Inhaled toxicants are used for diverse purposes, ranging from industrial applications such as agriculture, sanitation, and fumigation, to crowd control and chemical warfare, and acute exposure can induce lasting respiratory complications. The intentional release of chemical warfare agents (CWAs) during World War I caused life-long damage for survivors, and CWA use is outlawed by international treaties. However, in the past two decades chemical warfare use has surged in the Middle East and Eastern Europe with a shift toward lung toxicants. The potential use of industrial and agricultural chemicals in rogue activities are a major concern, as they are often stored and transported near populated areas, where intentional or accidental release can cause severe injuries and fatalities. Despite laws and regulatory agencies that regulate use, storage, transport, emissions, and disposal, inhalational exposures continue to cause lasting lung injury. Industrial irritants (e.g., ammonia) aggravate the upper respiratory tract, causing pneumonitis, bronchoconstriction, and dyspnea. Irritant gases (e.g., acrolein, chloropicrin) affect epithelial barrier integrity and cause tissue damage, through reactive intermediates or by direct adduction of cysteine-rich proteins. Symptoms from CWAs (e.g., chlorine gas, phosgene, sulfur mustard) progress from airway obstruction and pulmonary edema to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) that results in respiratory depression days later. Emergency treatment is limited to supportive care using bronchodilators to control airway constriction, and rescue with mechanical ventilation to improve gas-exchange. Complications from acute exposure can promote obstructive lung disease and/or pulmonary fibrosis which require long-term clinical care. Inhaled chemical threats are of growing concern in both civilian and military settings, and there is increased need to reduce acute lung injury and delayed clinical complications from exposures. This minireview highlights our current understanding of acute toxicity and pathophysiology of a select number of chemicals of concern. It discusses potential early-stage therapeutic development, as well as challenges in developing countermeasures applicable for administration in mass casualty situations.
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