This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200602-189OCv1 174/9/975    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barbato, A. Articles by Saetta, M. Search for Related Content PubMed PubMed Citation Articles by Barbato, A. Articles by Saetta, M.

Epithelial Damage and Angiogenesis in the Airways of Children with Asthma

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 2–15 yr), 12 with atopy without asthma (1–11 yr), and 15 control children without atopy or asthma (1–14 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

This article has been cited by other articles:

				S. Saglani, S. A. Mathie, L. G. Gregory, M. J. Bell, A. Bush, and C. M. Lloyd Pathophysiological Features of Asthma Develop in Parallel in House Dust Mite-Exposed Neonatal Mice Am. J. Respir. Cell Mol. Biol., September 1, 2009; 41(3): 281 - 289. [Abstract] [Full Text] [PDF]

				T.-L. Hackett, S. M. Warner, D. Stefanowicz, F. Shaheen, D. V. Pechkovsky, L. A. Murray, R. Argentieri, A. Kicic, S. M. Stick, T. R. Bai, et al. Induction of Epithelial-Mesenchymal Transition in Primary Airway Epithelial Cells from Patients with Asthma by Transforming Growth Factor-{beta}1 Am. J. Respir. Crit. Care Med., July 15, 2009; 180(2): 122 - 133. [Abstract] [Full Text] [PDF]

				P Paredi and P J Barnes The airway vasculature: recent advances and clinical implications Thorax, May 1, 2009; 64(5): 444 - 450. [Abstract] [Full Text] [PDF]

				G. Turato, A. Barbato, S. Baraldo, M. E. Zanin, E. Bazzan, K. Lokar-Oliani, F. Calabrese, C. Panizzolo, D. Snijders, P. Maestrelli, et al. Nonatopic Children with Multitrigger Wheezing Have Airway Pathology Comparable to Atopic Asthma Am. J. Respir. Crit. Care Med., September 1, 2008; 178(5): 476 - 482. [Abstract] [Full Text] [PDF]

				H. Meurs, R. Gosens, and J. Zaagsma Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models Eur. Respir. J., August 1, 2008; 32(2): 487 - 502. [Abstract] [Full Text] [PDF]

				N. Regamey, M. Ochs, T. N. Hilliard, C. Muhlfeld, N. Cornish, L. Fleming, S. Saglani, E. W. F. W. Alton, A. Bush, P. K. Jeffery, et al. Increased Airway Smooth Muscle Mass in Children with Asthma, Cystic Fibrosis, and Non-Cystic Fibrosis Bronchiectasis Am. J. Respir. Crit. Care Med., April 15, 2008; 177(8): 837 - 843. [Abstract] [Full Text] [PDF]

				S. Saglani, D. N. Payne, J. Zhu, Z. Wang, A. G. Nicholson, A. Bush, and P. K. Jeffery Early Detection of Airway Wall Remodeling and Eosinophilic Inflammation in Preschool Wheezers Am. J. Respir. Crit. Care Med., November 1, 2007; 176(9): 858 - 864. [Abstract] [Full Text] [PDF]

				W. C. Moore and S. P. Peters Update in Asthma 2006 Am. J. Respir. Crit. Care Med., April 1, 2007; 175(7): 649 - 654. [Full Text] [PDF]

				A. J Knox, K. Deacon, and R. Clifford Blanching the airways: steroid effects in asthma Thorax, April 1, 2007; 62(4): 283 - 285. [Full Text] [PDF]

				N. F. Voelkel, I. S. Douglas, and M. Nicolls Angiogenesis in Chronic Lung Disease Chest, March 1, 2007; 131(3): 874 - 879. [Abstract] [Full Text] [PDF]