Mediators of neutrophil function in children with protracted bacterial bronchitis

Katherine Baines, John Upham, Stephanie Yerkovich, Anne Chang, Julie Marchant, Melanie Carroll, Jodie Simpson, Peter Gibson

    Research output: Contribution to journalArticle

    Abstract

    BACKGROUND: Protracted bacterial bronchitis (PBB) is a common and treatable cause of chronic wet cough in children in which the mechanisms are not understood. Th is study investigates the IL-1 pathway and a neutrophil gene expression signature in PBB.

    METHODS: BAL was collected from children in an experimental cohort (n = 21, PBB; n = 33, control subjects), and a second validation cohort (n = 36, PBB; n = 11, control subjects). IL-1? , IL-1 receptor antagonist (IL-1RA), and ? -defensins 1-3 were assayed by enzyme-linked immunosorbent assay, western blot, and quantitative real-time polymerase chain reaction, together with selected IL-1 pathway members and neutrophil-related molecules.

    RESULTS: In the experimental cohort, children with symptomatic PBB had significantly higher levels of IL-1? and ? -defensin gene and protein expression. Expression of the neutrophil chemokine receptor C-X-C motif receptor 2 was also higher in PBB. IL-1RA protein was higher, however, the IL-1RA:IL-1? ratio was lower in children with PBB than control subjects. In the validation cohort, protein and gene expression of IL-1? and ? -defensins 1-3 were confirmed higher, as was gene expression of IL-1 pathway members and C-X-C motif receptor 2. IL-1? and ? -defensin 1-3 levels lowered when PBB was treated and resolved. In children with recurrent PBB, gene expression of the IL-1? signaling molecules pellino-1 and IL-1 receptor-associated kinase 2 was significantly higher. IL-1? protein levels correlated with BAL neutrophilia and the duration and severity of cough symptoms. IL-1? and a -defensin 1-3 levels were highly correlated.

    CONCLUSIONS:
    PBB is characterized by increased IL-1? pathway activation. IL-1? and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.

    Original languageEnglish
    Pages (from-to)1013-1020
    Number of pages8
    JournalChest
    Volume146
    Issue number4
    DOIs
    Publication statusPublished - 2014

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    Baines, K., Upham, J., Yerkovich, S., Chang, A., Marchant, J., Carroll, M., Simpson, J., & Gibson, P. (2014). Mediators of neutrophil function in children with protracted bacterial bronchitis. Chest, 146(4), 1013-1020. https://doi.org/10.1378/chest.14-0131