Asthma/allergic airways disease: Does postnatal exposure to environmental toxicants promote airway pathobiology?

Charles Plopper, Suzette M. Smiley-Jewell, Lisa Miller, Michelle V. Fanucchi, Michael J. Evans, Alan R Buckpitt, Mark V Avdalovic, Laurel J Gershwin, Jesse P. Joad, Radhika Kajekar, Shawnessy Larson, Kent E Pinkerton, Laura S. Van Winkle, Edward S Schelegle, Emily M. Pieczarka, Reen Wu, Dalla M. Hyde

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)97-110
Number of pages14
JournalToxicologic Pathology
Volume35
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Allergen
  • Asthma
  • Children
  • Environment
  • Macaca
  • Ozone

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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