David Sherson

Biological monitoring of foundry workers exposed to polycyclic aromatic hydrocarbons.

This investigation describes benzo(a)pyrene (BP) serum protein adduct concentrations in 45 foundry workers and 45 matched non-occupationally exposed controls. High and low BP exposure groups were defined using breathing zone hygienic samples for both quartz and BP exposures. A newly developed enzyme linked immunosorbent assay detected benzo(a)pyrenediolepoxide-I binding to serum protein. Mean BP protein adduct concentrations (SD) for non-smoking (24.0 BP equivalents/100 micrograms protein (21.0] and smoking (28.0 (18.2] foundry workers were significantly higher than mean values for non-smoking (7.23 (8.72] and smoking (14.2 (24.4] controls. Foundry workers with high exposures to either quartz (28.4 (15.5] or BP (30.7 (19.3] had slightly raised mean adduct concentrations compared with foundry workers with low exposure for quartz (23.9 (23.1] or BP (24.5 (19.4). Highest mean adduct concentrations were found among a small group of workers with simultaneous high exposures to both quartz and BP (39.2 (6.5] suggesting an additive effect. These data support the ideas of a possible aetiological connection between an increased risk of lung cancer and BP exposure among foundry workers, and an additive effect between BP and quartz. Measurement of BP serum protein adduct concentrations appears to be a useful method by which groups exposed to BP may be biologically monitored.

Exposure of iron foundry workers to polycyclic aromatic hydrocarbons: benzo(a)pyrene-albumin adducts and 1-hydroxypyrene as biomarkers for exposure

Exposure to polycyclic aromatic hydrocarbons (PAHs) in foundry workers has been evaluated by determination of benzo(a)pyrene-serum albumin adducts and urinary 1-hydroxypyrene. Benzo(a)pyrene binding to albumin and 1-hydroxypyrene were quantitatively measured by enzyme linked immunosorbent assay (ELISA) and reverse phase high performance liquid chromatography (HPLC), respectively. 70 male foundry workers and 68 matched controls were investigated. High and low exposure groups were defined from breathing zone hygienic samples, consisting of 16 PAH compounds in particulate and gaseous phase. Mean total PAH was 10.40 micrograms/m3 in the breathing zone, and mean dust adsorbed PAH was 0.15 microgram/m. All carcinogenic PAH was adsorbed to dust. Median benzo(a)pyrene-albumin adduct concentrations (10-90% percentiles) were similar in foundry workers (smokers 0.55 (0.27-1.00) and non-smokers 0.58 (0.17-1.15)) pmol/mg albumin and age matched controls (smokers 0.57 (0.16-1.45) and non-smokers 0.70 (0.19-1.55) pmol/mg albumin). Median 1-hydroxypyrene concentrations were significantly higher (P < 0.0001) in smoking and non-smoking foundry workers (0.022 (0.006-0.075) and 0.027 (0.006-0.164)) mumol/mol creatinine than in smoking and non-smoking controls (0 (0-0.022) and 0 (0-0.010) mumol/mol creatinine). Dose-response relations between total PAH, pyrene, carcinogenic PAHs, and 1-hydroxypyrene for smokers, and polycyclic aromatic hydrocarbons adsorbed to dust for non-smokers are suggested. Exposure to PAHs adsorbed to dust showed an additive effect. There was no correlation between the concentrations of 1-hydroxypyrene and benzo(a)pyrene-albumin adducts. The change in 1-hydroxypyrene over a weekend was also studied. Friday morning median 1-hydroxypyrene concentrations were significantly higher in both smokers and non-smokers (0.021 (0-0.075) and 0.027 (0.06-0.164)) mumol/mol creatinine than Monday morning median concentrations (0.007 (0-0.021) and 0.008 (0-0.021) mumol/mol creatinine). Smoking did not affect the concentrations of 1-hydroxypyrene or benzo(a)pyrene-albumin adducts. These data suggest that 1-hydroxypyrene is a sensitive biomarker for low dose PAH exposure. Exposure to PAHs may be aetiologically related to increased risk of lung cancer in foundry workers.

Occupational Asbestos Exposure and Lung Cancer—A Systematic Review of the Literature

ABSTRACT The objective of this study was to evaluate the scientific literature concerning asbestos and lung cancer, emphasizing low-level exposure. A literature search in PubMed and Embase resulted in 5,864 citations. Information from included studies was extracted using SIGN. Twenty-one statements were evidence graded. The results show that histology and location are not helpful in differentiating asbestos-related lung cancer. Pleural plaques, asbestos bodies, or asbestos fibers are useful as markers of asbestos exposure. The interaction between asbestos and smoking regarding lung cancer risk is between additive and multiplicative. The findings indicate that the association between asbestos exposure and lung cancer risk is basically linear, but may level off at very high exposures. The relative risk for lung cancer increases between 1% and 4% per fiber-year (f-y)/mL, corresponding to a doubling of risk at 25–100 f-y/mL. However, one high-quality case-control study showed a doubling at 4 f-y/mL.

Consequences of asthma on job absenteeism and job retention

Aims: Various social and economic effects are associated with asthma. This quantitative study describes the effects of current asthma on work life evaluated from the number of weeks receiving transfer incomes. Methods: The study population comprised 7,241 persons answering the ECRHS II screening questionnaire, which was sent to a random age and gender stratified sample of 10,000 persons aged 20 to 44 years. Participants with current asthma were identified by positive answers to a set of validated questions. Transfer incomes for a five-year period were registered from a study-independent national database, which collects all public administered transfer incomes in Denmark. The numbers of weeks receiving unemployment, welfare, sick-leave and disability benefits were identified for each participant and differences between asthmatics and non-asthmatics were analyzed. Results: Asthmatics had significantly more annual weeks receiving welfare (36.6 vs. 20.7, p=0.00), sick leave (9.2 vs. 6.6, p=0.00) and disability (19.3 vs. 11.4, p=0.00) benefits than non-asthmatics. Adult-onset asthmatics had increased prevalence rate ratios for disability of 2.40 (95% confidence interval 1.70–3.40). Blue collar work significantly increased the probability of all public transfer incomes. Conclusions: Current asthma makes it harder to keep a job. Adult-onset asthmatics and blue collar workers are particularly affected.

Sex determines the influence of smoking and gene polymorphism on glutathione peroxidase activity in erythrocytes

Objective. Glutathione peroxidase 1 (GPX1) is one of the major oxidative enzymes. Our aim was to characterize factors influencing its activity and to determine whether or not the activity is associated with asthma. Material and methods. Serum selenium concentration was measured, GPX1 polymorphisms were genotyped and smoking history was obtained in a Danish population‐derived case‐base cohort of 1,191 subjects designed to evaluate risk factors for asthma. GPX1 activity was measured in 134 male and 164 female subjects equally distributed according to genotype of GPX1. Among these subjects, 82 (28 %) had doctor‐diagnosed asthma. Results. The average serum selenium concentration was too low for optimal enzyme activity (mean (SE), 83.4 (0.76) ng/mL). GPX1 activity in men was lower than in women, 52.6 (0.66) and 56.4 (0.59) U/g protein, respectively (p<0.001). In men, activity was positively associated with serum selenium concentration (p = 0.005) and negatively associated with both active smoking (p = 0.009) and exposure to environmental tobacco smoke (p = 0.02). In women, activity was associated with genotypes with 59.2 (1.4), 56.0 (1.4) and 54.2 (1.4) U/g protein in the homozygote wild‐type, the heterozygote and the homozygote variant type, respectively (p = 0.001). Doctor‐diagnosed asthma was unrelated to GPX1 activity in either sex. Conclusion. Determinants for activity in the oxidative enzyme GPX1 show marked differences between the sexes, but the activity is not associated with asthma. Sex ought to be taken into consideration when analysing the activity of the enzyme.

Differences in associations between markers of antioxidative defense and asthma are sex specific

BACKGROUND Lungs are exposed to high levels of oxygen, air pollutants, and smoke, all of which stimulate the production of reactive oxygen species (ROS). In addition, inflammatory cells produce ROS, and thus there may be increased demand for antioxidants, including antioxidant enzymes, in inflammatory lung diseases such as asthma. Sex-specific differences have been noted for asthma, which in postpubertal subjects is predominantly found in females. These sex-specific differences may be associated with differences on the molecular level as well. OBJECTIVE The aim of this cross-sectional study was to examine associations between markers of antioxidative defense and asthma, and to investigate whether these associations were different between women and men. METHODS Based on the European Community Respiratory Health Survey protocol, subjects were enrolled in a study of asthma risk factors. The multicenter study was conducted in 5 west Danish counties between 2003 and 2006, and the subjects were recruited as a case-enriched random sample of 10,000 Danish inhabitants aged 20 to 44 years selected by their civil registration number. Participants were identified by positive answers to asthma questions on a screening questionnaire, random sampling, or both. Serum selenium concentrations and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase [GPX], glutathione reductase [GR], and glucose-6-phosphate dehydrogenase [G6PD]) in erythrocytes were measured. Asthma was defined as either current asthma symptoms with bronchial hyperresponsiveness (BHR) or a continuous asthma score based on 8 questions. RESULTS A total of 1191 mostly white women and men (mean [SD] age, 34.0 [7.1] and 35.1 [7.1] years, respectively) were enrolled in the study. Current asthma symptoms were present in 29.9% (200/670) of women and 22.5% (117/521) of men, with women reporting more positive answers (51.1% vs 40.9%, respectively; P < 0.01) to asthma questions. Serum selenium concentrations were measured in 1151 subjects (640 women, 511 men), and antioxidant enzyme activities were measured in 295 subjects (161 women, 134 men). Women had higher enzyme activities of most antioxidant enzymes (GPX, P = 0.006; GR, P < 0.001; and G6PD, P = 0.009) than did men. Although the serum selenium concentration was inversely associated with asthma in both sexes, there was a female preponderance, with 3.5% lower serum selenium in subjects with current asthma symptoms with BHR (n = 77) compared with controls (n = 287). GR activity was associated with asthma in men, with 5.7% higher enzyme activity in subjects with current asthma symptoms with BHR (n = 14) compared with controls (n = 77). However, a significant interaction with gender was observed for analyses of GR (P = 0.02), but not for analyses of selenium. CONCLUSIONS In this study of asthma risk factors, women had higher levels of enzyme activities than did men in a randomly selected Danish population, and sex-specific differences were found in the associations between markers of antioxidative defense and asthma.

Factors influencing quality of life in asthmatics – a case–control study

The quality of life (QOL) in persons with asthma is reduced and different factors such as demography, asthma severity and psychiatric comorbidity play an influential role. However, little is known about the interplay of these factors.

Asthma from the patient’s perspective

Abstract Background: Asthma is a chronic disease with considerable burden on health and economy. Despite growing knowledge about causes and treatment, many patients have uncontrolled asthma, activity and social limitations and reduced quality of life (QOL). Coping with asthma could be developed in a social and scientific context and influenced by personal experience. Objective: To investigate the asthmatic’s perspective on asthma and how coping mechanisms with this disease were influenced by health professionals and networks. Methods: Asthma and QOL questionnaires were sent to 1191 individuals, who had participated in a population-based clinical study in 2004. Of the 7271 responders (72.7%), 10 chronic asthmatics (4 males and 6 females) with different asthma severity grades were recruited to in-depth interviews. The results were interpreted according to selected theories, especially Antonovsky’s salutogenic theory on how comprehensibility, manageability and meaningfulness contribute to sense of coherence and successful coping with stressor/disease. Results and conclusion: Asthma comprehensibility was limited by both the lack of structured information about asthma diagnosis, treatment and prognosis and insufficient follow-up. The informants experimented with what worked and developed individual ways to accomplish satisfactory management. They adjusted their own medication and sometimes stopped prophylactic medicine as they did not detect an immediate effect. Many informants put their asthma into perspective, comparing it to what could have been worse. The unnoticeable development of asthma had probably triggered a gradual adaptation making it more complex for asthmatics to estimate severity. This together with their relative view of asthma might have led to gradual and uncritical accept of bothersome symptoms and reduced the need to seek professional advice or make important changes, e.g. eliminating exposure to irritating agents at work. Avoidance was a recurrent phenomenon as the asthmatics tended to drop physical activities with others instead of improving treatment. Several stated that they did not like to flash their asthma. They had concerns about being labelled as ‘inadequate’. Physicians are urged to consider these tendencies and underlying the some of the mechanisms of ‘living with asthma’ in order to achieve proper asthma treatment and insure their patients’ wellbeing.

Genetic polymorphisms in antioxidative enzymes are associated to forced expiratory volume in 1 s (FEV1) in smokers independently of asthma.

Introduction:  In this study, we hypothesised that the genotypes coding for low antioxidative enzyme activity are associated with asthma and reduced lung function.

Are allergen batch differences and the use of double skin prick test important

BackgroundSkin prick tests (SPT) are widely used both in clinical diagnostics and in research. The standardization of allergen extracts is well documented to be crucial for the validity of SPT, whereas less emphasis has been placed on reproducibility and the SPT procedure itself. The objectives of this study are to clarify how the double skin prick test procedure influence the sensitivity and specificity of the test and to analyse the differences in weal size in skin prick tests between two batches of allergen extracts from the same vendor.MethodsThe association between rhinitis and SPT was assessed among 1135 persons from a general population sample. SPT was performed twice with 10 common aeroallergens. In a subsample of 90 persons SPT was performed simultaneously with five of the allergens using different batches.ResultsThirty percent had at least one positive SPT. Among asthmatics this number was 62%. Only minor differences were seen between the sizes of two weals from the same batch. A second SPT with the same batch did not change the association between rhinitis and sensitization. When performing SPT with two different batches disagreement was observed in 2% (Birch) to 11% (Cat) of the subjects.ConclusionsPerforming SPT twice with the same allergen batch does not enhance the validity of the test, and value of double testing can be questioned. Considerable differences in SPT response with different batches from the same manufacturer were observed. Thus inter batch differences in allergen extracts might be a source of variability.