Published ahead of print on August 17, 2006, doi:10.1164/rccm.200602-189OC
Am. J. Respir. Crit. Care Med., Volume 174, Number 9, November 2006, 975-981
A more recent version of this article appeared on November 1, 2006
Submitted on February 8, 2006
Accepted on August 16, 2006
Epithelial Damage and Angiogenesis in the Airways of Children with Asthma
Angelo Barbato1, Graziella Turato2, Simonetta Baraldo2, Erica Bazzan2, Fiorella Calabrese3, Cristina Panizzolo1, Maria Elena Zanin2, Renzo Zuin2, Piero Maestrelli4, Leonardo M Fabbri5, and Marina Saetta2*
1 Department of Paediatrics, University of Padova, Padova, Italy,
2 Department of Cardiothoracic and Vascular Sciences, University of Padova, Padova, Italy,
3 Institute of Pathology, University of Padova, Padova, Italy,
4 Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy,
5 Department of Respiratory Diseases and Radiology, University of Modena and Reggio Emilia, Modena, Italy
* To whom correspondence should be addressed. E-mail: marina.saetta{at}unipd.it.
Rationale. Airway remodelling and inflammation are characteristic features of adult asthma which 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 2-15 years), 12 with atopy without asthma (1-11 years) and 15 controls without atopy or asthma (1-14 years). 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 asthmatic children compared to controls (p=0.005, p=0.0002) and atopic children (p=0.002, p=0.005).
The number of vessels and eosinophils was increased not only in asthmatic children (p=0.03, p=0.0002) but even in atopic children without asthma (p=0.03, p=0.008) compared to controls. When we stratified the analysis according to age, we observed that asthmatic children younger than 6 years had increased epithelial loss, basement membrane thickening and eosinophilia compared to controls 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 pathological 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: paediatrics asthma, epithelial loss, basement membrane thickening, angiogenesis
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