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Title: | Lower airway inflammation in infants with cystic fibrosis detected by newborn screening. | Authors: | Nixon G.M. ;Grimwood K.;Jamsen K.M.;Carzino R.;Robertson C.F.;Carlin J.B.;Armstrong D.S.;Hook S.M. | Monash Health Department(s): | Paediatric - Respiratory and Sleep (Melbourne Children's Sleep Centre) | Institution: | (Armstrong) Department of Paediatrics, Monash Medical Centre, Monash University, Clayton, Vic., Australia (Hook) Malaghan Institute of Medical Research, Wellington, New Zealand (Jamsen, Carlin) Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Vic., Australia (Nixon, Carzino, Robertson) Department of Respiratory and Sleep Medicine, Royal Children's Hospital, Parkville, Vic., Australia (Grimwood) Department of Paediatrics and Child Health, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand (Grimwood) Department of Paediatrics and Child Health, Wellington School of Medicine and Health Sciences, PO Box 7343, Wellington, New Zealand | Issue Date: | 18-Oct-2012 | Copyright year: | 2005 | Publisher: | Wiley-Liss Inc. (111 River Street, Hoboken NJ 07030-5774, United States) | Place of publication: | United States | Publication information: | Pediatric Pulmonology. 40 (6) (pp 500-510), 2005. Date of Publication: December 2005. | Abstract: | Controversy exists over whether the lower airway inflammation that characterizes cystic fibrosis (CF) is initiated primarily by the genetic defect. To determine if inflammation precedes infection, we examined bronchoalveolar lavage (BAL) fluid cytology, cytokines (interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha), and free neutrophil elastase activity from 70 CF (aged 1.5-71 months) children detected by newborn screening and 19 (aged 2.0-48 months) controls with chronic stridor. CF subjects were selected and categorized as pristine (13 aged <=6 months, lacking prior respiratory symptoms and exposure to antibiotics, and without respiratory pathogens on BAL), infected (42 with viruses or >=105 colony-forming units/ml of pathogenic bacteria in BAL), and uninfected (15 aged >=6 months, asymptomatic, not taking antibiotics at bronchoscopy, and free of pathogens in their BAL). To further resolve if inflammation develops without infection, inflammatory mediators in paired annual BAL samples from 38 CF subjects were measured, and results were grouped according to whether BAL showed persistence (n = 6), acquisition (n = 8), clearance (n = 13), or absence (n = 11) of infection. While pristine, uninfected, and control subjects had similar BAL profiles, infected patients showed elevated inflammatory indices, including increased IL-10 (P < 0.001). Pristine subjects had the fewest signs of inflammation. Analysis of BAL pairs found differences between the four infection groups for changes in neutrophil percentages, IL-8 (P < 0.001), and free neutrophil elastase (P = 0.009). Infection was associated with elevated inflammatory mediators in BAL fluid. In contrast, minimal or reduced signs of inflammation accompanied absence of eradication of infection from BAL fluid. We conclude that in CF, infection initiates and sustains airway inflammation. © 2005 Wiley-Liss, Inc. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1002/ppul.20294 | PubMed URL: | 16208679 [http://www.ncbi.nlm.nih.gov/pubmed/?term=16208679] | ISSN: | 8755-6863 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/32258 | Type: | Article | Subjects: | *lung disease/dt [Drug Therapy] *lung disease/et [Etiology] lung lavage major clinical study newborn newborn disease/di [Diagnosis] newborn screening priority journal antibiotic agent/dt [Drug Therapy] cytokine/ec [Endogenous Compound] elastase/ec [Endogenous Compound] interleukin 10/ec [Endogenous Compound] interleukin 1beta/ec [Endogenous Compound] interleukin 4/ec [Endogenous Compound] interleukin 5/ec [Endogenous Compound] interleukin 6/ec [Endogenous Compound] interleukin 8/ec [Endogenous Compound] tumor necrosis factor alpha/ec [Endogenous Compound] lower respiratory tract infection/dt [Drug Therapy] airway article controlled study *cystic fibrosis/di [Diagnosis] cytokine production enzyme assay enzyme linked immunosorbent assay female Gram negative bacterium Gram positive bacterium human infant inflammation longitudinal study lower respiratory tract infection/co [Complication] lower respiratory tract infection/di [Diagnosis] male lower respiratory tract infection/et [Etiology] *lung disease/co [Complication] *lung disease/di [Diagnosis] infant inflammation longitudinal study lower respiratory tract infection / complication / diagnosis / drug therapy / etiology *lung disease / *complication / *diagnosis / *drug therapy / *etiology lung lavage major clinical study male newborn controlled study newborn screening priority journal article airway newborn disease / diagnosis *cystic fibrosis / *diagnosis cytokine production enzyme assay enzyme linked immunosorbent assay female Gram negative bacterium Gram positive bacterium human |
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