autoimmune hemolytic anemia, and (e) if animal models of the disease show induction by chemical exposure. Using these criteria, a group of diseases that need to be studied is given in Table 1. We do not claim that all of these diseases rigorously meet each of the above criteria. Common features of these diseases are a waxing and waning course, localized tissue inflammation, and ultimately tissue destruction. They are candidates for Stage 2 and Stage 3 illnesses of the Hypothetical Chemical Stress Syndrome, discussed elsewhere in these proceedings.

TABLE 1

Some of the Diseases Whose Relationship to Environmental Chemicals Needs Clarification

Asthma

Autoimmune hemolytic anemia

Crohn's Disease

Depression

Manic depressive illness

Multiple sclerosis

Rheumatoid Arthritis

Schizophrenia

Systemic Lupus Erythematosis

Ulcerative Colitis

Clinical research protocols must be designed to incorporate suitable control groups. Investigators must recognize that the entire population is exposed to low-level volatile organic chemicals (VOC's), and there is data suggesting that normal volunteers exposed in challenge chambers to mixtures of VOC's can become symptomatic. Some effects of chronic low-level VOC exposure may be seen in both normal individuals and patients.

Clinical studies of adverse effects of chemicals must be double-blinded, but unique difficulties arise in the case of odorous inhalants. Odor masking by exposing the subject to a high dose chemical considered innocuous and a low dose chemical to be tested presents unique problems in this setting and will require systematic study. Anesthetizing the olfactory bulb may mask olfactory mediated physiologic reactions. The experience of blinding techniques in the study of food allergy and food intolerance should be heeded, and these investigators have found that blinding techniques should not be accepted a priori, but should be subjected to scientific scrutiny. Exposures of patients during sleep may be the most effective technique, but will need controlled investigation due to altered physiology during sleep.

Clinical studies must allow for psychiatric illnesses in the patient population. It is recognized that there are behavioral aspects to this illness. In the original description of the multiple chemical sensitivity syndrome, it was claimed that psychiatric symptoms including depression, hallucinations, and manic states can be induced in some patients by chemical



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