Do corticosteroids have a role in preventing or reducing acute toxic lung injury caused by inhalation of chemical agents?

OBJECTIVE: To assess the evidence that treatment with corticosteroids improves the outcome in those exposed to lung-damaging agents.

METHODS: We searched Pubmed, Toxnet, Cochrane database, Google Scholar, and Embase from 1966 to January 2010 using the search terms "steroid", "corticosteroid", "lung injury", "lung damage", and "inhalation". These searches identified 287 papers of which 118 contained information on animal studies. However, most were reviews or case reports and only a few were controlled animal experiments of which 13 were considered relevant. ROLE OF CORTICOSTEROIDS:

ANIMAL STUDIES: Corticosteroids have no beneficial effect at the alveolar level on acute lung injury, which is caused by inhalation of poorly water-soluble compounds (e.g. nitrogen dioxide, ozone, phosgene) or following severe exposure to water-soluble compounds (e.g. chlorine, ammonia). In the recovery phase, corticosteroids may even be harmful, because corticosteroids hamper the division of type II alveolar cells and hamper the differentiation from type II into type I alveolar cells. The latter is important for the re-epithelialization of the alveolus and removal of excess of water in the alveolus. Furthermore, the quality of animal studies does not always allow extrapolation to human exposures. Differences between humans and animals in anatomy, pulmonary defense systems, breathing physiology, as well as the way the animals have been exposed, and the timing and route of corticosteroids in animal studies make predictions difficult. ROLE OF CORTICOSTEROIDS:

HUMAN STUDIES: An abundance of uncontrolled case reports and a few human crossover studies have evaluated the outcome of human volunteers exposed to various lung-damaging agents. Only a few reports contained systematic information on corticosteroid treatment. Data on the efficacy of corticosteroids after human exposure to lung-damaging agents are inconclusive. Often the number of patients involved is small or the severity of exposure is unclear or not well determined. These reports are therefore limited in their ability to establish a cause-effect relationship for the treatments involved. In some studies involving mild to moderate exposure to water-soluble agents (e.g. chlorine, ammonia), corticosteroid treatment was beneficial for some physiological parameters, such as airway resistance or arterial oxygen tension. However, severe lung injury and inflammation appear not to be improved by corticosteroid treatment. The optimal duration of treatment to obtain these beneficial effects has not been assessed adequately, but it only seems to be useful in the first hours after exposure. Generally, studies evaluating exposure to water-soluble compounds have too short a follow-up, which hampers the evaluation of the efficacy of corticosteroid treatment. The results of studies with longer follow-up suggest that the initial slight improvement in some variables is lost several hours after exposure.

CONCLUSIONS: Clinical data on the efficacy of corticosteroids after human exposure to lung-damaging agents are inconclusive as the number of well-structured controlled studies is small and the indications for administration of corticosteroids are unclear. There have been no human controlled studies of high-dose exposure to lung-damaging agents. Furthermore, treatment with corticosteroids is limited by the potential side effects, such as prolonged neuromuscular weakness, deregulation of glucose metabolism, superinfection, and sepsis, which could diminish the chances for recovery.