Bronchoalveolar lavage cytokine patterns in children with severe neutrophilic and paucigranulocytic asthma - 04/02/21
Abstract |
Background |
Asthma is a complex heterogeneous disease occurring in adults and children that is characterized by distinct inflammatory patterns. While numerous studies have been performed in adults, little is known regarding the heterogeneity of severe asthma in children, particularly inflammatory signatures involving the air spaces.
Objective |
We sought to determine the relationship of bronchoalveolar lavage (BAL) cytokine/chemokine expression patterns in children with severe therapy-resistant asthma stratified according to neutrophilic versus nonneutrophilic BAL inflammatory cell patterns.
Methods |
Children with severe asthma with inadequate symptom control despite therapy underwent diagnostic bronchoscopy and BAL. Inflammatory cytokine/chemokine concentrations were determined using a multiplex protein bead assay.
Results |
Analysis of BAL constituents with an unbiased clustering approach revealed distinct cytokine/chemokine patterns, and these aligned with pathways associated with type 2 innate lymphoid cells, monocytes, neutrophil trafficking, and T effector cells. All cytokines examined (n = 27) with 1 exception (vascular endothelial growth factor) were overexpressed with BAL neutrophilia compared with nonneutrophilic asthma, and this was confirmed in a cross-validation analysis. Cytokines specifically responsible for Th17 (IL-17, IL-6, G-CSF) and Th1 differentiation and expression (IL-12, TNF-α, IFN-γ) were enhanced in the neutrophilic cohorts. Neutrophilic groups were also characterized by higher prevalence of bacterial and viral pathogens; however, cytokine expression patterns manifested independently of pathogen expression.
Conclusions |
The results demonstrate that children with refractory asthma and neutrophilic inflammation had a BAL cytokine pattern consistent with a mixed Th17/Th1/Th2 response. In contrast, nonneutrophilic asthma presented independently of cytokine overexpression.
Le texte complet de cet article est disponible en PDF.Key words : Severe asthma, BAL granulocytes, neutrophilic asthma, eosinophilic asthma, asthma phenotypes, asthma heterogeneity, cytokine, chemokine, rhinovirus
Abbreviations used : BAL, CCL, CCS, CXCL, FGF, PDGF, VEGF, YI
Plan
| This work was supported by The Ivy Foundation of Charlottesville, National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program U10HL109250-07 (W.G.T.), National Institute of Allergy and Infectious Diseases U01A123337 (L.B.), and American Lung Association/American Academy of Allergy, Asthma, and Immunology Allergic Respiratory Diseases Award (M.L.). |
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| Disclosure of potential conflict of interest: J. W. Steinke has changed jobs and now works for Genentech; however, all work was completed prior to starting the job. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 2
P. 686 - février 2021 Retour au numéro
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