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Asthma Research Strategy 

1. Introduction 

1.1. Factors in the Development of Asthma 

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ASTHMA 

Induction

Exacerbation

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Respiratory Viruses, 

Tobacco Smoke 

Irritants, Promoters 

Genetic 

Predisposition 

Immunologic 

Sensitization 

(asymptomatic) 

Mild Moderate Severe 

Genetics, Health Status, 

Lifestyle, Housing, 

Socioeconomic Status 

Susceptibility Factors 

Allergen Exposure 

Dust Mites, Cockroaches, 

Molds, Pollens, Pets, 

Allergenic Chemicals 

Death 

Figure 1. Induction of asthma may occur in genetically susceptible individuals upon exposure to common allergens 

or certain chemicals. Nonspecific irritants and promoters may facilitate induction through injury and increased 

uptake of allergens or by modulating immune responses (dashed arrow). Both allergens and irritants may 

exacerbate existing asthma. Inflammation and airway obstruction in asthma are reversible. Consequently, severity 

of the disease is variable (double-headed arrows) depending on environmental influences as well as susceptibility 

factors as indicated here. 
Asthma Research Strategy 

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1.2. Overview of Environmentally-Related Asthma 

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• Induction and exacerbation of asthma 

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asthma induction or exacerbation 

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9 
Asthma Research Strategy 

Research Agenda Items: CRPs Exposure 

• Determine exposures to CRPs from outdoor and indoor sources 

• Develop exposure models linking source to exposure and ambient to indoor air 

concentrations. 

• Determine distributions of peak and mean personal exposure to NO

relationship between NO2 exposure and asthma. 2 and the 

Effects 

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GHWHUPLQHZKHWKHUVKRUWWHUPH[SRVXUHWRDPELHQW&53VOHDGVWRDQLQFUHDVHLQDFXWH

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DWRSLFKXPDQV3UHYLRXVVWXGLHVKDYHEHHQFRQGXFWHGWRH[DPLQHWKHHIIHFWVRIQDVDOLQVWLOODWLRQ

RIGLHVHOH[KDXVWSDUWLFOHVRQORFDODOOHUJLFUHVSRQVHV'LD]6DQFKH]HWDO7KHSRVVLELOLW\

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LQDQLPDOPRGHOVRUFRQWUROOHGKXPDQH[SRVXUHVRIDVWKPDWLFVVKRXOGEHGHWHUPLQHG

Research Agenda Items: CRPs Effects 

• Examine exposure to CRPs (especially fine PM) in relation to asthma outcomes (e.g., 

symptoms, pulmonary function, medication use, doctors visits, ER visits, 

hospitalizations, quality of life). 

• Determine acute exposure-exacerbation response relationships in clinical and animal 

studies. 

• Examine whether fine PM or other CRPs enhance sensitization to common 

allergens. 

• Study cellular and molecular mechanisms of inflammatory and physiological 

responses. 

Risk Management 

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VRXUFHVILQH30LQSDUWLFXODU$VGHWHUPLQHGE\ SULRULWLHVWKHRQJRLQJFKDUDFWHUL]DWLRQRI

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DOVROHDGWRDEHWWHUXQGHUVWDQGLQJRISDUWLFOHVL]HGLVWULEXWLRQDQGFKHPLFDOFRPSRVLWLRQ

'UDZLQJ IURPWKHVHUHILQHGFKDUDFWHUL]DWLRQUHVXOWVH[SHULPHQWDODQGHQJLQHHULQJ VWXGLHVFRXOG

EHFRQGXFWHGWRGHYHORSDQGLPSURYHWKHDSSURSULDWHFRQWUROWHFKQRORJLHVIRU&53V

10 
Asthma Research Strategy 

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VXOIXUR[LGHVWKDWFDQUHDFWLQWKHDWPRVSKHUHWRIRUP30DQGWKDWLQWKHLUXQUHDFWHGJDVHRXV

IRUPFDQLQGHSHQGHQWO\FRQWULEXWHWRDVWKPDV\PSWRPV

,QGRRUVRXUFHVRI&53VWREHFRQVLGHUHGLQFOXGHLQGRRUFRPEXVWLRQVRXUFHV30

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HIIHFWLYHO\ GHVLJQDULVNPDQDJHPHQWSURJUDPWKDWUHGXFHV&53VLQLQGRRUDLU

Research Agenda Items: CRPs Risk Management 

• Continue to characterize the indoor and outdoor sources of selected CRPs, 

emphasizing the development of basic models defining these sources. 

• From these results, develop appropriate prevention and control approaches and 

technologies. 

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Exposure 

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11 
Asthma Research Strategy 

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SROOXWDQWVVXFKDV&53VDQGDLUWR[LFVPD\ HQKDQFHDVWKPDWLFV\PSWRPV

Research Agenda Items:Bioaerosol Exposure 

• Characterize the degree of exposure to major fungal allergens that have been shown 

to induce sensitization and airway obstruction. 

• Develop innovative methods and measurement protocols for characterizing and 

quantifying bioaerosols identified as major contributors to asthma related 

health outcomes. 

• Examine building environment factors (e.g., dampness, ventilation) which contribute 

to fungal exposure. 

• Assess the relative exposures to indoor and outdoor sources of molds. 

• Examine the importance of regional differences in fungal exposures as a factor in 

the prevalence of asthma. 

• Assess the importance of exposure to mold allergens relative to better studied 

allergens. 

Effects 

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12 
Asthma Research Strategy 

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DQLPDOPRGHOVDQGKXPDQRUDQLPDOFHOOFXOWXUHV\VWHPV

Research Agenda Items:Bioaerosol Effects 

• Examine the spectrum of fungal allergen sensitivity in asthmatics in the home and 

workplace. 

• Carry out allergen bronchoprovocation of clinically-identified mold-sensitive 

asthmatics to determine dose-response relationships. 

• Examine the adjuvant effects of toxic compounds produced by bioaerosols on 

induction and exacerbation of asthma-related responses. 

• Examine the interactions of bioaerosols with viruses or environmental agents such as 

CRPs. 

• Analyze mechanisms of responses with appropriate cell culture or animal models. 

Risk Management 

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Research Agenda Items: Bioaerosol Risk Management 

• Develop improved understanding and basic models characterizing the sources of 

indoor bioaerosols. 

13 
Asthma Research Strategy 

• Improve, develop, and demonstrate source management techniques to reduce 

bioaerosol exposure, such as mold-resistant materials and environmental 

controls, and define their effectiveness in outreach programs in affected 

communities. 

• Assess the effectiveness of improved ventilation and indoor air cleaning and 

filtration in reducing bioaerosol exposure. 

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Research Agenda Items: Air Toxics Exposure 

• Monitor personal exposures to asthma-associated air toxics in different 

environments. 

• Characterize major pathways and routes of exposure to key air toxics, evaluate key 

determinants of exposure, and characterize important activities leading to 

enhanced exposures in different population sectors (i.e, children, elderly) 

14 
Asthma Research Strategy 

• Characterize sources of asthma-related air toxics, and develop multimedia/ 

multipathway aggregate exposure and exposure-to-dose models for key air 

toxics used in source to dose estimations. 

Effects 

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LQGXFHGDVWKPDFDQEHH[DPLQHGLQWKHVHPRGHOV

Research Agenda Items: Air Toxics Effects 

• Conduct studies of asthma prevalence and respiratory effects in relation to air toxics 

exposures. 

• Define exposure-response relationships for asthma induction/exacerbation using 

occupational data and clinical studies. 

• Develop practical test methods for assessing the allergenicity of air toxics. 

• Determine whether air toxics induce hyper-responsiveness or exacerbate responses 

in animal models sensitized to common allergens. 

• Study interactive effects of air toxics and CRPs. 

Risk Management 

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FRPSRXQGVRIFRQFHUQWRDVWKPDWLFV7RDOORZWKHULVNPDQDJHPHQWHIIRUWWREHIRFXVHGRQ

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15 
Asthma Research Strategy 

Research Agenda Items: Air Toxics Risk Management 

• Characterize emissions from priority indoor and outdoor air toxics sources, 

emphasizing the development of basic models defining these sources. 

• Develop approaches and technologies for preventing or reducing emissions from the 

most important sources. 

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FDUEDPDWHVLQKLELWDFHW\OFKROLQHVWHUDVHOHDGWRUHGXFHGHQ]\PDWLFGHJUDGDWLRQRIDFHW\OFKROLQH

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H[DFHUEDWHDVWKPD/LWWOHLVNQRZQDERXWWKHVSHFLILFHIIHFWVRIRUJDQRFKORULQHLQVHFWLFLGHVRQ

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Research Agenda Items:Pesticide Exposures 

• Examine levels of pesticide exposure and usage in geographic regions and 

demographic groups with different asthma incidence rates. 

• Develop biomarkers for exposure to pesticides. 

16 
Asthma Research Strategy 

Effects 

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Research Agenda Items:Pesticide Effects 

• Examine immunologic and neurologic mechanisms of responses to pesticides, and 

distinguish from the effects of vehicle compounds. 

• Develop methods for screening pesticides for potential to cause or exacerbate asthma 

• Determine whether pesticide exposure facilitates induction of asthma or responses to 

common allergens. 

• Examine asthma prevalence, incidence, and severity associated with exposure to 

pesticides. 

Risk Management 

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SRVVLEOHFRQFHUQWRDVWKPDWLFV

17 
Asthma Research Strategy 

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Research Agenda Items: Pesticide Risk Management 

• Develop improved models characterizing the airborne emissions resulting from 

pesticide use and the transport and fate of these emissions in the indoor 

environment. 

• Develop pollution prevention and other alternatives for reducing pesticide exposures 

associated with induction and exacerbation of asthma. 

4.2. Research Area 2: Susceptibility Factors 

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18 
Asthma Research Strategy 

Research Agenda Items:Genetic Susceptibility 

• Define differences in responses of asthmatics and healthy individuals to 

environmental pollutants as a step towards quantifying genotypes common to 

asthmatics. 

• Establish DNA bank of samples associated with phenotypic markers of response in 

asthmatics and healthy individuals for use in conducting genetic analysis 

experiments to identify genetic markers of susceptibility. 

• Utilize in vitro studies and animal models to examine effects of specific genes. 

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Research Agenda Items: Health Status 

• Perform dosimetry and dose-response studies on asthmatics with a broad range of 

asthma severity with representative compounds. 

• Develop mathematical models to understand the effect of asthma severity on 

dosimetry of gaseous and particulate air pollutants. 

• Examine the influence of asthma severity and recent respiratory infections on 

responses to air pollution episodes. 

• Study models of cardiopulmonary disease to understand mechanisms of enhanced 

responses to pollutants. 

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19 
Asthma Research Strategy 

Research Agenda Items: Socioeconomic Status 

• Examine gradients of SES in relation to asthma incidence and severity with 

emphasis on their relationship to ambient and indoor air pollution levels. 

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Research Agenda Items: Residence and Exposure History 

• Assess environmental exposure history in asthmatic patients. 

• Develop biomarkers of exposure to pollutants to assess the potential contribution of 

individual pollutants. 

• Define patterns of asthma prevalence and severity relative to area and point sources 

of pollutants in residential locations. 

• Compare existing geographic information system (GIS) data on the location of 

sources and their emission inventories to patterns of asthma prevalence and 

severity. 

• Define the building and structural factors associated with living in an urban 

environment that contribute to the high incidence of asthma among inner-city 

residents. 

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KLJKHUDVWKPDUDWHV([HUFLVHDQGRXWGRRUDFWLYLW\LQFUHDVHYHQWLODWLRQDQGWKHLQKDOHGGRVHRI

20 
Asthma Research Strategy 

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Research Agenda Items: Lifestyle / Activity Patterns 

• Examine the balance of lifestyle factors, including physical activity, time indoors, 

and nutrition, which influence allergen and air pollution exposure and their 

relationship to subsequent asthma outcomes. 

4.3. Risk Assessment 

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21 
Asthma Research Strategy 

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Research Agenda Items: Asthma Induction 

• Improve exposure information for bioaerosols, pesticides, and toxics in focused 

areas of concern (e.g., indoors, occupational, and agricultural settings). 

• Develop improved exposure/activity profiles for susceptible populations (e.g., 

children of asthmatic parents). 

• Examine induction of asthma in an occupational setting for key chemicals of 

ambient interest. 

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Bioaerosols 

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22 
Asthma Research Strategy 

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FRPPRQDOOHUJHQVFDXVLQJDVWKPDHJGXVWPLWHFRFNURDFKHV

Combustion-Related Products, Pesticides, and Air Toxics 

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Research Agenda Items: Asthma Exacerbation 

• Develop risk assessment tools to assess risk of bioaerosols. 

• Clarify the relationship of asthma severity to dose-response for asthma exacerbation 

by CRPs, Toxics, and Pesticides. 

• Collect better data on population exposure and the prevalence of sensitivity. 

• Evaluate the risks of mixtures of chemicals using data on exposure to mixtures 

(simultaneous or sequential) in well characterized asthmatics and in validated 

animal models. 

5. Research Prioritization and Timeline 

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23 
Asthma Research Strategy 

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5.1. Prioritization Tables 

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24 
Asthma Research Strategy 

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TABLE 1. PRIORITIZATION OF THE RESEARCH AREAS 

Induction / 

Criteria Exacerbation Susceptibility Factors Risk Assessment 

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TABLE 2. INDUCTION / EXACERBATION 

Criteria CRPs Bioaerosols Air Toxics Pesticides 

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25 
Asthma Research Strategy 

TABLE 3. SUSCEPTIBILITY FACTORS 

Socio- Residence/ Lifestyle/ 

Genetic Health conomic Exposure Activity 

Criteria Susceptibility Status Status History Pattern 

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TABLE 4. RISK ASSESSMENT PRIORITIZATION 

Criteria Induction Exacerbation 

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5.2. Timeline of Research Activity 

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26 
Asthma Research Strategy 

TABLE 5. TIMELINE OF RESEARCH ACTIVITY 

FY01 FY02 FY03 FY04 FY05 FY06 FY07 FY08 FY09 Total 

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%LRDHURVROV      

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Induction/Exacerbation 

Total 

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Susceptibility 

Factors Total 

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Total 

0 6 11 10 9 6 56 

Total ffor E t 8 9 37 3 42 1 35 9 10 254 

   

  

   

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27 

Asthma Research Strategy 

6. References 

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29 
Asthma Research Strategy 

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30 
Asthma Research Strategy 

Appendix A 

Abbreviations and Acronyms 

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31 

30

Asthma Research Strategy 

Appendix B 

U.S. Environmental Protection Agency 

Office of Research and Development 

Inventory of Asthma Research 

Preface to the Appendix 

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33 

Asthma Research Strategy 

Introduction 

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35 
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