title: Is Alveolar Macrophage Phagocytic Dysfunction in Children With Protracted Bacterial Bronchitis a Forerunner to Bronchiectasis?
abstract: 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.
authors: Chronic Inflammatory Lung Disease Research Laboratory, Lung Research Unit, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, and The School of Medicine, The University of Adelaide, Adelaide, SA, Australia. Electronic address: sandra.hodge@health.sa.gov.au.
authors: Sandra
authors: S
authors: Hodge
authors: Princess Alexandra Hospital, Brisbane, QLD, Australia; The School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
authors: John W
authors: JW
authors: Upham
authors: Child Health Division, Menzies School of Health Research, Darwin, NT, Australia.
authors: Susan
authors: S
authors: Pizzutto
authors: Queensland University of Technology, South Brisbane, QLD, Australia.
authors: Helen L
authors: HL
authors: Petsky
authors: The School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
authors: Stephanie
authors: S
authors: Yerkovich
authors: Respiratory and Sleep Medicine, School of Medicine and Public Health, Centre for Asthma and Respiratory Disease, The University of Newcastle, Callaghan, NSW, Australia.
authors: Katherine J
authors: KJ
authors: Baines
authors: Respiratory and Sleep Medicine, School of Medicine and Public Health, Centre for Asthma and Respiratory Disease, The University of Newcastle, Callaghan, NSW, Australia.
authors: Peter
authors: P
authors: Gibson
authors: Respiratory and Sleep Medicine, School of Medicine and Public Health, Centre for Asthma and Respiratory Disease, The University of Newcastle, Callaghan, NSW, Australia.
authors: Jodie L
authors: JL
authors: Simpson
authors: Queensland Children's Health Service, Brisbane, QLD, and Queensland Children's Medical Research Institute, Brisbane, QLD, Australia.
authors: Helen
authors: H
authors: Buntain
authors: The School of Medicine, The University of Queensland, Brisbane, QLD, Australia.
authors: Alice C H
authors: ACH
authors: Chen
authors: Chronic Inflammatory Lung Disease Research Laboratory, Lung Research Unit, Hanson Institute and Department of Thoracic Medicine, Royal Adelaide Hospital, and The School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
authors: Greg
authors: G
authors: Hodge
authors: Child Health Division, Menzies School of Health Research, Darwin, NT, Australia; Queensland Children's Health Service, Brisbane, QLD, and Queensland Children's Medical Research Institute, Brisbane, QLD, Australia.
authors: Anne B
authors: AB
authors: Chang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001424:Bacterial Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D001987:Bronchiectasis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D001991:Bronchitis / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010587:Phagocytosis / Q000502:physiology*
keywords: bronchiectasis; childhood lung disease; inflammation; macrophage; phagocytosis; protracted bacterial bronchitis