Atopy, symptoms and indoor environmental perceptions, tear film stability, nasal patency and lavage biomarkers in university staff.

OBJECTIVE: Study associations between airway symptoms, complaints on environmental perceptions, atopy definitions and biomarkers including tear film stability (BUT), nasal patency and nasal lavage (NAL). Personal predictors (gender, age, smoking, infections) for the biomarkers as well as associations between the biomarkers were also assessed. METHODS: A cross-sectional study of 173 employees in four university buildings, response rate 86%. Tear film break up time (BUT) was measured by a non-invasive method (NIBUT) and self-reported (SBUT). NAL-analysis included eosinophilic cationic protein (ECP), myeloperoxidase (MPO), lysozyme and albumin. Total serum IgE, and specific IgE using Phadiatop was measured. Data on subjective symptoms, environmental perceptions and background data were collected by use of a questionnaire. Multiple regression analyses were applied. RESULTS: Mean age was 43 years, 21% had weekly ocular, 21% nasal, and 17% laryngeal symptoms. Women had more complaints on environmental perceptions, shorter BUT and less nasal patency. Neither atopy (Phadiatop) nor Total IgE or allergy in the family, but asthma and hay fever was associated with mucosal symptoms or perceptions. Subjects with positive Phadiatop had higher levels of all NAL-biomarkers. Those with ocular symptoms had shorter BUT. Nasal symptoms were related to respiratory infections and laryngeal symptoms to NAL-lysozyme. Perceiving dry air was associated with lower BUT and reduced nasal volume difference before and after decongestion. Older subjects had greater nasal patency, and less atopy. All NAL-biomarkers were positively correlated. Higher lysozyme level was associated with less nasal patency and greater nasal decongestion. CONCLUSIONS: BUT and NAL-lysozyme was associated with ocular, nasal, laryngeal symptoms and indoor environmental perceptions. Ever having had asthma and ever having had hay fever were predictors for symptoms and perceived air quality, respectively. Phadiatop, Total IgE, familiar allergy and ever eczema were not associated to symptoms or perceived environments. Age, gender and Phadiatop were main predictors for ocular and nasal biomarkers.

Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms.

Occupants of water-damaged buildings (WDBs) with evidence of microbial amplification often describe a syndrome involving multiple organ systems, commonly referred to as "sick building syndrome" (SBS), following chronic exposure to the indoor air. Studies have demonstrated that the indoor air of WDBs often contains a complex mixture of fungi, mycotoxins, bacteria, endotoxins, antigens, lipopolysaccharides, and biologically produced volatile compounds. A case-series study with medical assessments at five time points was conducted to characterize the syndrome after a double-blinded, placebo-controlled clinical trial conducted among a group of study participants investigated the efficacy of cholestyramine (CSM) therapy. The general hypothesis of the time series study was that chronic exposure to the indoor air of WDBs is associated with SBS. Consecutive clinical patients were screened for diagnosis of SBS using criteria of exposure potential, symptoms involving at least five organ systems, and the absence of confounding factors. Twenty-eight cases signed voluntary consent forms for participation in the time-series study and provided samples of microbial contaminants from water-damaged areas in the buildings they occupied. Twenty-six participants with a group-mean duration of illness of 11 months completed examinations at all five study time points. Thirteen of those participants also agreed to complete a double-blinded, placebo-controlled clinical trial. Data from Time Point 1 indicated a group-mean of 23 out of 37 symptoms evaluated; and visual contrast sensitivity (VCS), an indicator of neurological function, was abnormally low in all participants. Measurements of matrix metalloproteinase 9 (MMP9), leptin, alpha melanocyte stimulating hormone (MSH), vascular endothelial growth factor (VEGF), immunoglobulin E (IgE), and pulmonary function were abnormal in 22, 13, 25, 14, 1, and 7 participants, respectively. Following 2 weeks of CSM therapy to enhance toxin elimination rates, measurements at Time Point 2 indicated group-means of 4 symptoms with 65% improvement in VCS at mid-spatial frequency-both statistically significant improvements relative to Time Point 1. Moderate improvements were seen in MMP9, leptin, and VEGF serum levels. The improvements in health status were maintained at Time Point 3 following a 2-week period during which CSM therapy was suspended and the participants avoid re-exposure to the WDBs. Participants reoccupied the respective WDBs for 3 days without CSM therapy, and all participants reported relapse at Time Point 4. The group-mean number of symptoms increased from 4 at Time Point 2 to 15 and VCS at mid-spatial frequency declined by 42%, both statistically significant differences relative to Time Point 2. Statistically significant differences in the group-mean levels of MMP9 and leptin relative to Time Point 2 were also observed. CSM therapy was reinstated for 2 weeks prior to assessments at Time Point 5. Measurements at Time Point 5 indicated group-means of 3 symptoms and a 69% increase in VCS, both results statistically different from those at Time Points 1 and 4. Optically corrected Snellen Distance Equivalent visual acuity scores did not vary significantly over the course of the study. Group-mean levels of MMP9 and leptin showed statistically significant improvement at Time Point 5 relative to Time Points 1 and 4, and the proportion of participants with abnormal VEGF levels was significantly lower at Time Point 5 than at Time Point 1. The number of participants at Time Point 5 with abnormal levels of MMP9, leptin, VEGF, and pulmonary function were 10, 10, 9, and 7, respectively. The level of IgE was not re-measured because of the low incidence of abnormality at Time Point 1, and MSH was not re-measured because previously published data indicated a long time course for MSH improvement. The results from the time series study supported the general study hypothesis that exposure to the indoor air of WDBs is associated with SBS. High levels of MMP9 indicated that exposure to the complex mixture of substances in the indoor air of the WDBs triggered a pro-inflammatory cytokine response. A model describing modes of action along a pathway leading to biotoxin-associated illness is presented to organize current knowledge into testable hypotheses. The model links an inflammatory response with tissue hypoxia, as indicated by abnormal levels of VEGF, and disruption of the proopiomelanocortin pathway in the hypothalamus, as evidenced by abnormalities in leptin and MSH levels. Results from the clinical trial on CSM efficacy indicated highly significant improvement in group-mean number of symptoms and VCS scores relative to baseline in the 7 participants randomly assigned to receive 2 weeks of CSM therapy, but no improvement in the 6 participants assigned placebo therapy during that time interval. However, those 6 participants also showed a highly significant improvement in group-mean number of symptoms and VCS scores relative to baseline following a subsequent 2-week period of CSM therapy. Because the only known benefit of CSM therapy is to enhance the elimination rates of substances that accumulate in bile by preventing re-absorption during enterohepatic re-circulation, results from the clinical trial also supported the general study hypothesis that SBS is associated with exposure to WDBs because the only relevant function of CSM is to bind and remove toxigenic compounds. Only research that focuses on the signs, symptoms, and biochemical markers of patients with persistent illness following acute and/or chronic exposure to WDBs can further the development of the model describing modes of action in the biotoxin-associated pathway and guide the development of innovative and efficacious therapeutic interventions.

Antibodies against molds and mycotoxins following exposure to toxigenic fungi in a water-damaged building.

Exposure to molds in water-damaged buildings can cause allergy, asthma, hypersensitivity pneumonitis, mucus membrane irritation, and toxicity--alone or in combination. Despite this, significant emphasis has been placed only on Type I allergy and asthma, but not on the other 3 types of allergies. In this study, we sought to evaluate simultaneous measurements of immunoglobulin (Ig) G, IgM, IgA, and IgE antibodies against the most common molds, and their mycotoxins, cultured from water-damaged buildings. Antibodies against 7 different molds and 2 mycotoxins were determined by enzyme-linked immunosorbent assay (ELISA) in the blood of 40 controls and 40 mold-exposed patients. The IgG antibody levels against all 7 of the molds used, as well as the 2 mycotoxins, were significantly greater in patients than in controls. The IgM antibody levels were significantly different in patients for only 6 of 9 determinations. Regarding IgA determinations, antibodies were elevated significantly against all antigens tested, except Epicoccum. However, the differences in IgE levels in controls and mold-exposed patients were significant only for Aspergillus and satratoxin. These differences implied that, overall, the healthy control group was different from the mold-exposed patients for IgG, IgM, and IgA antibodies, but not for the IgE anti-mold antibody. Most patients with high levels of antibodies against various mold antigens also exhibited elevated antibodies against purified mycotoxins, indicating that the patients had been exposed to mold spores and mycotoxins. Detection of high levels (colony-forming units per cubic meter) of molds--which, in this study, strongly suggested that there existed a reservoir of spores in the building at the time of sampling--along with a significant elevation in IgG, IgM, or IgA antibodies against molds and mycotoxins, could be used in future epidemiologic investigations of fungal exposure. In addition to IgE, measurements of IgG, IgM, and IgA antibodies should be considered in mold-exposed individuals.