Published ahead of print on May 29, 2008, doi:10.1164/rccm.200712-1818OC Am. J. Respir. Crit. Care Med., Volume 178, Number 5, September 2008, 476-482 A more recent version of this article appeared on September 1, 2008
Submitted on December 13, 2007 Non-atopic Children with Multi-trigger Wheezing have Airway Pathology Comparable to Atopic AsthmaGraziella Turato1,1 Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy, 2 Department of Paediatrics, University of Padova, Padova, Italy, 3 Department of Diagnostic Medical Sciences and Special Therapies, University of Padova, Padova, Italy, 4 Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy, 5 Department of Oncology and Haematology, University of Modena and Reggio Emilia, Modena, Italy * To whom correspondence should be addressed. E-mail: marina.saetta{at}unipd.it.
Rationale: Epidemiological studies have shown that in atopic children wheezing is more likely to persist into adulthood, eventually becoming asthma, while it appears to resolve by adolescence in non-atopic children. Objectives: To investigate whether among children with multi-trigger wheeze responsive to bronchodilators the airway pathology would be different in non-atopic wheezers, who are often considered non-asthmatic, compared to atopic wheezers, who are more frequently diagnosed as having asthma. Methods: Bronchial biopsies were obtained from 55 children undergoing bronchoscopy for appropriate clinical indications: 18 non-atopic children with multi-trigger wheeze (median age, range: 5, 2-10 yrs), 20 atopic children with multi-trigger wheeze (5, 2-15 yrs) and 17 control children with no atopy or wheeze (4, 2-14 yrs). By histochemistry and immunohistochemistry, we quantified epithelial loss, basement membrane thickness, angiogenesis, inflammatory cells, IL-4+ and IL-5+ cells in subepithelium. Measurements and Main Results: Unexpectedly, all pathological features examined were similar in atopic and non-atopic wheezing children. Compared to controls, both non-atopic and atopic wheezing children had increased epithelial loss (p=0.03; p=0.002), thickened basement membrane (both p<0.0001), increased number of vessels (p=0.003; p=0.03) and of eosinophils (p<0.0001; p=0.002). Moreover, they had increased cytokine expression, which was highly significant for IL-4 (p=0.002; p=0.0001) and marginal for IL-5 (p=0.02; p=0.08). Conclusions: This study shows that the airway pathology typical of asthma is present in non-atopic wheezing children just as in atopic wheezing children. These results suggest that when multi-trigger wheezing responsive to bronchodilators is present, it is associated with pathological features of asthma even in non-atopic children. Key words: paediatric asthma, atopy, inflammation, airway remodelling, Th2 cytokines.
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