI (P = 0.006). The immune response pattern associated with LRI was characterized by perturbed production of several cytokines rather than production of one specific cytokine, and was independent of concurrent asthma. TNF-α and IL-5 were key drivers but did not explain the entire variation in LRI susceptibility.

CONCLUSIONS: Children at risk of future LRI present a perturbed systemic immune response upon exposure to common airway pathogens in early life.

Original language	English
Journal	The Pediatric Infectious Disease Journal
Volume	35
Issue number	5
Pages (from-to)	561-566
Number of pages	6
ISSN	0891-3668
DOIs	https://doi.org/10.1097/INF.0000000000001092
Publication status	Published - 1 May 2016

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Vissing, N. H., Larsen, J. M., Rasmussen, M. A., Chawes, B. L. K., Thysen, A. H., Bønnelykke, K., Pedersen, S. B., & Bisgaard, H. (2016). Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria. The Pediatric Infectious Disease Journal, 35(5), 561-566. https://doi.org/10.1097/INF.0000000000001092

Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria. / Vissing, Nadja Hawwa; Larsen, Jeppe Madura; Rasmussen, Morten Arendt et al.
In: The Pediatric Infectious Disease Journal, Vol. 35, No. 5, 01.05.2016, p. 561-566.

Research output: Contribution to journal › Journal article › Research › peer-review

Vissing, NH, Larsen, JM, Rasmussen, MA, Chawes, BLK, Thysen, AH, Bønnelykke, K, Pedersen, SB & Bisgaard, H 2016, 'Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria', The Pediatric Infectious Disease Journal, vol. 35, no. 5, pp. 561-566. https://doi.org/10.1097/INF.0000000000001092

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title = "Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria",

abstract = "BACKGROUND: Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy. The objective was to characterize in vitro the early life systemic immune response to pathogenic bacteria and study the possible association with incidence of LRI during the first 3 years of life.METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) is a clinical birth cohort study of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2, IL-5, IL-10, IL-13 and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy.RESULTS: A multivariable model including all cytokine responses from the 3 different bacterial stimulations significantly identified children at risk of LRI (P = 0.006). The immune response pattern associated with LRI was characterized by perturbed production of several cytokines rather than production of one specific cytokine, and was independent of concurrent asthma. TNF-α and IL-5 were key drivers but did not explain the entire variation in LRI susceptibility.CONCLUSIONS: Children at risk of future LRI present a perturbed systemic immune response upon exposure to common airway pathogens in early life.",

author = "Vissing, {Nadja Hawwa} and Larsen, {Jeppe Madura} and Rasmussen, {Morten Arendt} and Chawes, {Bo Lund Krogsgaard} and Thysen, {Anna Hammerich} and Klaus B{\o}nnelykke and Pedersen, {Susanne Brix} and Hans Bisgaard",

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doi = "10.1097/INF.0000000000001092",

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T1 - Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria

AU - Vissing, Nadja Hawwa

AU - Larsen, Jeppe Madura

AU - Rasmussen, Morten Arendt

AU - Chawes, Bo Lund Krogsgaard

AU - Thysen, Anna Hammerich

AU - Bønnelykke, Klaus

AU - Pedersen, Susanne Brix

AU - Bisgaard, Hans

PY - 2016/5/1

Y1 - 2016/5/1

N2 - BACKGROUND: Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy. The objective was to characterize in vitro the early life systemic immune response to pathogenic bacteria and study the possible association with incidence of LRI during the first 3 years of life.METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) is a clinical birth cohort study of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2, IL-5, IL-10, IL-13 and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy.RESULTS: A multivariable model including all cytokine responses from the 3 different bacterial stimulations significantly identified children at risk of LRI (P = 0.006). The immune response pattern associated with LRI was characterized by perturbed production of several cytokines rather than production of one specific cytokine, and was independent of concurrent asthma. TNF-α and IL-5 were key drivers but did not explain the entire variation in LRI susceptibility.CONCLUSIONS: Children at risk of future LRI present a perturbed systemic immune response upon exposure to common airway pathogens in early life.

AB - BACKGROUND: Neonatal colonization of the airways with respiratory pathogens is associated with increased risk of lower respiratory infections (LRI) in early childhood. Therefore, we hypothesized that children developing LRI have an aberrant immune response to pathogenic bacteria in infancy. The objective was to characterize in vitro the early life systemic immune response to pathogenic bacteria and study the possible association with incidence of LRI during the first 3 years of life.METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) is a clinical birth cohort study of 411 children born of mothers with asthma. LRI incidence was prospectively captured from 6-monthly planned visits and visits at acute respiratory episodes. The in vitro systemic immune response to Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was characterized by the production of TNF-α, IFN-γ, IL-2, IL-5, IL-10, IL-13 and IL-17 in peripheral blood mononuclear cells isolated at age 6 months from 291 infants. Data were analyzed by Poisson regression against incidence of LRI in infancy.RESULTS: A multivariable model including all cytokine responses from the 3 different bacterial stimulations significantly identified children at risk of LRI (P = 0.006). The immune response pattern associated with LRI was characterized by perturbed production of several cytokines rather than production of one specific cytokine, and was independent of concurrent asthma. TNF-α and IL-5 were key drivers but did not explain the entire variation in LRI susceptibility.CONCLUSIONS: Children at risk of future LRI present a perturbed systemic immune response upon exposure to common airway pathogens in early life.

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DO - 10.1097/INF.0000000000001092

M3 - Journal article

C2 - 26910587

SN - 0891-3668

VL - 35

SP - 561

EP - 566

JO - The Pediatric Infectious Disease Journal

JF - The Pediatric Infectious Disease Journal

IS - 5

ER -

Susceptibility to lower respiratory infections in childhood is associated with perturbation of the cytokine response to pathogenic airway bacteria

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