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Mediators of Neutrophil Function in Children With Protracted Bacterial Bronchitis

Baines, Katherine J., Upham, John W., Yerkovich, Stephanie T., Chang, Anne B., Marchant, Julie M., Carroll, Melanie, Simpson, Jodie L. and Gibson, Peter G. (2014). Mediators of Neutrophil Function in Children With Protracted Bacterial Bronchitis. Chest,146(4):1013-1020.

Document type: Journal Article
Citation counts: Altmetric Score Altmetric Score is 1
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IRMA ID 11436xPUB63
Title Mediators of Neutrophil Function in Children With Protracted Bacterial Bronchitis
Author Baines, Katherine J.
Upham, John W.
Yerkovich, Stephanie T.
Chang, Anne B.
Marchant, Julie M.
Carroll, Melanie
Simpson, Jodie L.
Gibson, Peter G.
Journal Name Chest
Publication Date 2014
Volume Number 146
Issue Number 4
ISSN 0012-3692   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84907921105
Start Page 1013
End Page 1020
Total Pages 8
Place of Publication United States of America
Publisher American College of Chest Physicians
HERDC Category C1 - Journal Article (DIISR)
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. This 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-1β, IL-1 receptor antagonist (IL-1RA), and α-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-1β and α-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-1β ratio was lower in children with PBB than control subjects. In the validation cohort, protein and gene expression of IL-1β and α-defensins 1-3 were confirmed higher, as was gene expression of IL-1 pathway members and C-X-C motif receptor 2. IL-1β and α-defensin 1-3 levels lowered when PBB was treated and resolved. In children with recurrent PBB, gene expression of the IL-1β signaling molecules pellino-1 and IL-1 receptor-associated kinase 2 was significantly higher. IL-1β protein levels correlated with BAL neutrophilia and the duration and severity of cough symptoms. IL-1β and α-defensin 1-3 levels were highly correlated.
CONCLUSIONS:
PBB is characterized by increased IL-1β pathway activation. IL-1β and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.

DOI http://dx.doi.org/10.1378/chest.14-0131   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Description for Link Link to publisher's version
URL http://journal.publications.chestnet.org/article.aspx?articleid=1876884
 
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