Concentrations and number size distribution of fine and nanoparticles in a traditional Finnish bakery.

In bakeries, high concentrations of flour dust can exist and ovens release particles into the air as well. Particle concentrations (mass, number) and number size distribution may vary considerably but the variation is not commonly studied. Furthermore, the role of the smallest size fractions is rarely considered in the exposure assessment due to their small mass. The objectives of this work were to find out how concentrations and number size distribution of fine and nanoparticles vary in a traditional Finnish bakery and to determine the exposure of a dough maker to the nanoparticle fraction of the inhalable dust. Two measurement campaigns were carried out in a traditional, small-scale bakery. Sampling was performed at the breathing zone of the dough maker and three stationary locations: baking area, oven area, and flour depository. Both real-time measurements and conventional gravimetric sampling were conducted. Nanoparticle fraction of the inhalable dust was determined using an IOM sampler with a customized precyclone. Number concentration of fine and nanoparticles, and mass concentrations of both the inhalable dust and nanoparticles were high. The nanoparticle fraction was 9-15% of the inhalable dust at the breathing zone of the dough maker. Different sources, such as ovens and doughnut baking affected the number size distribution. Flour dust contained nanoparticles but most of the fine and nanoparticles were released into the air from the oven operations. However, nanoparticles are not a primary concern in bakeries compared to health effects linked to the large flour particles such as flour-induced sensitization or asthma and development of occupational rhinitis.

Developing a framework for assessing chemical respiratory sensitization: A workshop report.

Respiratory tract sensitization can have significant acute and chronic health implications. While induction of respiratory sensitization is widely recognized for some chemicals, validated standard methods or frameworks for identifying and characterizing the hazard are not available. A workshop on assessment of respiratory sensitization was held to discuss the current state of science for identification and characterization of respiratory sensitizer hazard, identify information facilitating development of validated standard methods and frameworks, and consider the regulatory and practical risk management needs. Participants agreed on a predominant Th2 immunological mechanism and several steps in respiratory sensitization. Some overlapping cellular events in respiratory and skin sensitization are well understood, but full mechanism(s) remain unavailable. Progress on non-animal approaches to skin sensitization testing, ranging from in vitro systems, -omics, in silico profiling, and structural profiling were acknowledged. Addressing both induction and elicitation phases remains challenging. Participants identified lack of a unifying dose metric as increasing the difficulty of interpreting dosimetry across exposures. A number of research needs were identified, including an agreed list of respiratory sensitizers and other asthmagens, distinguishing between adverse effects from immune-mediated versus non-immunological mechanisms. A number of themes emerged from the discussion regarding future testing strategies, particularly the need for a tiered framework respiratory sensitizer assessment. These workshop present a basis for moving towards a weight-of-evidence assessment.

Positive exercise test and obstructive spirometry in young male conscripts associated with persistent asthma 20 years later.

BACKGROUND: Asthma often begins in childhood or early adulthood and is a common disease among conscripts. The identification of long-term predictive factors for persistent asthma may lead to improved treatment opportunities and better disease control. OBJECTIVE: Our aim was to study the prognostic factors of the severity of asthma among 40-year-old male conscripts whose asthma began in youth. METHODS: We studied 119 conscripts who were referred to the Central Military Hospital during 1987-1990 due to asthma and who attended a follow-up visit approximately 20 years later. Asthma severity was evaluated during military service according to the medical records, and 20 years later during a follow-up visit using Global Initiative for Asthma guidelines. We used the results of lung function and allergy tests at baseline as predictors of current persistent asthma. RESULTS: Compared with baseline, asthma was less severe at follow-up: 11.8% of subjects were in remission, 42.0% had intermittent asthma, 10.9% had mild persistent asthma, and 35.3% had moderate/severe persistent asthma (p < .001). In multivariate models, a positive exercise test at baseline yielded an odds ratio (OR) of 3.2 (95% CI 1.0-9.8, p = .046), a decreased FEV1/FVC % predicted an OR of 4.0 (95% CI 1.7-9.3, p = .002), and a decreased FEF50% % predicted an OR of 2.8 (95% CI 1.3-6.4, p = .012) for current persistent asthma. CONCLUSIONS: About half of the men had persistent asthma at the 20-year follow-up. Positive exercise tests and obstructive spirometry results were related to the persistence of asthma and may be useful long-term prognostic factors for asthma severity.

Controlling flour dust exposure by an intervention focused on working methods in Finnish bakeries: a case study in two bakeries.

Objectives. The purpose of this study was to examine the effectiveness of intervention strategies to control mass concentrations and peak exposures of flour dust in two Finnish bakeries. The effect of the intervention on the proportion of various particle size fractions of the total particulate matter was also investigated. Methods. Mass concentrations of flour dust were measured during three working days in a pre-intervention and post-intervention study in both an industrial and a traditional bakery. Gravimetric sampling and real-time measurements were performed. Relevant intervention strategies focused on working methods were planned in collaboration with the managers of the bakeries. Results. The average mass concentration of inhalable flour dust reduced in most of the stationary locations post intervention. The reductions in exposure levels were between 39 and 45%. However, the exposure levels increased 28-55% in the breathing zone. Real-time measurements showed reductions in the peak mass concentrations in the traditional bakery post intervention. In both bakeries, the total particulate matter size fraction consisted predominantly of particles with an aerodynamic diameter lower than 1 µm and greater than 10 µm. Conclusion. Further studies are needed to plan more effective intervention measures supplemented by technical control methods in both bakeries.

Proteomic detection of cancer in asbestosis patients using SELDI-TOF discovered serum protein biomarkers.

OBJECTIVES: To identify biomarkers for cancer in asbestosis patients. METHODS: SELDI-TOF and CART were used to identify serum biomarker profiles in 35 asbestosis patients who subsequently developed cancer and 35 did not develop cancer. RESULTS: Three polypeptide peaks (5707.01, 6598.10, and 20,780.70 Da) could predict the development of cancer with 87% sensitivity and 70% specificity. The first two peaks were identified as KIF18A and KIF5A, respectively, and are part of the Kinesin Superfamily of proteins. CONCLUSIONS: We identified two Kinesin proteins that can be potentially used as blood biomarkers to identify asbestosis patients at risk of developing lung cancer.

Molecular alterations at 9q33.1 and polyploidy in asbestos-related lung cancer.

PURPOSE: Asbestos causes DNA damage and the fibers, together with tobacco smoke, have a synergistic effect on lung cancer risk. We recently identified 18 chromosomal regions that showed differences in DNA copy number between the lung tumors of asbestos-exposed and nonexposed patients. One of the previously identified asbestos-associated chromosomal regions at 9q was further analyzed for allelic imbalance and DNA copy number alterations (CNA) in the lung tumors of asbestos-exposed and nonexposed patients. In addition, the ploidy level of the tumors was studied. EXPERIMENTAL DESIGN: Allelic imbalance was analyzed at 9q31.3-34.3 with 15 microsatellite markers in 52 lung tumor samples from asbestos-exposed and nonexposed patients. CNA at 9q32-34.3 were characterized by fluorescent in situ hybridization (FISH) with six bacterial artificial chromosome probes in 95 lung tumors. The ploidy level was analyzed in 100 lung tumors with FISH using three to five centromere probes. RESULTS: Allelic imbalance at 9q31.3-q34.3 was found in all asbestos-exposed patient tumors (100%, 17 of 17) compared with 64% (14 of 22) in the nonexposed cases (P = 0.005). The most significant difference was detected at 9q33.1 (P = 0.002). FISH results showed that also CNA were more frequent at 9q33.1 in the three major histologic types of non-small-cell lung tumors of exposed patients, and the association showed a dose-dependent trend (P = 0.03). Furthermore, we detected more frequent polyploidy among the exposed (48%, 28 of 58) than among the nonexposed (29%, 12 of 42) patient tumors (P < 0.05). CONCLUSIONS: These results provide a basis for the development of a method to identify asbestos-related lung cancer on a molecular level.

Serum growth factors in asbestosis patients.

Various growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta, have been implicated in the pathogenesis of asbestos-induced disease. PDGF and TGF-beta levels were determined by enzyme-linked immunosorbent assays in the banked serum samples of a cohort of workers with asbestosis, and the relationships of the growth factor levels to the subsequent development of cancer and to the radiographic severity and progression of asbestosis in the cohort were examined. Serum levels of PDGF and TGF-beta were found to be unrelated to the development of cancer, and serum levels of PDGF were found to be unrelated to the severity and progression of asbestosis. However, serum levels of TGF-beta were found to be statistically significantly related to disease severity (p = 0.01), increasing approximately 2.4-fold from ILO radiographic category 0 to category 3, and they were marginally related to disease progression (p = 0.07), in multivariate analysis controlling for other contributory factors including cumulative asbestos exposure. This suggests that serum TGF-beta may be a useful biomarker for asbestos-induced fibrotic disease.

Ecological association between asbestos-related diseases and historical asbestos consumption: an international analysis.

BACKGROUND: The potential for a global epidemic of asbestos-related diseases is a growing concern. Our aim was to assess the ecological association between national death rates from diseases associated with asbestos and historical consumption of asbestos. METHODS: We calculated, for all countries with data, yearly age-adjusted mortality rates by sex (deaths per million population per year) for each disease associated with asbestos (pleural, peritoneal, and all mesothelioma, and asbestosis) in 2000-04 and mean per head asbestos consumption (kg per person per year) in 1960-69. We regressed death rates for the specified diseases against historical asbestos consumption, weighted by the size of sex-specific national populations. FINDINGS: Historical asbestos consumption was a significant predictor of death for all mesothelioma in both sexes (adjusted R2=0.74, p<0.0001, 2.4-fold [95% CI 2.0-2.9] mortality increase was predicted per unit consumption increase for men; 0.58, p<0.0001, and 1.6-fold [1.4-1.9] mortality increase was predicted for women); for pleural mesothelioma in men (0.29, p=0.0015, 1.8-fold [1.3-2.5]); for peritoneal mesothelioma in both sexes (0.54, p<0.0001, 2.2-fold [1.6-2.9] for men, 0.35, p=0.0008, and 1.4-fold for women [1.2-1.6]); and for asbestosis in men (0.79, p<0.0001, 2.7-fold [2.2-3.4]). Linear regression lines consistently had intercepts near zero. INTERPRETATION: Within the constraints of an ecological study, clear and plausible associations were shown between deaths from the studied diseases and historical asbestos consumption, especially for all mesothelioma in both sexes and asbestosis in men. Our data strongly support the recommendation that all countries should move towards eliminating use of asbestos.

Recent mortality from pleural mesothelioma, historical patterns of asbestos use, and adoption of bans: a global assessment.

BACKGROUND: In response to the health risks posed by asbestos exposure, some countries have imposed strict regulations and adopted bans, whereas other countries have intervened less and continue to use varying quantities of asbestos. OBJECTIVES: This study was designed to assess, on a global scale, national experiences of recent mortality from pleural mesothelioma, historical trends in asbestos use, adoption of bans, and their possible interrelationships. METHODS: For 31 countries with available data, we analyzed recent pleural mesothelioma (International Classification of Diseases, 10th Revision) mortality rates (MRs) using age-adjusted period MRs (deaths/million/year) from 1996 to 2005. We calculated annual percent changes (APCs) in age-adjusted MRs to characterize trends during the period. We characterized historical patterns of asbestos use by per capita asbestos use (kilograms per capita/year) and the status of national bans. RESULTS: Period MRs increased with statistical significance in five countries, with marginal significance in two countries, and were equivocal in 24 countries (five countries in Northern and Western Europe recorded negative APC values). Countries adopting asbestos bans reduced use rates about twice as fast as those not adopting bans. Turning points in use preceded bans. Change in asbestos use during 1970-1985 was a significant predictor of APC in mortality for pleural mesothelioma, with an adjusted R(2) value of 0.47 (p < 0.0001). CONCLUSIONS: The observed disparities in global mesothelioma trends likely relate to country-to-country disparities in asbestos use trends.

Asthma incidence in wood-processing industries in Finland in a register-based population study.

OBJECTIVES: This register-based population study determined incidence rates of clinically verified asthma among woodworkers, other blue-collar workers, and administrative personnel employed in wood-processing industries in Finland. Exposure to wood dust was under special scrutiny. METHODS: All Finns employed in wood-processing industries were followed for asthma incidence via record linkage in the years 1986-1998. Incident cases included people with asthma reimbursed for medication by the national health insurance or registered as having occupational asthma. Age-adjusted incidence rates and relative risks (RR) by gender were estimated for wood workers, other blue-collar workers, and administrative employees (referents) in wood industries. RESULTS: The relative risk of asthma was increased for all woodworkers among both genders [men: RR 1.5, 95% confidence interval (95% CI) 1.2-1.8; women: RR 1.5, 95% Cl 1.2-1.7]; a similarly elevated risk was also found for other blue-collar workers (men: RR 1.5, 95% Cl 1.2-1.8; women: RR 1.4, 95% Cl 1.2-1.6) in the same wood industries. Statistically increased relative risks were found for low and medium exposure to wood dust, but not for high exposure. Altogether 217 of the 4074 clinically verified asthma cases were reported as occupational asthma in the Finnish Register on Occupational Diseases. CONCLUSIONS: The incidence rates for asthma were significantly increased both among the woodworkers and the other blue-collar workers in wood industries but without a clear dose-response. Cases recognized as occupational asthma accounted for only a small part of the total asthma excess, indicating that much of the work-related asthma excess remains unrecognized in these industries.

Identification of specific gene copy number changes in asbestos-related lung cancer.

Asbestos is a well-known lung cancer-causing mineral fiber. In vitro and in vivo experiments have shown that asbestos can cause chromosomal damage and aberrations. Lung tumors, in general, have several recurrently amplified and deleted chromosomal regions. To investigate whether a distinct chromosomal aberration profile could be detected in the lung tumors of heavily asbestos-exposed patients, we analyzed the copy number profiles of 14 lung tumors from highly asbestos-exposed patients and 14 matched tumors from nonexposed patients using classic comparative genomic hybridization (CGH). A specific profile could lead to identification of the underlying genes that may act as mediators of tumor formation and progression. In addition, array CGH analyses on cDNA microarrays (13,000 clones) were carried out on 20 of the same patients. Classic CGH showed, on average, more aberrations in asbestos-exposed than in nonexposed patients, and an altered region in chromosome 2 seemed to occur more frequently in the asbestos-exposed patients. Array CGH revealed aberrations in 18 regions that were significantly associated with either of the two groups. The most significant regions were 2p21-p16.3, 5q35.3, 9q33.3-q34.11, 9q34.13-q34.3, 11p15.5, 14q11.2, and 19p13.1-p13.3 (P < 0.005). Furthermore, 11 fragile sites coincided with the 18 asbestos-associated regions (P = 0.08), which may imply preferentially caused DNA damage at these sites. Our findings are the first evidence, indicating that asbestos exposure may produce a specific DNA damage profile.

Methylation of cytochrome P4501A1 promoter in the lung is associated with tobacco smoking.

Cytochrome P4501A1 (CYP1A1), which is involved in the metabolic activation of polycyclic aromatic hydrocarbon procarcinogens derived from tobacco smoke, is induced in the lung up to 100-fold because of tobacco smoking. Our aim was to study whether promoter methylation has any role in the smoking-associated expression of CYP1A1 in human lung. Methylation of CpG sites up to 1.4 kb upstream of CYP1A1 gene was studied first by sequencing. Because methylation was observed between nucleotides -1400 and -1000, a methylation-specific single-strand conformational polymorphism method was designed for the region between nucleotides -1411 and -1295 that contains five potential methylation sites, one of them at the xenobiotic responsive element core sequence. Single-strand conformational polymorphism was used on DNA from normal lung samples and peripheral WBCs of smokers and nonsmokers, and on human lung adenocarcinoma (A549) and bronchial epithelial (Beas-2B) cell lines. In lung tissue complete or partial methylation occurred in 33% of heavy smokers (>15 cigarettes/day, n = 30), 71% of light smokers (< or =15 cigarettes/day or quitted 1-7 days earlier, n = 42), and in 98% of nonsmokers (never and ex-smokers, n = 49). Methylation was found to increase in 1-7 days after quitting smoking. In active smokers the lack of methylation in the studied region of CYP1A1 promoter was associated with a slightly higher pulmonary 7-ethoxyresorufin O-deethylase activity in the regression models allowing for the daily tobacco consumption and age. No association was observed in WBC between methylation and tobacco smoking. In lung-derived cell lines the methylation remained stable regardless of induction with benzo(a)pyrene, but a higher induction was observed in Beas-2B cells, which also had less methylation than A549 cells. The association of tobacco smoking with CYP1A1 methylation in the lung suggests that promoter methylation is involved in the regulation of CYP1A1 induction in vivo.

Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array.

No clear patterns in molecular changes underlying the malignant processes in lung cancer of different histological types have been found so far. To identify critical genes in lung cancer progression we compared the expression profile of cancer related genes in 14 pulmonary adenocarcinoma patients with normal lung tissue by using the cDNA array technique. Principal component analyses (PCA) and permutation test were used to detect the differentially expressed genes. The expression profiles of 10 genes were confirmed by semi-quantitative real-time RT-PCR. In tumour samples, as compared to normal lung tissue, the up-regulated genes included such known tumour markers as CCNB1, PLK, tenascin, KRT8, KRT19 and TOP2A. The down-regulated genes included caveolin 1 and 2, and TIMP3. We also describe, for the first time, down-regulation of the interesting SOCS2 and 3, DOC2 and gravin. We show that silencing of SOCS2 is not caused by methylation of exon 1 of the gene. In conclusion, by using the cDNA array technique we were able to reveal marked differences in the gene expression level between normal lung and tumour tissue and find possible new tumour markers for pulmonary adenocarcinoma.

Myosin-II-mediated cell shape changes and cell intercalation contribute to primitive streak formation.

Primitive streak formation in the chick embryo involves large-scale highly coordinated flows of more than 100,000 cells in the epiblast. These large-scale tissue flows and deformations can be correlated with specific anisotropic cell behaviours in the forming mesendoderm through a combination of light-sheet microscopy and computational analysis. Relevant behaviours include apical contraction, elongation along the apical-basal axis followed by ingression, and asynchronous directional cell intercalation of small groups of mesendoderm cells. Cell intercalation is associated with sequential, directional contraction of apical junctions, the onset, localization and direction of which correlate strongly with the appearance of active myosin II cables in aligned apical junctions in neighbouring cells. Use of class specific myosin inhibitors and gene-specific knockdown shows that apical contraction and intercalation are myosin II dependent and also reveal critical roles for myosin I and myosin V family members in the assembly of junctional myosin II cables.

Indoor dampness and molds and development of adult-onset asthma: a population-based incident case-control study.

Previous cross-sectional and prevalent case-control studies have suggested increased risk of asthma in adults related to dampness problems and molds in homes. We conducted a population-based incident case-control study to assess the effects of indoor dampness problems and molds at work and at home on development of asthma in adults. We recruited systematically all new cases of asthma during a 2.5-year study period (1997-2000) and randomly selected controls from a source population consisting of adults 21-63 years old living in the Pirkanmaa Hospital district, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls, after we excluded 76 (7.5%) controls with a history of asthma. In logistic regression analysis adjusting for confounders, the risk of asthma was related to the presence of visible mold and/or mold odor in the workplace (odds ratio, 1.54; 95% confidence interval, 1.01-2.32) but not to water damage or damp stains alone. We estimated the fraction of asthma attributable to workplace mold exposure to be 35.1% (95% confidence interval, 1.0-56.9%) among the exposed. Present results provide new evidence of the relation between workplace exposure to indoor molds and adult-onset asthma.

Reduced Fhit protein expression and loss of heterozygosity at FHIT gene in tumours from smoking and asbestos-exposed lung cancer patients.

The FHIT gene, at 3p14.2, has been suggested to form a molecular target to damage induced by human lung carcinogens. We examined aberrant expression of the Fhit protein and allele loss at the FHIT gene in a series of lung cancer cases, mainly of non-small cell carcinoma (NSCLC) histology. We had detailed data on tobacco smoke exposure and occupational asbestos exposure available for the cases. The principal aim of the present study was to investigate whether absent or reduced Fhit expression or FHIT allele loss was associated with exposure to these pulmonary carcinogens. We detected reduced Fhit expression in 62% (33/53) of the cases analysed. Prevalence of allele loss at the FHIT locus was 22% (20/89). Reduced protein expression was common both in the asbestos-exposed (67%) and non-exposed cases (59%); [odds ratio (OR) 1.4, 95% confidence interval (CI) 0.4-4.9]. LOH frequencies differed somewhat between the two groups and were 25% vs. 16%, respectively (OR 1.8; 95% CI 0.5-5.9). Absent or reduced expression was common in smokers, with no significant difference found between current smokers and non-smokers (mainly former smokers) (OR 1.4, 95% CI 0.5-4.5). NSCLCs with squamous cell histology exhibited both aberrant expression (OR 3.1, 95% CI 0.9-10.3) and allele loss (OR 3.3, 95% CI 0.9-12.7) more frequently than adenocarcinoma. Finally, we found that FHIT allele loss was increased in stage II or more advanced disease (OR 2.5, 95% CI 0.9-7.4), and in poorly differentiated tumours (grade 3, OR 2.6, 95% CI 0.8-8.1). In conclusion, our present data support significance of FHIT inactivation in development of lung cancer.

Risk of asthma among Finnish patients with occupational rhinitis.

STUDY OBJECTIVES: To determine the risk of asthma among patients with occupationally induced rhinitis. DESIGN: Patients with confirmed occupational rhinitis were followed for asthma incidence through register linkage. Patients with other occupational diseases were used as a reference population. SUBJECTS: Patients entered into the Finnish Register of Occupational Diseases in from 1988 to 1999 for occupational rhinitis (n = 3,637) or other occupational disease (n = 31,457) were observed until December 31, 2000, through two national registers of individuals who were eligible for the reimbursement of asthma medication and the Population Register Center. METHODS: Incidence rates of asthma were calculated, and a log-linear model, adjusted for age, gender, and occupation, was used to estimate the relative risks (RRs) of asthma among those with occupational rhinitis compared to those with other occupational diseases. RESULTS: There were 420 and 972 incident cases of asthma, respectively, among those with occupational rhinitis and the reference population. The crude RR of asthma was 4.8 (95% confidence interval [CI], 4.3 to 5.4) for all patients with occupational rhinitis, 5.4 (95% CI, 4.8 to 6.2) for those with occupational rhinitis accepted for compensation, and 3.7 (95% CI, 3.1 to 4.5) for patients with unaccepted occupational rhinitis. The RR varied according to occupation and was the highest among farmers and wood workers, both groups having a sevenfold risk. The risk was especially high during the year following notification, but a roughly threefold risk persisted several years thereafter. CONCLUSIONS: Patients with occupationally induced rhinitis have a high risk of asthma, but further studies are needed to establish the effect of preventive interventions.

Differentially expressed genes in nonsmall cell lung cancer: expression profiling of cancer-related genes in squamous cell lung cancer.

The expression patterns of cancer-related genes in 13 cases of squamous cell lung cancer (SCC) were characterized and compared with those in normal lung tissue and 13 adenocarcinomas (AC), the other major type of nonsmall cell lung cancer (NSCLC). cDNA array was used to screen the gene expression levels and the array results were verified using a real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). Thirty-nine percent of the 25 most upregulated and the 25 most downregulated genes were common to SCC and AC. Of these genes, DSP, HMGA1 (alias HMGIY), TIMP1, MIF, CCNB1, TN, MMP11, and MMP12 were upregulated and COPEB (alias CPBP), TYROBP, BENE, BMPR2, SOCS3, TIMP3, CAV1, and CAV2 were downregulated. The expression levels of several genes from distinct protein families (cytokeratins and hemidesmosomal proteins) were markedly increased in SCC compared with AC and normal lung. In addition, several genes, overexpressed in SCC, such as HMGA1, CDK4, IGFBP3, MMP9, MMP11, MMP12, and MMP14, fell into distinct chromosomal loci, which we have detected as gained regions on the basis of comparative genomic hybridization data. Our study revealed new candidate genes involved in NSCLC.

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.

Different measures of asbestos exposure in estimating risk of lung cancer and mesothelioma among construction workers.

To analyze occupation, expert-evaluated cumulative exposure, and radiographic abnormalities as indicators of asbestos-related cancer risk we followed 16,696 male construction workers for cancer in 1990-2000. We calculated standardized incidence ratios (SIR) in comparison to the Finnish population and relative risks (RR) in a multivariate analysis in comparison to the internal low-exposure category of each indicator. Overall, the risk was increased for mesothelioma (SIR 2.0, 95% CI = 1.0-3.3), but not for lung cancer (SIR 1.1, 95% CI = 0.9-1.2). Radiographic lung fibrosis indicated a 2-fold and a high value of the exposure index a 3-fold RR of lung cancer, while there was no risk among those with pleural plaques. The risk of lung cancer was the highest in insulators (RR 3.7, 95% CI = 1.4-9.9). Occupation, expert-evaluated cumulative exposure, and lung fibrosis are useful indicators of lung cancer risk among construction workers.