Disease-modifying treatment of chemical threat agent-induced acute lung injury

Abstract

Acute respiratory distress syndrome (ARDS) is a highly morbid lung pathology induced by exposure to chemical warfare agents, including vesicants, phosgene, chlorine, and ricin. In this review, we describe the pathology associated with the development of ARDS in humans and experimental models of acute lung injury following animal exposure to these high-priority threat agents. Potential future approaches to disease-modifying treatment used in preclinical animal studies, including antioxidants, anti-inflammatories, biologics, and mesenchymal stem cells, are also described. As respiratory pathologies, including ARDS, are the major cause of morbidity and mortality following exposure to chemical threat agents, understanding mechanisms of disease pathogenesis is key to the development of efficacious therapeutics beyond the primary intervention principle, which remains mechanical ventilation.

Keywords: acute respiratory distress syndrome; chemical warfare agents; inflammation; mustards; oxidative stress.

Figure 1.

ARDS histopathology in humans and rats. Left panel: Human diffuse alveolar damage (original magnification, 100×). Note thickened alveolar interstitium with inflammatory cell infiltrate (black arrows), hyaline membrane formation (black arrowheads), proteinaceous fluid accumulation in alveoli (blue arrow), and alveolar hemorrhage (blue arrowhead). Right panel: Rat ALI 3 days following NM exposure (original magnification, 40×). Note thickened alveolar interstitium with inflammatory cell infiltrate (black arrows).

Figure 2.

Pathophysiology of hypoxemia in ARDS. Pictured is a Venn diagram displaying the development of hypoxemia. The top left and top right circles represent processes resulting in shunting of deoxygenated blood. The bottom circle represents processes increasing dead space ventilation.