Chest
Original Research: BronchiectasisIs Alveolar Macrophage Phagocytic Dysfunction in Children With Protracted Bacterial Bronchitis a Forerunner to Bronchiectasis?
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.
References (43)
- et al.
Longitudinal growth and lung function in pediatric non-cystic fibrosis bronchiectasis: what influences lung function stability?
Chest
(2010) - et al.
Bronchiectasis in Central Australia: a young face to an old disease
Respir Med
(2008) - et al.
Evaluation and outcome of young children with chronic cough
Chest
(2006) - et al.
Diagnosing and preventing chronic suppurative lung disease (CSLD) and bronchiectasis
Paediatr Respir Rev
(2011) - et al.
T cells and eosinophils cooperate in the induction of bronchial epithelial cell apoptosis in asthma
J Allergy Clin Immunol
(2002) - et al.
Decreased efferocytosis and mannose binding lectin in the airway in bronchitis obliterans syndrome
J Heart Lung Transplant
(2011) - et al.
Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease
Chest
(2006) - et al.
Respiratory bacterial pathogens in the nasopharynx and lower airways of Australian indigenous children with bronchiectasis
J Pediatr
(2010) - et al.
Mediators of neutrophil function in children with protracted bacterial bronchitis
Chest
(2014) - et al.
Prospective characterization of protracted bacterial bronchitis in children
Chest
(2014)
Bronchoarterial ratio on high resolution CT scan of the chest in children without pulmonary pathology: need to redefine bronchial dilatation
Chest
A multicenter study on chronic cough in children: burden and etiologies based on a standardized management pathway
Chest
Childhood respiratory illness and lung function at ages 14 and 50 years: childhood respiratory illness and lung function
Chest
Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial
Lancet Respir Med
Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study
Lancet
Management of bronchiectasis and chronic suppurative lung disease in indigenous children and adults from rural and remote Australian communities
Med J Aust
Time trends in incidence and prevalence of bronchiectasis in the UK [abstract]
Thorax
Hospitalisation of Indigenous children in the Northern Territory for lower respiratory illness in the first year of life
Med J Aust
Indigenous children from three countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis
Pediatr Pulmonol
Cough in children: definitions and clinical evaluation
Med J Aust
BTS guidelines: recommendations for the assessment and management of cough in children
Thorax
Cited by (39)
Efferocytosis in lung mucosae: implications for health and disease
2022, Immunology LettersCitation Excerpt :Protracted bacterial bronchitis (PBB) is characterized by a chronic wet or productive cough that is accompanied by intense neutrophilia and a large number of respiratory bacterial pathogens, especially Haemophilus influenzae in the airways [150]. Lung inflammation with marked neutrophil infiltration and defective efferocytosis by AMs was found in PBB, which may contribute to long-term inflammation and disease progression [101]. Deficiencies in macrophage efferocytosis are also related to non-eosinophilic and eosinophilic/allergic asthma physiopathology [151–154].
Bronchiectasis in Childhood
2022, Clinics in Chest MedicineCitation Excerpt :Comparing the stimulated peripheral blood mononuclear cells of 80 children with chronic suppurative lung disease (CSLD) and 51 controls, Pizzutto and colleagues found that those with CSLD produced significantly less IFN-γ in response to NTHi than healthy controls.41 Furthermore, in a study of efferocytosis in children, a reduced ability of alveolar macrophages from children with bronchiectasis or PBB to phagocytose NTHi has been shown.42 It has been proposed that children and adults with bronchiectasis likely have the necessary cell-mediated immune architecture to respond to NTHi.
Bronchiectasis in Childhood (Including PBB)
2021, Encyclopedia of Respiratory Medicine, Second EditionEfferocytosis and Its Associated Cytokines: A Light on Non-tumor and Tumor Diseases?
2020, Molecular Therapy OncolyticsCitation Excerpt :The mechanism involves impaired efferocytosis via the Src/PI3K/Rac1 pathway, as well as inhibited Akt activation.86,87 Similarly, a reduced efferocytotic ability of alveolar macrophage to ACs, with increased IL-1β, encourages neutrophilic inflammation in bronchiectasis and asthma.88,89 Of note, one study indicated that IL-6 attenuates the macrophage pro-inflammatory phenotype and constitutes a protective response by eliminating excess cholesterol in human macrophages and phagocytes.
Bronchiectasis and Chronic Suppurative Lung Disease
2019, Kendig's Disorders of the Respiratory Tract in ChildrenBronchiectasis in children: diagnosis and treatment
2018, The LancetCitation Excerpt :The link between protracted bacterial bronchitis and bronchiectasis is reflected in the microbiology1,31 and microbiota41 of the lower airway, the inflammatory profile (eg, airway neutrophilia, elevated interleukin-1β concentration, and matrix metalloproteinases),1,39 and supported by longitudinal studies.8 Also, pathobiological studies describe impaired efferocytosis42 and elevated expression of genes32 related to macrophage function and impaired resolution of inflammation in both protracted bacterial bronchitis and bronchiectasis; and the values of the above in children with protracted bacterial bronchitis were intermediate between controls and individuals with bronchiectasis. Our framework emphasises the importance of pre-vention, early diagnosis, and optimal management, since early (cylindrical) bronchiectasis is potentially reversible in children, as described by earlier bronchogram-based studies28–30 and later substantiated by CT-based data.43
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).