Cutaneous Exposure to Arsenicals is Associated with Development of Constrictive Bronchiolitis in Mice.

Organoarsenicals, such as Lewisite and related chloroarsine, Di-phenyl Chloro Arsine (DPCA), are chemical warfare agents developed during WWI. Stockpiles in Eastern Europe remain a threat to humans. The well-documented effects of cutaneous exposure to these organoarsenicals include skin blisters, painful burns, and life-threatening conditions such as Acute Respiratory Distress Syndrome. In survivors, long-term effects such as the development of respiratory ailments are reported for the organoarsenical sulfur mustard (SM), however no long-term pulmonary effects are documented for lewisite and DPCA. No animal models exist to explore the relationship between skin exposure to arsenicals and constrictive bronchiolitis. We developed and characterized a mouse model to study the long-term effects of cutaneous exposure on the lungs in survivors. We exposed mice to lewisite, DPCA, or a less toxic surrogate organo-arsenic chemical phenyl arsine oxide (PAO) on the skin. The surviving mice were followed for 20 weeks following skin exposure to arsenicals. The lung micro-computed tomography, lung function, and histology demonstrated increased airway resistance, increased thickness of the smooth muscle layer, increased collagen deposition in the sub-epithelium, and l peribronchial lymphocyte infiltration in the mice exposed to arsenical on skin.