Sandra Hodge1, John W Upham2, Susan Pizzutto3, Helen L Petsky4, Stephanie Yerkovich5, Katherine J Baines6, Peter Gibson6, Jodie L Simpson6, Helen Buntain7, Alice C H Chen5, Greg Hodge8, Anne B Chang9. 1. 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. 2. Princess Alexandra Hospital, Brisbane, QLD, Australia; The School of Medicine, The University of Queensland, Brisbane, QLD, Australia. 3. Child Health Division, Menzies School of Health Research, Darwin, NT, Australia. 4. Queensland University of Technology, South Brisbane, QLD, Australia. 5. The School of Medicine, The University of Queensland, Brisbane, QLD, Australia. 6. Respiratory and Sleep Medicine, School of Medicine and Public Health, Centre for Asthma and Respiratory Disease, The University of Newcastle, Callaghan, NSW, Australia. 7. Queensland Children's Health Service, Brisbane, QLD, and Queensland Children's Medical Research Institute, Brisbane, QLD, Australia. 8. 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. 9. 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.
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.
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: Sandra Hodge; Hai B Tran; Rhys Hamon; Eugene Roscioli; Greg Hodge; Hubertus Jersmann; Miranda Ween; Paul N Reynolds; Arthur Yeung; Jennifer Treiberg; Sibylle Wilbert Journal: Am J Physiol Lung Cell Mol Physiol Date: 2017-03-03 Impact factor: 5.464
Authors: Ahmad Kantar; Anne B Chang; Mike D Shields; Julie M Marchant; Keith Grimwood; Jonathan Grigg; Kostas N Priftis; Renato Cutrera; Fabio Midulla; Paul L P Brand; Mark L Everard Journal: Eur Respir J Date: 2017-08-24 Impact factor: 16.671
Authors: Alice C-H Chen; Hai B Tran; Yang Xi; Stephanie T Yerkovich; Katherine J Baines; Susan J Pizzutto; Melanie Carroll; Avril A B Robertson; Matthew A Cooper; Kate Schroder; Jodie L Simpson; Peter G Gibson; Greg Hodge; Ian B Masters; Helen M Buntain; Helen L Petsky; Samantha J Prime; Anne B Chang; Sandra Hodge; John W Upham Journal: ERJ Open Res Date: 2018-03-23
Authors: Agnieszka Strzelak; Aleksandra Ratajczak; Aleksander Adamiec; Wojciech Feleszko Journal: Int J Environ Res Public Health Date: 2018-05-21 Impact factor: 3.390
Authors: Hai B Tran; Hubertus Jersmann; Tung Thanh Truong; Rhys Hamon; Eugene Roscioli; Miranda Ween; Melissa R Pitman; Stuart M Pitson; Greg Hodge; Paul N Reynolds; Sandra Hodge Journal: PLoS One Date: 2017-11-07 Impact factor: 3.240