exposure, will lead to attenuation of the estimates of relative risk (RR) and to a diminution of statistical power. Moreover, diagnosis of the primary cause of death from respiratory and cardiovascular diseases (CVDs) is often inconsistent. In particular, when persons have both conditions concurrently and both contributed to death, there may be some uncertainty about which cause should be selected as the primary underlying cause. In other instances, errors may arise in selecting one underlying cause in a complex chain of health events (for example, if COPD leads to congestive heart failure and then to respiratory failure).
Many study populations are small, so investigators group deaths from all noncancerous respiratory diseases into one category that combined pneumonia, influenza, and other diseases with COPD and asthma. The committee notes that an association for the grouping of all noncancerous respiratory diseases with any of the chemicals of interest would be too nonspecific to be clinically meaningful; at most, such a pattern would be an indication that within this broad classification some particular disease entity might be impacted by an exposure of interest.
Conclusions from VAO and Previous Updates
The committee responsible for Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam, hereafter referred to as VAO (IOM, 1994) concluded that there was inadequate or insufficient information to determine whether there is an association between exposure to the chemicals of interest and the respiratory disorders specified above. Additional information available to the committees responsible for Veterans and Agent Orange: Update 1996 (IOM, 1996) and Update 1998 (IOM, 1999) did not change that finding.
Veterans and Agent Orange: Update 2000 (IOM, 2001) drew attention to findings on the Seveso cohort that suggested a higher mortality from noncancerous respiratory disorders in study subjects, particularly males, who were more heavily exposed to TCDD. Those findings were not replicated in several other relevant studies, although one showed an increase that did not attain statistical significance. The committee responsible for Update 2000 concluded that although new evidence suggested an increased risk of noncancerous respiratory disorders, particularly COPD, in people exposed to TCDD, the observation was tentative and the information insufficient to determine whether there is an association between exposures to the chemicals of interest and respiratory disorders. Additional information available to the committee responsible for Veterans and Agent Orange: Update 2002 (IOM, 2003) did not change that finding.
Veterans and Agent Orange: Update 2004 (IOM, 2005) included a new cross-sectional study of residents near a wood-treatment plant (Dahlgren et al., 2003). Soil and sediment samples from a ditch in the neighborhood contained dioxins and furans. Although exposed residents reported a greater frequency of chronic bronchitis by history (17.8% vs 5.7%; p < 0.0001) and asthma by history (40.5% vs 11.0%; p < 0.0001) than a “nonexposed” control group, the committee