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Original Research: Signs and Symptoms of Chest Diseases |

Mediators of Neutrophil Function in Children With Protracted Bacterial BronchitisInflammation in Protracted Bacterial Bronchitis

Katherine J. Baines, PhD; John W. Upham, PhD; Stephanie T. Yerkovich, PhD; Anne B. Chang, PhD; Julie M. Marchant, PhD; Melanie Carroll, BSc (Hons); Jodie L. Simpson, PhD; Peter G. Gibson, MBBS
Author and Funding Information

From the Priority Research Centre for Asthma and Respiratory Diseases (Drs Baines, Simpson, and Gibson), The University of Newcastle, Callaghan, NSW; Department of Respiratory and Sleep Medicine (Drs Baines, Simpson, and Gibson), Hunter Medical Research Institute, John Hunter Hospital, New Lambton Heights, NSW; School of Medicine (Drs Upham, Yerkovich, and Marchant and Ms Carroll), The University of Queensland, Brisbane, QLD; Qld Lung Transplant Service (Dr Yerkovich), The Prince Charles Hospital, Brisbane, QLD; Department of Respiratory Medicine (Drs Chang and Marchant), Queensland Children’s Medical Research Institute, Royal Children’s Hospital, Brisbane, QLD; and Child Health Division (Dr Chang), Menzies School of Health Research, Darwin, NT, Australia.

CORRESPONDENCE TO: Katherine J. Baines, PhD, Level 2 West, HMRI Bldg, Lot 1 Kookaburra Circuit, New Lambton Heights, NSW 2305, Australia; e-mail: katherine.baines@newcastle.edu.au


FUNDING/SUPPORT: Drs Gibson, Upham, and Chang are supported by National Health and Medical Research Council (NHMRC; Commonwealth of Australia) fellowships [Grants 569240, 511019, and 545216, respectively]. Dr Baines is supported by a research fellowship from The University of Newcastle. The study was funded by the Financial Markets Foundation for Children [Grant 2010-005], NHMRC [Grant 1042601], and NHMRC Centre of Research Excellence (CRE) in Lung Health of Aboriginal and Torres Strait Islander Children [Grant 1040830].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;146(4):1013-1020. doi:10.1378/chest.14-0131
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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.

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