T H 1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status.

BACKGROUND: The pathogenesis of severe asthma in childhood remains poorly understood.

OBJECTIVE: We sought to construct the immunologic landscape in the airways of children with severe asthma.

METHODS: Comprehensive analysis of multiple cell types and mediators was performed by using flow cytometry and a multiplex assay with bronchoalveolar lavage (BAL) specimens (n = 68) from 52 highly characterized allergic and nonallergic children (0.5-17 years) with severe treatment-refractory asthma. Multiple relationships were tested by using linear mixed-effects modeling.

RESULTS: Memory CCR5+ TH 1 cells were enriched in BAL fluid versus blood, and pathogenic respiratory viruses and bacteria were readily detected. IFN-γ+ IL-17+ and IFN-γ- IL-17+ subsets constituted secondary TH types, and BAL fluid CD8+ T cells were almost exclusively IFN-γ+ . The TH 17-associated mediators IL-23 and macrophage inflammatory protein 3α/CCL20 were highly expressed. Despite low TH 2 numbers, TH 2 cytokines were detected, and TH 2 skewing correlated with total IgE levels. Type 2 innate lymphoid cells and basophils were scarce in BAL fluid. Levels of IL-5, IL-33, and IL-28A/IFN-λ2 were increased in multisensitized children and correlated with IgE levels to dust mite, ryegrass, and fungi but not cat, ragweed, or food sources. Additionally, levels of IL-5, but no other cytokine, increased with age and correlated with eosinophil numbers in BAL fluid and blood. Both plasmacytoid and IgE+ FcεRI+ myeloid dendritic cells were present in BAL fluid.

CONCLUSIONS: The lower airways of children with severe asthma display a dominant TH 1 signature and atypical cytokine profiles that link to allergic status. Our findings deviate from established paradigms and warrant further assessment of the pathogenicity of TH 1 cells in patients with severe asthma.