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Toxicologic Pathology
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Nedocromil Sodium Inhibits Canine Adenovirus Bronchiolitis in Beagle Puppies

Kurt A. Anderson

Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724

Richard J. Lemen

Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724, rlemen{at}umcaz.edu

Natalie S. Weger

Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724

Huizhong Chen

Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724

Mark C. Bowers

Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724

Mark L. Witten

Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724

R. Clark Lantz

Department of Pediatrics, Steele Memorial Children's Research Center, Department of Pediatrics, Respiratory Sciences Center, and Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona 85724

David E. Bice

The Lovelace Respiration Institute, Albuquerque, New Mexico 87111

Bruce A. Muggenburg

The Lovelace Respiration Institute, Albuquerque, New Mexico 87111

Nedocromil sodium is a nonsteroidal anti-inflammatory drug used to control asthmatic attacks. Our hypothesis is that nedocromil sodium inhibits virus-induced airway inflammation, a common trigger of asthma. We nebulized nedocromil sodium into beagle dogs (n = 10, mean ± SEM ages: 149 ± 13 days) before and after inoculation with canine adenovirus type 2 (CAV2). Control dogs (n = 10) received saline aerosols and were either infected with CAV2 (Sa1/CAV2, n = 7, mean ± SEM ages: 140 ± 11 days) or were not infected (Sal/Sal, n = 3, ages: 143 ± 0 days). All dogs were anesthetized with choralose (80 mg/kg IV), intubated, and mechanically ventilated. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed using standard techniques. Pulmonary function tests revealed no significant change between the nedocromil sodium and non-nedocromil-treated groups. The percentage of infected bronchioles was quantitated as the number of inflamed airways of 40 bronchioles examined times 100 for each dog. Nedocromil-treated dogs had significantly (p < 0.05) less mucosal inflammation (mean ± SEM, 39% ± 5%), epithelial denudation (36% ± 5%), and BAL neutrophilia (11 ± 3) than did Sal/CAV2 dogs (51% ± 6%, 57% ± 4%, and 33% ± 8%, respectively). We concluded that pretreatment with nedocromil sodium aerosols attenuated CAV2-induced airway inflammation in these beagle puppies.

Key Words: Nedocromil sodium • bronchiolitis • viral infections • inflammation • pulmonary function

Toxicologic Pathology, Vol. 28, No. 2, 317-325 (2000)
DOI: 10.1177/019262330002800212


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