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Published ahead of print on August 16, 2007, doi:10.1164/rccm.200702-212OC

Am. J. Respir. Crit. Care Med., Volume 176, Number 9, November 2007, 858-864

A more recent version of this article appeared on November 1, 2007
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Submitted on February 8, 2007
Accepted on August 15, 2007

Early Detection of Airway Wall Remodelling and Eosinophilic Inflammation in Preschool Wheezers

Sejal Saglani1, Donald N Payne2, Jie Zhu3, Zhuo Wang3, Andrew G Nicholson4, Andrew Bush2, and Peter K Jeffery3*

1 Department of Respiratory Paediatrics, Imperial College London, National Health and Lung Institute, Royal Brompton Hospital, London, United Kingdom; Department of Lung Pathology, Imperial College London and The Royal Brompton Hospital, London, United Kingdom, 2 Department of Respiratory Paediatrics, Imperial College London, National Health and Lung Institute, Royal Brompton Hospital, London, United Kingdom, 3 Department of Lung Pathology, Imperial College London and The Royal Brompton Hospital, London, United Kingdom, 4 Department of Histopathology, Royal Brompton Hospital, London, United Kingdom

* To whom correspondence should be addressed. E-mail: p.jeffery{at}imperial.ac.uk.

Rationale: It is unclear when the pathological features of asthma first appear. We hypothesised that eosinophilic airway inflammation and epithelial reticular basement membrane (RBM) thickening, absent in wheezy infants, would be present in preschool children with severe, recurrent wheeze. Objectives: To compare RBM thickness and inflammation in endobronchial biopsies (EB) from wheezy preschool children and age-matched controls. Methods: EB were obtained from wheezy preschool children (aged 3 months to 5 years), undergoing a clinically indicated fibreoptic bronchoscopy (FOB). Subjects undergoing FOB to investigate stridor acted as non-asthma controls. RBM thickness was measured and the density of subepithelial, immunologically distinct inflammatory cells was determined and expressed as a volume fraction(%). EB from 16 children (median age 29 [7-57] months) with wheeze confirmed by video questionnaire (CW), 14 with reported wheeze (RW) (17 [8-58] months) and 10 controls (19 [5-42] months) were assessed. Measurements and main results: RBM thickness in the three groups was: CW (median 4.6 [range 2.9-8.0]µm), RW (3.5 [2.1-5.4]µm), Controls (3.8 [2.5-4.7]µm). RBM was significantly thicker in CW than Controls, p<0.05. Eosinophil density was: CW (median 1.07 [range 0.0-3.52]%), RW (0.72 [0.0-2.04]%), Controls (0.0 [0.0-1.05]%). Eosinophilic inflammation was significantly greater in CW compared to Controls, p<0.05. There were no between-group differences for any other inflammatory cell phenotype. Conclusion: The characteristic pathological features of asthma in adults and school-aged children develop in preschool children with confirmed wheeze between the ages of one and three years, a time when intervention may modify the natural history of asthma.
Key words: asthma, paediatrics, pathology




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