Prospective assessment of protracted bacterial bronchitis: airway inflammation and innate immune activation.
Protracted bacterial bronchitis (PBB) is a common cause of paediatric chronic moist cough. PBB is defined as the presence of isolated chronic moist cough which resolves with antibiotic therapy within 2 weeks and an absence of pointers suggesting alternative diagnoses. Our aim was to describe the clinical profile and examine the airway cellularity and likely promoters of neutrophilic inflammation in the bronchoalveolar lavage (BAL) of children with PBB compared with chronic cough due to other causes and controls. We explored the innate immune signaling receptors, toll-like receptors (TLR)-2 and TLR-4, as well as relevant effector molecules. A cross-sectional comparison was made of 100 children median age 2.58 years (with either PBB, coughing due to another cause or no cough controls) who underwent flexible bronchoscopy with lavage. BAL was evaluated for airway cytology, microbiology, inflammatory mediators interleukin 8 (IL-8) and active matrix metalloproteinase 9 (MMP-9) and TLR-2 and TLR-4 messenger RNA (mRNA) expression. Children with PBB had marked airway neutrophilia and increased median cytokine levels when compared to those with cough that resolved naturally and no cough controls: IL-8 0.67 versus 0.07 and 0.06 ng/ml (P < 0.005) and active MMP-9 7.25 versus 1.35 and 0.38 ng/ml (P < 0.005). The values for TLR-2 and TLR-4 mRNA expression were significantly elevated in children with PBB when compared to the control group. PBB is a paediatric condition which presents with chronic moist cough and its airway profile is characterized by intense neutrophilic airway inflammation with marked inflammatory mediator response and evidence of innate immune activation.
Marchant
Julie M
JM
Department of Respiratory Medicine, Royal Children's Hospital, Brisbane, Australia.|School of Medicine, Discipline of Paediatrics and Child Health, University of Queensland, Royal Children's Hospital, Brisbane, Australia.
Gibson
Peter G
PG
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
Grissell
Terry V
TV
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
Timmins
Naomi L
NL
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
Masters
I Brent
IB
Department of Respiratory Medicine, Royal Children's Hospital, Brisbane, Australia.|School of Medicine, Discipline of Paediatrics and Child Health, University of Queensland, Royal Children's Hospital, Brisbane, Australia.
Chang
Anne B
AB
Department of Respiratory Medicine, Royal Children's Hospital, Brisbane, Australia.|Child Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
D001991:Bronchitis / Q000276:immunology* / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003371:Cough / Q000276:immunology; D005260:Female; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000032:analysis; D007964:Leukocytosis / Q000276:immunology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D016209:Interleukin-8; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D020780:Matrix Metalloproteinase 9