Published ahead of print on May 29, 2008, doi:10.1164/rccm.200712-1818OC
© 2008 American Thoracic Society doi: 10.1164/rccm.200712-1818OC
Nonatopic Children with Multitrigger Wheezing Have Airway Pathology Comparable to Atopic AsthmaDepartments of 1 Cardiac, Thoracic, and Vascular Sciences, 2 Pediatrics, 3 Diagnostic Medical Sciences and Special Therapies, and 4 Environmental Medicine and Public Health, University of Padova, Padova, Italy; and 5 Department of Oncology, Hematology, and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy Correspondence and requests for reprints should be addressed to Marina Saetta, M.D., Unità Operativa di Pneumologia, Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari Università degli Studi di Padova, via Giustiniani 3, 35128 Padova, Italy. E-mail: marina.saetta{at}unipd.it Rationale: Epidemiologic studies have shown that, in atopic children, wheezing is more likely to persist into adulthood, eventually becoming asthma, whereas it appears to resolve by adolescence in nonatopic children. Objectives: To investigate whether among children with multitrigger wheeze responsive to bronchodilators the airway pathology would be different in nonatopic wheezers, who are often considered nonasthmatic, compared with 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 nonatopic children with multitrigger wheeze (median age, 5 yr; range, 2–10 yr), 20 atopic children with multitrigger wheeze (medan age, 5 yr; range, 2–15 yr), and 17 control children with no atopy or wheeze (median age, 4; range, 2–14 yr). 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 pathologic features examined were similar in atopic and nonatopic wheezing children. Compared with control subjects, both nonatopic and atopic wheezing children had increased epithelial loss (P = 0.03 and P = 0.002, respectively), thickened basement membrane (both P < 0.0001), and increased number of vessels (P = 0.003 and P = 0.03, respectively) and eosinophils (P < 0.0001 and P = 0.002, respectively). Moreover, they had increased cytokine expression, which was highly significant for IL-4 (P = 0.002 and P = 0.0001, respectively) and marginal for IL-5 (P = 0.02 and P = 0.08, respectively). Conclusions: This study shows that the airway pathology typical of asthma is present in nonatopic wheezing children just as in atopic wheezing children. These results suggest that, when multitrigger wheezing responsive to bronchodilators is present, it is associated with pathologic features of asthma even in nonatopic children.
Key Words: pediatric asthma • atopy • inflammation • airway remodeling • Th2 cytokines
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