Published ahead of print on August 17, 2006, doi:10.1164/rccm.200602-189OC
American Journal of Respiratory and Critical Care Medicine Vol 174. pp. 975-981, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200602-189OC
Epithelial Damage and Angiogenesis in the Airways of Children with Asthma
Angelo Barbato,
Graziella Turato,
Simonetta Baraldo,
Erica Bazzan,
Fiorella Calabrese,
Cristina Panizzolo,
Maria Elena Zanin,
Renzo Zuin,
Piero Maestrelli,
Leonardo M. Fabbri and
Marina Saetta
Departments of Pediatrics, Cardiothoracic and Vascular Sciences, and Environmental Medicine and Public Health, and Institute of Pathology, University of Padova, Padova; and Department of Respiratory Diseases and Radiology, University of Modena and Reggio Emilia, Modena, Italy
Correspondence and requests for reprints should be addressed to Marina Saetta, M.D., Divisione 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: Airway remodeling and inflammation are characteristic features of adult asthma that are still poorly investigated in childhood asthma.
Objectives: To examine epithelial and vascular changes as well as the inflammatory response in airways of children with asthma.
Methods: We analyzed bronchial biopsies obtained from 44 children undergoing bronchoscopy for appropriate clinical indications other than asthma: 17 with mild/moderate asthma (aged 215 yr), 12 with atopy without asthma (111 yr), and 15 control children without atopy or asthma (114 yr). By histochemistry and immunohistochemistry, we quantified epithelial loss, basement membrane thickness, number of vessels, and inflammatory cells in subepithelium.
Results: Epithelial loss and basement membrane thickness were increased in children with asthma compared with control subjects (p = 0.005 and p = 0.0002, respectively) and atopic children (p = 0.002 and p = 0.005, respectively). The number of vessels and eosinophils was increased not only in asthmatic children (p = 0.03 and p = 0.0002, respectively) but also in atopic children without asthma (p = 0.03 and p = 0.008, respectively) compared with control subjects. When we stratified the analysis according to age, we observed that children with asthma younger than 6 yr had increased epithelial loss, basement membrane thickening, and eosinophilia compared with control subjects of the same age.
Conclusions: Epithelial damage and basement membrane thickening, which are pathologic features characteristic of adult asthma, are present even in childhood asthma. Other changes, such as airway eosinophilia and angiogenesis, were also observed in atopic children without asthma. These observations suggest that pathologic changes occur early in the natural history of asthma and emphasize the concept that some of these lesions may characterize atopy even in the absence of asthmatic symptoms.
Key Words: angiogenesis basement membrane thickening epithelial loss pediatric asthma
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