Development of medical countermeasures (MCM) to mitigate and/ or treat the pulmonary complications associated with exposure to chemical, radiological, and/ or nuclear weapons is a national, public health preparedness posture priority in the United States (US). Pulmonary exposure to either sulfur mustard vapor or radiation causes oxidative damage, vascular injury, hyperinflammation, and pro-fibrotic signaling cascades that lead to life-threatening and potentially debilitating lung disease. There is no MCM currently approved by the US Food and Drug Administration (FDA) to mitigate and/ or treat lung injury caused by sulfur mustard or radiation exposure. Thus, there remains a major unmet public health need for development of threat-agnostic, host-directed therapeutics that target common pathophysiological mechanisms underlying the progression of acute and/ or late lung injury independent of the etiology of disease. This review describes the clinical manifestations and underlying mechanisms of sulfur mustard and radiation-induced lung injury and regulatory considerations for MCM development under the non-traditional Animal Rule pathway.

Fluorescence in vivo endomicroscopy (FIVE) is a state-of-the-art endoscopy technique used to image tissue interactions and molecular events in a cell. In Part 1 of this series, the history, types of confocal laser endomicroscopy (CLE), and limitations of the technology were discussed. In Part 2 of the series, we describe several applications of FIVE technology, including advances in cancer, gastrointestinal, liver, rectal mucosal barrier function, acute lung injury, and brain imaging. Future perspectives for the technology are also presented.

Critically ill patients frequently suffer from gastrointestinal dysfunction as the intestine is a vulnerable organ. In critically ill patients who require nutritional support, the current guidelines recommend the use of enteral nutrition within 24–48 h and advancing towards optimal nutritional goals over the next 48–72 h; however, this may be contraindicated in patients with acute gastrointestinal injury because overuse of the gut in the acute phase of critical illness may have an adverse effect on the prognosis. We propose that trophic feeding after 72 h, as a partial gut rest strategy, should be provided to critically ill patients during the acute phase of illness as an organ-protective strategy, especially for those with acute gastrointestinal injury.

The current hypothesis of alveolar capillary membrane dysfunction fails to completely explain the severe and persistent leak of protein-rich fluid into the pulmonary interstitium, seen in the exudative phase of acute lung injury (ALI). The presence of intact red blood cells in the pulmonary interstitium may suggest mechanical failure of pulmonary arterioles and venules. These studies involved the pathological and ultrastructural evaluation of the pulmonary vasculature in Staphylococcal enterotoxin B (SEB)-induced ALI. Administration of SEB resulted in a significant increase in the protein concentration of bronchoalveolar lavage fluid and vascular leak in SEB-exposed mice compared to vehicle-treated mice. In vivo imaging of mice demonstrated the pulmonary edema and leakage in the lungs of SEB-administered mice. The histopathological studies showed intense clustering of inflammatory cells around the alveolar capillaries with subtle changes in architecture. Electron microscopy studies further confirmed the diffuse damage and disruption in the muscularis layer of the terminal vessels. Cell death in the endothelial cells of the terminal vessels was confirmed with TUNEL staining. In this study, we demonstrated that in addition to failure of the alveolar capillary membrane, disruption of the pulmonary arterioles and venules may explain the persistent and severe interstitial and alveolar edema.