Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease

Melanie R Neeland; Liam Gubbels; Anson Tsz Chun Wong; Hannah Walker; Sarath C Ranganathan; Shivanthan Shanthikumar

doi:10.1016/j.mucimm.2024.03.001

Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease

Mucosal Immunol. 2024 Mar 16:S1933-0219(24)00020-5. doi: 10.1016/j.mucimm.2024.03.001. Online ahead of print.

Authors

Melanie R Neeland¹, Liam Gubbels², Anson Tsz Chun Wong³, Hannah Walker⁴, Sarath C Ranganathan⁵, Shivanthan Shanthikumar⁵

Affiliations

¹ Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia. Electronic address: melanie.neeland@mcri.edu.au.
² Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
³ Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
⁴ Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia; Children's Cancer Centre, Royal Children's Hospital, Parkville, Australia.
⁵ Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia; Respiratory and Sleep Medicine, Royal Children's Hospital, Parkville, Australia.

PMID: 38492745
DOI: 10.1016/j.mucimm.2024.03.001

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.