Asbestos, Smoking and Lung Cancer: An Update.

This review updates the scientific literature concerning asbestos and lung cancer, emphasizing cumulative exposure and synergism between asbestos exposure and tobacco smoke, and proposes an evidence-based and equitable approach to compensation for asbestos-related lung cancer cases. This update is based on several earlier reviews written by the second and third authors on asbestos and lung cancer since 1995. We reevaluated the peer-reviewed epidemiologic studies. In addition, selected in vivo and in vitro animal studies and molecular and cellular studies in humans were included. We conclude that the mechanism of lung cancer causation induced by the interdependent coaction of asbestos fibers and tobacco smoke at a biological level is a multistage stochastic process with both agents acting conjointly at all times. The new knowledge gained through this review provides the evidence for synergism between asbestos exposure and tobacco smoke in lung cancer causation at a biological level. The evaluated statistical data conform best to a multiplicative model for the interaction effects of asbestos and smoking on the lung cancer risk, with no requirement for asbestosis. Any asbestos exposure, even in a heavy smoker, contributes to causation. Based on this information, we propose criteria for the attribution of lung cancer to asbestos in smokers and non-smokers.

Diagnosis of epithelial mesothelioma using tree-based regression analysis and a minimal panel of antibodies.

AIMS: Immunohistochemistry with panels of antibodies is a standard procedure to distinguish between malignant mesothelioma and metastatic adenocarcinoma. Most studies assess only the sensitivity and specificity for single antibodies, even when the paper concludes by recommending an antibody panel. It was the aim of this study to use a novel statistical approach to identify a minimal panel of antibodies, which would make this distinction in the majority of cases. METHODS: Two hundred consecutive cases of pleural malignancy (173 pleural mesotheliomas of epithelial type and 27 cases of secondary adenocarcinoma) were investigated using a standard panel of 12 antibodies (CAM5.2, CK5/6, calretinin, HBME-1, thrombomodulin, WT-1, EMA, CEA, CD15, B72.3, BG8, and TTF-1). Regression and classification tree-based methods were applied to select the best combination of markers. The modelling procedures used employ successive, hierarchical predictions computed for individual cases to sort them into homogeneous classes. RESULTS: Labelling for calretinin and lack of labelling for BG8 were sufficient for definite correlation with a diagnosis of malignant mesothelioma. CD15 provided further differentiating information in some cases. CONCLUSION: A panel of three antibodies was sufficient in most cases to diagnose, or to exclude, epithelial mesothelioma. Calretinin exhibits the strongest correlative power of the antibodies tested.

Worklife expectancies of fixed-term Finnish employees in 1997-2006.

OBJECTIVES: Fixed-term employment is prevalent in the Finnish labor force. This form of employment contract is marked by fragmentary work periods, demands for flexibility in workhours, and concern for multiple insecurities. A nonpermanent employee may also incur adverse health consequences. Yet there exist no exact statistics on the duration of fixed-term employment. This paper estimated the future duration of the time that a Finn is expected to be engaged in irregular work. METHODS: Multistate regression modeling and stochastic analysis were applied to aggregated data from surveys conducted among the labor force by Statistics Finland in 1997-2006. RESULTS: In 2006, a Finnish male was expected to work a total of 3.8 years in fixed-term employment, combined over consecutive or separate time spans; this time amounts to 8% of his remaining work career from entry into the work force until final retirement. For a woman the expectancy was greater, 6.5 years or 13%. For the age interval 20-29 years, the total was 16% for men and 23% for women. CONCLUSIONS: The type and duration of employment is influenced by security factors and economic cycles, both of which affect men and women differently. Over the past decade, fixed-term employment increased consistently in the female labor contingent, and it was more pronounced during economic slowdowns. This labor market development calls for standards for flexibility and guarantees for security in the fragmented future worklives of fixed-term employees.

15-lipoxygenase-1 prevents vascular endothelial growth factor A- and placental growth factor-induced angiogenic effects in rabbit skeletal muscles via reduction in growth factor mRNA levels, NO bioactivity, and downregulation of VEGF receptor 2 expression.

Human 15-lipoxygenase-1 (15-LO-1) is an oxidizing enzyme capable of producing reactive lipid hydroperoxides. 15-LO-1 and its products have been suggested to be involved in many pathological conditions, such as inflammation, atherogenesis, and carcinogenesis. We used adenovirus-mediated gene transfers to study the effects of 15-LO-1 on vascular endothelial growth factor (VEGF)-A165- and placental growth factor (PlGF)-induced angiogenesis in rabbit skeletal muscles. 15-LO-1 significantly decreased all angiogenic effects induced by these growth factors, including capillary perfusion, vascular permeability, vasodilatation, and an increase in capillary number. The effects are attributable to the reduction in the amount of VEGF-A165 and PlGF transcripts by 15-LO-1, resulting in reduced protein expression. The most likely mediator of the VEGF family-induced capillary vasodilatation is nitric oxide (NO), which is produced by NO synthases. Endothelial NO synthase protein expression and NO synthase activity were significantly induced by VEGF-A165, and these inductions were reduced by 15-LO-1. VEGF-A165 induces its angiogenic effects primarily via vascular endothelial growth factor receptor (VEGFR)2, and also PlGF mediates angiogenic signaling via VEGFR2, even though it binds to VEGFR1. VEGFR2 expression is induced by peroxisome proliferator-activating receptor . We showed by quantitative RT-PCR and immunohistochemistry that expression of endogenous rabbit peroxisome proliferator-activating receptor and VEGFR2 were significantly increased in the growth factor-transduced muscles, but these inductions were efficiently prevented by 15-LO-1. In conclusion, the results suggest that expression of 15-LO-1 has an efficient antiangiogenic effect in vivo via reduction in growth factor mRNA levels, NO bioactivity, and VEGFR2 expression.

Multistate worklife expectancies.

This communication reviews the demographic concept of worklife expectancy and draws the epidemiologists' attention to its usefulness in occupational health research and pension policy making. The distinctions between different analytic approaches to the quantification of expected workforce status and mobility are pointed out. A recently developed multivariate large-sample regression method for the analysis of worklife tables is placed into the general context of life tables. Given aggregated data from multiple cross-sectional or longitudinal population surveys, a multistate regression model can be used to estimate consistently marginal probabilities that a person is in a given work-health state or transition probabilities between the states and, thereby, worklife expectancies. The methodology is illustrated through the application to data from Finnish population statistics on employment, disability, retirement, and mortality. The paper closes with a discussion of the methodological issues and empirical findings on pension policy in Finland.

Smoking prevalence, smoking-related lung diseases, and national tobacco control legislation.

OBJECTIVES: To review statistics on smoking prevalence and to analyze whether the implementation of national tobacco control legislation had an association with the prevalence of smoking, and thereby, with the occurrence of smoking-related lung diseases. DESIGN: Smoking prevalence rates (from 1960 to 2000), lung cancer incidence rates (from 1980 to 2000), and respiratory disease mortality rates (from 1980 to 1998) were obtained from Finnish national surveys and registers. Regression models with 20-year lag times for disease occurrence were applied in the statistical analysis. RESULTS: Daily smoking prevalence among men decreased continuously from 58 to 28% in the period from 1960 to 2000. Between 1965 and 1971, male lung cancer incidence was still on the increase, but from 1971 it decreased from 80 to 32 per 100,000 men. The male respiratory disease mortality rate declined steeply during the study period. From 1960 to 1973, women's smoking prevalence increased from 12 to 20%. At the introduction of the tobacco control bill in 1975, the increase leveled off and female smoking prevalence slightly decreased, but then rose again after 1985 to remain at 20%. Lung cancer incidence among women increased throughout the study period, but the gradient of the curve lowered in the 1980s. CONCLUSIONS: National legislative actions were found to be associated with a change in smoking prevalence among women from a linear rise to a plateau. The results of the present study showed a very strong association between reduced smoking prevalence and the occurrence of lung cancer.

Working population health metrics.

This review is concerned with population health metrics that simultaneously consider information on mortality and nonfatal health outcomes as probabilistic measures representing the level of health in a working population. The optimal properties that such a measurement system should have are briefly discussed, and the merits and limitations of health expectancies are compared versus health gap measures. The conceptual basis of these measures are considered, especially with a view to health promotion. The application of worklife expectancies is illustrated with the data obtained from sequential surveys on the work ability status of aging Finnish municipal workers. In conclusion, the developed worklife expectancies are considered to be appropriate indicators for measuring the future duration of occupancy in a given state of work ability, and they should be preferred to alternative measures of population health in the context of occupational health.

The occurrence of anular tears and their relation to lifetime back pain history: a cadaveric study using barium sulfate discography.

STUDY DESIGN: The occurrence of anular tears and general disc degeneration of the lumbar spine was studied in relation to the lifetime frequency of back pain. SUMMARY OF BACKGROUND DATA: Although anular tears and ruptures are common targets for diagnostic and therapeutic approaches, the relationship between disc findings and back pain has been weak or nonexistent. METHODS: The data comprised barium sulfate discograms of lumbar spine levels from 157 male cadavers. The extent of "anular tears" and "general disc degeneration" based on posterior-anterior and side views were evaluated separately using a 4-point scale. Lifetime history of back pain occurrence and work were obtained from the families of 86 cadavers. To assess whether the risk of back pain changed with the severity of findings or the level of disc, we applied trend tests and proportional-odds logistic models for occurrence data. RESULTS: In early adulthood, the risk of anular tears was 0.6 to 0.7, whereas at retirement age, tears were practically unavoidable. The risk of full anular tears with barium sulfate leaking ("leaking" tear) was estimated to be 0.10 and 0.35 among the men in the age groups of 20 to 49 and 50 to 59 years, respectively. The risk of "leaking" tears was greatest at the L5-S1 levels. There were less severe degenerative findings associated with sedentary occupation but no differences between driving and physically light and heavy occupations. Overall, the risk of any anular tears and any general degeneration as defined was similar. The frequency of back pain had a highly significant relation to the occurrence of tears (model-based P = 0.0009). With a "leaking" tear, the model-based estimate of the risk of frequent lifetime back pain was 0.42, with an "outer" tear the risk was 0.20, and with no tears or "inner" tears the risk was 0.10 (the observed prevalence was 0). The effect of occupational loading was of borderline significance (P = 0.045). CONCLUSION: Anular degeneration of the lumbar discs appear earlier and are more clearly related to back pain than previously thought, most probably due to the better sensitivity of the BaSO4 discography method to detect tears.

Liver echogenicity: measurement or visual grading?

OBJECTIVE: Two methods to assess liver echogenicity were compared. METHODS: Liver/kidney echogenicity ratio was measured in 41 persons with the ultrasound software and visually graded by two radiologists and a radiographer. These echogenicity ratios and grades were related to risk factors for fatty liver and to liver enzyme levels. RESULTS: These determinants explained 55% of the radiologists' mean grades, 14% of the radiographer's and 31% of the measured echogenicity ratios. CONCLUSION: Radiologists' visual gradings correlated best with the indirect determinants of early liver pathology. Computerized measurements may be inferior to visual grading due to the lack of holistic tissue diagnostics.

Results of common laboratory tests in solvent-exposed workers.

OBJECTIVES: The screening and identification of occupational liver or other organ-system injury related to long-term, low-level solvent exposure are difficult in clinical practice. We studied the feasibility of the use of common laboratory tests combined with a detailed exposure history. METHODS: The relationships between laboratory tests and exposure to organic solvents were studied in regression modelling adjusted to age, alcohol consumption, gender and body mass index (BMI). The subjects were 29 solvent-exposed workers and 19 referents. Laboratory tests included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), carbohydrate-deficient transferrin (CDT), alkaline phosphatase (ALP), creatinine, cholesterol, HDL-cholesterol, triglycerides, blood glucose and total and conjugated bilirubin. Positive hepatitis serology, systemic diseases or medications with known hepatic effects and current pregnancy were exclusion criteria. The main exposures of each subject were identified. Current solvent exposure status, exposure during the past 3 months, exposure during the past 5 and 10 years, and total life-time exposure were recorded. RESULTS: AST (P=0.0031), ALT (P=0.0015) and cholesterol (P=0.0110) correlated positively with cumulative solvent exposure in the past 5 years, total bilirubin with current exposure (P=0.0380), and glucose with exposure in the past 5 (P<0.0001) and 10 (P=0.0003) years. Triglycerides correlated positively with exposure in the past 5 (P=0.0025) and 10 (P=0.0059) years and with life-time exposure (P=0.0005). Creatinine correlated negatively with exposure in the past 10 years (P=0.0300) and life-time exposure (P=0.0005). Most laboratory values were within the normal range. CONCLUSIONS: These results suggest a multi-system health effect of solvents. The laboratory data had some similarities with those in the metabolic syndrome. The screening and diagnostics of solvent-related conditions should be based on a thorough work history and a set of carefully selected laboratory tests. No single test seems sufficient for this purpose.

Estimating the induction period of pleural mesothelioma from aggregate data on asbestos consumption.

This study aimed to estimate the induction period from causal action of asbestos exposure to the manifestation of mesothelioma. We included the 9 countries for which we could find published aggregate data on the use of raw asbestos for a relevant time period. We extracted the annual numbers of cases of pleural cancer among men from the World Health Organization mortality database for those years using the International Classification of Diseases, 9th revision, classification. For the Scandinavian countries, we used published national cancer incidence data. In autoregressive Poisson regression modeling, we invoked different time lags of the mean annual use of asbestos to specify which time span produced the best correlation between the 2 time series. The ecologic analysis suggested that the most probable estimate for the mean induction period (use versus morbidity at society level) is approximately 25 years.

Nasal cell micronuclei, cytology and clinical symptoms in stainless steel production workers exposed to chromium.

The objective of the present study was to determine whether workers in stainless steel production with low exposure to various forms of chromium show an increase in micronucleated nasal cells or an excess of nasal symptoms or disease. Altogether, 48 workers employed in a stainless steel production chain were studied, 29 of them in the steel melting shop with exposure to hexavalent chromium (Cr(6+)), 14 in the sintering and crushing departments of the ferrochromium plant with exposure to trivalent chromium (Cr(3+)) and five in the mine with exposure to chromite ore (Cr(3+)). Thirty-nine workers from the cold rolling mill, with very low exposure to chromium, served as referents. All the subjects were never smokers with a minimum of 14 years employment in the same department. There were no significant differences between the exposure groups and the referents regarding the mean frequency of centromere-negative or centromere-positive micronuclei (studied by pancentromeric fluorescence in situ hybridization), nasal diseases and symptoms or mucociliary clearance of the nasal cavity. No statistically significant differences in the incidence of cell atypia or inflammatory cells were detected between the exposed workers and the reference group, except for an increase in lymphocytes among the chromite ore workers. Anterior rhinoscopy indicated slight inflammatory changes in nasal mucosa and secretion more often in the Cr(6+) and Cr(3+) groups than in the referents, the Cr(6+)-exposed workers showing more livid or oedemic epithelium. In conclusion, the stainless steel production workers, with low exposure to dusts or fumes containing hexavalent or trivalent chromium, did not show clinical changes in the nasal mucosa or an increase in nasal cell micronuclei or symptoms of nasal diseases, except for slight changes in the nasal epithelium and secretion.

The quality of spirometric examinations in Finland: results from a national questionnaire survey.

National treatment programmes for asthma and chronic obstructive pulmonary disease (COPD) have in the past few years increased the need for spirometry in Finland. The purpose of this study was to determine, by means of a national questionnaire survey, the quality and number of spirometric examinations performed in Finland in 1998, the year when the national COPD programme was initiated. We estimated that 395 000-425 000 spirometric examinations were performed in Finland in 1998. The mean quality of spirometry was evaluated as moderate, and the quality index developed for this study indicated an average of scores of 67 (max 100), ranging between 43 and 88 in the whole country. The most common qualitative insufficiencies in spirometric examinations were found in preparation of the subject for the examination, performance of the examination, recognition of a successful spirometric curve and evaluation of reproducibility of the examination. Furthermore, the time reserved in the reports for performing the examination was often very short. However, in comparison with the previous questionnaire survey in Finland (in 1990), the quality of spirometry had markedly improved.

Monoterpene and wood dust exposures: work-related symptoms among Finnish sawmill workers.

BACKGROUND: Monoterpenes and wood dust are released into the work environment during sawing of fresh wood. Symptoms related to exposure to monoterpenes and wood dust include irritation of the eyes, mucous membrane, and skin. METHODS: We studied 22 sawhouse workers who process pine and spruce in 1997-99. Exposure to monoterpenes was assessed by determining monoterpenes in air and verbenols in urine by gas chromatography using flame ionization detection. Wood dust was determined gravimetrically. A questionnaire was used to evaluate work-related subjective symptoms. RESULTS: Exposures to monoterpenes (geometric mean, GM) among sawhouse workers were 61-138 mg/m(3) and 2.0-13 mg/m(3) during processing of pine and spruce, respectively. Urinary verbenol correlated well with worker exposure to the alpha-pinene fraction of monoterpenes. The inhalable dust concentration in the breathing zone was 0.5- 2.2 mg/m(3) during pine processing and 0.4-1.9 mg/m(3) during spruce processing. The prevalence of symptoms, in the eyes or respiratory tract, was high during both seasons and in connection with either tree species. CONCLUSIONS: The highest monoterpene concentration (GM), in the breathing zone, measured during processing of pine, was less than one-fourth of the Finnish occupational exposure limit (OEL, 570 mg/m(3)). Verbenol concentrations in postshift urine samples reflected accurately the exposure to monoterpenes. The concentrations of inhalable dust (GM) were less than one-half the Finnish OEL (5 mg/m(3)). No significant differences in dust exposure were observed among tree species processed. Work-related symptoms appeared to correlate with monoterpene exposure during processing of pine and with wood dust exposure during processing of spruce.