Completing the evidence in this area were findings published Summer 2008 in what is believed to be the first-ever "follow-up study of patients previously referred to hospital" with "non-specific building-related symptoms", SBS.(8) The study followed the experience of approximately 200 such patients who had indeed received hospital clinic treatment, observing that:
"The level and severity of symptoms decreased over time, although nearly half of the patients claimed that symptoms were more or less unchanged after 7 years or more, despite actions taken. Twenty-five percent of the patients were on the sick-list, and 20% drew disability pension due to persistent symptoms at follow-up."(8)
The study also found that only about 7% of those patients followed had fully recovered from SBS's effects.(8)
Evidence would seem to exist that repeated low-level exposures, in cases of both GWI and SBS, do appear to yield chronic and delayed consequences to physiological systems. It is unfortunate though that the phrase 'low-level' can be somewhat misleading.
500-Fold Larger Exposures and Aerosolized Fungal Fragments
Examining the question of AChEi exposure via the inhalation of aerosolized fungal agents, 2002 research demonstrated that Aspergillus versicolor and Pencillium melinii fungal fragments were found to be "aerosolized simultaneously with spores from contaminated agar and ceiling tile surfaces."(9) The study emphasized that the "considerable immunological reactivity, the high number, and the small particle size of the fungal fragments may contribute to human-health effects that have been detected in buildings with mold problems but had no scientific explanation until now."(9)
Coupling the 2007 study's findings with those from the independent 2002 research, a possible delivery mechanism for mycotoxins -- and potentially AChEis -- at levels hundreds of times higher than previously realized, would indeed seem suggested.
"Why are some ill and not others?"
Exploring beyond the possible role of AChEis in mold-related SBS, beyond the question as to how AChEi exposure might occur, the question of individual sensitivity to an AChEi exposure is raised. Given that we are addressing an onset of symptoms resulting from extended 'low-level' exposures, a question regarding the effects of individual differences in AChEi-detoxification levels exists. We feel that the efforts of several studies are significant to cite in regards to this, with their findings of genetic variants noteworthy.
Supporting such genetic linkage, a 1999 study's title suffices: "Association of Low PON1 Type Q (Type A) Arylesterase Activity with Neurologic Symptom Complexes in Gulf War Veterans".(11) An independent 2004 study also noted that their "finding parallels others' observation of a link between PON1 heterozygosity" and symptoms in GWV.(12)
Paraoxonase (PON) is an enzyme which is HDL-associated, and "one of many circulating antioxidants thought to play a vital protective role".(13) "The level of PON-1 gene expression is a major determinant of paraoxonase-1 status", according to a 2003 French study.(14)
Evidence of a genetically based susceptibility to AChEi exposure appears to exist. Of course, the key question raised by this hypothesis is the impact mycotoxin-derived AChEi exposures may have, particularly upon those most susceptible, and whether we have come to often term such impact SBS.
AChEi exposure, via inhaled AChEi-rich mycotoxins carried by aerosolized fungal agents, may be a primary but unrealized cause of SBS. Genetic variance, specifically involving low PON activity levels and concentrations, may be a key determinant of susceptibility to SBS. Research is needed to determine the answers to both these questions, as well as potentially that of how broadly, and in what configurations and potencies, AChEis may exist within the range of those fungi typically associated with SBS problems - Penicillium sp, Aspergillus sp, and Stachybotrys sp.
Potential Path for Research
The path forward is fairly simple, though the execution of it is not. A statistically significant sample of SBS sufferers would be secured, sufferers whose environment had remained essentially unaltered from the point of their symptoms' onset, and where the environmental factors suggested the presence of mold (ie, dampness). An AChEi 'inventory' of each subject's environment is then required, with a key factor in this being a complete environmental analysis to determine both the specific agents present, their concentrations, and their AChEi values. Testing the subjects to determine low PON-activity levels and concentration would then further clarify the results. This PON testing would be particularly significant in cases where a number of individuals experienced similar exposures which resulted in markedly differing outcomes. A 'control' environment would also need to be 'inventoried', one where the environmental quality is known to be 'high'. Then, pursuing an examination of the correlation between environmental AChEi levels and their components, individual PON levels, and subject outcomes, should highlight the validity of this paper's hypothesis.
1. Golomb BA. Acetylcholinesterase inhibitors and Gulf War illnesses. 2008, PNAS, vol. 105 no. 11, 4295-4300
2. Research Advisory Committee on Gulf War Veterans' Illnesses Gulf War Illness and the Health of Gulf War Veterans. Research Advisory Committee on Gulf War Veterans' Illnesses Home. November 2008. http://www1.va.gov/RAC-GWVI/
3. Redlich CA, Sparer J, Cullen MR. Sick-building syndrome. Lancet 1997; 349: 1013-16