Chest
Volume 149, Issue 2, February 2016, Pages 508-515
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Original Research: Bronchiectasis
Is Alveolar Macrophage Phagocytic Dysfunction in Children With Protracted Bacterial Bronchitis a Forerunner to Bronchiectasis?

https://doi.org/10.1016/j.chest.2015.10.066Get rights and content

Background

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.

Section snippets

Subjects

Children younger than 10 years old who underwent flexible bronchoscopy at two Australian centers (Darwin and Brisbane) were eligible for inclusion. Bronchoscopy for children with bronchiectasis and PBB has been standard clinical practice in our setting for years in accordance to local and international guidelines.8, 9, 26 Upon informed consent, a standardized medical history was taken (focus on respiratory history including cough quality [wet vs dry]).27 Groups were (1) bronchiectasis (n = 55),

Results

Clinical characteristics of the children studied are presented in Table 1. Children with PBB were symptomatic at the time of the bronchoscopy. Children in the bronchiectasis group were significantly older, and the group contained more indigenous children compared with the control and PBB groups. Neutrophils were significantly increased and macrophages decreased in the BALF from children with PBB or bronchiectasis compared with control subjects (Table 1).

Discussion

In this first paper to study efferocytosis in children, our key findings were demonstration of dysfunctional alveolar macrophage phagocytic immune response to NTHi or apoptotic cells in children with either protracted bacterial bronchitis (PBB) or bronchiectasis, further identifying similar mechanisms underlying both diseases.

PBB is a very common diagnosis among children presenting with chronic wet cough to pediatric pulmonologists. Our single-center (n = 108)6 and multicenter prospective

Acknowledgments

Author contributions: S. H. contributed to study conception and design, experimental analysis, result interpretation, and manuscript drafting for important intellectual content. She is the guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article. G. H. contributed to study conception and design, experimental analysis, result interpretation, and manuscript drafting for important intellectual content. A. B. C. and J. W. U.

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    FUNDING/SUPPORT: This work was supported by the National Health and Medical Research Council (NHMRC), Australia (project grant 1042601); and the Channel 7 Children’s Research Foundation, Australia (grant 13688).

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