title: Airway inflammation in asymptomatic children with episodic wheeze.
abstract: Airway pathologies have been comprehensively researched in adult asthma, but in children, the extent of airway inflammation associated with episodic wheeze, often diagnosed as asthma, has not been fully characterized. It is not clear whether persistent airway inflammation is present in the absence of wheezing symptoms, and there is controversy regarding the role of age and atopy. This study assessed cellular and cytokine markers of airway inflammation in asymptomatic children with a history of episodic wheeze. Children with a history of episodic wheeze and cough (study group) and nonasthmatic patients requiring elective surgery (control group) were recruited. All subjects in the study group had a history of significant episodic wheezing (>2 episodes per year), and used only as-needed beta-agonist treatment. Bronchoalveolar lavage (BAL) was obtained using bronchoscopic lavage (study group) and nonbronchoscopic lavage (control group). Differential cell counts of BAL and flow cytometry were performed to identify T-lymphocyte phenotypes, and intracellular cytokine profiles were measured after phorbol-12-myristate 13-acetate (PMA) stimulation of BAL fluid T-cells. Twenty-one children with a history of 2-12 episodes of wheeze per year and 21 nonasthmatic subjects without respiratory symptoms were recruited. Study and control subjects were matched for age (median age, 5 years) and demographic characteristics. Study subjects had higher IgE levels, but their measurements were still within normal range. No significant differences in BAL differential cell counts were noted, and in both groups, the majority of T-cells were CD3+ CD8+, with a median CD4:CD8 ratio of 0.6. There was no significant difference in T-cell expression of the activation markers HLA-DR and CD25 (IL-2 receptor), or in PMA-induced production of the intracellular cytokines IFN-gamma, IL-2, IL-4, IL-5, and IL-10. The results of this study suggest that significant T-cell-driven airway inflammation is absent in mild or nonatopic, asymptomatic children of this age group who have episodic wheeze. Our findings support asthma management guidelines that do not recommend long-term treatment of this group of patients with anti-inflammatory medications.
authors.affiliation: Department of Respiratory and Sleep Medicine, Monash Medical Centre, Monash University, Melbourne, Victoria, Australia.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Maclennan
authors.forename: Paul
authors.initials: P
authors.lastname: Hutchinson
authors.forename: Stephen
authors.initials: S
authors.lastname: Holdsworth
authors.forename: Philip G
authors.initials: PG
authors.lastname: Bardin
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Freezer
mesh_terms: D001249:Asthma / Q000097:blood / Q000276:immunology / Q000473:pathology; D020126:Brefeldin A / Q000494:pharmacology; D001980:Bronchi / Q000737:chemistry / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D004804:Eosinophils / Q000166:cytology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D007378:Interleukins / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology; D008297:Male; D009504:Neutrophils / Q000166:cytology; D012135:Respiratory Sounds / Q000209:etiology* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D017252:CD3 Complex; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D020126:Brefeldin A; D007073:Immunoglobulin E; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate