The injured lung: clinical issues and experimental models

Abstract

Exposure of military and civilian populations to inhaled toxic chemicals can take place as a result of deliberate release (warfare, terrorism) or following accidental releases from industrial concerns or transported chemicals. Exposure to inhaled toxic chemicals can result in an acute lung injury, and in severe cases acute respiratory distress syndrome, for which there is currently no specific medical therapy, treatment remaining largely supportive. This treatment often requires intensive care facilities that may become overwhelmed in mass casualty events and may be of limited benefit in severe cases. There remains, therefore, a need for evidence-based treatment to inform both military and civilian medical response teams on the most appropriate treatment for chemically induced lung injury. This article reviews data used to derive potential clinical management strategies for chemically induced lung injury.

Neutrophil‐endothelial interactions of murine cells is not a good predictor of their interactions in human cells

“…6,7 Furthermore, the underlying pathophysiology of neutrophil-mediated tissue damage is poorly understood and there are no specific pharmacologic therapies available that protect from neutrophil-mediated tissue damage. 24,25 By the same token, therapeutics that do not work well in animal models are often abandoned before their applicability to human disease is determined. To address these challenges, we have used a novel bMFA that reproduces the entire neutrophil adhesion cascade in a physiologically realistic three-dimensional environment and has already been validated against in vivo data.…”

“…23 However, the underlying pathophysiology of neutrophil-mediated tissue damage is yet to be understood and there are no specific pharmacologic therapies available that protect from neutrophilmediated tissue damage. 24,25 Most in vivo studies of mechanisms of inflammatory disease primarily employ murine models. However, concerns regarding the level of correspondence between mice and cell culture models, as well as phenotypic heterogeneity of different types of endothelial cells, and their relevance to human disease, have been expressed in the literature.…”

Chemosensory TRP Channels in the Respiratory Tract: Role in Toxic Lung Injury and Potential as “Sweet Spots” for Targeted Therapies

“…Of note, seven SNPs of TRPV1 showed a statistically significant association with cough in non-asthmatics (six SNPs with nocturnal cough and one with usual cough). Furthermore, four SNPs of TRPV1 were associated with an increased risk of cough in persons (asthmatics and nonasthmatics) with exposure to irritants (Jugg et al 2011). For other TRP channels like TRPV4 and TRPA1 no significant relationship of SNPs with cough could be detected in this study.…”

In Vivo Models of Lung Disease

“…Acute Lung Injury: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) results from severe injury to the lung parenchyma (11). Animal modeling experiments of ALI and ARDS have been very useful in providing some directions into the mechanisms related to disease pathogenesis and providing opportunities to explore new and innovative therapeutic targets.…”