TY - JOUR
T1 - Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants
AU - Larsen, Jeppe Madura
AU - Brix, Susanne
AU - Thysen, Anna Hammerich
AU - Birch, Sune
AU - Rasmussen, Morten Arendt
AU - Bisgaard, Hans
N1 - Funding Information:
Disclosure of potential conflict of interest: S. Brix has received research support from the Danish Strategic Research Council . H. Bisgaard has received research support from the Danish Strategic Research Council , the Lundbeck Foundation , the Danish State Budget , the Capital Region of Denmark , and the Danish Council for Independent Research, Medical Sciences . The rest of the authors declare that they have no relevant conflicts of interest.
Funding Information:
The Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) is funded by private and public research funds, all of which are listed at www.copsac.com . The Lundbeck Foundation , the Strategic Research Foundation , the Pharmacy Foundation of 1991 , the Augustinus Foundation , the Danish Medical Research Council , and the Danish Pediatric Asthma Centre provided core support for COPSAC.
PY - 2014/4
Y1 - 2014/4
N2 - BACKGROUND: Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonization of neonatal airways with the pathogenic bacterial strains Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that children with asthma have an abnormal immune response to pathogenic bacteria in infancy.OBJECTIVE: We aimed to assess the bacterial immune response in asymptomatic infants and the association with later development of asthma by age 7 years.METHODS: The Copenhagen Prospective Studies on Asthma in Childhood birth cohort was followed prospectively, and asthma was diagnosed at age 7 years. The immune response to H influenzae, M catarrhalis, and S pneumoniae was analyzed in 292 infants using PBMCs isolated and stored since the age of 6 months. The immune response was assessed based on the pattern of cytokines produced and T-cell activation.RESULTS: The immune response to pathogenic bacteria was different in infants with asthma by 7 years of age (P = .0007). In particular, prospective asthmatic subjects had aberrant production of IL-5 (P = .008), IL-13 (P = .057), IL-17 (P = .001), and IL-10 (P = .028), whereas there were no differences in T-cell activation or peripheral T-cell composition.CONCLUSIONS: Children with asthma by school age exhibited an aberrant immune response to pathogenic bacteria in infancy. We propose that an abnormal immune response to pathogenic bacteria colonizing the airways in early life might lead to chronic airway inflammation and childhood asthma.
AB - BACKGROUND: Asthma is a highly prevalent chronic lung disease that commonly originates in early childhood. Colonization of neonatal airways with the pathogenic bacterial strains Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae is associated with increased risk of later childhood asthma. We hypothesized that children with asthma have an abnormal immune response to pathogenic bacteria in infancy.OBJECTIVE: We aimed to assess the bacterial immune response in asymptomatic infants and the association with later development of asthma by age 7 years.METHODS: The Copenhagen Prospective Studies on Asthma in Childhood birth cohort was followed prospectively, and asthma was diagnosed at age 7 years. The immune response to H influenzae, M catarrhalis, and S pneumoniae was analyzed in 292 infants using PBMCs isolated and stored since the age of 6 months. The immune response was assessed based on the pattern of cytokines produced and T-cell activation.RESULTS: The immune response to pathogenic bacteria was different in infants with asthma by 7 years of age (P = .0007). In particular, prospective asthmatic subjects had aberrant production of IL-5 (P = .008), IL-13 (P = .057), IL-17 (P = .001), and IL-10 (P = .028), whereas there were no differences in T-cell activation or peripheral T-cell composition.CONCLUSIONS: Children with asthma by school age exhibited an aberrant immune response to pathogenic bacteria in infancy. We propose that an abnormal immune response to pathogenic bacteria colonizing the airways in early life might lead to chronic airway inflammation and childhood asthma.
KW - Asthma
KW - Bacteria
KW - Bacterial Infections
KW - Child
KW - Child, Preschool
KW - Cytokines
KW - Female
KW - Humans
KW - Infant
KW - Lymphocyte Activation
KW - Male
KW - Phenotype
KW - Prospective Studies
KW - Respiratory Tract Infections
KW - T-Lymphocyte Subsets
U2 - 10.1016/j.jaci.2014.01.010
DO - 10.1016/j.jaci.2014.01.010
M3 - Journal article
C2 - 24612682
SN - 0091-6749
VL - 133
SP - 1008-1013.e4
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -