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NIOSH Respiratory Diseases Research Program

Evidence Package for the National Academies' Review 2006-2007

6.4 Understanding the Effect and Mechanisms of Occupational Exposures on Pulmonary Susceptibility to Infection

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Epidemiologic data suggest that inhalation of air contaminants generated in the workplace and pollutants generated in the environment may be associated with increased incidence and severity of acute respiratory infections (A6-97).174 The resulting reduced productivity represents an important cost to industry and the nation. The cost to employers of patients with respiratory infections in the U.S. was $112 billion in 1997 and $132 billion in 2005, including costs of medical treatment and time lost from work (A6-98).175 Understanding the possible adverse health effects of exposure to various air contaminants (e.g. mixed dusts, diesel exhaust particulates, and welding fumes) is essential to risk assessment and the development of prevention strategies that will impact a large population of workers.

 Issue

 Exposure to bottom ash is common among boilermakers during the servicing of electrical generating plants using fossil fuels. As many as one million U.S. workers in the construction, transportation, mining, and other industries have at least part-time exposure to diesel exhaust particulate (A6-99).176 Thousands more workers are exposed daily to other types of particulate matter, such as welding fume (estimates indicate that there are over 358,000 full-time welders in the U.S. (A6-100),177 silica, or asphalt fume. With the emergence of nanotechnology, hundreds of thousands of workers are now being potentially exposed to nanoparticles, such as single-walled carbon nanotubes. Repeated inhalation exposure to different workplace particulates has been observed to predispose some workers in certain industries (e.g. welders, boilermakers) (A6-101)178 to an increased prevalence of respiratory infections.

Evidence verifying a potential link and an understanding of the mechanisms by which workers exposed to inhaled particulate matter could become susceptible to infection and possible immunosuppression is incomplete. An understanding of possible adverse health effects of exposure to these mixed exposures is essential to risk assessment and to the development of prevention strategies and could beneficially impact on a large population of workers.

Approach

 Evidence verifying a potential link and an understanding of the mechanisms by which exposed workers could become susceptible to infection is incomplete. RDRP scientists started conducting research in this area when DOD requested collaboration on a study of the effects of diesel exhaust particulate on the ability of alveolar macrophages to fight pulmonary infections in garage mechanics.

RDRP is conducting research on: the magnitude of lung injury and inflammation after occupational exposures; the effects of occupational exposures on the lungs’ natural defenses and antimicrobial activity; and the magnitude of pulmonary infection compared to control animals not pretreated with an exposure agent (e.g. crystalline silica, diesel exhaust particulate, asbestos fibers, or welding fumes). Elucidation of these mechanisms by RDRP will enable development of guidance to educate workers and employers about health risks (previously largely unrecognized) associated with exposure to these agents and to potentially prevent adverse health effects.

 Outputs and Transfer

 RDRP scientists have produced 35 presentations, 33 peer-reviewed manuscripts, and have organized one conference in this area of research (A6-102). 

RDRP studies have found that exposure of rats to diesel exhaust particulate, but not carbon black (the carbonaceous core of diesel exhaust particulate without the organic compounds adsorbed onto it), significantly increased the susceptibility of lungs to Listeria monocytogenes infection ( 13,  A6-103).

RDRP scientists have reported that sub-chronic exposure to stainless steel welding fume may have a greater effect on the pulmonary clearance of L. monocytogenes as compared to mild steel fumes and demonstrated that silicosis impairs host defense to pulmonary L. monocytogenes infection. They have also developed a model to assess lung clearance function and the pulmonary clearance of a bacterial agent, L. monocytogenes, after exposure to diesel exhaust particulate, different welding fumes, and silica (14-17, A6-104, A6-105, A6-106, A6-107).

RDRP scientists have developed an innovative, automated, robotic welding fume generator and inhalation exposure system for laboratory animals to simulate real workplace exposures (18, A6-108). The system comprised a programmable six-axis robotic welding arm, a water-cooled arc welding torch, and a wire feeder that supplies welding wire to the torch at a programmed rate. Gas metal arc and flux-cored arc welding processes can be simulated to investigate how welding fumes affect health.

RDRP scientists have determined the mechanisms of how workers such as welders in construction and boilermakers who have inhaled metal-containing particles of mixed composition become more susceptible to infection than the general population. RDRP research on occupational respiratory diseases in welders won the 2006 American Welding Society Safety and Health Award. This award is given annually to an individual who best encourages the advancement of welder safety and health through research, education activities, development of safe practices or the dissemination of knowledge through publications or other means, thereby, fostering public awareness, welfare and education (A6-109).

 Intermediate Outcomes

 RDRP research publications in this area (A6-102) have been extensively cited by other scientists (over 280 times).

RDRP research is used by other agencies to write documents and develop strategies. EPA’s Office of Research and Development, National Center for Environmental Assessment, used RDRP research findings to develop their document “Health Assessment Document for Diesel Engine Exhaust” (A6-110).

This work is of such interest to DOD that it entered into an Interagency Agreement with NIOSH titled "Effects of Mixed Dusts on Asthma and Pulmonary Infectivity" (A6-111). DOD plans on using the results of the study conducted under this Interagency Agreement to assist in the eventual development of exposure standard for diesel exhaust particulate. DOD estimates such as standard could have the potential to protect over one million workers exposed to diesel exhaust at work. DOD is also providing funding for RDRP scientists to research pulmonary and central nervous system toxicity associated with welding fume exposure in a project entitled “Neurotoxicity After Pulmonary Exposure to Welding Fumes Containing Manganese” (A6-112).

NTP funded RDRP scientists to study the lung immune responses associated with welding fume exposure. This NTP-NIOSH Interagency Agreement was entitled “Design, Construction, and Characterization of a Welding Fume Generation and Inhalation Exposure System.” NTP will use a model of the welding fume generator and inhalation system that was developed by RDRP scientists for NTP-sponsored, chronic neurotoxicity, carcinogenicity, and lung immune studies (A6-113).

 What’s Ahead

 Scientific evidence from RDRP studies and others indicates that particulate matter composed of specific metals (e.g. chromium, nickel) may alter immune cell function when inhaled. RDRP studies will evaluate the effects of particles composed of a complex mixture of metals (e.g. welding fume) on lung defenses against infection. To this end, improved methods of generating welding fume in the laboratory to expose cellular systems and animal models will be developed. Long-term animal exposures will be performed to assess the effect of welding fume inhalation on lung and systemic immune responses. RDRP will also determine how diesel exhaust particulate changes the chemical balances in the lungs that may render them more susceptible to bacterial infection; characterize the effect of diesel exhaust particulate on pulmonary metabolic enzymes; evaluate the roles of these enzymes in diesel exhaust particulate-mediated mutagenicity/genotoxicity in the lung; and characterize the DNA damage in diesel exhaust particulate-exposed lungs.

The desired outcome for this RDRP research is an understanding of possible adverse health effects of exposure to mixed dusts. Having this understanding could lead to the development of prevention strategies that reduced susceptibility to respiratory infectious diseases in a large population of workers.

 

174. Schwartz J [1994]. Air pollution and daily mortality: a review and meta-analysis. Environ Res 64:36–52.

175. Birnbaum HG, Morley M, Greenberg PE, Colice GL [2002]. Economic Burden of Respiratory Infections in an Employed Population. Chest 122;603-611.

176. U.S. Department of Labor, Occupational Safety and Health Administration, Safety and Health Topics – Diesel Exhaust [2006].
External link: http://www.osha.gov/SLTC/dieselexhaust/index.html. Accessed September 6, 2006.

177. Bureau of Labor Statistics [2006]. Welders, cutters, solderers, and brazers. In: Occupational Employment Statistics: Occupational Employment and Wages, May 2005. U.S. Department of Labor
External link: http://www.bls.gov/oes/current/oes_nat.htm#b47-0000. Accessed September 6, 2006.

178. Howden DG [1988]. Respiratory hazards of welding: occupational exposure characterization. Am. Rev. Respir. Dis. 138:1047–1048.