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Published on: August 7, 2017
Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease
Melanie R Neeland1, Liam Gubbels2, Anson Tsz Chun Wong1
1Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
Insights
Researchers identified two immune endotypes in children with chronic suppurative lung disease and wheezing. These distinct inflammatory profiles, a hyper-inflammatory and a non-inflammatory type, could guide better treatment strategies for pediatric respiratory diseases.
Area of Science:
- Pediatric Pulmonology
- Immunology
- Respiratory Medicine
Background:
- Childhood wheeze and chronic suppurative lung disease (CSLD) are prevalent respiratory conditions.
- Limited understanding of their pathobiology restricts treatment options and leads to frequent recurrence.
- Novel therapeutic targets are needed to improve clinical management and patient outcomes.
Purpose of the Study:
- To profile pulmonary and systemic immune responses in children with wheeze and CSLD.
- To identify distinct immune endotypes that could inform improved clinical management.
- To compare immune profiles in bronchoalveolar lavage (BAL) fluid and systemic circulation.
Main Methods:
- Utilized clinical microbiology data, multiplex flow cytometry, and immunoassays.
- Compared pulmonary (BAL) and systemic immunity in pediatric patients and controls.
- Applied unsupervised analysis to BAL immune data to define biological endotypes.
Main Results:
- Identified two analogous immune endotypes across both wheeze and CSLD.
- The hyper-inflammatory endotype showed a 12-fold increase in neutrophils and elevated type 2 inflammatory markers.
- The non-inflammatory endotype did not differ significantly from controls and is definable by three BAL immune factors.
Conclusions:
- Discovered common hyper-inflammatory and non-inflammatory endotypes in pediatric wheeze and CSLD.
- These endotypes are measurable in a clinical setting.
- Further validation may enable personalized treatment strategies for these common childhood respiratory diseases.
Abstract:
Suppurative lung disease and wheezing are common respiratory diseases of childhood, however, due to poor understanding of underlying pathobiology, there are limited treatment options and disease recurrence is common. We aimed to profile the pulmonary and systemic immune response in children with wheeze and chronic suppurative lung disease for identification of endotypes that can inform improved clinical management. We used clinical microbiology data, highly multiplexed flow cytometry and immunoassays to compare pulmonary [bronchoalveolar lavage (BAL)] and systemic immunity in children with lung disease and controls. Unsupervised analytical approaches were applied to BAL immune data to explore biological endotypes. We identified two endotypes that were analogous in both frequency and immune signature across both respiratory diseases. The hyper-inflammatory endotype had a 12-fold increase in neutrophil infiltration and upregulation of 14 soluble signatures associated with type 2 inflammation and cell recruitment to tissue. The non-inflammatory endotype was not significantly different from controls. We showed these endotypes are measurable in a clinical setting and can be defined by measuring only three immune factors in BAL. We identified hyper-inflammatory and non-inflammatory endotypes common across pediatric wheeze and chronic suppurative lung disease that, if validated in future studies, have the potential to inform clinical management.
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