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In de West-australische plaats Wittenoom werd van 1943 tot 1966 het gevaarlijke blauwe asbest gewonnen (crocidoliet). In 2002 werden 1885 inwoners, waarvan 1042 (ex-)werknemers onderzocht op asbestose (stoflongen) en bepaalde vitamine-niveaus in het bloed (retinol, caroteen en vitamine E). De onderzoekers vonden een relatie tussen chronisch lagere vitamine-niveaus en een grotere kans om aan asbestose te overlijden. Van de onderzoeksgroep overleden 76 personen aan asbestose, een te kleine groep om causaliteit te kunnen bepalen. Meer onderzoek is nodig.

Bron: Alfonso, H.S. et al. (2005). Plasma Concentrations of Retinol, Carotene, and Vitamin E and Mortality in Subjects With Asbestosis in a Cohort Exposed to Crocidolite in Wittenoom, Western Australia. Journal of occupational and environmental medicine. vol. 47, afl. 6, pag. 573-579 (7)

Alfonso, Helman S.. Fritschi, Lin. de Klerk, Nicholas H.. Ambrosini, Gina. Beilby, John. Olsen, Nola. Musk, A William (2005). Plasma Concentrations of Retinol, Carotene, and Vitamin E and Mortality in Subjects With Asbestosis in a Cohort Exposed to Crocidolite in Wittenoom, Western Australia. Journal of occupational and environmental medicine. vol. 47, afl. 6, pag. 573-579 (7).

Abstract

Objective:We sought to examine the relationships between plasma concentrations of retinol, carotene, and vitamin E and mortality associated with asbestosis in people previously exposed to crocidolite.

Methods:Cox regression modeling was applied to examine these relationships at the first measurement of each vitamin, at the measurement at each visit, and with the rate of change of each vitamin during the follow-up.

Results:There were 76 deaths of people with asbestosis during the follow-up period and 1885 subjects censored. Mortality in subjects with asbestosis was inversely related to plasma levels of retinol and Vitamin E concentrations and to their rate of increase during the follow-up. Carotene concentrations at first visit were associated with lower mortality but not during the follow up period.

Conclusions:Chronically low levels of these vitamins are associated with an increased risk of dying with asbestosis.

Asbest bestaat uit microscopisch kleine vezels. Er zijn verschillende soorten, onderverdeeld in serpentijnen en amfibolen. Serpentijnen hebben gekrulde vezels, de vezels van amfibolen hebben de vorm van staafjes en zijn gevaarlijker. Een groep ratten werd gedurende 5 dagen herhaaldelijk blootgesteld aan een groot aanta calidria chrysotiel vezels (serpentijn), een andere groep aan een aantal tremolietvezels (amfibool). Tot één jaar na de proef werd bij de ratten die aan chrysotiel waren blootgesteld geen ontstekingsreactie gezien. Dit in tegenstelling tot de aan tremoliet blootgestelde ratten die sterk reageerden, ondanks blootstelling aan 16 x minder vezels dan de aan chrysotiel blootgestelde ratten. Bernstein, D. et. al., (2005). Comparison of Calidria Chrysotile Asbestos to Pure Tremolite : Final Results of the Inhalation Biopersistence and Histopathology Examination Following Short-Term Exposure. Inhalation toxicology. vol. 17, afl. 9, pag. 427-450 (24).
Bernstein, David. Chevalier, Jörg. Smith, Paul (2005). Comparison of Calidria Chrysotile Asbestos to Pure Tremolite : Final Results of the Inhalation Biopersistence and Histopathology Examination Following Short-Term Exposure. Inhalation toxicology. vol. 17, afl. 9, pag. 427-450 (24).

Abstract:

Calidria chrysotile asbestos, which is a serpentine mineral, has been shown to be considerably less biopersistent than the durable amphibole mineral tremolite asbestos, which persists once deposited in the lung. The initial results of this inhalation biopersistence study in rats that demonstrates this difference were reported in Bernstein et al. (2003). This article presents the full results through 1 yr after cessation of the 5-day exposure. This study was based upon the recommendations of the European Commission (EC) Interim Protocol for the Inhalation Biopersistence of synthetic mineral fibers (Bernstein & Riego-Sintes, 1999). In addition, the histopathological response in the lung was evaluated following exposure. In order to quantify the dynamics and rate by which these fibers are removed from the lung, the biopersistence of a sample of commercial-grade chrysotile from the Coalinga mine in New Idria, CA, of the type Calidria RG144 and that of a long-fiber tremolite were studied. For synthetic vitreous fibers, the biopersistence of the fibers longer than 20 µm has been found to be directly related to their potential to cause disease. This study was designed to determine lung clearance (biopersistence) and the histopathological response. As the long fibers have been shown to have the greatest potential for pathogenicity, the aerosol generation technique was designed to maximize the number of long respirable fibers. The chrysotile samples were specifically chosen to have 200 fibers/cm 3 longer than 20 µm in length present in the exposure aerosol. These longer fibers were found to be largely composed of multiple shorter fibrils. The tremolite samples were chosen to have 100 fibers/cm 3 longer than 20 µm in length present in the exposure aerosol. Calidria chrysotile has been found to be one of the most rapidly cleared mineral fibers from the lung. The fibers longer than 20 µm in length are cleared with a half-time of 7 h. By 2 days postexposure all long fibers have dissolved/disintegrated into shorter pieces. The fibers between 5 and 20µm in length were cleared with a half-time of 7 days. This length range represents a transition zone between those fibers that can be fully phagocytosed and cleared as particles and the longer fibers that cannot be fully engulfed by the macrophage. The fibers/objects shorter than 5 µm in length were cleared with a half-time of 64 days, which is faster than that reported for insoluble nuisance dusts such as TiO 2 . By 12 months postexposure, 99.92% of all the remaining chrysotile was less than 5 µm in length. Following the 5 days of repeated exposure to more than 48,000 chrysotile fibers/cm 3 (190 fibers L > 20 µm), histopathological examination revealed no evidence of any inflammatory reaction either after the cessation of the last exposure or at any time during the subsequent 12-mo period. This is in marked contrast to the amphibole tremolite, which was also investigated using the same inhalation biopersistence protocol. The long tremolite fibers, once deposited in the lung, remain over the rat’s lifetime with essentially an infinite half-time. Even the shorter fibers, following early clearance, also remain with no dissolution or further removal. At 365 days postexposure, there was a mean lung burden was of 0.5 million fibers L > 20 µm and 7 million fibers 5-20 µm in length with a total mean lung burden of 19.6 million fibers. The tremolite exposed rats, even with exposure to 16 times fewer total fibers than chrysotile, showed a pronounced inflammatory response with the rapid development of granulomas as seen at day 1 postexposure, followed by the development of fibrosis characterized by collagen deposition within these granulomas and by 90 days even mild interstitial fibrosis. With the short exposure, this study was not designed specifically to evaluate pathological response. however, it is quite interesting that even so there was such a marked response with tremolite. These findings provide an important basis for substantiating both kinetically and pathologically the differences between chrysotile and the amphibole tremolite. As Calidria chrysotile has been certified to have no tremolite fiber, the results of the current study together with the results from toxicological and epidemiological studies indicate that this fiber is not associated with lung disease.

Nog steeds is niet helemaal duidelijk hoe asbest kanker veroorzaakt. Men denkt dat ijzer daarbij een rol speelt. De meest gevaarlijke asbestsoorten hebben een relatief hoog ijzergehalte. Baldys en Aust onderzochten de werking van asbestvezels en ijzer op de Epidermale Groei Factor Receptor (EGFR) in menselijke epitheel en mesotheelcellen uit long en longvlies. Zij gebruikten drie soorten asbest, t.w. crocidoliet, amosiet en chrysotiel met respectievelijk 27, 27 en 2% ijzer. Zij vonden dat ingekapselde crocidoliet asbestvezels de EGFR receptor inactiveerden en daarmee indirect de celdeling kunnen ontregelen. IJzer lijkt daarbij een mediërende werking te hebben. Baldys, A. & Aust, A.E. (2005). Role of Iron in Inactivation of Epidermal Growth Factor Receptor after Asbestos Treatment of Human Lung and Pleural Target Cells. American journal of respiratory cell and molecular biology. vol. 32, afl. 5, pag. 436-442 (7).
American Journal of Respiratory Cell and Molecular Biology. Vol. 32, pp. 436-442, 2005

Abstract

Although the mechanism by which asbestos causes cancer remains unknown, iron associated with asbestos is thought to play a role in the pathogenic effects of fibers. Here, we examined the effects of asbestos on the epidermal growth factor receptor (EGFR) in human lung epithelial (A549) cells, human pleural mesothelial (MET5A) cells, and normal human small airway epithelial (SAEC) cells. Treatment of A549, MET5A, and SAEC cells with asbestos caused a significant reduction of EGFR tyrosine phosphorylation. This was both time- (15 min to 24 h) and concentration-dependent (1.5, 3, and 6 µg/cm2) in A549 cells. Also, treatment with 6 µg/cm2 crocidolite for 24 h diminished the phosphorylation levels of human EGFR 2 (HER2). Exposure of A549 cells to 6 µg/cm2 crocidolite for 3–24 h resulted in no detectable Y1045 phosphorylation and no apparent degradation of the EGFR. Inhibition of fiber endocytosis resulted in a considerable inhibition of EGFR dephosphorylation. Removal of iron from asbestos by desferrioxamine B or phytic acid inhibited asbestos-induced decreases in EGFR phosphorylation. The effects of crocidolite, amosite, and chrysotile on the EGFR phosphorylation state appeared to be directly related to the amount of iron mobilized from these fibers. These results strongly suggest that iron plays an important role in asbestos-induced inactivation of EGFR.

Australische onderzoekers hebben een bloedtest ontwikkeld die kan helpen bij het opsporen van mesothelioom. De niet invasieve test, Mesomark genaamd, werd ontwikkeld door onderzoekers van de Universiteit van West Australië. In Australië krijgen ongeveer 700 mensen per jaar deze ziekte.

Bron: The Advertiser, 20 april / The West Australian, 19 april.

The Advertiser

April 20, 2005 Wednesday

HEADLINE: Breakthrough

AUSTRALIAN researchers have developed a world-first blood test which could help people worldwide in the early detection of mesothelioma, a deadly asbestos-related cancer of the lung lining. The non-invasive blood test developed by University of Western Australia Professor Bruce Robinson and researchers is a breakthrough in the early detection of the disease. About 700 people each year are diagnosed with the disease in Australia, which has the highest reported incidence in the world.

The West Australian (Perth)

April 19, 2005 Tuesday

HEADLINE: Test offers hope on mesothelioma

Rockingham man David Saw believes a new blood test for mesothelioma, which is being launched today, could have saved him a three-day hospital visit and a lot of trauma.

Mr Saw went to his doctor last year believing he had pulled a muscle.

He was suffering chest pain and shortness of breath.

After a CAT scan and biopsy, it was revealed the 49-year-old had contracted the deadly lung cancer from working with asbestos as a young man.

“A test would have been a lot easier, I ended up in hospital and they had to cut me open,” he said.

The test, called MESOMARK, will be available from general practitioners or specialists who can order it from a pathology provider.

The head of the mesothelioma research team at Sir Charles Gairdner Hospital which developed the test, Professor Bruce Robinson, said it would not only help in diagnoses of the disease, but also in treatment.

“Until now you could only gauge whether treatment was working effectively by doing a CAT scan, and they’re difficult to do. With this test, we can gauge treatment and also diagnose it at an earlier stage,” Professor Robinson said. Biopsy would be needed to confirm diagnosis.

The blood test measures levels of a substance called soluble mesothelin-related peptide, a distinctive biomarker released by mesothelioma cells.

About 700 Australians are diagnosed with the disease every year and WA has the highest rate of mesothelioma in the world.

Asbestos Diseases Society of Australia president Robert Vojakovic said the test could help the possible 6000 people who were children in Wittenoom when the town still had an active blue asbestos mine.

Bij mannen die geen asbestose (“stoflongen” door asbest) hebben komt asbestgerelateerde longkanker vaker voor dan was verwacht. “Pleurale plaques” (een goedaardige verdikking van het borstvlies) is een belangrijke voorspeller van asbestgerelateerde longkanker. Deze nieuwe inzichten komen uit een onderzoek van meer dan 10 jaar onder 4000 Amerikaanse mannen die aan asbest blootgesteld zijn geweest.
Increased lung cancer among asbestos workers with no evidence of asbestosis

Below, details of a new paper on asbestos and lung cancer, forwarded by Frank Mirer, director of health and safety at the US autoworkers’ union UAW.

The paper looks important for two reasons – firstly because of the lung cancer without asbestosis finding – in some jurisdictions official workers’ compensation schemes only pay benefits to lung cancer sufferers who also have asbestosis.

Secondly, the paper is valuable because it establishes the importance of pleural plaques as a predicator of lung cancer. Insurers and employers in the UK, USA and elsewhere are at this moment trying to play down the significance of the association between pleural plaques and asbestos.

Their motive is to reduce their compensation liabilities. One consequence of this might be a lower likelihood of diagnosis of pleural plaques (many of the health checks are the result of compensation inquiries), so we could lose our early warning system or “sentinel health event” for an enormous lung cancer risk. In the UK at the moment there are several thousand asbestos related lung cancers ever year – the combined annual death toll for asbestos related lung cancers and mesothelioma is expect to reach 10,000 within 20 years.

Yours, Rory

Rory O’Neill

International Federation of Journalists

Increased lung cancer among asbestos workers with no evidence of asbestosis

A very important study giving quantitative measures of risks of asbestos exposure was just published. The study is an important data source for evaluating medical criteria for compensation of asbestos exposed workers, now being discussed in Congress.

The project was a chemoprevention test whether Vitamin A – an antioxidant – protected against future effects of past asbestos exposure. The investigators had enrolled over 4,000 asbestos workers and followed them for over a decade. Recruitment must have been a huge task The chemoprevention study was terminated because Vitamin A increased the risk of lung cancer.

The study confirmed excessive rates of lung cancer among men with radiographic asbestosis, but also among workers with no evidence of asbestosis. Among workers with no evidence of asbestosis at baseline, men with more than 40 years’ exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years. Pleural plaques on the baseline x-ray and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer.

Hopefully, people with access to the full text of this study will comment further.

American Journal of Epidemiology 2005 161(3):260-270.

Predictors of Lung Cancer among Asbestos-exposed Men in the µ-Carotene and

Retinol Efficacy Trial

Mark R. Cullen1 , Matt J. Barnett2, John R. Balmes3, Brenda Cartmel1, Carrie

A. Redlich1, Carl A. Brodkin4, Scott Barnhart4, Linda Rosenstock5, Gary E.

Goodman2,6, Sam P. Hammar7, Mark D. Thornquist2 and Gilbert S. Omenn8,9

Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The µ-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years’ exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.

Dit artikel in de Lancet beschrijft de hypothese dat asbestblootstelling een oorzaak is van bindweefseltoename rond organen achter het buikvlies. De onderzoekers concluderen dat dat beroepsmatige asbestblootstelling een belangrijke oorzaak van deze aandoening is. RPF zou daarom als een beroepsziekte moeten worden gezien.

Bron: the Lancet, mei 2004.
Asbestos exposure as a risk factor for retroperitoneal fibrosis

Summary

Background Retroperitoneal fibrosis (RPF) is an uncommon disease with unknown causation in most cases. The pathognomonic finding is a fibrous mass covering the abdominal aorta and the ureters. Our aim was to clarify the possible role of asbestos exposure in the development of RPF. The hypothesis was based on the ability of asbestos to cause fibrosis in pulmonary and pleural tissue. Methods We undertook a case-control study of 43 patients with the disease (86% of eligible cases) treated in three university hospital districts of Finland in 1990-2001. For every patient, five population-based controls were selected, matched by age, sex, and central hospital district. We assessed asbestos exposure and medical history using a postal questionnaire and a personal interview. Of the 215 eligible controls, 179 (83%) participated in the study. Findings The age-standardised incidence of RPF was 0-10 (95% CI 0-07-0-14) per 100 000 person-years. The disease was strongly associated with asbestos exposure. The odds ratio (OR) was 5-54 (1-64-18-65) for less than 10 fibre-years of asbestos exposure and 8-84 (2-03-38-50) for 10 or more fibre-years, the attributable fraction being 82% and 89%, respectively. Other risk factors were previous use of ergot derivates (OR 9-92 [1-63-60-26]), abdominal aortic aneurysm (OR 6-73 [0-81-56-08]), and smoking for more than 20 pack-years (OR 4-73 [1-28-17-41]). Interpretation Our results show that occupational asbestos exposure is an important causal factor for RPF. For patients with work-related asbestos exposure, RPF should be considered an occupational disease.

Toomas Uibu, Panu Oksa, Anssi Auvinen, Eero Honkanen, Kaj Metsärinne, Heikki Saha, Jukka Uitti, Pekka Roto. Lancet 2004. 363: 1422-26.

Dit onderzoek beschrijft het geval van een 76 jarige vrouw met buikvlieskanker door het eten van met asbest besmet voedsel. Zij vertelde dat ze gewend was groenten te koken in regenwater dat verzameld werd uit een dakgoot van asbestgolfplaat.

Bron: Van Kesteren et al. (2004). International Journal of Gynecological Cancer.
Malignant peritoneal mesothelioma in a 76-year-old woman with a history of asbestos fiber ingestion

Author(s): P. Van Kesteren . J. Bulten . C. Schijf . H. Boonstra . L. Massuger

Source: International Journal of Gynecological Cancer Volume: 14 Number: 1 Page: 162 — 165

DOI: 10.1111/j.1048-891x.2004.14149.x

Publisher: Blackwell Publishing

Abstract: Abstract. van Kesteren P, Bulten J, Schijf C, Boonstra H, Massuger L. Malignant peritoneal mesothelioma in a 76-year-old woman with a history of asbestos fiber ingestion.

We report on a woman with malignant mesothelioma of the peritoneum. This is the first report of a subject with this disease who revealed a history of asbestos ingestion by asbestos-contaminated food. She presented with episodes of sweating and fever, ascites, and weight loss. At laparotomy, small tumor deposits were noted on the peritoneum. The omental cake was removed, together with the uterus, ovaries, and tubes which were all macroscopically normal. The diagnosis was established by immunohistochemistry and electron microscopy. Postoperatively, her complaints of fever and sweating disappeared. She refused further chemotherapy. After questioning her for asbestos exposure, she told us that, years ago, she used to prepare vegetables for cooking in rain water collected from a roof made of asbestos.