Respiratory Diseases Research at NIOSH: Reviews of Research Programs of the National Institute for Occupational Safety and Health (2008)

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4 Recommendations The previous chapter summarized the evaluation committee’s reviews of the components of the National Institute for Occupational Safety and Health (NIOSH) Respiratory Diseases Research Program (RDRP) and discussed emerging issues r ­ elated to each of the five goals listed by the program in the evidence package. This chapter provides the RDRP with specific recommendations for each of the strategic goals and for issues that cut across the programs. Major recommenda- tions are summarized in Box 4-1. Greater detail is then presented for each goal and cross-cutting issue. For each of them, a brief summary of the goal or issue and the potential impact of relevant activities is presented; then specific recommendations are provided for the RDRP to consider when planning future work. Finally, recom- mendations on broader programmatic goals are presented. Strategic Goal 1: Prevent and reduce work-related airway diseases Work-Related Airway Diseases The RDRP has divided work-related airway diseases into two main categories, work-related asthma (WRA) and fixed obstructive airway disease. The RDRP identified four subgoals related to WRA in the evidence package. Because the con- tribution of occupational exposures to the burden of adult asthma is high, work in pursuit of the four WRA subgoals can have a potentially large impact through 132 

R e c o m m e n dat i o n s 133 improved occupational safety and health among the U.S. workforce. This potential has been demonstrated by previous RDRP WRA activities. The evaluation com- mittee is concerned, however, that the new second National Occupational Research Agenda (NORA2) industrial-sector-based priority-setting approach may lead to a decreased emphasis on needed asthma-focused research. Recommendation: The RDRP should systematically evaluate whether WRA activi- ties are being weakened under the new NORA2 approach. Other specific recommendations to enhance the relevance and impact of the RDRP’s WRA research activities are organized by the subgoals as delineated by NIOSH. Subgoal: Preventing and reducing natural rubber latex asthma and allergy among health care workers. Recommendation: The RDRP’s efforts to prevent latex allergy and asthma have been highly successful. RDRP investigators have documented that the prevalence of latex sensitization fell as a result of the intervention effort that began with the 1996 NIOSH Alert. The evaluation committee recommends that the RDRP assess how its successful work on latex and asthma can be extended to other high-molecular- weight sensitizers that cause occupational asthma and occupational rhinitis. Subgoal: Preventing and reducing WRA in the isocyanate production industry. Recommendation: Previous RDRP work on diisocyanates directly addressed the most common low-molecular-weight sensitizing cause of asthma in the developed world and led to important knowledge that has been transferred to prevent disease. The committee recommends that the RDRP assess how its research on ­diisocyanates and asthma can be extended to other low-molecular-weight sensitizers that cause occupational asthma, especially in terms of mechanisms of disease. Subgoal: Preventing and reducing WRA related to nonindustrial indoor environ- mental quality. Recommendation: While the indoor environmental quality work of the RDRP is judged to be relevant to occupational health and safety in the general sense, it is not always clearly related to WRA. The committee recommends that the RDRP reexamine whether its indoor air-quality-related research is sufficiently relevant to work-aggravated asthma. Moreover, the RDRP should reevaluate the relative commitment of resources to indoor air-quality investigations, as the health effects are often not airway in nature (that is, systemic or neurologic complaints). 

134 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH Box 4-1 Summary of Recommendations Strategic Goal 1: Prevent and Reduce Work-Related Airway Diseases Improve detection of work-related asthma, work-related fixed obstructive airway dis- ease, and relevant exposures. The evaluation committee is concerned that the new, second National Occupational Research Agenda industrial-sector-based priority-setting approach may lead to a decreased emphasis on needed disease-focused research related to airway diseases. The RDRP should systematically evaluate whether work-related asthma (WRA) activities are being compromised under the new approach. Because the contribution of occu­pational exposures to the burden of adult asthma is high, work in pursuit of the four WRA subgoals (preventing and reducing rubber-latex asthma and allergy among health- care ­workers, preventing and reducing work-related asthma in the isocyanate-production industry, preventing and reducing work-related asthma related to nonindustrial indoor envi- ronmental quality, and improving detection of work-related asthma and relevant exposures, described in more detail in Chapter 4), can have a potentially large impact on improved occupational safety and health among the U.S. workforce. In terms of chronic obstructive pulmonary disease (COPD), understanding the contribution of occupational exposures is difficult. To understand this issue, the evaluation committee strongly recommends that, for planning preventive strategies, the RDRP continue to support population-based ­studies of associations between occupational exposures and COPD to better define groups of ­workers at greatest risk. In the flavoring industry, the RDRP response to the identification of ­diacetyl- induced bronchiolitis obliterans has led to surveillance efforts in multiple locations in an effort to detect and prevent disease. The evaluation committee agrees that continued surveil- lance, prevention of exposures, and mechanistic research to better understand this disease should continue to be a high priority for the RDRP. Strategic Goal 2: Prevent and Reduce Work-Related Interstitial Lung Diseases Continue and expand efforts to prevent coal workers’ pneumoconiosis (CWP), silicosis, fiber-induced interstitial lung disease, and chronic beryllium disease. The activities related to interstitial lung diseases form a critical core of the RDRP and have provided well-documented improvements in occupational health. It is important that the RDRP continue to expand its activities in these areas so it can build on its earlier successes while responding to new challenges. In particular, the committee recommends giving high priority to research into the increasing incidence of CWP, “hot spots” of rapidly progressive CWP, and the possible role of concentration and duration of exposure, coal rank, and silica level in the rapidly pro- gressive cases of CWP. Other important areas of research recommended by the evaluation committee are experimental studies of silica-induced cytotoxicity and fibrogenesis and the development of control technologies, including silica substitutes, particle surface coatings, and dust reduction measures. In addition, fibers that are asbestiform, such as vermiculite, or 

R e c o m m e n dat i o n s 135 of synthetic origin, such as nylon flock and refractory ceramic fiber, require continued study with attention to fiber characteristics, such as cleavage fragments and low-level exposures, respectively. The committee recommends that the RDRP target work in support of a new recommended OSHA standard that would lead to improved controls to reduce airborne and dermal exposure to beryllium in all workplaces where it is used. The committee recommends that the effectiveness of digital radiography in CWP surveillance should be an important continuing research priority, which will extend to all interstitial lung diseases. Strategic Goal 3: Prevent and Reduce Work-Related Infectious Respiratory Diseases Continue to support efforts to protect workers from occupational exposures and to define mechanisms that make workers susceptible to respiratory infections. Enhance surveil- lance for outbreaks of known occupational respiratory infections as well as emerging respira- tory infections. Develop an overarching structure for the infectious disease component and coordinate with other federal agencies to adopt technologies for the detection of bioterrorism agents for the protection of workers. The RDRP’s efforts on infectious diseases are appro- priately concentrated on preventing infection with respirator controls and understanding the mechanisms that underlie susceptibility. More robust surveillance for disease outbreaks is needed in occupational settings. These three approaches represent NIOSH’s primary tools to prevent and reduce known and unknown (emerging) respiratory infectious diseases. The committee recommends that the RDRP collect specific occupational TB surveillance data and explore ways to improve TB surveillance. It also should consider dropping its subgoal of preventing outbreaks of histoplasmosis, because no new RDRP research is planned and no resources are available for specific surveillance activities. Strategic Goal 4: Prevent and Reduce Work-Related Respiratory Malignancies Develop a comprehensive plan for addressing respiratory malignancies in the workplace while assuring the integration of this plan with NIOSH and other federal agency research program efforts to study malignancies. Refocus research on diagnostic tools to research on biomarkers of exposure or early detection of risk specific to occupational cohorts. The impact of the respiratory malignancies program has been strong with regard to the three specific carcinogenic exposures listed as subgoals by the RDRP: hexavalent chromium, silica, and diesel exhaust. Ongoing research on respiratory malignancies resulting from workplace exposures continues to address challenging problems related to occupational lung cancer risk, and the RDRP has been effective in engaging stakeholders from industry and the workforce. To enhance its efforts, the RDRP needs to develop, in collaboration with other relevant federal agencies (National Cancer Institute, National Institute of Environmental Health Sciences, Food and Drug Administration, Department of Defense, Department of Labor), a coordinated planning process to address occupational cancer risks to provide a continued 

136 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH Box 4-1 Continued comprehensive approach to detection, surveillance, and prevention. The committee recom- mends that the RDRP ensure that respiratory malignancies are well integrated into an overall program of occupational cancer research, and not arbitrarily separated from those efforts. The RDRP should consider refocusing its research on biomarkers for early detection to biomarkers of exposure or to early detection that addresses the needs of specific workers at high occupational risk of contracting lung cancer. The RDRP should continue efforts to develop and validate exposure methods for diesel particulate matter, especially in the pres- ence of other sources of carbon aerosols, and to validate the methods used to measure diesel particulate matter in coal mines. The RDRP should consider developing long-term follow-up of workers exposed to asbestos and should consider enhancing surveillance for asbestos-related risks. Strategic Goal 5: Prevent Respiratory and Other Diseases Potentially Resulting from Occupational Exposures to Nanomaterials NIOSH should continue to play a leading role in informing and guiding national and international efforts to address potential occupational hazards and risks associated with the use of manufactured nanomaterials. The growing recognition of the usefulness of nano­ materials in various industrial applications has created an urgent need to study the potential health effects of exposures to nanoparticles and methods to control exposures to these particles. The RDRP has taken a lead at the national and international levels to address these questions. The RDRP is well-suited to continue to develop exposure assessment methods and technology to monitor effective control of exposures to nanomaterials in work settings. The committee generally supports the RDRP’s research efforts on nanomaterial toxicity, exposure, and dose-response as part of a coordinated effort with other federal agencies and with appropriate prioritization for resource allocation to this problem. However, the com- mittee is concerned that available data—especially on human-health effects—might not be sufficient for quantitative risk assessments, and therefore that the RDRP should consider other approaches for dealing with the potential health impacts of these new materials in a precautionary manner. Cross-Cutting Issues Systems for Surveillance: NIOSH should provide appropriate resources for and engage in high-priority occupational disease surveillance. The United States is practically alone 

R e c o m m e n dat i o n s 137 among highly developed countries with regard to its lack of comprehensive surveillance of occupational diseases. The effectiveness of past NIOSH surveillance activities for coal- dust-related diseases, both CWP and COPD, highlight the importance of improved surveil- lance for other occupational respiratory disorders. NIOSH should engage in development and evaluation of surveillance methods as a high priority for surveillance of occupational respiratory disease, including methods to systematically review and analyze the findings of reports through the health hazard evaluation and technical assistance program and other data-collection approaches. Exposure Assessment: Develop a programmatic approach to the development of s ­ ampling and analytic methods that include exposure assessment scientists as an integral part of RDRP activities. Exposure assessment is a core component of occupational respira- tory disease research and prevention activities. However, the RDRP does not present an explicit or comprehensive focus on exposure assessment methods. Also, while the RDRP has focused on exposure assessment research in the past, no specific mention of current or future needs for exposure assessment activities is made explicitly. Emergency Response: The RDRP is encouraged to explore research strategies in its emergency response efforts. For example, the RDRP should assess how NIOSH-supported research and medical surveillance of World Trade Center disaster emergency responders and recovery workers may or may not be relevant to WRA, work-related fixed obstructive airway disease, interstitial lung disease, and possibly malignancies. The RDRP has made important contributions to the emergency response to recent disasters, including the World Trade Center and anthrax terror attacks, and hurricanes Katrina and Rita. However, much more could be learned about exposure-response relationships and ultimately about protect- ing emergency responders by conducting longitudinal cohort studies relating to catastrophic events. Information from emergency responses to toxicant exposures should be applicable to models of irritant-induced asthma, fixed airway obstruction, interstitial lung disease, and possibly even malignancies. The RDRP is encouraged to continue to develop cooperative work with other agencies that have mandates in infection and terrorism. RDRP Resource Allocation: The RDRP should prioritize all research proposals under consideration for funding, whether intramural or extramural, according to the RDRP strate- gic plan, which needs to be updated periodically. The RDRP has recently been organized to emphasize sector-based as opposed to disease-based research; an emerging issue is how research priorities for respiratory diseases that cut across sectors will be treated, particularly since the RDRP encompasses many divisions and laboratories across NIOSH. The RDRP needs systems to govern the awarding of extramural grants, contracts, and cooperative agreements and integrating the results of this external research into the intramural program. This system should ensure that unnecessary duplication and inappropriate expenditure on low-priority research projects are avoided. 

138 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH Subgoal: Improving detection of WRA and relevant exposures. Recommendation: The RDRP effort to improve the detection of WRA is of the highest relevance. While the quality of transfer activities to increase the awareness of WRA has been high, the evaluation committee recommends that greater atten- tion be paid to irritant-induced asthma given its relative importance as demon- strated by SENSOR data. Irritant-induced asthma warrants specific RDRP planning and goal setting that would build on accomplishments already made in this area. In addition, because of the key role of SENSOR data in surveillance for WRA, the RDRP should consider aggressively expanding this program beyond the collabora- tions that currently exist with four states as well as including “active” elements of surveillance. Chronic Obstructive Pulmonary Disease The RDRP identified four subgoals related to fixed obstructive airway diseases. As noted for WRA, the likely contribution of occupational exposures to the burden of chronic obstructive pulmonary disease (COPD) is high, and thus work in pursuit of the four fixed obstructive airway disease subgoals potentially can have a great impact on improved occupational safety and health among the U.S. workforce. Subgoal: Establish the work-relatedness of COPD. Recommendation: The previous research of RDRP investigators on the risk of COPD due to exposure to coal dust has been cited by a number of investigators and policy makers in their assessment of the links between dust exposure and COPD, not only for this specific industry but also as a measure of biologic plausibility for COPD related to other exposures. RDRP studies using data from the National Health and Nutrition Examination Survey (NHANES) have contributed to a greater recogni- tion of the role of occupational factors in the U.S. population burden of COPD. The committee strongly recommends that RDRP support for population-based studies of associations between occupational exposures and COPD continue in order to better define groups of workers at greatest risk and to assist in planning preventive strategies. RDRP efforts to retain spirometry and occupational exposure questions as components of NHANES are critical to better understanding of both the epide- miology of COPD in general and the occupational contribution to the population burden of this disease. Subgoal: Develop tools and identify at-risk workers in industries and occupations to assess the extent, severity, and burden of work-related COPD. Recommendation: RDRP work on spirometry, especially the development of new reference equations for normative values, has had a major impact on respira- 

R e c o m m e n dat i o n s 139 tory disease research in general and, more specifically, on preventing COPD. The evaluation committee encourages the RDRP to continue its valuable work on the use of spirometry for longitudinal surveillance of populations known to be at risk for fixed obstructive airway diseases. The committee also recommends that RDRP surveillance activities for work-related COPD and fixed obstructive airways among the general population be established (e.g., there is no SENSOR activity for these conditions). Finally, the committee thought that methods development in the analysis of longitudinal studies of pulmonary function warrants more intense investigations. Subgoal: Develop, test, and disseminate recommendations for preventing COPD in the workplace. Recommendation: The RDRP should continue its efforts to support this important subgoal. Subgoal: Prevent and reduce flavoring-related bronchiolitis obliterans. Recommendation: The RDRP response to the initial outbreak of diacetyl-induced bronchiolitis obliterans has led to surveillance efforts in multiple locations in an effort to detect and prevent disease. The committee agrees that preventing this disease, both in and of itself and as a model novel disease process, should be a high priority for the RDRP. Because RDRP inhalational toxicologic studies of agents newly recognized to cause airway diseases (e.g., diacetyl) have provided crucial information about mechanisms of disease, the committee strongly recommends that the capacity to conduct such studies be preserved. In addition, because work of the health hazard evaluation (HHE) and technical assistance program was key to identifying both diacetyl and nylon flock as agents that can cause respiratory disease, the RDRP should explore ways to systematically mine data from HHEs that share a common exposure and outcome focus. Strategic Goal 2: Prevent and reduce work-related interstitial lung diseases Much of the RDRP research on interstitial lung diseases is focused on pre- venting well-known pneumoconioses—coal workers’ pneumoconiosis (CWP), s ­ ilicosis, asbestosis—and chronic beryllium disease (CBD), although the program has contributed greatly to the identification of a disease process caused by exposure to nylon flock. Other newly discovered causes of interstitial lung disease associated with occupational exposures are likely to be identified in the future. The evaluation committee recommendations follow the organizational structure for Chapter 3 of the evidence package. 

140 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH Subgoal: Coal workers’ pneumoconiosis. Recommendation: NIOSH programs that were established in the 1970s, now under the purview of the RDRP, led to a marked reduction in miners’ exposure to respirable coal dust and a decreased annual prevalence of pneumoconiosis through 1999. Despite progress in reducing CWP, surveillance reports have identi- fied hot spots of rapidly progressive CWP in a geographic area that includes eastern Kentucky and southern West Virginia and, more alarmingly, an upward trend in disease prevalence in national data that may be accelerating. On the basis of these new surveillance data, the committee recommends that the RDRP reexamine the organization and efficacy of the CWP surveillance effort, including the interaction between NIOSH and the Mine Safety and Health Administration (MSHA), with additional focus on the adequacy of exposure assessment and compliance deter- mination. The evaluation committee also recommends that the RDRP continue to conduct research to further support MSHA’s adoption of the NIOSH recom- mended exposure limit of 1.0 mg/m3 as the actual permissible exposure limit for coal mine dust. The committee also recommends research on the possible role of coal rank and silica level in the rapidly progressive cases of CWP as well as other putative risk factors highlighted in NIOSH’s hot spot research. Finally, assess- ment of the strengths and limitations of digital radiography in pneumoconioses in ­ general and its effectiveness in silicons surveillance specifically should be an important continuing research priority. Subgoal: Silicosis. Recommendation: The RDRP has made significant contributions to mechanistic understanding of the toxicity of silica and prevention of silicosis. More work in both areas is needed. The evaluation committee recommends that the RDRP continue to support experimental studies of silica-induced cytotoxicity and fibrogenesis and the development of control technologies that include silica substitutes, particle sur- face coatings, and dust reduction measures. New or overlooked ongoing sources of silica exposure and silicosis should also receive appropriate programmatic attention from NIOSH. As for CWP, assessment of the effectiveness of digital radiography in silicons surveillance should be an important continuing research priority. Subgoal: Fiber-induced interstitial lung diseases. Recommendation: The RDRP has played an important role in the epidemio- logic evaluation of commercial products that contain asbestos. Despite the well- u ­ nderstood epidemiology of asbestos exposure and significant progress in the control of commercial asbestos exposures, more work needs to be done in this area, especially in terms of understanding fiber-specific cancer risk and the mechanisms of carcinogenesis. Fibers that are asbestiform, such as wincherite and tremolite, 

R e c o m m e n dat i o n s 141 which were found as containments of vermiculite mined in Libby, Montana, or of synthetic origin, such as nylon flock and refractory ceramic fiber, require contin- ued study with attention to fiber characteristics, such as cleavage fragments, and low-level exposures, respectively. The RDRP has also contributed greatly to our understanding of a newly discovered interstitial lung disease among nylon flock workers. While RDRP-assisted control efforts in this industry have been effective, continued surveillance of the industry is needed as well as attention to other, emerging fiber-related respiratory health risks. Subgoal: Chronic beryllium disease. Recommendation: The RDRP has made substantial contributions to our under- standing of the risks of sensitization to beryllium and progression to CBD. RDRP epidemiologic studies have documented that the Occupational Safety and Health Administration (OSHA) permissible exposure limit does not prevent sensitization or the onset of CBD. Current RDRP efforts are appropriate, but the committee rec- ommends that work be targeted in support of a new recommended OSHA standard that would lead to improved controls to reduce airborne and dermal exposure in all workplaces where beryllium is used. Extending research to other, work-related granulomatous lung diseases is also encouraged. Strategic Goal 3: Prevent and reduce work-related infectious respiratory diseases The evidence package presented five intermediate goals, or subgoals, for the infectious disease component of the NIOSH RDRP. These subgoals largely are a continuation of the work being carried out by the RDRP. There is no overarching structure that binds the elements of the infectious disease component into a coher- ent entity. The work on engineering controls and personal respirator technology runs through the other four elements and could be the unifying theme. Another potential unifying approach would be to structure research activities around the goal of improved understanding of mechanisms of susceptibility to infection result­ ing from occupational inhalational exposures. An important component that is missing is the need for surveillance activities across known infectious diseases and for emerging threats. In the absence of a unifying theme, the committee recom- mendations will follow the organizational approach of the evidence package. Subgoal: Maintain reductions in occupational incidence of tuberculosis (TB) in high-risk work settings. Recommendation: The goal of the occupational TB program appears to be to pre- vent and reduce occupationally related TB in the context of the broader response 

142 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH of the Centers for Disease Control and Prevention to eliminate TB in the United States. This is appropriate, but the lack of specific occupational TB surveillance programs represents a major challenge. Given the continued immigration of docu- mented and undocumented workers from areas with high prevalence of TB, the committee recommends that more specific occupational TB surveillance data be collected, along with exploration of improved methods for TB surveillance. Subgoal: Protect workers from bioterrorism agents and from occupational acquisi- tion of emerging diseases (including severe acute respiratory syndrome and avian and pandemic flu). Recommendation: The RDRP played a major role in the national effort to protect workers from the threat of anthrax-contaminated mail in 2001. Improved under- standing of how workers became infected from the contaminated mail is needed to increase the “readiness” of government response to a future bioterrorism attack. The RDRP has also been responsive to the specific needs of stakeholders and the public with respect to extramural research on emerging infectious diseases. The committee recommends that research on bioterrorism and emerging infectious diseases be prioritized for extramural funding within the constraints of limited budgetary resources. In addition, NIOSH should coordinate with other federal agencies, such as the Department of Homeland Security, to adopt recently devel- oped technologies for the detection of bioterrorism agents for the protection of workers. Subgoal: Protect workers from occupational exposures that make them susceptible to respiratory infections. Recommendation: The RDRP is to be commended for its work on personal r ­ espirators and engineering controls for preventing the transmission of infectious agents to workers. The committee recommends that support for these areas remains a high priority. Subgoal: Prevent outbreaks of occupational histoplasmosis by maintaining worker and employer awareness. Recommendation: The RDRP histoplasmosis research activity appears to be of historical interest, and the evidence package states that no new RDRP research is planned. In the absence of an operational definition of “awareness” and the docu- mented lack of adequate resources for specific surveillance activities, it is unclear how the RDRP can achieve this subgoal. Given the limited budgetary resources of the agency, the committee recommends that consideration be given to dropping this subgoal. 

R e c o m m e n dat i o n s 143 Strategic Goal 4: Prevent and reduce work-related respiratory malignancies Before NORA, the strategic plan for preventing occupational lung diseases did not include lung cancer as a disease target. As a result of the NORA plan- ning process, the RDRP has assumed responsibility for research on lung cancer caused by occupational exposures. The evidence package presented five subgoals relating to determining the occupational etiologies of lung cancer; reducing the incidence of metal-induced lung cancer (hexavalent chromium), silica-induced lung cancer, and lung cancer induced by diesel engine exhaust; and producing lung cancer diagnostic tools. The impact of the respiratory malignancies program has been strong with regard to the three specific carcinogenic exposures in the workplace listed above— hexavalent chromium, silica, and diesel exhaust—and no specific recommenda- tions are given with respect to these subgoals. In fact, the comprehensive approach to addressing specific carcinogens such as these may serve as a model for developing future initiatives on occupational respiratory malignancies. To aid in future plan- ning, the committee recommends that subgoals with greater specificity for work- related respiratory malignancies be developed to guide the evaluation of research products and productivity. Subgoal: Determination of occupational etiologies of lung cancer. Recommendation: The program activities that address the contribution of occu- pational exposures to the burden of lung cancer in general have led to important work and have partially served as a planning process for addressing respiratory malignancies. However, it is unclear whether separating lung cancer from other important occupationally related cancers is the best way to approach risk, detection, and prevention. The committee recommends that the RDRP ensure that respiratory malignancies are well integrated into an overall program of occupational cancer research and prevention and not arbitrarily segregated from similar research and prevention efforts. In doing so, the RDRP should address the priorities identified in the published report of the NORA1 Task Force on Cancer Research Methods. The committee further recommends that the RDRP develop, in collaboration with other relevant federal agencies (National Cancer Institute [NCI], National Insti- tute of Environmental Health Sciences [NIEHS], Food and Drug Administration, Department of Defense, Department of Labor), a coordinated planning process to identify significant occupational cancer risks in need of a comprehensive approach to detection, surveillance, and prevention. 

144 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH Subgoal: Development of early diagnostic tools for lung cancer. Recommendation: The committee questions the relevance and impact of the research into biomarkers for early detection of lung cancer. While this area of investigation is relevant to lung cancer in general, there is little advantage to having this work located at NIOSH instead of at NCI and NIEHS, especially in light of available resources. Focusing the study of such biomarkers on workplace-specific prevention efforts would make these efforts more relevant to NIOSH’s mission and would increase the likelihood of the program having a significant impact. The com- mittee recommends that the RDRP consider refocusing the research of biomarkers for early detection to biomarkers of exposure or for early detection that addresses the needs of specific occupational cohorts at high risk of contracting lung cancer. Recommendation: An emerging issue that could inform research on the risk for work-related respiratory malignancies concerns the inverse relationship between lung cancer and endotoxin exposures. There are a variety of settings with com- plex exposures to chemical materials where endotoxin exposure occurs, ranging from agricultural settings to metal machining operations. NIOSH should consider whether its expertise in endotoxin positions it to contribute to understanding the role of endotoxin and cancer. Recommendation: Despite significant contributions to technology for measure- ment of diesel particulate matter (DPM), NIOSH should continue efforts to develop and validate exposure methods for DPM, especially in the presence of other sources of carbon aerosols, and to provide validation of the methods used to measure DPM in coal mines. Recommendation: Finally, it is noted that cancers related to asbestos exposure continue to rise. NIOSH should consider developing long-term follow-up studies of exposed workers and interventions, as appropriate, to reduce mortality among these groups. Continued surveillance for asbestos-related risks should receive addi- tional attention. Strategic Goal 5: Prevent respiratory and other diseases potentially resulting frOm occupational exposures to nanomaterials The growing recognition of the usefulness of nanomaterials in various indus- trial applications has created an urgent need to study the potential health effects of exposures to nanoparticles and methods to control exposures to nanoparticles during manufacturing processes. The RDRP has taken a lead at the national and 

R e c o m m e n dat i o n s 145 international levels to address these questions. NIOSH should continue to play a leading role in informing and guiding national and international efforts to address potential occupational hazards and risks associated with the use of manufactured nanoparticles. NIOSH is particularly well suited to have an impact in continuing successful research into methods to monitor exposures to nanomaterials and to develop appropriate engineering controls to prevent such exposures. The follow- ing recommendations correspond to the three subgoals listed in the evidence package. Subgoal: Determine the relative toxicity of nanomaterials. Recommendation: The RDRP can continue to support some respiratory studies on the toxicology of nanoparticles but because of limited funding should address only those issues that complement studies being supported by other organizations. Thus, there needs to be a continued close interaction with other organizations involved in nanotechnology health-related research. Subgoal: Conduct exposure assessments and engineering control evaluations in 10 nanomaterial production or use facilities by 2008. Recommendation: The committee agrees that this is an appropriate and high- p ­ riority intermediate goal for the RDRP nanomaterials component. Subgoal: Produce dose-response data for carbon nanotubes sufficient to conduct a quantitative risk assessment by 2008. Recommendation: The committee agrees that this is an appropriate intermediate goal but is concerned that data may be insufficient to properly ground a quantita- tive risk assessment in this short time frame. In particular, data on human health effects are likely to be lacking. The RDRP should recognize that a quantitative risk assessment is not the only approach for dealing with the potential health impact of new materials in a precautionary manner. Cross-cutting Issues Recommendations Related to Cross-Cutting Issues During its information-gathering activities and deliberations, the committee identified several issues that cut across all program goals. In Chapter 3, the com- mittee briefly discusses continuing and emerging issues related to surveillance activities, exposure assessment, respirator policy, emergency response, and RDRP resource allocation. The committee provides further discussion and recommenda- tions related to these issues here. 

146 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH Systems for Surveillance For all five strategic goals discussed above, a limitation to RDRP research activities is the lack of adequate surveillance methods or data for specific diseases or health outcomes. Chapter 8 of the evidence package (Chapter 8, “Systems for Surveillance”) presents information related to RDRP surveillance activities. It is noteworthy that NIOSH has little control over some of the most important surveillance systems on which it depends for some of its most important activi- ties (e.g., NHANES and the National Center for Health Statistics, data for black lung disease). The SENSOR system, although under its control, has limited reach. Even in those areas where it has control and its activities have made important contributions (e.g., CWP), there are gaps in the breadth and depth of the surveil- lance. In the evidence package, a coherent plan detailing surveillance program needs and necessary resources is not presented, although some limited efforts have been made—for example, with the WoRLD Surveillance Report and the National Surveillance System of Pneumoconiosis Mortality. Articulating such a plan would enable the RDRP to identify places in the NORA2 matrix where the case can be made to compete for resources for such programs. Moreover, such a guiding plan would allow for more rational development and integration of special surveillance systems proposed in the RDRP vision statement into the large data resources of the RDRP and NIOSH. The success of the HHEs in identifying important occupational health hazards is a notable achievement of the RDRP. In particular, the contribution of HHEs to the recognition of both diacetyl and nylon flock as disease-causing agents underscores the potential value of this data source. However, the evidence package (Chapter 9, “HETA Program Inputs”) does not provide a coherent guiding plan as to how the RDRP can make better use of the HHE reports as a surveillance activity. Recommendation: The committee recommends in the strongest possible terms that NIOSH provide appropriate resources for high-priority surveillance of occu­ pational diseases. The United States is practically alone among highly developed countries with regard to its lack of comprehensive surveillance of occupational dis- eases. The effectiveness of past NIOSH surveillance activities for coal-dust-related diseases, both CWP and COPD, highlight the importance of improved surveillance for other occupational respiratory disorders. The RDRP should develop a plan that, at a minimum, includes (1) specific surveillance data needs and gaps in current systems, (2) surveillance unmet cur- rently by any extant system, (3) the specific plans and resource needs required to fill data gaps in items 1 and 2, (4) data integration, and (5) data review to identify new research opportunities. NIOSH should engage in development and evalua- 

R e c o m m e n dat i o n s 147 tion of surveillance methods as a high priority for surveillance of occupational respiratory diseases. Recommendation: The RDRP should seek to develop a systematic method to r ­ eview HHEs to mine this data source for identification of new causes of occupa- tional respiratory disorders. Public testimony by RDRP staff indicated that regular review of the HHEs takes place, but no programmatic integration of these activities with the overall surveillance activities and needs of the RDRP was articulated. The value of such articulation in programmatic terms is obvious and should be given high priority by the RDRP. Exposure Assessment Exposure assessment within the RDRP incorporates several closely related areas, including (1) development of instrumentation and techniques for sampling and analyzing environmental contaminants in various media, (2) quantitative estimation and modeling of exposure over time from measurement data in sup- port of epidemiologic or risk assessment evaluations, (3) use of existing data sets including administrative data for exposure estimation or surveillance of risk, and (4) estimation of biologically relevant dose by incorporating biomarkers of exposure and understanding the importance of biological processes such as toxico­ kinetics for peaks and other time-varying exposures. Chapters 2 and 3 describe many excellent examples of relevant and high-impact contributions related to all the program goals. The evidence package identifies sampling and analytic method development activities as distinct activities not directly linked to the RDRP and states that the RDRP is one of many NIOSH programs that rely on the exposure assess- ment capabilities. Specific examples of work related to RDRP studies cite the provision of sampling and analytic “support” for the field studies undertaken by RDRP ­scientists. Thus, the evidence package refers frequently to exposure assess- ment activities as services provided to the RDRP research activities rather than as an integral component of the research questions. The RDRP does not present these exposure assessment activities as part of an explicit or comprehensive focus on exposure­ assessment methods. The implication of this presentation is that, although exposure assessment is an important part of RDRP studies, exposure assessment scientists are not necessarily an integral part of the research effort. Further, while a number of RDRP scientists have provided a focus on exposure assessment research in the past, no specific mention of current or future staffing and programmatic needs for exposure assessment activities is made explicitly. 

148 R e s p i r ato ry D i s e a s e s R e s e a r c h at NIOSH Recommendation: The committee recommends strongly that the RDRP develop a programmatic goal that provides an explicit or comprehensive focus on exposure assessment methods. Emergency Response The RDRP has made important contributions to the emergency response to recent disasters, including the World Trade Center and anthrax terror attacks and hurricanes Katrina and Rita. However, there is no articulation of how this emergency response work is integrated into the framework of the RDRP research activities conducted under the five strategic goals, and it is unclear whether the RDRP plans to incorporate research activities related to emergency responses into future efforts. Much could be learned about exposure-response relationships and ultimately protecting emergency responders by conducting longitudinal cohort studies relating to catastrophic events. Information from emergency responses to toxicant exposures should be applicable to models of irritant-induced asthma, fixed airway obstruction, interstitial lung disease, and possibly even malignancies. Recommendation: The RDRP is encouraged to include research strategies in emergency response efforts. For example, the RDRP should assess how NIOSH- supported research and medical surveillance of World Trade Center disaster emer- gency responders and recovery workers may or may not be relevant to WRA, work-related fixed obstructive airway disease, interstitial lung disease, and possibly malignancies. RDRP Resource Allocation The RDRP was created during the recent NORA2 reorganization of NIOSH. NORA2 emphasizes industry-sector-based research as opposed to the previous organization, which emphasized disease-based research. As such, the emphasis on respiratory diseases is clearly no longer as targeted. Questions remain about how research priorities for respiratory diseases that cut across sectors will be treated and whether the quality and impact of RDRP research will remain. In addition, because NIOSH has limited funds available for extramural awards of any type, the RDRP needs a system(s) to ensure that unnecessary duplication and inappropriate expenditure on low-priority research projects are avoided. Recommendation: The committee recommends that careful regular review of programmatic goals and achievement of those goals be conducted to ensure that the respiratory disease components are being maintained under the matrix man- 

R e c o m m e n dat i o n s 149 agement structure of NORA2. All research proposals that are under consideration for funding, whether intramural or extramural, should be prioritized according to the RDRP strategic plan, which needs to be updated periodically. Broader programmatic goals Broader programmatic goals (visionary issues) have also been developed to assist the RDRP in identifying and effectively addressing issues that may arise in the future. • Research coordination: The RDRP should work closely with NIEHS; the National Heart, Lung, and Blood Institute; the Environmental Protection Agency; and other relevant federal agencies to develop a truly coordinated approach to research on occupational and environmental respiratory disorders. Current institutional silos obstruct the efficient use of resources and development of knowledge. • Surveillance: The RDRP should develop surveillance systems for occupa- tional and environmental respiratory disorders that generate adequate prevalence and incidence data for the appropriate targeting of resources for preventing and reducing the disease burden. Attention to developing systems that could capture evidence of unrecognized risks and new outbreaks is also needed. • Outreach to the pulmonary research community: The RDRP has played an important role in the past to focus and catalyze research efforts on important occupational exposures and work-related lung diseases by hosting or cosponsor- ing conferences and workshops. The evaluation committee strongly recommends continued support of such activities to stimulate extramural investigators to target priority issues identified by the RDRP strategic-planning process.