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Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Personal network inference identifies children at risk of recurrent wheezing and asthma
L A Coleman1, S K Khoo2, J A Bizzintino3
1Medical School, University of Western Australia, Perth, Australia; Wal-Yan Respiratory Research Centre, The Kids Research Institute Australia, Nedlands, Australia.
Insights
Blood biomarkers can identify immune endotypes in children with asthma, predicting those at high risk for recurrent exacerbations. This finding may lead to targeted therapies for severe pediatric wheezing.
Area of Science:
- Pediatric Pulmonology
- Immunology
- Genomics
Background:
- Recurrent wheezing and asthma exacerbations are major causes of pediatric hospitalizations.
- Predicting persistent exacerbations in children is difficult.
- Immune endotypes in nasal epithelium link low interferon and high inflammation to increased exacerbation risk.
Purpose of the Study:
- To determine if blood gene network biomarkers can identify immune endotypes in children with acute wheeze and asthma.
- To assess the predictive value of these biomarkers for future exacerbations.
Main Methods:
- Gene expression analysis of peripheral blood mononuclear cell (PBMC) samples from hospitalized pediatric patients.
- Personal network inference to identify gene expression patterns and classify immune endotypes.
Main Results:
- Three distinct immune endotypes were identified in pediatric patients.
- One endotype, marked by low interferon response and high innate/adaptive immune pathway expression, predicted increased risk of respiratory hospitalizations and persistent exacerbations.
Conclusions:
- PBMC gene network biomarkers can identify immune endotypes associated with clinical outcomes in pediatric asthma.
- A high-risk endotype was identified, suggesting a potential treatable trait.
- Therapies targeting interferon enhancement or inflammation reduction may benefit this high-risk subgroup.
Background:
Wheezing and asthma exacerbations are leading causes of pediatric hospital admissions. Predicting which children will experience persistent exacerbations remains challenging. Prior research has identified immune endotypes in the nasal epithelium of children with acute asthma and wheezing, characterized by varying balances of interferons and inflammatory markers. Notably, children exhibiting low interferon responses coupled with high inflammation are at an increased risk for recurrent respiratory exacerbations.
Objective:
This study aimed to determine if blood-based gene network biomarkers can detect immune endotypes in children presenting with acute wheeze and asthma, potentially serving as predictive tools for future exacerbations.
Methods:
We conducted gene expression analysis using microarrays of peripheral blood mononuclear cell samples from pediatric patients who presented to hospital for acute wheeze and asthma. Personal network inference was used to discern gene expression patterns, facilitating the classification of patients' disease into distinct immune endotypes.
Results:
Three immune endotypes were identified. One endotype, characterized by low interferon responses and elevated expression of both innate and adaptive immune pathways, was significantly associated with an increased risk of subsequent hospital respiratory presentations and a persistent pattern of respiratory exacerbations over time.
Conclusion:
Peripheral blood mononuclear cell-based personal gene network biomarkers can effectively identify immune endotypes correlating with clinical outcomes in pediatric asthma. The high-risk endotype represents a potential treatable trait in acute wheezing episodes. Therapeutic strategies aimed at enhancing interferon responses and/or reducing inflammation may benefit this subgroup.
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