Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical WarfareTABLE 10-4Mechanisms of Lung Injury of Gaseous Respiratory IrritantsIrritant GasAmmonia (NH 2)Source: Agriculture, rain, plastic, explosivesHydrogen chloride (HCl)Source: Dyes, fertilizers, textiles, rubber, thermal degradation of polyvinyl chlorideSulfur dioxide (SO 2)Source: Smelting, combustion of coal/oil, paper manufacturing, food preparationChlorine (Cl 2)Source: Paper, textile manufacturing, sewage treatmentOxides of nitrogen (NO, NO 2, N 2O 4)Source: Agriculture, mining, welding, manufacturing of dyes/lacquersPhosgene (COCl 2)Source: Firefighters, welders, paint strippers, chemical intermediates (isocyanate,pesticides, dyes, pharmaceuticals)mechanism of InjuryAlkali burnsAcid burnsAcid burnsAcid burns, free radical formationAcid burns, free radical formationAcid burnsColors indicate water solubility. Red: high; yellow: intermediate; green: low.Data source: Schwartz DA. Acute inhalational injury. Occup Med. 1987;2:298.inhalation of compounds that have limited solubilityresults in lower lung injury, whereas compounds thatare miscible in water affect the upper regions of therespiratory tree. Compounds discussed earlier, such asphosgene, chlorine, oxides of nitrogen, and PFIB, areconsidered lower airway (peripheral compartment)irritants based on their solubility characteristics. Gasessuch as ammonia, sulfur dioxide, and hydrochloricacid are generally considered upper airway (centralcompartment) irritants but can affect the lower lungregions if exposure concentration and duration aresufficient. Carbon monoxide, H 2S, and HCN are classifiedas systemic chemical asphyxiants.Rational and effective medical countermeasuresagainst the inhalational injury caused by gases,smokes, fumes, and mists depend on mechanisticevidence of exposure responses at the tissue and cellularlevels. The investigation required to determinethe correct treatment route, therapeutic window, anddosing levels is costly and time consuming. Study ofrepresentative compounds from a class of gases canprovide general insight into the mechanisms responsiblefor tissue and cellular injury and the subsequentrepair processes. In recent years extensive data on themechanisms of phosgene, chlorine, H 2S, and oxides ofnitrogen gas exposure have been published. 32–34 Thesestudies evaluated the following range of effects overtime and at various exposures:• histopathology of exposed lung tissue;• biochemical pathway assessment of lungtissue markers of exposure such as a simpledetermination of wet/dry weight ratio forpulmonary edema estimates;• inflammation pathways;• metabolic markers of exposure such as arachidonatemediators;• physiological assessment of blood gas andhemodynamic status;• cell differential counts;• pulmonary function as measured by plethysmography;• tissue and bronchoalveolar lavage fluid redoxand antioxidant status;• behavioral effects;• genomic expression markers;• immunosuppression effects; and• mortality as determined by survival rate studies.Mechanistic Effects of Inhaled Pulmonary AgentsExposure to inhaled agents can compromise theentire pulmonary tree through a range of altered physiological,biochemical, and pathophysiological processes.The general mechanisms of toxic gas exposure are shownin Figure 10-1. Researchers have used animal models toexamine these dysfunctional pathways in many ways.In an obligate nose-breathing experimental animal likethe rodent, the basic mammalian life processes are extrapolatedto humans, allowing for reasonable estimatesof potential human exposure responses. This chapterwill cover studies of prominent pathways through which346