William E. Daniell

Immunologic, psychological, and neuropsychological factors in multiple chemical sensitivity : a controlled study

During the last decade, physicians practicing primary care, occupational medicine, and allergy/immunology have encountered a growing number of patients with symptoms attributed to low-level chemical exposure. These patients typically have a wide array of respiratory, neuropsychological, and systemic symptoms without well-defined physical or laboratory findings. One syndrome, variously labeled environmental illness or multiple chemical sensitivity, has been described as an acquired disorder characterized by recurrent symptoms, referable to multiple organ systems, occurring in response to demonstrable exposures to many chemically unrelated compounds at doses far below those established in the general population to cause harmful effects [1]. Immunologic, neurotoxic, and psychiatric causes have been proposed, but the cause and treatment of chemical sensitivity remain controversial. Some physicians with special interest in chemical sensitivity, particularly clinical ecologists or environmental physicians, emphasize the role of immunologic abnormality in chemical sensitivity [2]. They contend that accumulated everyday exposure to synthetic chemicals causes immunologic overload and an immunologically mediated sensitivity to common chemical exposures. Treatment regimens may include dietary changes, unorthodox desensitization techniques, and strict avoidance of common low-level chemical exposures. These recommendations can cause major life disruption and severe social withdrawal. The limited scientific data available do not clarify the role of immunologic abnormality in multiple chemical sensitivity and similar disorders attributed to low-level chemical exposure. A number of small case series describe elevated immunoglobulin levels [3, 4], antichemical antibodies [5-9], autoantibodies [5], elevated levels of TA1-positive cells [5, 7, 8], and various changes in lymphocyte subsets [5, 7-9]. These reports, however, reveal no consistent pattern of immunologic abnormality. Results from two larger series of patients selected from a referral occupational medicine clinic [10] and from a group of disability applicants [11] showed no abnormality of immunoglobulin and complement levels, B-cell, T-cell, and T-cell subset levels. None of these investigations, however, included systematic selection of patients with chemical sensitivity from a defined population, blinded assessment, or comparison with appropriate controls. Traditional medical organizations express skepticism about the immunologic basis of chemical sensitivity and the practice of clinical ecologists [12-14]. A recent report of the American Medical Associations Council on Scientific Affairs concluded that multiple chemical sensitivity should not be considered a recognizable clinical syndrome [15]. After reviewing medical records of patients claiming compensation for work-related chemical sensitivity symptoms, Terr [16] reported that most patients reported similar symptoms before exposure at the workplace. A double-blind evaluation of the neutralization-provocation techniques used by some clinical ecologists found that patients with multiple food sensitivities were unable to distinguish placebo from low-level food or chemical exposures [17]. Previous psychological studies of patients with multiple chemical sensitivity have all reported elevated levels of anxiety and depression and have implicated psychological distress in the cause of the syndrome [18-22]. Two of these studies, however, considered patients specifically referred for psychiatric evaluation [18, 19], and none systematically sampled a defined population of patients with chemical sensitivity. Three of these reports included no control group [18-20], and the remaining two [21, 22] compared patients with multiple chemical sensitivity to community volunteers or mildly ill controls who might be expected to report less psychological distress. Fiedler and colleagues [10] recently described moderate levels of psychological morbidity in a series of eight patients with chemical sensitivity referred to a occupational health clinic, but no comparison group was included. To address some of these gaps in knowledge, we compared immunologic, psychologic, and neuropsychological factors in a systematically selected sample of patients with multiple chemical sensitivity and a medically ill control group. Methods Study Sample Patients with chemical sensitivity were recruited from the practice of a community allergist with special interest in treating chemical sensitivity. All patients with a recorded diagnosis of chemical sensitivity seen between January 1989 and June 1990 were identified from computerized billing records. We then reviewed standardized history questionnaires included in clinical records for the following eligibility criteria: duration of illness 3 months or more; symptoms reported in at least three organ systems, including the central nervous system; and reported sensitivity to 4 or more substances from a list of 14 common exposures including fresh paint, newspapers, perfume, hair spray, and solvent fumes. All potential participants were sent a letter requesting their participation. Of the 76 patients with chemical sensitivity identified from records, 32 did not respond to letters and 3 were judged to be ineligible (2 reported complete resolution of chemical sensitivity and 1 described respiratory symptoms only). The remaining 41 patients (56% of those potentially eligible) were enrolled. Controls were selected from two university-based clinics for patients with musculoskeletal injuries: an occupational musculoskeletal clinic and a back injury specialty clinic. We reviewed clinic charts to identify all patients seen between January 1989 and June 1990 whose ages were within the range of the chemical sensitivity cases and who resided within 25 miles of the study clinics. Patients with any systemic illness (such as rheumatoid arthritis) likely to affect the results of immunologic testing were excluded, and potential controls were frequency matched to cases by sex and 5-year age strata. This procedure identified 85 potential controls (34 from the occupational clinic and 51 from the back clinic) who were sent a letter requesting participation in the comparison group for a study of chemical-related health problems. Forty-nine did not respond (17 from the occupational clinic and 32 from the back clinic) and 2 patients (both from the back clinic) were judged ineligible because of reported symptoms of chemical sensitivity. The remaining 34 patients (41% of those potentially eligible) were enrolled. The primary diagnosis was low-back pain for all 17 control patients from the back clinic and for 4 from the musculoskeletal clinic. Of the remaining control patients, 8 had repetitive-motion syndromes and 5 had other chronic symptoms following work-related musculoskeletal injuries. Laboratory Methods All immunologic studies were performed by a commercial laboratory with special interest in the evaluation of chemical sensitivity. Laboratory personnel assisted in design of the immunologic battery but remained blinded to case/control status during testing. Total leukocyte count, red cell count, hemoglobin, and hematocrit concentration were measured on a Coulter T140 Cytometer (Coulter Electronics, Hialeah, Florida). For cell-surface marker studies, mononuclear cells were isolated using a Ficoll-induced density gradient followed by 50% dilution in saline and triple washing in Hanks balanced salt solution to remove serum protein. Phenotypic marking of lymphocytes was performed using monoclonal antibodies against CD5 (total T cells), CD4 (T-helper cells), CD8 (T-suppressor cells), CD19 (total B cells), and CD25 (interleukin-2 receptor-positive cells) (all from Becton Dickinson; Los Angeles, California), then counterstained with mouse antihuman IgG coupled to fluorescein. The monoclonal antibody against CD26 (TA1-positive cells) (Coulter) was directly coupled to rhodamine. The percentage of labeled cells was determined using fluorescence microscopic examination. Autoantibodies against parietal cells, mitochondria, smooth muscle, brush border, and nuclear components (Medica; Carlsbad, California) were screened at a dilution of 1:20 in phosphate-buffered saline, pH 7.0, by incubation with species substrate in a room temperature humidifier. Counterstaining was with Evans blue, and fluorescence was classified as present or absent. Each assay run included positive and negative controls. For assay of interleukin-1 generation, peripheral blood monocytes were isolated from sodium heparinized blood by differential centrifugation, washed, and isolated by adherence to tissue culture plates. Monocytes were incubated overnight at 37 C in the presence of lipopolysaccharide (1500 g/mL) and phorbol (1 mg/mL) in 10% fetal calf serum. The supernatant was collected and frozen for later assay. Generated interleukin-1 was measured with an enzyme-linked immunoassay technique using microtiter plates coated with a monoclonal capturing antibody and polyclonal second antibody (Cistron; Pine Brook, New Jersey) linked to peroxidase. Each run included standard and control specimens. Psychological and Neuropsychological Evaluation Patients in both groups completed a questionnaire assessing demographic data, work and chemical exposure history, as well as type, frequency, and duration of chemical sensitivity symptoms. Psychological evaluation included the Hopkins Symptom Checklist-90 (SCL-90), a self-report measure of psychiatric symptoms [23], and the Diagnostic Interview Schedule [24], a highly structured psychiatric diagnostic interview based on the criteria of the American Psychiatric Associations DSM-IIIR [25]. Diagnoses assessed by the structured interview included panic disorder, generalized anxiety, depression, and somatization (a tendency to seek care for physical symptoms that have no apparent medical explanation). The standard Diagnostic Interview Sc

Noise exposure and hearing loss prevention programmes after 20 years of regulations in the United States

Objectives: To evaluate noise exposures and hearing loss prevention efforts in industries with relatively high rates of workers’ compensation claims for hearing loss. Methods: Washington State workers’ compensation records were used to identify up to 10 companies in each of eight industries. Each company (n = 76) was evaluated by a management interview, employee personal noise dosimetry (n = 983), and employee interviews (n = 1557). Results: Full-shift average exposures were ⩾85 dBA for 50% of monitored employees, using Occupational Safety and Health Administration (OSHA) parameters with a 5 dB exchange rate (Lave), but 74% were ⩾85 dBA using a 3 dB exchange rate (Leq). Only 14% had Lave ⩾90 dBA, but 42% had Leq ⩾90 dBA. Most companies conducted noise measurements, but most kept no records, and consideration of noise controls was low in all industries. Hearing loss prevention programmes were commonly incomplete. Management interview scores (higher score = more complete programme) showed significant associations with percentage of employees having Lave ⩾85 dBA and presence of a union (multiple linear regression; R2 = 0.24). Overall, 62% of interviewed employees reported always using hearing protection when exposed. Protector use showed significant associations with percentage of employees specifically required to use protection, management score, and average employee time spent ⩾95 dBA (R2 = 0.65). Conclusions: The findings raise serious concerns about the adequacy of prevention, regulation, and enforcement strategies in the United States. The percentage of workers with excessive exposure was 1.5–3 times higher using a 3 dB exchange rate instead of the OSHA specified 5 dB exchange rate. Most companies gave limited or no attention to noise controls and relied primarily on hearing protection to prevent hearing loss; yet 38% of employees did not use protectors routinely. Protector use was highest when hearing loss prevention programmes were most complete, indicating that under-use of protection was, in some substantial part, attributable to incomplete or inadequate company efforts.

Neuropsychological performance among agricultural pesticide applicators

To assess the potential effects on neuropsychiatric performance of chronic occupational exposure to organophosphate insecticides, we performed a prospective longitudinal study of a cohort of apple orchard pesticide applicators and a comparison cohort of beef slaughter-house workers. The study group consisted of 49 applicators and 40 comparison subjects who completed both an initial evaluation (preseason) prior to the onset of the approximately 6-month pesticide spraying season and a follow-up evaluation (postseason) about 1 month following the end of spraying season. The applicator cohort had a greater number (n = 22, 45%) of individuals who identified primary preference for Spanish-language testing than did the comparison cohort (n = 5, 13%). Stratification by language preference revealed no significant differences in background characteristics between the two cohorts, except for fewer years of education in the Spanish-language preference applicators versus control subgroups (5.0 +/- 3.1 vs 7.8 +/- 3.7 years, respectively). After controlling for language preference, there were no statistically significant differences between the applicators and control cohorts on neuropsychological subtests of the computerized test battery. Preseason baseline performance on individual tests was a significant predictor of postseason test performance. After controlling for baseline performance, the only statistically significant exposure related across-season changes in neuropsychological performance was for one subtest (Symbol Digit Substitution) and was confined to the Spanish language preference subgroups, with worse adjusted postseason performance among applicators versus controls (P = 0.001). This study found no clear evidence of clinically significant decrements in neuropsychological performance following one 6-month season of pesticide exposure in a cohort of applicators who were felt to have generally low, intermittent, and well-controlled organophosphate exposures.

Neuropsychological function in retired workers with previous long-term occupational exposure to solvents

OBJECTIVES: It is plausible that neurodegenerative processes of aging might have a contributing role in the development of chronic effects of exposure to organic solvents. This study evaluated the risk for neuropsychological deficits among retired workers, relative to their histories of exposure to occupational solvents. METHODS: This cross sectional study evaluated retired male workers, 62-74 years of age, including 89 people with previous long-term occupational exposure to solvents (67 retired painters and 22 retired aerospace manufacturing workers), and 126 retired carpenters with relatively minimal previous exposure to solvents. Subjects completed a standardised neuropsychological evaluation and psychiatric interview, structured interviews for histories of occupational exposure and alcohol consumption, and questionnaires assessing neurological and depressive symptoms. RESULTS: By comparison with the carpenters, the painters on average reported greater cumulative alcohol consumption and had lower scores on the WAIS-R vocabulary subtest, usually presumed to reflect premorbid intellectual functioning. These findings, however, were not sufficient to account for the other study findings. Controlling for age, education, vocabulary score, and alcohol use, the painters had lower mean scores on test measures of motor, memory, and reasoning ability; and a subgroup of aerospace workers with moderate to high cumulative exposure to solvents (n = 8) had lower mean scores on measures of visuomotor speed, and motor, attention, memory, and reasoning ability. Subjects were more likely to have an increased number of relatively abnormal test scores (three or more outlier scores on 17 test measures) among both the painter group (odds ratio (OR), 3.1; 95% confidence interval (95% CI) 1.5 to 6.2) and the subgroup of aerospace workers with higher cumulative exposure (OR 5.6; 95% CI 1.0 to 38). The painters, but not the aerospace workers, reported significantly more neurological and depressive symptoms. CONCLUSIONS: The findings are consistent with residual central nervous system dysfunction from long-term exposure to organic solvents, persisting years after the end of exposure.

Predictors of Hearing Protection Use in Construction Workers

OBJECTIVES Although noise-induced hearing loss is completely preventable, it remains highly prevalent among construction workers. Hearing protection devices (HPDs) are commonly relied upon for exposure reduction in construction, but their use is complicated by intermittent and highly variable noise, inadequate industry support for hearing conservation, and lax regulatory enforcement. METHODS As part of an intervention study designed to promote HPD use in the construction industry, we enrolled a cohort of 268 construction workers from a variety of trades at eight sites and evaluated their use of HPDs at baseline. We measured HPD use with two instruments, a questionnaire survey and a validated combination of activity logs with simultaneous dosimetry measurements. With these measurements, we evaluated potential predictors of HPD use based on components of Penders revised health promotion model (HPM) and safety climate factors. RESULTS Observed full-shift equivalent noise levels were above recommended limits, with a mean of 89.8 +/- 4.9 dBA, and workers spent an average of 32.4 +/- 18.6% of time in each shift above 85 dBA. We observed a bimodal distribution of HPD use from the activity card/dosimetry measures, with nearly 80% of workers reporting either almost never or almost always using HPDs. Fair agreement (kappa = 0.38) was found between the survey and activity card/dosimetry HPD use measures. Logistic regression models identified site, trade, education level, years in construction, percent of shift in high noise, and five HPM components as important predictors of HPD use at the individual level. Site safety climate factors were also predictors at the group level. CONCLUSIONS Full-shift equivalent noise levels on the construction sites assessed were well above the level at which HPDs are required, but usage rates were quite low. Understanding and predicting HPD use differs by methods used to assess use (survey versus activity card/dosimetry). Site, trade, and the belief that wearing HPD is not time consuming were the only predictors of HPD use common to both measures on an individual level. At the group level, perceived support for site safety and HPD use proved to be predictive of HPD use.

Hepatic ultrasonic changes in workers exposed to perchloroethylene.

OBJECTIVE--To determine if subclinical hepatotoxicity is associated with exposure to perchloroethylene at concentrations commonly experienced in the workplace, and whether surveillance with serum hepatic transaminase activity underestimates such effects. METHODS--Hepatic parenchymal echogenicity on ultrasonography and serum hepatic transaminase activity were compared in 29 community based dry cleaning operators exposed to perchloroethylene, and a control group of 29 non-exposed laundry workers. Perchloroethylene exposure was assessed by work history and air monitoring. RESULTS--Mean hepatic transaminase activities were minimally increased in dry cleaners compared with laundry workers. Increased alanine aminotransferase activities, between 1.0 and 1.5 times the normal limits, were found in five of 27 (19%) dry cleaners compared with one of 26 (4%) laundry workers. In contrast, diffuse parenchymal changes in echogenicity, as determined by hepatic ultrasonography, were increased nearly twofold in dry cleaners, occurring in 18 of 27 (67%) dry cleaners compared with 10 of 26 (39%) laundry workers (P < 0.05), and were most strongly associated with increased perchloroethylene exposure in older dry to dry or wet transfer operations (odds ratio 4.2, 95% confidence interval 1.1-15.3). Mean eight hour time weighted average perchloroethylene exposure for dry cleaners was 16 ppm, which is less than the permissible exposure limit of 100 ppm in the United States. CONCLUSIONS--It was concluded that mild to moderate hepatic parenchymal changes occur more frequently in workers exposed to perchloroethylene than in populations not exposed to chemical solvents, and that these effects are underestimated by serum hepatic transaminase activity.

Organophosphate pesticide exposure in a group of washington state orchard applicators

As part of a study to investigate the potential for organophosphates to cause chronic neurologic sequelae, we assessed the pesticide exposure experience of a group of Washington State apple orchard applicators. Seasonal monitoring of cholinesterase activity for 48 regular organophosphate applicators and a control group of 40 slaughterhouse workers was performed. A subset of the pesticide applicators participated in an in-depth exposure assessment. This involved observation of spraying activities during 1 spray day, as well as cholinesterase monitoring and dermal exposure assessment using a fluorescent tracer in the pesticide formulation. Comparison of seasonal red blood cell cholinesterase change in pesticide workers according to exposure level, characterized by frequency of pesticide spraying and protective equipment use, showed lower cholinesterase levels among higher exposed groups compared to lesser exposed groups. In-depth exposure assessment revealed exposure primarily on the head and hand regions. Subclinical changes (less than 15% inhibition) in red cell cholinesterase correlated well with dermal exposure calculations. This study suggests that cholinesterase monitoring may be a useful biological marker for even subclinical organophosphate pesticide effects.

Evaluation and Comparison of Three Exposure Assessment Techniques

This study was conducted to verify the performance of a recently developed subjective rating (SR) exposure assessment technique and to compare estimates made using this and two other techniques (trade mean, or TM, and task-based, or TB, approaches) to measured exposures. Subjects (n = 68) each completed three full-shift noise measurements over 4 months. Individual measured mean exposures were created by averaging each subjects repeated measurements, and TM, TB, and SR estimates were created using noise levels from worksites external to the current study. The bias, precision, accuracy, and absolute agreement of estimates created using the three techniques were evaluated by comparing estimated exposures with measured exposures. Trade mean estimates showed little bias, while neither the TM nor the SR techniques produced unbiased estimates, and the SR estimates showed the greatest bias of the three techniques. Accuracy was essentially equivalent among the three techniques. All three techniques showed poor agreement with measured exposures and were not highly correlated with each other. Estimates from the SR technique generally performed similarly to the TM and TB techniques. Methods to incorporate information from each technique into exposure estimates should be explored.

Evaluation of a healthcare safety climate measurement tool

PROBLEM Psychometrically validated measurement tools are needed to evaluate an organizations safety climate. In 2000, Gershon and colleagues published a new healthcare safety climate measurement tool to determine its relationship to safe work behavior (Gershon, R., Karkashian, C., Grosch, J., Murphy, L., Escamilla-Cejudo, A., Flanagan, P., et al. (2000). Hospital safety climate and its relationship with safe work practices and workplace exposure incidents. American Journal of Infection Control, 28, 211-21). The present study evaluated the psychometric properties of the Gershon tool when modified to address respiratory rather than bloodborne pathogen exposures. METHOD Medical practitioners, nurses, and nurse aides (n=460) were surveyed using the modified Gershon tool. Data were analyzed by factor analysis and psychometric properties of the tool evaluated. RESULTS Eight safety climate dimensions were extracted from 25 items (Cronbachs alpha range: 0.62 - 0.88). Factor extractions and psychometric properties were reasonably consistent with those of the Gershon tool. IMPACT ON INDUSTRY The Gershon safety climate tool appears to have sufficient reliability and validity for use by healthcare decision makers as an indicator of employee perceptions of safety in their institution.

Neuropsychological performance and solvent exposure among car body repair shop workers.

A cross sectional study to evaluate symptom reporting and neuropsychological test performance among a cohort of car body repair workers (n = 124) was performed using a computer-administered test system. Subjects with high and medium current exposures to solvent and paint (n = 39 and 32), and low exposure subjects who formerly painted (n = 29) reported significantly more acute and chronic neurological symptoms than did low exposure subjects with no history of painting (n = 24). Subjects with higher current exposure performed significantly less well on selected tests of visual perception and memory, but there were no significant exposure related differences in mood state, motor speed, or visuomotor performance. The exposure related effects were most noticeable among subjects 35 years or older. The findings are consistent with age interactive central neurotoxic effects of current exposure to solvents or of cumulative past exposure, although the study is unable to distinguish between these possibilities. The computer administered test system was effective in this field based investigation involving multiple, geographically dispersed worksites.