Journal of Applied Physiology AJP: Regulatory, Integrative and Comparative Physiology
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J Appl Physiol (October 1, 2004). doi:10.1152/japplphysiol.00486.2004
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Submitted on May 7, 2004
Accepted on September 17, 2004

IMPACT OF POSTNATAL GLUCOCORTICOIDS ON EARLY LUNG DEVELOPMENT

Jana Kovar1, Karen E Willett2, Alison Hislop3, and Peter D Sly2*

1 Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia; Unit of Developmental Vascular Biology, Institute of Child Health, London, England, United Kingdom
2 Centre for Child Health Research, University of Western Australia, Perth, Western Australia, Australia
3 Unit of Developmental Vascular Biology, Institute of Child Health, London, England, United Kingdom

* To whom correspondence should be addressed. E-mail: peters{at}ichr.uwa.edu.au.

Inhaled glucocorticoid treatment during the first 2 years of life is controversial as this is a period of major structural remodeling of the lung. Rabbits received aerosolized budesonide (BUD) (250 µg/ml) or injected dexamethasone (DEX) (0.05 mg/ml/kg) between 1-5 weeks of age. Treatment with BUD caused specific growth retardation of the lung. DEX but not BUD affected the mechanical properties of the lung parenchyma, when corrected for lung volume. Small peripheral airway walls in both glucocorticoid groups were thinner, had fewer alveolar attachment points with greater distance between attachments, than controls but collagen content was not affected by glucocorticoids. DEX led to reduced body weight, lung volume, alveolar number and surface area. The alveolar size and number and elastin content, when related to lung volume was not affected by BUD suggesting normal structural development but inhibition of total growth. Arterial wall thickness and diameter were affected by BUD. This study demonstrates that developing lungs are sensitive to inhaled glucocorticoids. As such, the use of glucocorticoids in young infants and children should be monitored with caution and only the lowest doses that yield significant clinical improvement should be used.




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