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NIOSH Respiratory Diseases Research Program

Evidence Package for the National Academies' Review 2006-2007

NIOSH Programs > Respiratory Diseases > Evidence Package > 4. Airways Diseases > 4.1 Work-Related Asthma

4.1c) Indoor Environmental Quality and Asthma Risk

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Almost 70 percent of U.S. workers (approximately 89 million people) are employed in non-industrial, non-agricultural, indoor settings, referred to here as indoor work environments. Studies have associated some indoor environmental conditions with increased risks of nonspecific symptoms, respiratory disease (including asthma), and impaired performance.118,119,120,121,122,123

Available data suggest that improving building environments has the potential to result in health benefits for more than 15 million U.S. indoor workers, with estimated economic benefits of $5 to $75 billion annually.124 Thus, research on this topic offers enormous potential health and economic returns.

A historical review of the NIOSH Health Hazards Evaluation (HHE) program showed that the proportion of indoor environmental quality requests since 1978 has increased 100-fold to 52 percent of all requests. Building-related asthma is an issue in about a quarter of these indoor environmental quality requests, and the majority of requests mentioning asthma as a health concern also mention mold or water damage as environmental exposure concerns.

The 2004 CDC-sponsored Institute of Medicine (IOM) report, “Damp Indoor Spaces and Health,” states that preventing damp indoor environments is an important public health concern, but that specific causal agents for associated health problems have not yet been identified. However, sufficient evidence exists for an association between the presence of mold or other agents in damp buildings and nasal and throat symptoms, cough, wheeze, asthma symptoms in sensitized asthmatic persons, and hypersensitivity pneumonitis in susceptible persons. Limited or suggestive evidence exists for an association between exposure to damp indoor environments and shortness of breath, asthma development, and lower respiratory disease in otherwise-healthy children. This report changes the research landscape from documenting that damp buildings pose an occupational health risk to exploring effectiveness of interventions and means of monitoring indoor environments for health risk. The report also emphasized the characterization of fungal populations in indoor environments to make progress in clarifying the relationship between damp and/or moldy environments and the manifestation of adverse health effects.

The NIOSH SENSOR program has identified miscellaneous chemicals (19.7 percent), cleaning materials (11.6 percent) and indoor air pollutants (9.9 percent) as three categories most frequently associated with WRA cases in the four reporting States (California, Massachusetts, Minnesota, New Jersey). This information supports an association between chemicals/reactive, chemistry/emissions and human health effects, but the detailed dose response as well as identification of specific chemicals and their concentrations has not been specifically determined. 


WRA in offices and schools was the largest component project of the RDRP Asthma Research Program Project, funded initially from 2000-2005, and extended for 2006-2010 with intramurally-competed monies:

  • During 2000-2005, three sequential major research investigations in damp and comparison buildings documented the phenomenology of building-related asthma, its confirmation with objective health measures, and its substantial impact on sickness and absenteeism. During a multi-year study of a large office building, successful partnerships were formed with the University of Connecticut, the Connecticut Department of Health, and the Connecticut Department of Public Works.
  • Work-related respiratory symptoms correlated with observational indices of dampness (performed by our industrial hygiene investigators) and mold in two investigations, validating the usefulness of low-cost observational approaches to hazard assessment and priority setting in indoor environmental quality. These observational indices will be applied to current work.
  • Laboratory-based measurements of novel biomass indicators including b-(1, 3)-D-glucans, penicillium/aspergillus extracellular polysaccharides, ergosterol, and endotoxin in floor dust, in addition to total culturable fungi, were significant predictors of work-related respiratory symptoms.
  • Longitudinal studies in one damp building, before and after repair of the building envelope, documented that this remediation alone did not accomplish the intended improvement in work-related respiratory symptoms and prevention of incident asthma cases.

RDRP developed collaborations with the Maine Department of Education, the Maine Bureau of Health, and the Maine American Lung Association to further knowledge of the association between indoor environmental quality in schools and respiratory health with a focus on asthma. Phase one of this work began in 2005 and involves using existing Maine Department of Education databases on capital assessment and maintenance of Maine schools to score schools in terms of environmental quality measures, including water intrusion and water damage. In 2006 we will begin school-level studies to further refine our standardized semi-quantitative assessment for indicators of dampness and mold and our short health questionnaire and train school personnel in the use of these assessment tools.

Another approach taken by RDRP for the development of objective sample-assessment methods is based on the detection of fungi using monoclonal antibodies (mAbs). Our main research focuses on the development of mAb-based environmental and serological assays for personal exposure assessments.

In collaboration with the University of Sydney, Australia, we are designing new formats of the Halogen Immunoassay for the detection of personal fungal exposures. The Halogen Immunoassay can provide patient-specific fungal allergy and exposure profiles by immunostaining personal air samples with the patient’s serum antibodies and, at the same time, identify the fungi in the patient’s air sample with monoclonal antibodies.

RDRP and the University of Cincinnati’s Department of Environmental Health are developing immunoassay-compatible sampling techniques for fungal spores and fungal fragments, respectively. This collaboration has resulted in the development of a new two-stage bioaerosol sampler and a technique for the separation of fungal fragments from fungal spores. This will allow us to investigate the potential of fungal fragments to contribute to adverse respiratory health effects associated with the presence of fungi.

We are also working with EPA in Cincinnati on the development of serological monitoring assays for exposure assessments of fungi. This work aims at the development of monoclonal antibodies against hemolysins and the design of immunoassays for their detection in human serum as biological markers of fungal exposure. The work builds on previously-published EPA research using a polyclonal antibody-based immunoassay for stachylysin, a hemolysin produced by S. chartarum, as a biomarker for S. chartarum exposure. So far we have produced monoclonal antibodies against stachylysin and chrysolysin, a hemolysin produced by P. chrysogenum.

A RDRP Gas and Vapor Team was established in 2001 for investigations relating to the gas-phase and surface-phase chemistry of indoor environments. This team has built an experimental laboratory for investigations of Volatile Organic Compounds (VOC) and oxyradicals, namely:

  • Determining gas-phase hydroxyl reaction kinetics of VOCs
  • Determining gas-phase ozone reaction kinetics of VOCs
  • Identifying and quantifying oxygenated organic reaction products
  • Conducting surface-phase chemistry of VOCs

With additional support from the Harvard School of Public Health, RDRP sponsored a workshop titled, “Indoor Chemistry and Health” which was held in July 2004 at the University of California, Santa Cruz campus. This workshop was the first time that researchers had assembled for a meeting dedicated solely to the subject of "indoor air chemistry." This workshop generated hypotheses to test potential connections between indoor chemistry and human health and promote interdisciplinary and international collaborations. Approximately 70 participants from eight countries met to discuss adverse health effects that might result from exposure to the products of reactions among indoor pollutants. Scientists from multiple disciplines including chemistry, toxicology, medicine, epidemiology, and public health, were enlisted to address this complex subject.

Outputs and Transfer

From 1996 to date, 2849 HHEs concerning indoor environmental quality have been completed; these consisted of 213 site visits, 62 full reports, and 2787 letters and referrals. In this period there were 27 publications on indoor environmental quality and WRA.

There are nine recent publications in, or submitted to, the peer-reviewed literature that have the potential to have high impact (all are too recent to show results in the Science Citation Index), these are: (14-22, A4-31, A4-32, A4-33, A4-34, A4-35, A4-36, A4-37, A4-38, A4-39). One paper by Park et al., “Building-related Respiratory Symptoms Can Be Predicted with Semi-quantitative Indices of Exposure to Dampness and Mold,” (14, A4-31) won Best Paper Award from the Editorial Board of “Indoor Air.” Another by Cox-Ganser et al., “Respiratory morbidity in office workers in a water-damaged building,” has received attention nationally and internationally from employee unions, and professionals involved in mold and dampness assessment and remediation, and notably, a Market Wire press release in October of 2005 named our study as one of two landmark studies released in 2005 providing evidence that damp buildings are associated with developing asthma (15, A4-32).

Several monoclonal antibodies against S. chartarum and A. versicolor were patented by the Technology Transfer Office of the CDC (Patent title: Monoclonal antibodies against fungi and methods for their use; USA Patent Application No. 10/483,921, USA Publication No. U.S. 2004/0185051 A1, International Patent Application No. PCT/US02/25493, International Publication No. WO 03/016352 A1) and hybridoma 9B4 has been deposited at the American Type Culture Collection (Patent Deposit Designation PTA-4582).

Several of the monoclonal antibodies were licensed to commercial companies and in 2003 EnviroLogix, Portland, Maine, announced the availability of a dipstick kit for the detection of spores of S. chartarum. In March, 2006, a similar kit for the detection of Aspergillus/Penicillium spores was announced by the same company. This is the first time that such on-site tests have been made available for any fungus. The kits provide valuable tools for clinical and research allergists, environmental and health consultants, industrial hygienists and indoor air quality specialists, building maintenance personnel and managers as well as personnel of microbiology laboratories and the remediation industries RDRP scientists have developed new methods to assess irritant potential of chemicals used in cleaning, fragrances and common consumer products.

Partnerships between RDRP and a number of agencies including the PHS, NCEH, ATSDR, National Institutes of Health (NIH), EPA and National Aeronautics and Space Administration led to the Surgeon General's Workshop on Healthy Indoor Environment, held in January 2005. RDRP staff members served on the planning committee, played a large role in setting the agenda, gave presentations and served as moderator for the closing session “Vision for the Future.” The workshop report and the opening remarks of Surgeon General Richard Carmona can be found at (External link) (A4-40). The Surgeon General spoke on the key issues raised during the workshop at the White House Summit on Federal sustainable buildings in January 2006.

An HHE (HETA 2001-0445) documenting health problems in a damp building, and a state facility, in Hartford, CT was completed by RDRP in 2005 (A9-19). The State of Connecticut subsequently commissioned an independent assessment by a private company specializing in indoor environmental quality and building diagnostics. Their independent report corroborated RDRP findings. As a result of this, the building was kept open with no general relocation of employees but with alternative work locations given to employees with building-related health effects. The state is currently making repairs to the building based on the reports (A4-41, A4-42, A4-43).

An HHE (HETA 2003-0283) on indoor environmental quality carried out in a school in Maine in 2003 and 2004 (A4-44) in conjunction with an EPA-funded environmental management system pilot project helped keep the school open. The environmental management system pilot project team was one of seven Maine groups out of 70 nominations to receive the EPA 2005 Environmental Merit Awards that recognize significant contributions to environmental awareness and problem solving. The press release announcing the awards specifically mentioned the partnership with RDRP.

Intermediate Outcomes

The RDRP program of work in indoor environmental quality and asthma is relatively young. In view of the magnitude of the population potentially affected by this problem and the practical applicability of the research, there is a clear path for this work to motivate many others to action. This process has already started. As previously noted, this program has provided guidance on improvement of indoor air quality to literally thousands of workplaces. Monoclonal antibodies produced by RDRP researchers have been licensed to the private sector and used to develop commercial immunoassays for environmental fungal contamination. As noted previously, this research has received awards, documenting that it is well-received and influential to others. As the work more fully matures, particularly work evaluating the effectiveness of building interventions, it will clearly have the ability to influence the actions of others.

Findings from RDRP studies on WRA in office building and schools were part of a June 2005 article on the need to improve air quality in schools published in the “American School Board Journal,” a publication of the National School Boards Association. That organization has over 40,000 school board members and school administrators as subscribers.

The EPA sponsored an Environmental Management System (EMS) initiative in Memorial Middle School, Portland, ME. It was reported that the school and the EMS-team, in partnership with RDRP, developed a process to resolve and indoor air quality issue originating from mold contamination (External link) (A4-45, A4-46).

What’s Ahead

In our current and future intramural, competitively funded (2006-2010) studies on indoor environmental quality, we aim to document changes in the prevalence of respiratory health outcomes after building repairs aimed to reduce water incursions and dampness issues. These intervention effectiveness studies are much needed as very few have been carried out in this field.

At a time when asthma morbidity and mortality rates are increasing worldwide, our long-term objective for this five-year project is to prevent occupational asthma associated with damp indoor environments. To prevent building-related asthma, building owners, managers, and employers need to know how to evaluate damp environments for respiratory disease risk. Employees need to know when to seek medical counsel and environmental restrictions to change the natural history of occupational asthma. All parties need to understand what remediation of damp buildings and their contents is necessary to lower respiratory disease risk among unaffected and sick employees. Some of this needed information is available, but much remains to be explored in applied research. Thus, our specific aims for the program follow:

  • Disseminate a standardized dampness assessment approach for room-by-room school building evaluation for use in prioritizing maintenance and repair efforts by school administrations to 20 percent of the 288 K-12 public school districts in Maine.
  • Present findings at a national meeting and publish reports in the peer-reviewed literature on our evaluation of interventions in previously damp buildings for their effectiveness in improving the health of persons with building-related respiratory symptoms; on our evaluation of the potential utility of nasal disease indices in assessing building-related lower respiratory disease risk; and on novel biomass and chemical measures as environmental predictors of respiratory disease risk before and after intervention.
  • Determine the impact of VOC/nitrate (NO3) radical gas-phase chemistry in indoor environments by determining both VOC lifetimes and transformation products.
  • Determine the effect of VOC/surface chemistry on indoor environment exposure by exposing VOC contaminated surfaces to indoor reactants (ozone, hydroxyl radical and nitrate radical) and identifying emitted reaction products.
  • Complete local lymph node assay experiments to determine if the observed reaction products from VOC indoor chemistry are sensitizers or irritants.
  • Explore the development of improved sampling methods to better characterize the indoor office air.

With regard to the development of accurate fungal exposure methods based on biomarker immunoassays, we will produce monoclonal antibodies against the hemolysins nigerlysin, Asp-hemolysin and terrelysin that are produced by Aspergillus niger, A. fumigatus and A. terreus, respectively. The monoclonal antibodies will then be used to analyze hemolysin expression in fungal spores, develop prototype immunoassays for their detection in environmental samples, investigate the stability of hemolysins in blood samples and develop a prototype immunoassay for their detection in blood samples.

118. Mendell MJ [1993]. Non-specific symptoms in office workers: a review and summary of the epidemiologic literature. Indoor Air 3:227–236.

119. Sieber WK, Petersen MR, Stayner L, et al [1996]. The NIOSH indoor environmental evaluation experience: part three—associations between environmental factors and self-reported health outcomes. Appl Occup Environ Hyg 11:1387–1392.

120. Brundage JF, Scott RM, Lednar WM, Smith DW, Miller RN [1988]. Building-associated risk of febrile acute respiratory diseases in army trainees. JAMA 259: 2108–2112.

121. Fisk WJ, Rosenfeld AH [1997]. Estimates of improved productivity and health from better indoor environments. Indoor Air 7:158–172.

122. Institute of Medicine. Damp Indoor Spaces and Health [2004]. The National Academies Press.

123. Mendell MJ, Heath GA [2005]. Do indoor pollutants and thermal conditions in schools influence student performance? A critical review of the literature. Indoor Air Feb;15(1):27-52.

124. Mendell MJ, Fisk WJ, Kreiss K, Levin H, Alexander D, Cain WS, Girman JR, Hines CJ, Jensen PA, Milton DK, Rexroat LP, Wallingford KM [2002].  Improving the health of workers in indoor environments: priority research needs for a national occupational research agenda.  Am J Public Health Sep;92(9):1430-40.