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Asthma/Allergic Airways Disease: Does Postnatal Exposure to Environmental Toxicants Promote Airway Pathobiology?

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, cgplopper{at}ucdavis.edu, smsmiley@ ucdavis.edu, California National Primate Research Center, University of California, Davis, CA 95616, USA

Suzette M. Smiley-Jewell

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Lisa A. Miller

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Michelle V. Fanucchi

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Michael J. Evans

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Alan R. Buckpitt

Molecular Biosciences, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Mark Avdalovic

Medicine, School of Medicine, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Laurel J. Gershwin

Pathology Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616

Jesse P. Joad

Departments of Pediatrics, University of California, Davis, CA 95616, USA

Radhika Kajekar

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Shawnessy Larson

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA

Kent E. Pinkerton

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, Departments of Pediatrics, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Laura S. Van Winkle

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Edward S. Schelegle

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

Emily M. Pieczarka

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA

Reen Wu

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, Medicine, School of Medicine, University of California, Davis, CA 95616, USA

Dalla M. Hyde

Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA, California National Primate Research Center, University of California, Davis, CA 95616, USA

The recent, dramatic increase in the incidence of childhood asthma suggests a role for environmental contaminants in the promotion of interactions between allergens and the respiratory system of young children. To establish whether exposure to an environmental stressor, ozone (O3), and an allergen, house dust mite (HDMA), during early childhood promotes remodeling of the epithelial-mesenchymal trophic unit (EMTU) of the tracheobronchial airway wall by altering postnatal development, infant rhesus monkeys were exposed to cyclic episodes of filtered air (FA), HDMA, O3, or HDMA plus O3. The following alterations in the EMTU were found after exposure to HDMA, O3, or HDMA plus O3: (1) reduced airway number; (2) hyperplasia of bronchial epithelium; (3) increased mucous cells; (4) shifts in distal airway smooth muscle bundle orientation and abundance to favor hyperreactivity; (5) interrupted postnatal basement membrane zone differentiation; (6) modified epithelial nerve fiber distribution; and (7) reorganization of the airway vascular and immune system. Conclusions: cyclic challenge of infants to toxic stress during postnatal lung development modifies the EMTU. This exacerbates the allergen response to favor development of intermittent airway obstruction associated with wheeze. And, exposure of infants during early postnatal lung development initiates compromises in airway growth and development that persist or worsen as growth continues, even with cessation of exposure.

Key Words: Asthma • children • environment • ozone • allergen • Macaca.

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