Increased bronchial density of CD25+Foxp3+ regulatory T cells in occupational asthma: relationship to current smoking.

To identify activated T cell subset in the asthmatic bronchia, we developed a triple-colour immunohistofluorescence labelling technique on cryo-section to discriminate activated CD4+CD25+ T cells, (effector T cells) from Foxp3+ regulatory T cells (Treg). Additional coexpression of activation and proliferation markers was also examined in situ. Bronchial biopsies were taken from 20 aluminium potroom workers (12 smokers) with asthma (>12% reversibility), 15 non-asthmatic potroom workers (7 smokers) and 10 non-smoking, non-exposed controls. Non-smoking asthmatics had significantly higher subepithelial density of both Tregs, effector T cells, activated (HLA-DR+) CD8+ and activated CD4+ T cells. Moreover, both Tregs, effector T cells and CD8+ T cells proliferated in the non-smoking asthmatics, only. Although smoking asthmatics had no asthma-associated increase in bronchial T cell, both had a significantly increase in effector T cell to Treg ratios. The significantly increased bronchial density of Tregs, effector T cells, proliferative T cells and activated CD8+ T cells in non-smoking asthmatics clearly showed that both the effector T cells and the inhibitory Treg system were activated in asthma.

Hygroscopic properties of the workroom aerosol in aluminium smelter potrooms: a case for transport of HF and SO2 into the lower airways.

The hygroscopic behaviour of individual aerosol particles from workplaces in a primary aluminium smelter was investigated by environmental scanning electron microscopy. At a high relative humidity, comparable with the human respiratory tract, most particles encountered in the Søderberg and Prebake potrooms either undergo partial deliquescence (leading to a water droplet with an insoluble core) or form thin water films at the surface. As gaseous HF and SO(2) are highly soluble in water, the aerosol particles may act as carrier for these two gases into the alveolar region of the lower respiratory tract. Based on a one-dimensional mass balance model, it is estimated that under peak exposure conditions (particle surface area concentration of 10(-4) cm(2) cm(-3)) approximately 10% of the initial gaseous HF may be transferred to the particle phase. For SO(2), this fraction is much lower (approximately 1%). These results indicate that at least HF may penetrate deeper into the lung in the presence of soluble particles or particles that form surface water films compared to HF alone.

Beryllium sensitivity among workers at a Norwegian aluminum smelter.

BACKGROUND: Sensitivity to beryllium was investigated among workers at an aluminum smelter in Norway as a consequence of the findings in an occupational exposure survey. METHODS: Three hundred and sixty-two employees and 31 reference persons were tested for sensitization to beryllium with the beryllium lymphocyte proliferation test (BeLPT) based on specifications by the US Department of Energy in 2001. The results are reported as abnormal, borderline, or normal. RESULTS: One person (0.28%) from the aluminum smelter was found to have abnormal results in two separate blood samples and is sensitized to beryllium. Three other persons had one abnormal test that was not confirmed by a second test. One person in the reference group had one abnormal and one normal test result. No borderline samples were detected. None of the employees with one or more abnormal sample results had pot room asthma. The sensitized individual worked in a Soederberg line in 1972-1974. The beryllium concentration in the work atmosphere is estimated to have been similar as today (0.1-0.3 microg/m(3)), but work routines, etc. would cause higher total exposures. CONCLUSIONS: Only one sensitized person of 362 is in line with what is found in other studies in the aluminum industry. The low number, compared with the beryllium handling industry, may be attributable to lower work atmosphere concentrations, beryllium speciation effects, or use of respiratory protection equipment. Pot room asthma does not appear to be associated with beryllium sensitization.

Reduced bronchial CD4+ T-cell density in smokers with occupational asthma.

Cigarette smoking may alter bronchial inflammation in asthma. Multicolour immunohistofluorescent examination on bronchial cryosections was used to examine bronchial inflammatory cell infiltrate in patients with occupational asthma. Monoclonal antibodies to CD3, CD4, CD8, T-cell receptor-delta1, CD68 and human leukocyte antigen-DR were combined to identify T-cell subsets and macrophages in bronchial biopsies from 20 workers with occupational asthma (12 smokers and eight nonsmokers), 15 healthy workers (seven smokers and eight nonsmokers) and 10 nonsmoking, nonexposed controls. The increased subepithelial CD4+ T-cell density in nonsmoking asthmatics was not present in smoking asthmatics, who had the lowest CD4+ T-cell density of all groups. The decreased subepithelial CD4+ and CD8+ T-cell density correlated with a reduction in lung function, as measured by percentage predicted forced expiratory volume in one second, in smoking asthmatics only. Although smoking asthmatics had a significantly increased number of intraepithelial CD8+ T-cells and macrophages compared with nonsmoking asthmatics, the proportion of gammadelta-T-cells was significantly decreased in both asthmatic groups. Smoking asthmatics had a distinctly different distribution of T-cell subsets compared with nonsmoking asthmatics. The accumulation of subepithelial CD4+ T-cells, which was observed in nonsmoking asthmatics, appeared to be inhibited in smoking asthmatics, suggesting a smoking-induced bronchial immune modulation, at least in occupational asthma in the aluminium industry.

Airway inflammation in aluminium potroom asthma.

AIMS: To examine whether asthma induced by exposure to aluminium potroom emissions (potroom asthma) is associated with inflammatory changes in the airways. METHODS: Bronchial biopsy specimens from 20 asthmatic workers (8 non-smokers and 12 smokers), 15 healthy workers (8 non-smokers and 7 smokers), and 10 non-exposed controls (all non-smokers) were analysed. Immunohistofluorescent staining was performed to identify mucosal total leucocytes (CD45+ leucocytes), neutrophils, and mast cells. RESULTS: Median RBM thickness was significantly increased in both asthmatic workers (8.2 microm) and healthy workers (7.4 microm) compared to non-exposed controls (6.7 microm). Non-smoking asthmatic workers had significantly increased median density of lamina propria CD45+ leucocytes (1519 cells/mm2 v 660 and 887 cells/mm2) and eosinophils (27 cells/mm2 v 10 and 3 cells/mm2) and significantly increased concentrations of exhaled NO (18.1 ppb v 6.5 and 5.1 ppb) compared to non-smoking healthy workers and non-exposed controls. Leucocyte counts and exhaled NO concentrations varied with smoking habits and fewer leucocytes were observed in asthmatic smokers than in non-smokers Asthmatic smokers had significantly increased numbers of eosinophils in lamina propria compared to non-exposed controls (10 v 3 cells/mm2). Both eosinophilic and non-eosinophilic phenotypes of asthma were recognised in the potroom workers and signs of airway inflammation were also observed in healthy workers. CONCLUSIONS: Airway inflammation is a central feature of potroom asthma and exposure to potroom emissions induces pathological alterations similar to those described in other types of asthma. Cigarette smoking seems to affect the underlying mechanisms involved in asthma, as the cellular composition of airway mucosa appears different in asthmatic smokers and non-smokers.

Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6) in healthy individuals. Oral doses of vitamin B6 reduce concentrations of serum folate.

Plasma total homocysteine response was compared in four groups of healthy individuals given orally divided doses of vitamin supplementations for a duration of 5 weeks. The vitamin supplements; A, 0.3 mg folic acid; B, 120 mg vitamin B6; C, combination of 0.3 mg folic acid and 120 mg vitamin B6 or D, 0.6 mg folic acid reduced the concentrations of plasma total homocysteine 20, 17, 32 and 24%, respectively. However, the intergroup comparisons did not show a significant difference in the effects of vitamin supplements. Multivariate analysis with correction for differences in pre-supplement values indicated a significant effect of vitamin B6 supplementation on plasma total homocysteine and serum folate. Our data show that plasma total homocysteine concentrations are reduced with low to medium divided doses of folic acid alone or in combination with vitamin B6.

Absence of relation between sick leave caused by musculoskeletal disorders and exposure to magnetic fields in an aluminum plant.

This is a study of the relationship between occupational exposure to magnetic fields in pot rooms and occurrence of sick leave caused by musculoskeletal disorders. The average exposure to static magnetic fields was 8 mT in the pot rooms. Ripple fields were recorded as well. A cohort of 342 exposed workers and 222 unexposed workers from the same electrolysis plant was retrospectively followed for 5 years. The reference group had a type of work similar to the exposed group except for the exposure to magnetic fields. The occurrence of sick leave and the diagnoses causing the sick leave were obtained from the Occupational Health Care Unit: these data were stored in their computer files. The data were complete. No relationship between the occurrence of sick leave caused by musculoskeletal disorders and exposure to magnetic fields was found. This was the case for both the annual number of periods of sick leave and the total number of days with sick leave. The results must be interpreted with caution due to limitations in the design and available data. Also, static magnetic fields constituted the major exposure, and the results may be different when related to work in other types of magnetic-field exposure.

Symptoms of the musculoskeletal system and exposure to magnetic fields in an aluminium plant.

OBJECTIVE: The study was performed to examine the influence of the exposure to magnetic fields in the potrooms of an electrolysis plant on the occurrence of musculoskeletal symptoms among the employees. The study was performed after much discussion and worry in the aluminium industry about this issue. METHODS: A retrospective cohort study was performed at an aluminium plant. The occurrence of musculoskeletal symptoms registered at health controls performed by the occupational health care unit in 1986 and 1991 was assessed from employees exposed to magnetic fields in the potrooms (n = 342) and from a control group (n = 277). The data were collected before the discussion about the effects of magnetic fields started. The exposure to static magnetic fields was found to be 3-20 mT inside the potrooms. Ripple components (alternating currents (AC fields)) were registered as well. RESULTS: No difference between the exposed and unexposed groups was found for the reported musculoskeletal symptoms in 1986 or in 1991. CONCLUSIONS: There seems to be no relation between work in potrooms with exposure to static magnetic fields and the occurrence of musculoskeletal symptoms.

Studies of biomarkers in aluminum workers occupationally exposed to polycyclic aromatic hydrocarbons.

Evaluation of biomarkers for genotoxic exposure are important for future use of such biomarkers in cancer prevention. We have studied a group of aluminum plant workers for a period of 2.5 years. The level of polycyclic aromatic hydrocarbons (PAHs) has been monitored at the work place (cathode relining). During the study period, urine and blood were sampled up to seven times from the same workers. Mean level of urinary 1-hydroxypyrene varied from 1.08 to 2.44 mumol/mol creatinine in the exposed groups compared with 0.36 and 0.20 mumol/mol creatinine in the two reference groups. For a group of 14 workers the intraindividual variation of urinary 1-hydroxypyrene was analyzed. The relative standard deviation of the values was < or = 0.50 for half of the workers; the relative standard deviation was calculated for individual values divided by mean of each time point. Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from exposed and nonexposed workers were measured by both immunoassay and 32P-postlabeling. By 32P-postlabeling mean values of 12.0 adducts/10(8) and 10.8 adducts/10(8) nucleotides were found in a PAH-exposed group and a reference group, respectively. Intraindividual variation of PAH-DNA adducts was also analyzed.

Neuropsychological deficit among elderly workers in aluminum production.

A cross-sectional study was conducted at a Norwegian primary aluminum plant. All workers aged 61-66 years were offered early retirement benefits. Among the workers, 47 met the study criteria and 38 (81%), comprising 14 potroom workers, 8 foundry workers, and 16 controls, volunteered to participate. They were tested with a neuropsychological test battery. Workers in potrooms with Søderberg electrolytic cells were found to show signs of impairment of the nervous system. A test for tremor discriminated significantly between the potroom group and the controls. There was a suggestion of increased risk of impaired visuospatial organization and a tendency to a decline in psychomotor tempo in the potroom workers. We suggest that the above findings may be related to long-term occupational exposure in the potroom, and further to chronic low-dose exposure to aluminum.

Biomonitoring of genotoxic exposure of aluminium plant workers.

Humans are environmentally and occupationally exposed to polycyclic aromatic hydrocarbons (PAH). PAH's are a class of tumorigenic compounds which act through metabolic transformation to chemically reactive forms, epoxides, which covalently bind to DNA forming DNA adducts. To evaluate the genotoxic effects of PAH's, air and urine samples were analyzed for PAH. Blood samples were analyzed for benzo(a)pyrene-diol-epoxide-DNA (BPDE-DNA) adducts. New methods for analyzing DNA adducts in lymphocytes have been used to study the genotoxic effects of human exposure to carcinogens. BPDE-DNA adducts in lymphocytes have been used as internal dosimeters of exposure to PAH's and several studies have been conducted. We measured BPDE-DNA adducts in aluminium plant workers with immuno-assay and physico-chemical methods. PAH-DNA adducts were detectable to a lesser extent in subjects working in an aluminium plant compared to subjects working in a coke oven plant.

Cholestatic jaundice in infancy. The importance of familial and genetic factors in aetiology and prognosis.

One hundred and twenty-four infants admitted to hospitals in Norway between 1955 and 1974 during the first 3 months of life with cholestatic jaundice were studied retrospectively. Sixty-four infants had had extrahepatic atresia of the biliary tree and 60 had had intrahepatic cholestasis. This gives an incidence of about 1:9000 live births for cholestasis. In 4 of the 64 infants with extra-hepatic atresia a bile duct-to-bowel anastomosis had been performed but this was successful in only 2. Sixty of these infants had died by their 2nd birthday. Twenty-six of the infants with intrahepatic cholestasis had died by 1978 and the most common causes of death were cholestasis complicated by infection, bleeding, or hepatoma. The survivors aged between 4 and 23 years were followed up in 1978. In about two-thirds of them aetiological factors--such as alpha-1-antitrypsin deficiency, arteriohepatic dysplasia, cholestasis with lymphoedema--and other familial or genetic factors, or infections were found. Four of the 34 survivors are known to have cirrhosis. Twenty patients had biochemical abnormalities, and 12 had normal liver function tests. Two patients could not be examined. Of the 19 patients with familial or genetic aetiological factors, 4 had cirrhosis, 14 had biochemical abnormalities, and only 5 had normal liver function tests. Of 11 survivors with idiopathic disease or septicaemia, none had cirrhosis and only 4 had abnormal liver function tests.

Pulmonary complications, ventilation and blood gases after upper abdominal surgery.

Forty patients who underwent elective cholecystectomy were examined preoperatively and during the first postoperative week by physical examination, measurement of FVC and FEV1, arterial pH and blood gas analyses, and chest x-ray. Postoperative pulmonary complications (p.p.c.) were detected in 30 (75%) of the patients. Simple auscultation was the most sensitive tool in discovering p.p.c., but 18 of the 30 patients with complications also had a pathological chest x-ray. Obesity, smoking postoperative naso-gastric tube and postoperative wound infection were predisposing factors for p.p.c. Six patients with preoperative pulmonary disease all had a progress in their lung pathology. There was no definite relationship of duration of anaesthesia or drainage of the abdominal wound to development of p.p.c. The patients with p.p.c. showed a deeper and more prolonged fall in Pao2 postoperatively than the normal group. None of the normals showed an arterial Po2 below 70 mmHg in the postoperative course, while 63% of the p.p.c. group did. FVC and FEV1 showed marked reductions from preoperative values on the first postoperative day, and then gradually increased to near preoperative values after 1 week. Arterial pH and Pco2 showed no definite changes during the postoperative course.