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The Proceedings of the American Thoracic Society 6:324 (2009)
© 2009 The American Thoracic Society
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Inhaled Corticosteroids Alter Pulmonary Function and Lung Growth in Monkeys Exposed to House Dust Mite Allergen and O3

Dallas M. Hyde1, Lisa A. Miller1, Ed S. Schelegle1, Michelle V. Fanucchi1, Laura S. Van Winkle1, Nancy K. Tyler1, Mark V. Avdalovic1, Mike J. Evans1, Alan R. Buckpitt1, Kent E. Pinkerton1, Jesse P. Joad1, Laurel J. Gershwin1, Reen Wu1 and Charles G. Plopper1

1 California National Primate Research Center, University of California, Davis, California

Correspondence and requests for reprints should be addressed to Dallas M. Hyde, Ph.D., Director, California National Primate Research Center, Hutchinson Dr. and Rd. 98, University of California, Davis, CA 95616. E-mail: dmhyde{at}primate.ucdavis.edu

Infants and young children with persistent asthma are frequently treated with inhaled corticosteroids (ICS), such as budesonide. We previously showed that this exposure regimen to inhaled allergen/ozone resulted in a model of allergic asthma in infant monkeys. Infant rhesus monkeys (n = 24) were sensitized and then exposed to (1) filtered air and saline (FA), (2) house dust mite allergen + ozone and saline (HDMA/O3), (3) filtered air and ICS (FA/ICS), or (4) HDMA + ozone and ICS (HDMA/O3/ICS). Allergen/ozone exposures started at 1 month and ICS at 3 months and ended at 6 months of age. ICS had no effect on body weight, crown-rump length, fixed lung volume, airway growth, or basement membrane (BMZ) development between 1 and 6 months in FA monkeys. ICS had positive effects of resolving "asthma"-like conditions, including prevention of decreased compliance, decreased alveoli, BAL eosinophils, BMZ thickening, and partial prevention of airway stunting. ICS had no effect on resolving "asthma"-like conditions, including airway wall eosinophilia and eotaxin-3/CCL26 expression, changes in distribution and abundance of proliferating cell nuclear antigen (PCNA)-positive epithelial cells, and altered mucus composition or mucous cell abundance. ICS had negative effects on FA monkeys by increased proximal airway responsiveness, compliance, alveolar number, PCNA-positive epithelial cells, and altered mucus composition. ICS should be reserved for infants with the most severe asthma symptoms.

FOOTNOTES

Supported by NIEHS grant ES00628 and NIH grant RR00169.

Conflict of Interest Statement: D.M.H. has served as PI of a contract with Genentech, Inc. entitled "Rhesus Asthma Microarray Experiments" that was a fee for service agreement with The California National Primate Research Center (CNPRC). He serves as PI for most of the contracts at the CNPRC because he is the Director. L.A.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. E.S.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.V.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L.S.V.W. received $1,200 for speaking at a scientific conference sponsored by the Naphthalene Coalition and owns shares of Amgen, Inc. N.K.T. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.V.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.J.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. A.R.B. has a small contract with the American Petroleum Institute. His spouse has stocks in Pfizer and Exxon Mobil. K.E.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.P.J. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L.J.G. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.W. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.G.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form July 14, 2008; accepted in final form November 17, 2008)





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