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workers, building, architect

NORA Manufacturing Sector Strategic Goals

9278345 - Validation Studies in Occupational Immunotoxicology

Start Date: 10/1/1999
End Date: 9/30/2011

Principal Investigator (PI)
Name: Raymond Biagini
Phone: 513-533-8196
Organization: NIOSH
Sub-Unit: DART
Funded By: NIEHS

Primary Goal Addressed

Secondary Goal Addressed


Attributed to Manufacturing


Project Description

Short Summary

Validation Studies in Occupational Immunotoxicology, a continuing, multifaceted project, is addressing the development of occupational asthma and other immunotoxic diseases in numerous industries. Current efforts are focusing on enhancing diagnostic capabilities for occupational hypersensitivity and autoimmune diseases using 3rd generation immunoassays or multiplexed autoantibody analysis for workers exposed to numerous allergens (latex proteins, flour and wheat in the baking industry, as well as other occupational allergens (fel d1), autoimmune toxicants and bioterror agents. This work will address needs in Manufacturing and Health Care and Social Assistance Sectors and is associated with Emergency Preparedness and Response, Immune and Dermal Diseases, Respiratory Disease, and Exposure Assessment Cross-Sectors.


This multifaceted project, addresses numerous aspects of occupational immunotoxicology. There are numerous ongoing and new serodiagnostic studies: 1) Measurement of specific IgE and IgG to wheat, flour dust and alpha-amylase in bakers in collaboration with the University of Utrecht, Utrecht, Netherlands; 2.) Using an assay developed in FY2005, for the multiplexed measurement of antibodies to anthrax, Y. pestis, staphylococcal enterotoxin B, F. tularensis and ricin we are going to measure antibody levels to a novel multivalent vaccine in primates - this study is being done in collaboration with USAMRIID; and 3) The presence of autoantibodies, particularly in high titers and with high affinity, is the first step in diagnosing occupational autoimmune disease. Previous methods involved performing numerous sequential analyses of nuclear autoantibodies (ANA) by enzyme-linked immunosorbent assays (ELISA) or other methods. Recent developments allow for the measurement of 9 ANAs simultaneously using a multiplexed fluorescence covalent microbead immunosorbent assay (FCMIA). We plan to extend these results by measuring the ratios of ANAs to serum levels of IgG, IgA and IgM in sera from systemic lupus erythematosus patients; 4) Using multiplexed methods we developed previously, we plan to continue to measure anti-anthrax PA IgG in sera from anthrax vaccinated US Marines and laboratory response network workers; 5). Allergies to cats are widespread in the US, the major allergen being Fel d1, a protein present in cat saliva and sebaceous gland exudates. Cat owners transport Fel d1 from their homes to public places, mainly by contamination of their clothes. Non-cat owners have potential exposure to cat allergens from this source at the workplace. If these non-cat owners are cat sensitive, these exposures may elicit worsening symptoms of cat allergy. In a new project, we plan to measure personal cat allergen exposure in the workplace and correlate this with symptoms and immunological measurements. BHAB is uniquely qualified and productive in developing new, innovative and creative methodologies to diagnose immune diseases and responses to vaccination to numerous infectious diseases and bioterror vaccines. This is done using new, more efficient methodologies. As such, we are called on by the foremost leaders in these areas for assistance when workloads using older, less efficient technologies either overwhelm their capacities or make projects undoable because of technology limitations. The methods we use are technologically challenging, but our long-term experience in performing them makes us individually unique. For example, the National Immunization Program (NIP) wanted to evaluate the effect of progesterone levels on adverse responses to the FDA cleared anthrax vaccine (AVA). AVA vaccination can elevate antibody levels to 3 anthrax toxins, protective antigen (PA), lethal factor (LF) and edema factor (EF). There were existing tests for PA, but no quantitative tests for LF and EF. We had developed a multiplexed fluorescence covalent microbead immunosorbent assay (FCMIA) to quantitate all 3 toxins simultaneously. Using our FCMIA, we supplied quantitative toxin antibody levels in over 500 subjects in days to the NIP. This would have taken numerous man-years to perform using existing technology and the results would have been qualitative. This project is funded until 2011 and has resulted in over 23 peer-reviewed journal articles and over 55 abstracts presented at national and international meetings since 2000.


• Conduct internet searches using the ISI Web of Science to determine citation counts for our publications

• Continue to interact with partners to determine how they are using the information form this project

• Requests for collaborative research projects will be tracked as an indicator of successful marketing of our research

• Invited presentations will be tracked as an indicator of successful marketing of our research

Mission Relevance

An estimated 11 million workers in a wide range of industries and occupations are potentially exposed to at least one of the numerous agents known to be associated with the development of occupational asthma or other immunotoxic diseases. Occupational factors have been associated with up to 15% of the disabling asthma cases in the United States, including 1.4 million health care workers potentially exposed to latex products. Immunosuppression from exposure to occupational agents is less well understood. Occupational autoimmune disease has been demonstrated from exposure to occupational and environmental agents such as silica, solvents and ultraviolet radiation. Recent developments have allowed for the introduction of diagnostic instrumentation to detect frank immune diseases and immune system degradation earlier in their progression such that successful interventions can be applied. The immune system can also be used as a sentinel for exposure as specific antibodies can serve as biomarkers of exposure and effect. In general, this project applies state-of-the-art immunodiagnostic techniques to exposed occupational cohorts in order to detect and study immune diseases early in their progression. This project addresses the Healthcare and Social Assistance Strategic Goal 1

(09PPHSASG1): Reduce the incidence and severity of work-related accidents and injuries to workers in the healthcare and social assistance sector and Manufacturing Strategic Goal 5 (09PPMNFSG5): Reduce the number of respiratory conditions and diseases due to exposures in the manufacturing sector. This project directly addresses the following cross-sector goals with their activity/outcomes: Exposure Assessment Intermediate Goal 2.7 (09PPEXAIG2.7): develop direct reading or field deployable sensors or methods that can measure low concentrations or multiple analytes simultaneously and activity/output goal 2.7.1 (09PPEXAAOG2.7.1): assessment of stakeholders needs for direct reading or field deployable sensors or methods that can measure low concentrations or multiple analytes simultaneously; Immune Intermediate Goal 1.3 (09PPIMUIG1.3): contribute to the identification and advancement of knowledge regarding occupational allergens causing allergic rhinitis, asthma or other significant health effects for workers in various sectors and industries and activity/output goal 1.3.1 (09PPIMUAOG1.3.1) develop a fully characterized model of occupational asthma, including the contribution of inflammatory cells, antibodies, cytokines, and specific allergic mediators, to study potential biomarkers of the disease and possible disease intervention; Emergency Preparedness and Response Goal 1.6 (09PPEPRIG1.6): develop appropriate medical screening and monitoring programs for workers involved in rescue and recovery at the location of the threat and performance measure 1.6.1 (09PPEPRIG1.6.1): by 2014, issuance of a recommended medical screening/monitoring program, with flexibility for tailoring to event-specific circumstances; Respiratory Disease Intermediate Goal 1.1 (09PPRDRIG1.1): prevent and reduce the full range of work-related asthma (WRA), including work-exacerbated asthma; occupational asthma; and irritant-induced asthma and activity/output goal 1.1.1 (09PPRDRAOG1.1.1): assess the extent, severity, burden, and risk factors for work related asthma and approaches to prevention across a broad range of industries and occupations. This project aims to achieve NIOSH r2p goals to reduce illness and injury by increasing workplace use of effective NIOSH research findings and works with partners to focus research to translate research findings into practice, target dissemination efforts, and evaluate and demonstrate the effectiveness of these efforts in improving worker health and safety.