Asthma/allergic airways disease: does postnatal exposure to environmental toxicants promote airway pathobiology?
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.
Plopper
Charles G
CG
Department of Anatomy, Physiology, and Cell Biology, University of California, Davis, CA 95616, USA. cgplopper@ucdavis.edu
Smiley-Jewell
Suzette M
SM
Miller
Lisa A
LA
Fanucchi
Michelle V
MV
Evans
Michael J
MJ
Buckpitt
Alan R
AR
Avdalovic
Mark
M
Gershwin
Laurel J
LJ
Joad
Jesse P
JP
Kajekar
Radhika
R
Larson
Shawnessy
S
Pinkerton
Kent E
KE
Van Winkle
Laura S
LS
Schelegle
Edward S
ES
Pieczarka
Emily M
EM
Wu
Reen
R
Hyde
Dalla M
DM
D000393:Air Pollutants / Q000009:adverse effects* / Q000276:immunology; D000485:Allergens / Q000009:adverse effects* / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D001980:Bronchi / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D002648:Child; D002657:Child Development / Q000187:drug effects* / Q000502:physiology; D040001:Dermatophagoides farinae / Q000276:immunology; D004195:Disease Models, Animal; D048788:Growth and Development / Q000187:drug effects*; D006801:Humans; D019570:Inhalation Exposure; D008253:Macaca mulatta; D010083:Oxidants, Photochemical / Q000009:adverse effects; D010126:Ozone / Q000009:adverse effects
D000393:Air Pollutants; D000485:Allergens; D010083:Oxidants, Photochemical; D010126:Ozone