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Published on: August 7, 2017
Children with asthma by school age display aberrant immune responses to pathogenic airway bacteria as infants
Jeppe Madura Larsen1, Susanne Brix2, Anna Hammerich Thysen1
1Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark; Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen, Copenhagen University Hospital, Gentofte, Denmark.
Insights
Infants who later develop asthma show an abnormal immune response to common airway bacteria. This early immune dysregulation may contribute to the development of childhood asthma.
Area of Science:
- Pediatric immunology
- Respiratory medicine
- Microbiome research
Background:
- Childhood asthma is a prevalent chronic respiratory condition often starting in infancy.
- Neonatal airway colonization by Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae is linked to increased asthma risk.
- A hypothesis suggests children with asthma exhibit an abnormal infant immune response to these pathogenic bacteria.
Purpose of the Study:
- To evaluate the infant immune response to specific bacteria.
- To determine the association between this immune response and asthma development by age 7.
- To investigate early immune markers for predicting childhood asthma.
Main Methods:
- Prospective follow-up of the Copenhagen Prospective Studies on Asthma in Childhood birth cohort.
- Analysis of immune responses (cytokine production, T-cell activation) in 292 infants at 6 months of age.
- Asthma diagnosis at 7 years of age.
Main Results:
- Significant differences in immune responses to pathogenic bacteria were observed in infants who developed asthma by age 7 (P = .0007).
- Aberrant production of key cytokines including IL-5, IL-13, IL-17, and IL-10 was noted in future asthmatics.
- No significant differences were found in T-cell activation or peripheral T-cell composition.
Conclusions:
- Children diagnosed with asthma by school age displayed an aberrant infant immune response to pathogenic bacteria.
- This abnormal immune response to early-life airway pathogens may be a contributing factor to chronic airway inflammation and childhood asthma.
- Early immune profiling could offer insights into asthma pathogenesis.
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.
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