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.

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.

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.

Middle-aged men with asthma since youth: the impact of work on asthma.

OBJECTIVES: To evaluate current occupational exposure and its associations with asthma control, exacerbations, and severity in middle-aged men with asthma from youth. METHODS: We used the Finnish Defence Force registers, 1986 to 1990, to select conscripts with asthma to represent mild or moderate asthmatic group (asthma group 1; N = 505), men who were exempted from military service to represent relatively severe asthmatic group (asthma group 2; N = 393), and a control group without asthma (N = 1500). A questionnaire was sent out in 2009. RESULTS: The current self-reported or expert-evaluated exposure to asthma-aggravating factors differed only slightly between the asthmatic groups and the controls. In asthma group 2, being a manual worker or self-employed (odds ratio, 4.5; 95% confidence interval, 1.2 to 16.3) significantly associated with asthma exacerbations. CONCLUSIONS: Current work may associate with the asthma outcome of middle-aged men with relatively severe asthma in their youth.

Accumulation of genomic alterations in 2p16, 9q33.1 and 19p13 in lung tumours of asbestos-exposed patients.

We have previously demonstrated an association between genomic alterations in 19p13, 2p16, and 9q33.1 and asbestos exposure in patients' lung tumours. This study detected allelic imbalance (AI) in these regions in asbestos-exposed lung cancer (LC) patients' histologically normal pulmonary epithelium. We extended the analyses of tumour tissue to cover a large LC patient cohort and studied DNA copy number alteration (CNA) and AI in 19p13, 2p16, and 9q33.1 for the first time in combination. We found both CNA and AI in ≥2/3 of the regions to be significantly and dose-dependently (P < 0.001) associated with pulmonary asbestos fibre count. Twenty percent of the exposed patients' LC showed CNA in ≥2/3 of the regions, whereas none of the non-exposed patients' LC showed CNA in more than one region. AI was evident in 89% of the exposed and in only 26% of the non-exposed patients' LC. The genomic alterations in 19p13, 2p16, and 9q33.1 in compilation identified asbestos-exposed patients' lung tumours better than each of the regions alone. These alterations form the basis for the development of a combinatorial molecular assay that could be used to identify asbestos-related LC.

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.

Reduced work ability in middle-aged men with asthma from youth--a 20-year follow-up.

We studied, whether asthma diagnosed in childhood or early adulthood affects work ability 20 years later. We used Finnish Defence Force registers, 1986-1990, to select: (1) conscripts with asthma to represent a mild/moderate asthma group (n=485), (2) asthmatics who were exempted from military service to represent a relatively severe asthma group (n=393) and (3) a control group (n 1500) without asthma. A questionnaire consisting of validated questions on asthma and work ability was sent out in 2009. A total of 54% of the men in the first study group, 44% of those in the second study group and 44% of the controls answered. The mean age of the participants was 41 (range 37-51). Self-assessed current work ability compared with lifetime best had decreased in 28.9% of the first asthma group, in 31.1% of the second asthma group, and in 19.7% of the controls (p = 0.0007). Current smoking (OR 2.5), only basic education (OR 2.6), being a manual worker (OR 2.7) and current severe asthma (OR 3.8) associated most strongly with decreased work ability among the asthmatics. Both mild and more severe asthma at the age of around 20 seems to be associated with reduced work ability in 40-year-old males.

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.

National use of asbestos in relation to economic development.

BACKGROUND: National disparities in asbestos use will likely lead to an unequal burden of asbestos diseases. OBJECTIVES: As economic status may be linked to asbestos use, we assessed, globally, the relationship between indicators of national economic development and asbestos use. METHODS: For the 135 countries that have ever used asbestos, per capita asbestos use (kilograms per capita per year) was compared with per capita gross domestic product (GDP) in 1990 Geary-Khamis dollars (GKD) for the period 1920-2003. Countries were grouped into three income levels (high, middle, and low) that were adapted from the 2003 World Bank categories. RESULTS: The historical pattern of asbestos use followed the environmental Kuznets curve in which use by high-income countries peaked when incomes attained 10,000-15,000 GKD and essentially ceased at income levels over 20,000 GKD. Currently, middle- and low-income countries are increasing their use of asbestos, closely following the paths once traced by higher income countries. CONCLUSIONS: Developing countries have the opportunity to eliminate asbestos use sooner than high-income countries and thus reduce the future burden of asbestos diseases.

Military service-aggravated asthma improves at two-year follow-up.

BACKGROUND: During military service young men (age 19-21 years) are exposed to many predisposing factors for asthma. We aimed to study the short-term prognosis of asthma after the military service. METHODS: All 216 men with verified asthma in 2004-2005 from the register of the Central Military Hospital were included in the study. A questionnaire was mailed to them in autumn 2007 and the 146 responders (68%) formed the final study population. Asthma severity was evaluated during military service according to the medical records of the subjects and two years later based on the questionnaire using modified GINA guidelines. The results on lung function and allergy tests during military service and asthma history were used as predictors of asthma severity at two-year follow-up. RESULTS: Two groups of asthmatics were identified: those who already had asthma when entering the military service (n=71, 48.6%) and those, who had a new onset of asthma during the service (n=75, 51.4%). Overall asthma was less severe at two-year follow-up than during military service (p=0.036). Both during military service and at two-year follow-up, asthma was milder among the men, who had a new onset of asthma during military service. Atopy (p=0.002), number of positive skin-prick tests (p=0.005) and higher total serum IgE (p=0.001) were significant predictors for persistent asthma at follow-up. CONCLUSIONS: Asthma, which had aggravated or started during military service, was significantly less severe two years later. The degree of atopy was a major determinant of the two-year prognosis of asthma after military service.

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.

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.

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.

Evaluation of a national register on occupational exposure to carcinogens: effectiveness in the prevention of occupational cancer, and cancer risks among the exposed workers.

OBJECTIVES: The objective of this study was to evaluate the performance and effectiveness of a register of employees exposed to carcinogens (the ASA Register) which has been in operation in Finland since 1979, and to study cancer risks among the notified workers. METHODS: The impact of ASA at workplaces was studied by questionnaires mailed to 1448 work departments, which were notified to ASA in 1996, and to 1033 departments, which departed ASA in 1991-1996. The mailing was responded by 69% of departments. The cancer incidence of 35,138 workers notified to ASA in 1979-1988 was followed up through the files of the Finnish Cancer Register for the period 1980-2003. RESULTS: Changes eliminating or substantially reducing exposure to carcinogens were reported by 73% of departments notified to ASA in 1996. The ASA notification process had directly prompted measures to reduce exposure (8% of cases) or contributed to them (24% of cases). Estimations based on responses of the workplaces suggested that the ASA registration had decreased exposure of 600 workers year(-1) (out of approximately 15,000 notified workers, which is <1% of the employed in Finland), preventing thereby an unknown number of occupational cancers. Other benefits of ASA included the saving of the treatment costs of prevented cancers, the prevention of other health outcomes of carcinogens, improved safety behaviour of exposed workers and avoidance of human suffering among cancer patients and their families. The labour safety authorities had better possibilities to direct their activities against carcinogen exposure. These benefits should be considered against the annual costs, mainly due to 7-8 person-years of work required by tasks related to ASA. The results of the cancer incidence study among notified workers were based on a relatively short follow-up (on average 19 years). The incidence of mesothelioma was significantly increased in the ASA cohort, probably due to exposure to asbestos. CONCLUSIONS: These results suggest that a national exposure register may stimulate preventive measures at workplaces. Partially based on the results of the present study the Finnish Ministry of Social Affairs and Health continues ASA registration.

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.

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.

The complexation of two different ammonium ions with resorcarenes in protic solvent medium investigated by electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry.

The complexations of two ammonium ions (guests) with two resorcarenes (hosts) were investigated using electrospray ionisation Fourier transform ion cyclotron resonance mass spectrometry. Although the two guests and the two hosts were noticeably similar, the quantity of the corresponding supramolecular complexes formed varied significantly due to the differences in host conformations and guest ability to form non-covalent interactions.

Employment status of Finnish cancer patients in 1997.

We explored the impact of cancer diagnosis on the employment status of 46 312 working-aged people with cancer, alive on 31 December 1997 in Finland, and an equal number of age- and gender-matched referents. In general, 50% of the cancer patients were employed, in comparison to 55% of their referents. People with cancer were slightly less often employed, mainly because of their higher retirement rate: 34% of the cancer patients and 27% of the referents had retired. People with lung cancer as well as those with cancer of the nervous system were less likely to be employed. Our results suggest that cancer diagnosis does not usually lead to unemployment or early retirement, even though the employment rate of the people with cancer varied greatly according to the cancer site. Early retirement is common among people with highly disabling cancer or poor prognosis, but in general, the employment of cancer survivors seems optimistic.