response? This question has not been adequately studied. An association with dose is found for acute as well as chronic responses, which provides support for the association, but not for a relationship between the magnitude of the acute response and the magnitude of the chronic response. If the disease model invoked requires the acute exposure to cause acute irreversible damage, then one might reasonably expect the magnitude of acute response to predict the magnitude of the chronic response. However, if another disease model is invoked, one in which the acute exposure results in or leads to an alteration in individual risk factors, then it is quite likely that the magnitude of the acute and chronic responses would be unrelated.
What assurance is there that the absence of an acute pulmonary reaction identifies chemically exposed individuals who will not develop long-term sequelae? This may be the most important question to ask and, unfortunately, the one for which no direct evidence could be found. The indirect evidence, however, would suggest the need to invoke an unusual disease model, one in which changes in individual risk factors could be excluded from the list of possible mechanisms, so that the absence of an acute reaction would eliminate the possibility of any chronic effects related to a short-term or acute exposure.
There are few directly relevant data for evaluating the risk of chronic nonmalignant respiratory disease associated with the specific exposure conditions present in the WWII chamber and field studies. The range of exposure concentrations that were actually inhaled by the subjects can be only crudely estimated, but they may have reached the levels experienced by those exposed in combat or production facilities. Without precise knowledge about the exposures, the only way to estimate the true risk would be to identify the cohort of test subjects and follow them for the occurrence of respiratory morbidity. To date, the entire cohort of subjects has not been identified, nor has any subset of them been followed for long-term health effects. The absence of a follow-up study of the experimental subjects from the WWII testing programs is the single largest gap in the literature relevant to the assessment of chronic nonmalignant respiratory disease risk in individuals experiencing short-term exposures to sulfur mustard or Lewisite.