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Published ahead of print on January 18, 2005, doi:10.1164/rccm.200410-1404OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 7, April 2005, 722-727

A more recent version of this article appeared on April 1, 2005
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Submitted on October 22, 2004
Accepted on January 5, 2005

Airway Remodelling and Inflammation in Symptomatic Infants with Reversible Airflow Obstruction

Sejal Saglani1, Kristiina Malmstrom2, Anna S Pelkonen2, Pekka Malmberg2, Harry Lindahl3, Merja Kajosaari3, Markku Turpeinen2, Andrew V Rogers4, Donald N Payne5, Andrew Bush5, Tari Haahtela2, Mika J Makela2, and Peter K Jeffery4*

1 Lung Pathology, Department of Gene Therapy, Imperial College London at the Royal Brompton Hospital, London, United Kingdom; Department of Respiratory Paediatrics, Imperial College London at The Royal Brompton Hospital, London, United Kingdom, 2 Department of Allergology, Helsinki University Central Hospital, Helsinki, Finland, 3 Department of Paediatrics, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland, 4 Lung Pathology, Department of Gene Therapy, Imperial College London at the Royal Brompton Hospital, London, United Kingdom, 5 Department of Respiratory Paediatrics, Imperial College London at The Royal Brompton Hospital, London, United Kingdom

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

Rationale: We hypothesised that the epithelial reticular basement membrane (RBM) thickening and eosinophilic inflammation characteristic of asthma would be present in symptomatic infants with reversible airflow obstruction. Methods: RBM thickness and numbers of inflammatory cells were determined in ultra-thin sections of endobronchial biopsies obtained from 53 infants during clinical bronchoscopy for severe wheeze and/or cough. Group A; 16 infants of median age 12 months [range 3.4-26], with decreased specific airways conductance (sGaw) and bronchodilator reversibility (BDR); Group B; 22 infants median 12.4 months [5.1- 25.9], with decreased sGaw but without BDR and Group C; 15 infants median 11.5 months [3.4-24.3] with normal sGaw. Additional comparisons were made with: Group D; 17 children, median 10.3 years [6-16] with difficult asthma; Group E; 10 paediatric non-asthmatic controls, median 10 years [6-16] and group F; 9 adult normal healthy controls, median 27 years [21-42]. Main Results: There were no significant differences in RBM thickness or inflammatory cell number between the infant groups. RBM thickness was similar in the infants and Groups E and F. However, the RBM in all infant groups (Group A; median 4.3µm [range 2.8-9.2µm], Group B; median 4.15µm [range 2.7-5.8µm], Group C median 3.8µm [range 2.7-5.5µm]) was significantly less thick than that in the older children with asthma (group D; median 8.3µm [range 5.3-12.7µm]) p<0.001). Conclusion: RBM thickening and the eosinophilic inflammation characteristic of asthma in older children and adults is not present in symptomatic infants with reversible airflow obstruction, even in the presence of atopy.
Key words: asthma, pathology, remodelling, paediatric, inflammation




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