Changes in VEGF, MMP9 and leptin correlate with acute and chronic illness symptoms and visual contrast sensitivity in patients from water damaged buildings: Indicators of complex physiologic disturbances in Sick Building Syndrome
Authors: Ritchie C. Shoemaker¹, Dennis House¹
¹Center for Research on Biotoxin Associated Illnesses, Pocomoke, Md
BACKGROUND: A 5-step repetitive exposure protocol provides a mechanism to document causation of illness in symptomatic patients exposed to in door environments of water-damaged buildings (WDB). By demonstrating benefits of treatment with cholestyramine (CSM) of affected patients, with stability off medication away from exposure and then documenting changes in symptoms and biomarkers prospectively with re-exposure, followed by correction with re-treatment, we have previously shown that the physiologic disturbances underlying illness in Sick Building Syndrome are identical to those of a chronic biotoxin associated illness. We present data here to support use of leptin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9) as biochemical markers for both acute and chronic illness adjunctive to recording of symptoms and visual contrast sensitivity (VCS). We again present data on unique genotypes of HLA DR, analyzed by PCR, previously reported to be associated with a genetic basis of susceptibility to neurotoxic illness caused by exposure to resident indoor toxigenic fungi. The unique grouping of symptoms found in these patients, including fatigue, neurologic, respiratory and rheumatologic symptoms match changes of biomarkers with treatment and re-exposure.
METHODS: 26 consecutive patients exposed to buildings with growth of identified toxigenic fungi attending a private clinic for diagnosis and treatment of chronic fatiguing illness refractory to all prior modalities of therapy agreed to participate in an IRB approved, multiple intervention, longitudinal clinical treatment trial using CSM to assess the effect of exposure, treatment, re-exposure and re-treatment on multiple simultaneously measured clinical and laboratory parameters. Each patient provided informed consent. Exposure to tobacco smoke, IgE, pulmonary function testing results before and after interventions and HLA DR genotypes were recorded.
RESULTS: Each affected patient showed clinical improvement following treatment with CSM and was stable off drug, away from exposure to the known affected building. Each patient relapsed within 3 days of re-exposure to the contaminated building off CSM, with improvement following re-treatment. Change in clinical course was paralleled by symptoms, VCS, leptin, MMP9 and VEGF. Improvement in PFT testing was noted. HLA DR genotypes previously noted to confer susceptibility were again demonstrated. Tobacco smoke was not a relevant clinical parameter. Symptom rosters showed multiple organ system illness, with fatigue, chronic pain and cognitive problems most commonly identified.
DISCUSSION: Use of symptoms, VCS, leptin, VEGF and MMP9 gives the treating physician biomarkers useful in case identification and assessment of efficacy of therapy.