title: The effects of inhaled corticosteroids on intrinsic responsiveness and histology of airways from infant monkeys exposed to house dust mite allergen and ozone.
abstract: Inhaled corticosteroids (ICS) are recommended to treat infants with asthma, some with intermittent asthma. We previously showed that exposing infant monkeys to allergen/ozone resulted in asthma-like characteristics of their airways. We evaluated the effects of ICS on histology and intrinsic responsiveness of allergen/ozone-exposed and normal infant primate airways. Infant monkeys were exposed by inhalation to (1) filtered air and saline, (2) house dust mite allergen (HDMA)+ozone and saline, (3) filtered air and ICS (budesonide) or (4) HDMA+ozone and ICS. Allergen/ozone exposures started at 1 month and ICS at 3 months of age. At 6 months of age, methacholine-induced changes in luminal area of airways in proximal and distal lung slices were determined using videomicrometry, followed by histology of the same slices. Proximal airway responsiveness was increased by allergen/ozone and by ICS. Eosinophil profiles were increased by allergen/ozone in both proximal and distal airways, an effect that was decreased by ICS in distal airways. In both allergen/ozone- and air-exposed monkeys, ICS increased the number of alveolar attachments in distal airways, decreased mucin in proximal airways and decreased epithelial volume in both airways. ICS increased smooth muscle in air-exposed animals while decreasing it in allergen/ozone-exposed animals in both airways. In proximal airways, there was a small but significant positive correlation between smooth muscle and airway responsiveness, as well as between alveolar attachments and responsiveness. ICS change morphology and function in normal airways as well as allergen/ozone-exposed airways, suggesting that they should be reserved for infants with active symptoms.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California at Davis, Davis, CA 95616, USA. jesse.joad@ucdmc.ucdavis.edu <jesse.joad@ucdmc.ucdavis.edu>
authors.forename: Jesse P
authors.initials: JP
authors.lastname: Joad
authors.forename: Kayleen S
authors.initials: KS
authors.lastname: Kott
authors.forename: John M
authors.initials: JM
authors.lastname: Bric
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
authors.forename: Laurel J
authors.initials: LJ
authors.lastname: Gershwin
authors.forename: Charles G
authors.initials: CG
authors.lastname: Plopper
authors.forename: Janice L
authors.initials: JL
authors.lastname: Peake
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D039741:Antigens, Dermatophagoides / Q000633:toxicity*; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019819:Budesonide / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D007958:Leukocyte Count; D008253:Macaca mulatta; D009077:Mucins / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D010126:Ozone / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology
chemical_list: D000305:Adrenal Cortex Hormones; D039741:Antigens, Dermatophagoides; D001993:Bronchodilator Agents; D009077:Mucins; D019819:Budesonide; D010126:Ozone