Residents of Libby, MT, have been exposed to asbestiform minerals (Libby amphibole, or LA) including tremolite and other regulated amphibole types as well as unregulated fibers including winchite and richterite (Meeker et al. 2003) since the 1920s through the operation of a vermiculite mine and processing plant until 1990, when the mine was closed. Exposure prior to 1990 had been occupational, para-occupational (via residence with an LA-exposed worker) and/or environmental;the main exposure pathways have been detailed by Peipins (2003). Since closure of the mine, people in the Libby area have continued to be exposed to residual asbestos contamination principally via disturbance of LA-containing materials in place, mitigated by site cleanup efforts begun by the EPA in 2000. The health consequences of exposure to LA in the Libby community have been summarized by the ATSDR (2003) and include increased rates of asbestosis and pleural scarring, increased mortality from asbestosis, lung cancer and mesothelioma, and an increase in the prevalence of autoimmune antibody abnormalities and diagnosed systemic autoimmune diseases. The planned studies seek to address several questions regarding the health consequences of exposure to LA: 1) the possible particular risk of exposure during childhood, including effects at low cumulative exposure levels;2): the unusually rapid and impairing character of LA-related pulmonary disease;and 3) non-pulmonary health effects, specifically autoimmune disorders. The High School Graduates Study will investigate the consequences of exposure to LA that occurs only during childhood and adolescence and will permit an evaluation of the human health effects of exposure at low cumulative levels, an issue of considerable importance to the development of a Baseline Risk Assessment and determinations of levels of residual contamination of the environment that can be considered safe for the Libby community, including children. There is considerable clinical evidence that pulmonary disease associated with exposure to LA has a more aggressive course with more rapid progression of scarring and loss of lung function than is seen among workers heavily exposed to commercially used forms of asbestos. The CT Progression Study will evaluate whether asbestos-related scarring of the lung parenchyma and/or pleura evident on chest CT scans following only environmental exposure to LA progresses more rapidly than is seen in long-term asbestos insulators with high cumulative exposure levels. Non-pulmonary consequences of LA exposure, i.e. autoimmune abnormalities and diseases, will be evaluated in the Autoimmune Outcomes Study by assessing the prevalence of autoimmune antibody abnormalities and physician-diagnosed autoimmune diseases in relation to exposure measures.

Public Health Relevance

LIBBY EPIDEMIOLOGY RESEARCH PROGRAM Narrative: This proposal benefits from the strengths of the Center for Asbestos Related Disease (CARD) and its Medical Director, B. Black, M.D., and Program Manager, Kimberly Rowse, R.N., who have accumulated unmatched experience in the clinical evaluation and management of LA-associated disease in thousands of Libby residents. The CARD enjoys a close working relationship with the St. John's Lutheran Hospital in Libby, the confidence of the Libby community at large and the loyalty of the great majority of the over 2500 patients in its patient roster, and therefore represents the keystone in the overall research effort proposed. The PI of the grant, S. Levin, MD, has worked with Dr. Black and CARD as a consultant and scientific advisor since 2001, assisting in the development of all aspects of the CARD Screening Program, including the data collection instruments. Dr. Levin has considerable experience building and developing research activities within large-scale clinical epidemiological programs, having been Principal Investigator for the CDC-funded World Trade Center Worker and Volunteer Medical Screening and Medical Monitoring Programs in which over 26,000 responders were examined with a standardized protocol from 2002 - 2006.

Agency
National Institute of Health (NIH)
Institute
Agency for Toxic Substances and Disease Registry (ATSDR)
Type
Research Project (R01)
Project #
5R01TS000099-02
Application #
7932242
Study Section
Special Emphasis Panel (ZTS1-FXR (10))
Program Officer
Mehta, Paul
Project Start
2009-09-30
Project End
2014-09-29
Budget Start
2010-09-30
Budget End
2011-09-29
Support Year
2
Fiscal Year
2010
Total Cost
$965,000
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Miller, Albert; Szeinuk, Jaime; Noonan, Curtis W et al. (2018) Libby Amphibole Disease: Pulmonary Function and CT Abnormalities in Vermiculite Miners. J Occup Environ Med 60:167-173
Gilmer, John; Harding, Tanner; Woods, Linda et al. (2017) Mesothelial cell autoantibodies upregulate transcription factors associated with fibrosis. Inhal Toxicol 29:10-17
Taioli, Emanuela; Wolf, Andrea S; Flores, Raja M (2015) Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. Ann Thorac Surg 99:472-80
Noonan, Curtis W (2015) Pleural plaques and their effect on lung function: conclusions based on insufficient power to reject the null. Chest 147:e124
Taioli, Emanuela; Wolf, Andrea S; Moline, Jacqueline M et al. (2015) Frequency of Surgery in Black Patients with Malignant Pleural Mesothelioma. Dis Markers 2015:282145
Black, Bradford; Szeinuk, Jaime; Whitehouse, Alan C et al. (2014) Rapid progression of pleural disease due to exposure to Libby amphibole: ""Not your grandfather's asbestos related disease"". Am J Ind Med 57:1197-206
Ferro, Aaron; Zebedeo, Christian Nash; Davis, Chad et al. (2014) Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice. J Immunotoxicol 11:283-90
Taioli, Emanuela; Wolf, Andrea S; Camacho-Rivera, Marlene et al. (2014) Women with malignant pleural mesothelioma have a threefold better survival rate than men. Ann Thorac Surg 98:1020-4
Serve, Kinta M; Black, Brad; Szeinuk, Jaime et al. (2013) Asbestos-associated mesothelial cell autoantibodies promote collagen deposition in vitro. Inhal Toxicol 25:774-84