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Published on: April 13, 2010
Nonatopic children with multitrigger wheezing have airway pathology comparable to atopic asthma
Graziella Turato1, Angelo Barbato, Simonetta Baraldo
1Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Padova, Italy.
Insights
Nonatopic wheezing children exhibit airway pathology similar to atopic children, suggesting asthma features are present even without atopy. This finding challenges traditional views on childhood wheeze and asthma development.
Area of Science:
- Pediatric Pulmonology
- Allergy and Immunology
- Respiratory Pathology
Background:
- Epidemiologic studies indicate persistent wheezing in atopic children often leads to adult asthma.
- Nonatopic wheezing in children typically resolves by adolescence and is considered non-asthmatic.
Purpose of the Study:
- To compare airway pathology in nonatopic versus atopic children with multitrigger wheeze.
- To determine if nonatopic wheezers, often deemed nonasthmatic, share asthma-related airway changes with atopic wheezers.
Main Methods:
- Bronchial biopsies analyzed via histochemistry and immunohistochemistry in 55 children.
- Quantified epithelial loss, basement membrane thickness, angiogenesis, and inflammatory cell infiltration (IL-4, IL-5).
- Included nonatopic wheezers, atopic wheezers, and non-wheezing, non-atopic controls.
Main Results:
- Both atopic and nonatopic wheezing children showed similar airway pathology compared to controls.
- Increased epithelial loss, thickened basement membrane, and elevated vessel counts were observed in both wheezing groups.
- Higher levels of interleukin-4 (IL-4) and interleukin-5 (IL-5) expressing cells were found in both wheezing groups.
Conclusions:
- Airway pathology characteristic of asthma is present in nonatopic children with wheeze.
- Multitrigger wheeze responsive to bronchodilators is associated with asthma's pathologic features, irrespective of atopic status.
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.
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