Does Particulate Matter Cause or Exacerbate Asthma?Does Particulate Matter Cause or Exacerbate Asthma?P t D id B P dPresenter: David B. Peden

Center for Environmental Medicine Asthma and Lung Biology University of North Carolina at Chapel HillCenter for Environmental Medicine, Asthma and Lung Biology, University of North Carolina at Chapel Hill

Findings and ConclusionsLTG 1 Poster 1-13Impact and Outcomes

Findings and ConclusionsImpact and Outcomes

Animal, Human and in vitro studies Population studies show that PM traffic and Human time-series and controlled exposure Epidemiological and animal studies Background ,demonstrate that PM and components What are the public health and

Population studies show that PM, traffic and other air pollutants can increase the risk of

pstudies show that asthmatics may be at

p gdemonstrate that PM can exacerbate

g

augment antigen presentation which would h ti it ith ll d t

What are the public health and environmental outcomes of this

other air pollutants can increase the risk of developing asthma increased risk to the cardiac effects of PMasthma and increase atopy and airway

h ti itAir pollution is a significant cause for exacerbation of

enhance reactivity with allergen and promote asthma

research?E id th t di l fi d

p ghyperreactivity asthma, and may contribute to development of

disease as well Particulate matter has been asthma • Evidence that diesel, fine and coarse mode PM identify targets for regulation

disease as well. Particulate matter has been associated with exacerbation of asthma and mode PM identify targets for regulation

and community mitigation strategies toassociated with exacerbation of asthma and wheezing in children, and is a leading cause of

Methods/Approachand community mitigation strategies to protect asthmatics from PM-associated

g , gexacerbations, Air pollution is likely second only to

P Ai Q lit C E b t Methods/Approach health effects.P t ti l it iti ti

viral respiratory tract infections as a precipitating factor in acute events rescue medication use ER Poor Air Quality Can Cause AsthmaPoor Air Quality Can Exacerbate

• Potential community mitigation strategies include:

factor in acute events, rescue medication use, ER visits and hospitalizations

Poor Air Quality Can Cause AsthmayAsthma strategies include:

•Better emission controls on mobilevisits and hospitalizations. Asthma

Better emission controls on mobile sources for PMWhile earlier epidemiological studies demonstrate •Continue to examine state i l t ti l f i t

that PM contributes to exacerbation of asthma, the degree to which PM influences disease and the

Change in Pediatric Lung Odds ratios for daily asthma implementation plans for point source producers of PM that affect

degree to which PM influences disease, and the potential for PM to contribute to pathogenesis of

Prevalence of asthma by distance of residence to a major road

Function per 10 μg/m3 Change in PM i S ttl WA

symptoms associated with hift i ithi bj t

Hazard ratio of newly diagnosed asthma in 12 comm nities b producers of PM that affect

asthmaticspotential for PM to contribute to pathogenesis of chronic disease remain incompletely understood. It

of residence to a major roadPM in Seattle, WA shifts in within-subject concentrations of two

asthma in 12 communities by average ambient pollutants asthmatics

•Consider placement of schools and p y

is also unclear if PM of specific size ranges, or if concentrations of two pollutants

average ambient pollutants

residential buildings in proximity to d

specific components of PM are more likely to induce asthma PM is composed of bioaerosol components

pollutants

roadwaysasthma. PM is composed of bioaerosol components (e g endotoxin and lipoteichoic acid) metals

• Individual Intervention strategies(e.g. endotoxin and lipoteichoic acid), metals, organic molecules such as polyaromatic Individual Intervention strategies

include:g p y

hydrocarbons and elemental carbon. Biological •Use of anti-inflammatory medications t d ff t f PM ti

responses to these individual components agents likely play a central role in determining individual to decrease effect of PM on antigen

presenting cells and response tolikely play a central role in determining individual susceptibility to asthma presenting cells and response to

allergensusceptibility to asthma.

Trenga C. A. et.al. Chest 2006;129:1614-1622 allergen•Influence family decisions regarding Previous studies also indicate that a significant

g ;

E ffe c t o f O r g a ni c C om p o n en ts of D i es el E x h a us t

living in proximity to roadwaysH th t t t l th t

action of PM is to enhance atopic immune response to allergens and diverse agents such as PAHs on

E ffe c t o f O r g a ni c C om p o n en ts of D i es el E x h a us t on AH R in m ic e 4 8 h afte r OV A c h a lle n g e

•Have asthma treatment plans that minimize co exposures to allergens

to allergens, and diverse agents such as PAHs on diesel exhaust and endotoxin have been shown to minimize co –exposures to allergens

and indoor pollutantsdiesel exhaust and endotoxin have been shown to enhance primary and recall response to allergen. McConnell et al Environ Health Perspect 2006 and indoor pollutantsp y p gMechanisms by which this occurs are also

McConnell et al., Environ Health Perspect 2006 114: 766-772

incompletely understood.

Future DirectionsUnderstanding these mechanisms may provide Schildcrout et al., Am J E id i l 164 505 517

Islam et al., Thorax 2007 62:957-963

Future DirectionsUnderstanding these mechanisms may provide insight into targets for individual intervention

Epidemiol 164: 505-517

St di t d t i h PM h

g gapproaches and regulatory strategies to minimize S teven s , T. e t a l. T ox icol . Sc i . 2009 107:522-5 34;

• Studies to determine how PM enhances response to allergen Focus on effects

the impact of PM on asthmaresponse to allergen. Focus on effects on the following:PM i d d h d ti t tiScience Questionson the following:

•Antigen specific IgEPM exposure can cause cardiovascular effectsPM-induced enhanced antigen-presentation mayScience Questions •Antigen presenting cellsC ll hi h b I E (b hil

PM exposure can cause cardiovascular effectsi th ti

g p ypromote asthma

A number of scientific hypotheses have been•Cells which bear IgE (basophils, mast cells)

in asthmaticspromote asthmaA number of scientific hypotheses have been addressed in the research outlined in this poster.

mast cells)• Genetic Risks associated with pollutantadd essed t e esea c out ed t s poste

These hypotheses address the following questions:Genetic Risks associated with pollutant exposuresEffect o f Diesel PM on Antigen

Presenting Cell Surface Marker

Effect of concentrated coarse mode particles on human airway monocytic cells via chamber exposure Coarse PM exposure induces cardiac

D PM t ib t t b ti f th ?•Examination of gene expression

fil t id tif did texpression in mice

Effect of diesel exhaust exposure of dendritic cells to HLA-DR e pression in h man dendritic cells

CD23/Low Affinity IgE R

15

20Filtered AirCAPs*

*CD16/FcRIII

300

400Filtered AirCAPs*

Coarse PM exposure induces cardiac changes in asthmatics

• Does PM contribute to exacerbation of asthma? profiles to identify candidate mechanisms which mediate response

expression in human dendritic cells

5

10

15

MF

I

100

200

300 CAPs

*MF

I

• Does PM contribute to development of asthma?mechanisms which mediate response to PM in asthmaticsCD11b/CR3 CD40

0Monocytes Imm Macrophages

0Monoctyes Macrophages Change in HRV per 1 μg/m3 increase in PM oes co bu e o de e op e o as a to PM in asthmatics

•Examination of effect of oxidant CD11b/CR3

100

150

Filtered AirCAPs

* *MF

I

CD40

750

1000

Filtered AirCAPs

*

MF

I

in adults with asthma• How does PM influence immune function in the i t t th ?

stress genes thought to play a role in d di l i d d i

0

50

CAPs*M

Imm Macrophages Macrophages0

250

500CAPs

*

Imm Macrophages Macrophages

M

airway to promote asthma? ozone and diesel induced airway responses including GSTM1

Imm Macrophages Macrophages p g p g

W k i P Al i NE l

• Are patients with asthma at increased risk to the responses, including GSTM1

• Examine novel interventionse pa e s as a a c eased s o ecardiac health effects of PM?

Examine novel interventions•Pursue studies examining the role of antioxidants such as sulforaphane, it i C d it i E i i ivitamin C and vitamin E in minim

• Effect of co exposures on asthmaP M l A J R i C ll M l Bi l 2007 D 37(6) 706 19 • Effect of co-exposures on asthma outcomes

Porter M, et al, Am J Respir Cell Mol Biol. 2007 Dec;37(6):706-19.

outcomes•Determine if PM augments the effect

Alexis NE et al Ann Allerg Asthma R l i tiHRV Frequency

Y tt t l E i H lth P tt 2007 115 709 714 of other pollutants such as ozoneChan RC et al, J Allergy Clin Immunol 2006 Aug;118(2):455 65

Alexis NE et al, Ann Allergy Asthma Immunol. 2008 Mar;100(3):206-15.

Repolarization DomainYeatts et al., Environ Health Perspectt 2007 115: 709-714

Immunol. 2006 Aug;118(2):455-65.