Carl A. Brodkin

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.

The CARET Asbestos-Exposed Cohort: Baseline Characteristics and Comparison to Other Asbestos-Exposed Cohorts

The Carotene and Retinol Efficacy Trial (CARET) was a double-blind, placebo-controlled trial of the daily administration of 25,000 IU vitamin A and 30 mg beta-carotene for the prevention of lung cancer. Of close to 18,500 participants, more than 4,000 were asbestos-exposed men recruited from shipyard and construction trades at five study centers in the United States. While the primary endpoint of the trial was the incidence of lung cancer, a number of questions about the natural history of asbestos-related disease will also be addressed. The mean age at entry into the trial was 57 years and the mean duration of follow-up on active intervention was 4 years. With the exception of 133 never-smoker pilot participants (3%), all subjects recruited were by intention current (38%) or ex-smokers (58%), with a mean cumulative smoking exposure at entry of 43 pack-years. Mean years from first asbestos exposure were 35, and mean duration of asbestos exposure in a high-risk trade was 19 years. The distribution of radiographic abnormalities was as follows: normal, 34%; parenchymal opacities (ILO profusion score > 1/0) alone, 18%; pleural thickening alone, 27%; both parenchymal opacities and pleural thickening, 21%. The CARET cohort, when compared to previously reported asbestos-exposed cohorts, is characterized by substantial asbestos exposure and high proportion of asbestos-related radiographic findings. The active intervention was halted in 1996, after a mean duration of 40 years. Passive follow-up of the cohort will continue until the year 2000.

Serum hepatic biochemical activity in two populations of workers exposed to styrene

OBJECTIVE To determine whether hepatic biochemical changes, as measured by routinely available tests indicative of hepatocellular necrosis, cholestasis, or altered hepatic clearance of bilirubin, occur in association with low to moderate exposure to styrene commonly experienced in industrial production. METHODS Two independent cross sectional studies were performed comparing serum hepatic transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), cholestatic enzymes (alkaline phosphatase (AP) and γ glutamyl transpeptidase (GGT)), and bilirubin in (a) 47 workers of fibreglass reinforced plastics who were exposed to styrene and (b) 21 boat and tank fabricators, with separate referent groups of unexposed workers. Exposure to styrene was assessed in air by dosimetry, and in venous blood by headspace analysis. Hepatic biochemical variables were assessed across strata of exposure to styrene defined as 25 ppm in air, or 0.275 mg/l in blood, adjusting for age, sex, body mass index, and ethanol consumption. RESULTS A consistent and significant linear trend for increasing direct bilirubin and direct/total bilirubin ratio was found in association with increasing exposure to styrene, by both air and blood monitoring, in both studies. Mean direct bilirubin concentrations increased from 0.05–0.08 mg% in referents to 0.12–0.19 in workers exposed above 25 ppm, with a significant exposure-response trend (p<0.005). Significantly increased direct/total bilirubin ratios, ranging from 0.22 to 0.35 were associated with exposure to styrene (p<0.001), indicating diminished hepatic clearance of conjugated bilirubin. Also, a significant linear association between the hepatic transaminases ALT and AST and exposure to styrene was found in pooled regression analyses, with an increase in AP of about 10 IU/ml in workers exposed above 25 ppm air or 0.275 mg/l blood styrene in pooled analyses from both studies. CONCLUSIONS The consistent finding of increased direct bilirubin and AP concentrations in these two independent studies provides evidence for diminished hepatic clearance of conjugated bilirubin with associated cholestasis in workers exposed to styrene. The finding of a significant linear association between hepatic transaminase concentrations and exposure to styrene in pooled analyses is consistent with mild hepatic injury and associated metabolic dysfunction.

Psychological effects of hazardous materials exposures.

Objective To study psychological outcomes after hazardous materials incidents. Methods Individuals exposed to hazardous materials were contacted to complete a telephone questionnaire within 8 to 40 days of the incident. The Brief Symptoms Inventory was used for psychological assessment. General severity index, depression, anxiety, hostility, and somatization were analyzed. Positive findings were defined as two standard deviations above a normative mean. Results A total of 202 (60%) of the 339 subjects in 87 incidents were surveyed. For 159 adults with valid Brief Symptoms Inventory scores, all dimensions were within normal ranges of elevation, with 1% to 5% of the subject pool having elevation, except for somatization. Twenty-four (14%) of 160 subjects had elevated somatization scores. Based on logistic regression analysis, prior medical therapy for a psychological condition and transport to a health care facility were predictors of elevated somatization scores. Conclusions Somatization was the most frequently elevated score after exposure to hazardous materials incidents. Further research is needed to determine whether specific risk factors are useful in identifying individuals for intervention after hazardous materials incidents.

Use of a questionnaire to improve occupational and environmental history taking in primary care physicians

New patient charts were reviewed before and after the introduction of a self-administered questionnaire, designed to elicit occupational and environmental (OE) information from patients. The Occupational Health Risk Assessment questionnaire (OHRA) was expected to prompt primary care physicians to make further inquiries into OE health issues. Chart reviews determined the amount and type of information detailed in the primary care physicians’ notes. Twenty-three percent of completed OHRAs indicated a job-related health problem. Despite a high prevalence of self-reported work-related symptoms and exposures, the mean number of notations regarding OE exposures was less than one item per patient chart. A comparison of mean OE notations per chart before versus after introduction of the OHRA indicated a decline in notations after introduction of the OHRA (1.03 vs 0.72, P = 0.02). We detail the type of OE issues that patients presented to a primary care practice and the resulting information contained in primary care providers’ notes. Suggestions are made to improve a self-administered patient questionnaire to better diagnose, prioritize, and formulate treatment plans related to OE issues.

Reproductive endocrine effects of acute exposure to toluene in men and women.

OBJECTIVES: Despite observation of adverse reproductive effects of toluene, including alterations of serum gonadotropins (luteinising hormone (LH) and follicle stimulating hormone (FSH)) in humans, little is known of the mechanism of toxicity. The hypothesis was tested that toluene acutely suppresses pulsatile gonadotropin secretion by measuring LH and FSH at frequent intervals during controlled exposure to toluene. METHODS: Women in the follicular and luteal phases of the menstrual cycle and men were randomised to inhale filtered air with or without 50 ppm toluene through a mouthpiece for 3 hours (19% of the OSHA permissible exposure limit). Blood was sampled by intravenous catheter at 20 minute intervals for 3 hours before, 3 hours during, and 3 hours after exposure. Plasma LH, FSH, and testosterone were measured. Pulse amplitude, pulse frequency, and mean concentrations of LH and FSH for each of the 3 hour periods before, during and after exposure to toluene versus sham exposure were calculated with the ULTRA pulse detection program and compared by analysis of variance (ANOVA) with repeated measures. RESULTS: In men mean concentrations of LH showed a significant interaction (p < 0.05) between exposure and sampling period, with a greater LH decline during exposure to toluene than sham exposure. However, there was no concomitant effect on testosterone concentrations. The LH pulse frequency of women in the luteal phase showed a trend towards a significant interaction between exposure and sampling period (p = 0.06), with a greater decline in pulse frequency during exposure to toluene than sham exposure. There were no other significant effects of exposure to toluene. CONCLUSIONS: Three hour exposure to 50 ppm toluene did not result in abnormal episodic LH or FSH secretion profiles, however, subtle effects on LH secretion in men and women in the luteal phase were found. The clinical relevance of these effects is unclear, indicating the need for further study of reproductive function in exposed workers.

Nonmalignant Asbestos-Related Disease: Diagnosis and Early Management

In September 2004 the American Thoracic Society released a revised set of guidelines for the clinical diagnosis of nonmalignant asbestos-related disease (Am J Resp Crit Care Med. 2004;170:691–715). The conditions of concern are asbestosis, pleural disorders, and chronic airways obstruction. The criteria are evidence of structural lesion consistent with asbestos-related disease, evidence of causation by asbestos, and exclusion of alternative diagnoses. Findings that satisfy each are described. These guidelines are an extension of the 1986 ATS criteria and expand on them by establishing three explicit criteria, accommodating newer diagnostic modalities, recommending evaluation of impairment appropriate to the diagnosis, and outlining initial management measures following diagnosis. A history of significant asbestos exposure obligates the responsible physician to provide a management plan for the patient that takes into consideration current disease, impairment, and future risk. Persons identified as having asbestos-related disease or having significant exposure histories may benefit from management directed at preserving lung function, preventing complications, reducing the risk of lung cancer, and screening for potentially treatable asbestos-related disease including malignancies. Various issues arising since the publication of the guidelines are addressed, including evidence for pleural plaques being a marker of risk for lung disease apart from history of asbestos exposure; evidence against smoking being associated with a greater frequency of pleural plaques; an association between asbestos exposure and colon cancer; the diagnostic sensitivity of the chest film in smokers; and affirming the adequacy of findings on plain chest films as sufficient for the diagnosis of nonmalignant asbestos-related disease but not always sufficient to rule it out.

Risk factors for adverse health effects following hazardous materials incidents

Toidentify risk factors for persistent morbidity, we conducted a prospectivestudy of individuals involved in hazardous materials incidents reported to theWashington Poison Center. Between December 1997 and October 1999, 202 subjectsin 87 incidents were surveyed by telephone. Medical symptoms persisting for aminimum of 8 days after the incident were reported in 51 (25%) subjects, and18 (9%) left work or school for more than 2 days because of the exposure.Medical intervention was reported in 46 (58%) of 79 subjects for whom medicalrecords were available, and objective abnormalities were found in 57 (72%).Multiple logistic regression analysis indicated that subjects with dermalexposures, three or more alcoholic drinks per week, and previous use ofpsychiatric medications were more likely to report persistent symptoms.Divorced, widowed, or separated subjects, asthmatic subjects, and those havinginitial dermal symptoms were more likely to miss work or school for more than2 days. Of patients evaluated at a health care facility, subjects withpreexisting hypertension were more likely to receive medical treatment or haveobjective medical findings, whereas those with inhalation exposures and thosedecontaminated at the scene were less likely to be treated or haveabnormalities. In our study, both incident and individual factors werepredictive of adverse health effects, and these findings should be consideredin planning the care of patients involved in hazardous materialsincidents.

Occupational Interstitial Lung Diseases.

Objective: Evidence-based diagnostic and treatment guidelines for occupationally related interstitial lung diseases (ILDs) have been developed and are summarized herein. Methods: Comprehensive literature reviews were conducted with article abstraction, critiquing, objective grading, and evidence table compilation. A multidisciplinary expert panel drafted evidence- and consensus-based guidance. External peer-review was incorporated. Results: Recommendations for diagnosis (n = 12) and management (n = 4) of ILD were developed. Spirometric testing, chest radiographs, and high-resolution computerized tomographic scans were recommended based upon evidence. In addition to a detailed clinical history, carbon monoxide diffusion capacity, sputum sampling, exposure assessment, 6-minute walk test, and bronchoalveolar lavage were also recommended. There was no recommendation regarding chest magnetic resonance imaging due to lack of evidence. Conclusions: Recommendations for diagnosis and management of ILD are supported by quality evidence. These guidelines may be useful to help guide providers who are tasked with diagnosing and/or treating patients with occupationally related ILD.