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

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 (O 3 ), 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, O 3 , or HDMA plus O 3 . The following alterations in the EMTU were found after exposure to HDMA, O 3 , or HDMA plus O 3 : (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.

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…Additional subchronic and chronic ozone exposure studies (500 ppb) in rhesus monkeys have demonstrated structural changes in the distal and proximal airways (Fanucchi et al, 2006;Carey et al, 2011) and allergy-like patterns of response (increased globlet cells and eosinophils) to allergen and ozone co-challenges (Kajekar et al, 2007;Miller et al, 2009;van Winkle et al, 2010;Plopper et al, 2007). These studies would therefore seem to support the epidemiological observations that reported impaired lung growth (peak flow: Gauderman et al, 2002;FVC and FEV1: Rojas-Martinez et al, 2007) and a worsening of asthma symptoms in children with high ozone exposures (asthma incidence: McConnell et al, 2002;Islam et al, 2009;asthma medication usage: Millstein et al, 2004).…”

House dust mite extract downregulates C/EBP in asthmatic bronchial smooth muscle cells

“…Exposure to allergens during the early years of life leads to a persistent increase in BSM cells by an unknown mechanism, independent of the immune system [1,2]. Therefore, airway remodelling might not be a secondary event, but rather one of the fundamental pathological causes of asthma [3][4][5].…”

The Role of Mnk-1, Eukaryotic Translation Initiation Factors and Translation Control in the Pathogenesis of Asthma

“…The rhesus monkey presents the best model to study lung development, structure and function in the context of the pathogenesis of chronic inflammatory lung diseases [15]. These studies provided first evidence that lung maturation is lastingly altered when mothers were exposed risk factors for asthma or COPD.…”

“…Data in cohorts of preterm born people suggest that such a condition during embryogenesis pre-sets the lung to develop asthma or COPD later in life [11,12]. This correlation had been described earlier in rhesus monkeys exposed to ozone or allergens enriched air during pregnancy, which led to permanent rearrangement of airway smooth muscle cells and asthma like symptoms after birth [13][14][15]. These animal studies provided first evidence that exposure to asthma triggers during embryogenesis start a process that alters lung maturation lastingly and which stays active even after the stimulus was removed for long term, suggesting epigenetic events.…”