Is alveolar macrophage phagocytic dysfunction in children with protracted bacterial bronchitis a forerunner to bronchiectasis?

dc.contributor.authorHodge, S.
dc.contributor.authorUpham, J.
dc.contributor.authorPizzutto, S.
dc.contributor.authorPetsky, H.
dc.contributor.authorYerkovich, S.
dc.contributor.authorBaines, K.
dc.contributor.authorGibson, P.
dc.contributor.authorSimpson, J.
dc.contributor.authorBuntain, H.
dc.contributor.authorChen, A.
dc.contributor.authorHodge, G.
dc.contributor.authorChang, A.
dc.date.issued2016
dc.description.abstractBackground: Children with recurrent protracted bacterial bronchitis (PBB) and bronchiectasis share common features, and PBB is likely a forerunner to bronchiectasis. Both diseases are associated with neutrophilic inflammation and frequent isolation of potentially pathogenic microorganisms, including nontypeable Haemophilus influenzae (NTHi), from the lower airway. Defective alveolar macrophage phagocytosis of apoptotic bronchial epithelial cells (efferocytosis), as found in other chronic lung diseases, may also contribute to tissue damage and neutrophil persistence. Thus, in children with bronchiectasis or PBB and in control subjects, we quantified the phagocytosis of airway apoptotic cells and NTHi by alveolar macrophages and related the phagocytic capacity to clinical and airway inflammation. Methods: Children with bronchiectasis (n = 55) or PBB (n = 13) and control subjects (n = 13) were recruited. Alveolar macrophage phagocytosis, efferocytosis, and expression of phagocytic scavenger receptors were assessed by flow cytometry. Bronchoalveolar lavage fluid interleukin (IL) 1β was measured by enzyme-linked immunosorbent assay. Results: For children with PBB or bronchiectasis, macrophage phagocytic capacity was significantly lower than for control subjects (P = .003 and P < .001 for efferocytosis and P = .041 and P = .004 for phagocytosis of NTHi; PBB and bronchiectasis, respectively); median phagocytosis of NTHi for the groups was as follows: bronchiectasis, 13.7% (interquartile range [IQR], 11%-16%); PBB, 16% (IQR, 11%-16%); control subjects, 19.0% (IQR, 13%-21%); and median efferocytosis for the groups was as follows: bronchiectasis, 14.1% (IQR, 10%-16%); PBB, 16.2% (IQR, 14%-17%); control subjects, 18.1% (IQR, 16%-21%). Mannose receptor expression was significantly reduced in the bronchiectasis group (P = .019), and IL-1β increased in both bronchiectasis and PBB groups vs control subjects. Conclusions: A reduced alveolar macrophage phagocytic host response to apoptotic cells or NTHi may contribute to neutrophilic inflammation and NTHi colonization in both PBB and bronchiectasis. Whether this mechanism also contributes to the progression of PBB to bronchiectasis remains unknown.
dc.description.statementofresponsibilitySandra Hodge, John W. Upham, Susan Pizzutto, Helen L. Petsky, Stephanie Yerkovich, Katherine J. Baines, Peter Gibson
dc.identifier.citationChest, 2016; 149(2):508-515
dc.identifier.doi10.1016/j.chest.2015.10.066
dc.identifier.issn0012-3692
dc.identifier.issn1931-3543
dc.identifier.orcidHodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]
dc.identifier.urihttp://hdl.handle.net/2440/105336
dc.language.isoen
dc.publisherAmerican College of Chest Physicians
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1042601
dc.rightsCopyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.chest.2015.10.066
dc.subjectBronchiectasis; childhood lung disease; inflammation; macrophage; phagocytosis; protracted bacterial bronchitis
dc.titleIs alveolar macrophage phagocytic dysfunction in children with protracted bacterial bronchitis a forerunner to bronchiectasis?
dc.typeJournal article
pubs.publication-statusPublished

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