Arsenic exposure via drinking water adversely affects lung health

Introduction: The contamination of drinking water with arsenic is a global health problem. Early life exposure to arsenic increases the risk of lower respiratory tract infections during infancy and increases the risk of mortality from bronchiectasis in adulthood. We aimed to characterize the effect of arsenic exposure via drinking water on lung development and responses to early life viral infection.

Methods: C57BL/6 mice were exposed to 100 μg/L arsenic in prenatal and postnatal life with or without influenza infection. Somatic growth, lung structure, lung function and airway hyperresponsiveness were measured using stereology, plethysmography and the forced oscillation technique. Differential gene expression was determined by microarray and confirmed with qRT-PCR.

Results: Mice exposed to arsenic in early life were smaller, had smaller lungs and impaired lung function. Early life exposure to arsenic altered the expression of genes that function in innate immunity (Lplunc1, Reg3γ), lung morphogenesis (Sox2) and airway mucous regulation (mClca3, Muc5b). Upregulation of mClca3 corresponded to mucous cell metaplasia. Adult mice that were exposed to arsenic early in life had increased airway smooth muscle and airways that were hyperresponsive to methacholine, while mice exposed to arsenic for the same period of time in adulthood were not affected. Arsenic exposure increased the acute inflammatory response to early life influenza infection and had additive effects on long term lung function impairment and airway hyperresponsiveness.

Conclusions: Arsenic is a potent developmental toxicant that adversely affects the lung by altering lung structure, mucous expression, innate immunity, responses to bronchoconstricting agents and exacerbating respiratory viral infection.