3/13/2014
Health Effects of Air Pollution
James M Seltzer, MD
University of California, Irvine
Presentation March 21, 2014
Big Sky Pulmonary Conference
© AAAAI Revised 2013
Learning Objectives
1. Recognize the indoor and outdoor airborne pollutants
the can adversely impact respiratory health
2. Understand how airborne pollutants cause disease
3. Recognize synergistic interactions between causative
agents
Definition of Air Pollutants
• Primary – pollutants directly emitted into
the atmosphere (eg. SO2, some NOx
species, CO, PM)
• Secondary – pollutants that form in the
air as a result of chemical reactions with
other pollutants and gases (eg. Ozone,
NO2, some particulates)
*PM=particulate matter; SO2=sulfur dioxide; CO=carbon
Monoxide; NO2=nitrogen dioxide; NOx=nitrogen oxides
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Gaseous Pollutants
•
•
•
•
•
•
NOx
SO2
Ozone
CO
CO2
SVOC (semi-volatile organic
compounds include aldehydes, dioxins,
benzene, 1,3-butadiene)
Particulate Matter (PM)
• Coarse PM (aerodynamic diameter 2.5-10um)
- major sources are abraded soil, road dust from
brakes and tires, construction debris, aggregation of
smaller combustion particles.
• Fine PM (≤ 2.5 um) and Ultrafine PM (<0.1 um)
- byproducts formed during the combustion of fossil
fuel products
• Coarse and Fine PM have been associated with
increased cardiorespiratory morbidity and mortality
• Much less is know about the adverse health effects
of Ultrafine PM which is more abundant and potentially
more toxic
Indoor Air Pollutants
• Sources
- cooking
- combustion
- particle resuspension
- building materials
- air conditioning/cleaning
- consumer products
- tobacco smoke (active and passive)
- heating
- biologic agents
- pets
• Products
- NOx, CO, CO2, SVOCs, ozone (O3-), bacteria, moldbyproducts, endotoxin
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Outdoor Air Pollutants
• Sources
- industrial
- commercial
- mobile
- urban
- regional
- agricultural
- natural
acute – volcano eruption
chronic – climate change
• Products
- SO2, O3-, NOx, CO, PM, SVOC
Summary
Pollutants
• NO2
Sources
Outdoor: automobiles, burning fossil fuels
Indoor: gas appliances, kerosene heaters, wood
stoves, tobacco products (side stream smoke)
• SO2
• PM2.5
• O3
Heating fuels, coal fired plants
Diesel engines, fossil fuels
Created when sunlight reacts with VOCs, NO2
Pollutant Health EffectsBiochemical Mechanisms
• Oxidative stress: common mechanisms involving
oxidant/anti-oxidant imbalance and generation of
reactive oxygen and nitrogen species
– ozone, PM, SO2, transition metals, polyaromatic
hydrocarbons, acrolein
• Activation of aryl hydrocarbon receptor
– polyaromatic hydrocarbons
• Covalent modification of proteins/enzymes
– acrolein, formaldehyde
• Acid formation
– SO2 (formation of airway sulfuric acid)
Prows DR, Shertzer HG, Daly MJ, Sidman CL, Leikauf GD. Nature Genetics 1997; 17(4):471-4.
Li N, Hao M, Phalen RF, Hinds WC, Nel AE. Clin Immunol 2003; 109:250-65.
Kehrer JP, Biswal SS. Toxicol Sci 2000; 57:6-15.
Collaco CR, Hochman DJ, Goldblum RM, Brooks EG. Ann Allergy Asthma Immunol 2006; 96(4):550-6.
Leikauf GD. Environ Health Perspect 2002; 110 Suppl 4:505-26.
Ito T, Nagai H, Lin TM, Peterson RE, Tohyama C, Kobayashi T et al. J Immunotoxicol 2006; 3:21-30.
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Pollutant Health EffectsBiological Mechanisms
• Adjuvant effects: enhancement of allergenicity and viral
susceptibility
– DEP, nickel, O3, NO2
• Activation of innate immune responses through TLR, CD14,
HLA-DR
– Nickel, bioorganic pollutants: glucans, endotoxin, O3
• Suppression of macrophage function with reduced immune
responses to infectious agents
– NOX, O3, LPS
• Procoagulant activity
– ultrafine PM, NO2, CO
• Stimulation of the autonomic nervous system
– SO2, acrolein
Diaz-Sanchez D, Garcia MP, Wang M, Jyrala M, Saxon A. J Allerg Clin Immunol 1999; 104(6):1183-8.
Bind MA, Baccarelli A, Zanobetti A, Tarantini L, Suh H, Vokonas P et al. Epidemiology 2012; 23:332-40.
Olker C, Siese A, Stumpf S, Muller B, Gemsa D, Garn H. Free Radic Biol Med 2004; 37:977-87.
Schmidt M, Goebeler M. J Mol Med (Berl) 2011; 89:961-70.
Kesic M et al, PLoS One. 2012;7(4):e35108.
Long NC, Abraham J, Kobzik L, Weller EA, Krishna Murthy GG, Shore SA. Eur Respir J 1999; 14:46-56.
Ozone, Sulfur Dioxide,
Nitrogen Dioxide and
Carbon Dioxide
Sulfur Dioxide, Nitrogen Dioxide,
Carbon Monoxide
• Epidemiologic studies have
demonstrated that exposure to SO2,
NO2 and CO increase cardiopulmonary
mortality, respiratory and cardiovascular
hospital admissions caused by stroke
(NO2) and myocardial infarction (NO2
and CO)
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Epidemiologic Studies Of Specific Air
Pollutants And Aeroallergens On Asthma
Exacerbation
• Ozone and fungal spores have been
demonstrated to be cofactors in increasing
asthma symptoms and SABA use
• Ozone, NO2 and SO2 individually or in
combination may enhance airway response
to inhaled allergens
• Short term increases in ozone levels are
associated increase in acute respiratory
diseases in children.
Delfino RJ, et.al. Am J Resp Crit Care Me 1996;154:633-41.
Delfino RJ, et.al. Environ Health Perspect 1997;105:622-35.
D’Amato G, et.al. Environ Res 2003;91:21-8.
Schwartz, J. Pediatrics. 2004;43:113:1037-1043..
Ozone (03-)
• O3-, absorbs UV radiation and creates a warm layer of
air responsible for the thermal structure of the
stratosphere
• O3- present in the troposphere is mainly due to manmade pollution; higher concentrations are found in urban
areas
•O3- is formed when NOX combines with volatile organics
compounds (VOC, i.e. chemical vapors) in the presence
of sunlight
VOC + NOx + Sunlight = Ozone
• O3- linked to causing new onset asthma and
exacerbating pre-existing asthma
[Chemical and Engineering News; v72; 6-7; 1994.]
[Aviation Week and Space Technology; v140; 20-21; 1994.]
Sulfur Dioxide (SO2)
Referred to as ‘SOX’
• Sulfur dioxide is a major primary pollutant in the
atmosphere
• Originates mostly from coal fired power plants and other
fossil fuel combustion
• Sulfur dioxide is usually oxidized by ozone and hydrogen
peroxide to form sulfur trioxide, a secondary pollutant that
is extremely soluble in water
• Sulfur oxides present in the atmosphere when
condensation occurs results in droplets of sulfuric acid
called “acid rain”
Science; v265; 497-9; 1994.
Nature; v366; 327-9; 1993.
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Sulfur Dioxide
• Controlled exposure studies (5 min) to inhaled SO2
induces rapid onset bronchocontriction in healthy and
asthmatic subjects
• Asthmatic patients experience increased symptoms
and a greater decrease in lung function at lower
concentrations (0.25 ppm) compared to healthy
volunteers that are unresponsive at concentrations
less than 0.5 ppm
• Exposed asthmatic patients are refractory to the
effects of SO2 for up to 4 hours after exposure
• Exposure to ozone or cold air before SO2 exposure
increases BHR to SO2 in asthma patients
NOx (pronounced "nox") Gases
• NO (nitric oxide) is the principal emitted NOx gas from high temperature
combustion in air.
- Reacts with ozone and tropospheric radicals to help form NO2,
ozone, and other secondary pollutants such as peroxyacetyl nitrate.
• NO2 is the lesser of the two emitted NOx gases from high temperature
combustion in air.
- It is an important species in the atmosphere as it absorbs in the
visible wavelength region
- Manifests as the “Brown Cloud” seen over large polluted cities (eg.
Denver, LA, Mexico City, Beijing…)
- NO2 is a precursor to photochemical smog; can be photolyzed to yield
oxygen atoms that can react with molecular oxygen to create ozone
(UV sunlight + hydrocarbons=ozone).
Environmental; v30; 22-23; 1988.
Environmental Science and technology; v26; 74-79; 1992.
Science; v242; 555-558; 1988.
Nitrogen Dioxide
• Most likely health effect as an outdoor pollutant is
through the formation of ozone
• High NO2 exposure (0.02 ppb) 1 week before a
respiratory URI has been associated with increased
asthma exacerbations
• Healthy subjects and smokers exposed to NO2 (26ppm) manifest increased PMNs in the airways and
reduced lymphocyte subpopulations
• Exposure to 0.4 ppm NO2 for 4 hours enhances the
immediate and late phase response to inhaled
allergen
Chauhan AJ, et.al. Lancet 2003;361:1939-44.
Sandstrom T, et.al. Eur Respir J 1991;4:332-9.
Strand V, et.al. Am J Respir Crit Care Med 1997;155:881-7.
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Asthma and Air Pollution
•
•
•
•
•
•
Air pollution has been associated with:
Increased bronchial hyperresponsiveness
Increased airway inflammation
Decreased lung function
Increased hospital admissions and ER visits
Enhancing airway inflammation induced by
allergen exposure
• Priming of the airways to allergic responses
• High exposure is an independent risk factor for
wheezing during infancy and early childhood.
Molfino, Lancet, 1991; Peden, AJRCCM, 1995
Bernstein DI, Traffic related pollutants and wheezing in children.
J Asthma. 2012 Feb;49(1):5-7.
Lung Function and Air Pollutants
• Inhalation of 1 ppm of SO2 for 10 minutes during
moderate exercise decreased FEV1 by 23% in
adolescents with asthma.1
• An association between ambient ozone levels below
EPA limits and asthma symptoms was found in children
with asthma living in New England.2
• Air pollution decreases the typical increase in FEV1 in
children as the level of air pollution goes up3.
1Koenig JQ, et al Effects of SO2 plus NACL aerosol combined with moderate exercise on pulmonary function in
asthmatic adolescents. Environ Res 1981;25:340-8.
2Gent et al Association of Low-Level Ozone and Fine Particles with respiratory symptoms in children with asthma.
JAMA 2003;290:1859-1867
3Gauderman
WJ et. al. The effect of air pollution on lung development from 10-18 years of age. NEJM.
2004;35:1037-1062.
Community-Specific Average Growth in FEV1 among Girls
and Boys During the Eight-Year Period from 1993 to 2001
Plotted against Average Nitrogen Dioxide (NO2) Levels
Gauderman WJ et. al. The effect of air pollution on lung development from
10-18 years of age. NEJM. 2004;35:1037-1062
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ER Visits for Respiratory
Complaints and Air Pollutants
•Numerous studies have found an association between PM
10 levels and ER visits for asthma.
•In Seattle, an increase of 11 µg/m3 in fine PM was
associated with an 11% increase in asthma ER visits.1
• Ozone and SO2 have been associated with ER visits for
asthma in Mexico.2
•Exposure to air pollution is an important determinant of ER
visits for acute respiratory symptoms, particularly during
warm season3.
1Norris
et al An association between fine particles and asthma emergency department visits for children in Seattle.
Environ Health Perspect 1999;107:489-93.
2Romieu
et al Effects of urban air pollutants on emergency visits for childhood asthma in Mexico City. Am J
Epidemiol 1995;141:546-53.
3Tramuto
F et. al. Urban air pollution and emergency room admissions for respiratory symptoms: a case-crossover
study in Palermo, Italy. Environ Health. 2011. Apr 13;10:31.
Inflammatory Markers and Air Pollutants
•
Exposure to ozone results in an influx of neutrophils and
alveolar macrophages into the airway.1,2
IL-6, IL-8, LTB4, and thromboxane B2 are increased in the
airways after exposure to ozone.
mCD14 surface expression on airway macrophages is
enhanced following ozone exposure.3
PM10 exposure increases allergen specific IgE production
leading to increased airway inflammation.
Diesel exhaust particles increase production of C-C
chemokines, induce a TH2 cytokine milieu in the presence of
allergen, and enhance total and allergen specific IgE responses
to allergen.4
•
•
•
•
1Peden
DB, Ann Allergy Asthma Immunol 2001;87(Suppl):12-17.
M, Am J Respir Cri Car Med 2005;172:427-32.
N et al, Clin Immunol. 2004 Apr;111(1):126-31.
M, JACI. 2005 Feb;115(2):221-8.
2Arjomandi
3Alexis
4Riedl
Interactions Between Air Pollutants and
Allergen
•
Exposure to 0.12 ppm ozone decreased the amount of ragweed
allergen required to provoke a 20% decrease in FEV1.1
NO2 exposure has been shown to increase airway
hyperresponsiveness to tree pollen.2
Exposure to PM increases total serum IgE levels.
Nasal histamine levels are increased 3-fold when diesel exhaust
particles are co-administered with allergen.
Exposure to airborne endotoxin enhances response to inhaled
allergen3
Exposure to diesel exhaust particles, increases number of IgE
secreting cells in the nasal mucosa.4
Lowering Th-2 inflammation reduces the inflammatory response to
LPS in asthmatics.5
•
•
•
•
•
•
1Molfino
et. Al., Lancet 1991;338:199-203.
et. al. Eur Resp J 1998;12:6-12.
Boehlecke et. Al., J Allergy Clin Immunol. 2003;112(6):1241-3.
4 Riedl M, JACI. 2005;115(2):221-8.
5 Alexis N, et.al., JACI, 2001;108(4):577-80.
2Strand
3
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Interaction Between Air Pollutants and
Allergens
• Epidemiologic studies of pollution and
aeroallergens on causing asthma
• Epidemiologic studies of pollution and
aeroallergens on the exacerbation of asthma
• Experimental studies on the adjuvant effects of
DEPs on specific TH2 responses
• Role of pollution and global warming on natural
allergen production
• Increasing levels of CO2 and temperature are
associated with a increased pollen levels.
Bernstein JA, et.al. J Allergy Clin Immunol 2004;114:1116-23.
Beggs PJ, Clin Exp Allergy 2004;34:1507-1513.
Epidemiologic Studies Of Pollution And Aeroallergens On
Causing Asthma
• Many studies have investigated the
effects of automobile related pollutants
in heavily traveled expressways on
causing asthma symptoms in allergic
children
• Living near highways with high vehicle
traffic is associated with asthma
symptoms in children with known
allergen sensitization
Janssen NA, et.al. Environ Health Perspect 2003;111:1512-18.
Venn AJ, et.al. Am J Respir Crit Care Med 2001;164:2177-80.
Wyler C, et.al. Epidemiology 2000;11:450-6.
Nicolai T, et.al. Eur Respir J 2003:21:956-63.
Schwartz, J. Pediatrics. 2004;43:113:1037-1043.
Environmental Tobacco Smoke Exposure
• Passive smoke exposure has been
demonstrated to have a direct and adjuvant
effect on asthma in children and adults.
• Passive smoke exposure in early life might lead
to increased vulnerability of the lungs to
air pollution.1
• Passive smoke exposure is a risk factor for
respiratory disease in early childhood.2
1Sonnenschein-van
2Herr
der Voort AM, et.al. Environ Health. 2012 Dec 11;11:91.
M, J Allergy Clin Immunol. 2012 Aug;130(2):389-96.
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What is Smog?
• A term used to describe a mixture of smoke and fog.
• Occurs when high concentrations of moisture are combined
with smoke (often containing oxides of sulfur and nitrogen) in
the presence of high temperatures or thermal inversions and
the absence of wind.
• These conditions cause polluted air to stagnate over industrial
areas causing potential respiratory health hazards.
• Large coastal industrial centers with surrounding high ground
are more prone to smog.
• There is often a diurnal variation in smog formation since a
necessary component for its formation is sunlight.
Journal of Environmental Health; v56; p38; 1994.
Science News; v144; p326; 1993.
Air Quality Index
• If the AQI is below 50, the air quality is
considered good
• If the AQI value is in the 100-150 range, there
may be some adverse effects in sensitive people
(e.g. those with respiratory disease)
• At AQI values greater than 150, everyone may
experience some adverse effects, with more
severe effects in those who are more sensitive.
• An AQI value of 200 or higher may cause serious
adverse effects on a large proportion of those
exposed.
Air Quality Index( AQI) Values and Pollutant
Concentration Equal to the Upper AQI Value
AQI
value
≤50
51-100
101-150
O3 ppm
(8 hour
avg.)
PM2.5
g/m3
(24-hr
avg.)
PM10
g/m3
(24-hr
avg.)
SO2
ppm
(1-hr avg.)
NO2
ppm
(1-hr
avg.)
CO
ppm
(8-hr
avg.)
Good
0.059
12
54
35
53
4.5
Moderate
0.075
35
154
75
100
9.0
Unhealthy
for Sensitive 0.095
Groups
55
254
185
360
15
AQI
Descriptor
151-200
Unhealthy
0.115
150
354
304
644
30
201-300
Very
Unhealthy
0.116
250
424
(24-hr ) 604
1244
40
>300
Hazardous
(1-hr) 0.405
>250
>424
(24-hr) ≥605
≥1245
50
Source:http://www.epa.gov/airnow/aqi_tech_assistance.pdf
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What Should We Advise Patients With Respiratory
Diseases?
• Be aware of air quality health advisories and
smog alerts
• Minimize outdoor activities during poor air quality
days (i.e., exercise indoors)
• Advise against living in areas near high
automobile traffic, power plants or chemical
manufacturing plants
• Take environmental control measures (keep
windows closed, run A/C, filtration, avoid passive
smoke, encourage smokers in the home to stop
or at least smoke outdoors)
2012 US EPA proposed revisions to the
PM NAAQS
• In accordance with a court ordered deadline, on June 14, 2012 US
EPA proposed revisions to the PM NAAQS:
– Retain current 150 mcg/m3 24-hour PM10 standard
– Retain current 35 mcg/m3 24-hour PM2.5 standard
– Strengthen the 15 mcg/m3 annual PM2.5 standard to a level
between 12 to 13 mcg/m3
– Require near-roadway monitoring of PM2.5 in cities with more
than a million people
• The proposed standards will be open for public comment before a
Final Rule is announced in December 2012.
If finalized as proposed, community-oriented and near-road monitoring
will be required for 3 Criteria Pollutants: PM2.5, NO2, and CO.
Indoor Allergens
© AAAAI Revised 2013
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Importance of Allergic Sensitization
in Asthma
• In the US, ~56% asthma cases attributable to
atopy
• Specific sensitization more important risk factor
than total IgE
• Total IgE associated with asthma, but only among
atopics
• ≥80% of school age children with asthma
sensitized to ≥1 common aeroallergen
• More positive skin tests  more severe asthma
Arbes S et al, JACI 2007 Nov 120: 1139-45.
Gergen PJ et al, JACI 2009 Sept 124: 447-53.
Carroll WD et al, Arch Dis Childhood 2006 May 91: 405-9.
Indoor Allergen Exposure: A
Therapeutic Target?
• Critical questions for assessing role of
allergen avoidance in managing asthma:
• Is exposure to the allergen associated with
asthma symptoms/disease activity?
• Is reduction of exposure feasible?
• Does reduction of exposure result in improved
asthma control?
Major Indoor Allergens
•
•
•
•
•
Dust mite
Cockroach
Cat and dog
Mouse and rat
Mold
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House Dust Mites
• Some important household
mites:
• Dermatophagoides
pteronyssiunus
• Dermatophagoides farinae
• Blomia tropicalis
• Live in bedding, upholstered
furniture, stuffed animals and
carpet.
• Feed on human skin scales.
• Grow best in relative humidity
above 50-70%.
Arlian LG et al. J Med Entomology 1998;35:46-53.
Dust Mite Antigens and the Particles on
Which They Travel
• Much research has been focused on the group 1 (Der p 1 and
Der f 1) and group 2 (Der p 2 and Der f 2) allergens.
• Group 1 are found in mite fecal particles.
• Airborne characteristics
• Airborne with active disturbance (vacuum cleaning, bed
making, etc…)
• The majority of the allergens are found on 10-40 μm
particles.
• These particles settle rapidly (20 – 30 minutes).
Tovey E. et al. Nature 1981;289:592-3
Tovey E. et al Am Rev Respir Dis. 1981; 124:630-5
Dust Mite Allergen Exposure is a Risk
for Sensitization
Sporik et al. reported that children
exposed to >2μg/g Der p 1 are more likely
to develop sensitization (n=59).
Sporik et al. NEJM 1990;323:502-7.
Prevalence of sensitization to house
dust mite stratified by highest and
lowest quartiles of house dust mite
exposure as age 6 months (n=648).
Lau et al. Lancet 2000;356:1392-97
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Dust Mites and asthma
Asthma development in children
Lung function in adult asthmatics
Custovic et al, JACI 1996;98:64-72
Sporik et al. NEJM 1990;323:502-7.
Reducing Dust Mite Allergen Exposure
in the Home
First Line
• Mattress, pillow covers
• Wash bedding
• Remove stuffed animals
• Control humidity
Second Line
• Remove carpets
• Remove upholstered furniture
• HEPA vacuum cleaners
• Acaricides in fabrics
• Tannic acid
• Air filters unlikely to help
Dust mite on bedding encasement material.
John Vaughan and Thomas Platts-Mills
Dust Mite Allergen and Asthma Morbidity
• double blind,
placebo-controlled
RCT
• 52 school-age
children
• Significant reduction
in house dust mite
and inhaled
corticosteroid dose
in active group
Halken JACI 2003; 111:169-76.
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Bed Covers for Adults
with Asthma
Methods: Randomized double blind
placebo controlled study of allergen
impermeable mattress covers.
Results:
• Mite allergen lower for the active
than placebo group at 6, but not 12
months.
Conclusion: Mattress covers alone
are not sufficient to control asthma
symptoms in allergic adults.
Woodcock et al. NEJM 2003;349:225-36.
Dust Mite Allergen - Summary
• Exposure related to development of allergic sensitization
• Sensitization associated with asthma in areas where dust
mites are common
• Exposure is associated with increased asthma morbidity
among sensitized individuals
• Reduction of exposure has been associated with
improvements in disease activity
• Interventions that involve only mattress encasings may be
ineffective
Cockroach Allergen
• Blattella germanica most common
in U.S. inner cities
• Bla g 1 and Bla g 2 are major
allergens from German cockroach
• Allergens found in cockroach feces
and typically carried on larger
particles (>10µM)
• Proposed cut-points for cockroach
allergen exposure:
1-2 U/g (allergic sensitization)
2-8 U/g (asthma symptoms)
Cohn et al., Environmental Health Perspectives, 114: 522-526, 2006
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Cockroach Allergen Exposure
Percent of Homes
Bla g 1 level
50
40
Detectable
Sensitization (>2 U/gram)
Asthma symptoms (>8 U/gram)
38.4
28.5
30
17.6
20
10
44.4
13.4
6.7
6.1
1.3 0.5
0
10.7
9.5
3.2
Bedroom Bedroom
Bed
Floor
8.8
2.7
Kitchen
Floor
Living
Room
Floor
1.1
Living
Room
Sofa
Cohn et al., Environmental Health Perspectives, 114: 522-526, 2006
Cockroach Allergen Exposure
Risk Factors for High Bla g 1 Levels
Risk Factor
Odds Ratio (95% CI)
Type of dwelling
Detached (reference)
High rise apartment
1.0
70.0 (16.6-295.9)
No of units in building
Single family (reference)
Multifamily
Construction year
1978-1998 (reference)
pre-1940
Urbanization
population < 1 million (reference)
population > 1 million
1.0
4.89 (1.87-12.8)
1.0
3.29 (0.87-12.4)
1.0
3.15 (1.06-9.37)
Household income
> $60,000 (reference)
< $20,000
1.0
12.1 (2.05-71.7)
Cohn et al., Environmental Health Perspectives, 114: 522-526, 2006
Cockroach Allergen Sensitization
• Prevalence of sensitivity to cockroach:
18.1% in general U.S. population
33.2% in asthmatics
• Sensitization rates vary by age, sex, race/ethnicity
and poverty status
1-5
6-19 10-39 40-59
60+
Age (years)
Female
Male
Sex
White
Black Mexican
Other
Race/Ethnicity
Data from NHANES 2005-2006, unpublished
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Relationship between Cockroach
Allergen Sensitization, Exposure, and
Asthma
• The combination of cockroach sensitization and
exposure is a risk factor for asthma
(Call RS et al., J Pediatr, 1992 Dec; 121:862-6 and
Gelber LE et al, Am Rev Respir Dis, 1993 Mar; 147:573-8)
• Recent data from NHANES III indicates that
cockroach sensitization is associated with a 2-fold
increase in asthma risk in the U.S. population;
however, this association is attenuated when
adjusting for other allergen sensitivities
(Arbes et al., J Allergy Clin Immunol, 2007 Nov; 120:1139-45)
Inner City Asthma Study (ICAS)
Multi-component Intervention
Reductions in cockroach and dust mite allergens highly
correlated with reduced asthma morbidity
Morgan et al., N Eng J Med, 351: 1068-1080, 2004
Cockroach Allergen Mitigation
Principles of Integrated Pest Management (IPM)
• Targeted placement of insecticide bait to reduce exposure to potentially
toxic pesticides
• Sealing of cracks and crevices to prevent re-infestation
• Removal of food and water sources
• Thorough cleaning of all surfaces including floors, cabinets, appliances
• Occupant education
Living Room Floor / Sofa
intervention
Bla g 1 (U/g)
Bla g 1 (U/g)
Kitchen Floor
Month
control
Month
Arbes et al., JACI, 112: 339-345, 2003
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Cockroach Allergen - Summary
• Bla g 1 and Bla g 2 are the major cockroach allergens
• Elevated cockroach allergen levels occur in high rise
apartments, older homes and low income homes
• Cockroach sensitization is common in the US
• Exposure to high levels of cockroach allergen is associated
with excess asthma morbidity in inner city children
• Effective cockroach allergen mitigation involves basic
principles of integrated pest management (IPM)
• Reductions in cockroach allergen in inner city asthmatic
children leads to improved asthma symptoms
Cat and Dog Allergens
• The major allergens are
• Cat - Fel d 1: produced in sebaceous and salivary glands
• Dog - Can f 1: found in dander and saliva
• Particles that carry cat and dog allergens can be small (210μm), become airborne with minimal disturbance and
remain airborne for hours.
• Travel on particles that are passively transferred.
• Are ubiquitous in public buildings and moderate exposure in
communities with domestic cat ownership is unavoidable.
• Homes with pets have allergen levels ~100x higher than
homes without
Asthma Symptoms Associated with
Passive Transfer of Cat Allergen
<18% Cat owners in class
>18% Cat owners in class
Change in morning PEFR
15
10
Week 2
P=0.04
Week 3
P=0.04
Change in symptoms
Week 2
P<0.01
Week 3
P=0.06
5
0
-5
-10
-15
Study Population: Swedish school
children with asthma and cat
sensitization
Reprinted with permission of the American Thoracic Society. Copyright © American Thoracic Society.
Almqvist C, Wickman M, Perfetti L, Berglind N, Renström A, Hedrén M, Larsson K, Hedlin G, Malmberg P,
2001, “Worsening of asthma in children allergic to cats, after indirect exposure to cat at school” American
Journal Respiratory Critical Care Medicine, Mar;163(3 Pt 1):694-8. Official Journal of the American
Thoracic Society
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Recommendations for Allergen
Avoidance for Pet Allergic Patients
• First Line
• Do not have pets
• Find existing pet a new home
• Second line
• Keep the pet outside at all times
• Isolate the pet from the bedroom
• Air cleaners
• Wash pet regularly
Cat Allergen in Home Declines Slowly
After Pet Removal
Fel d 1 content in the dust from homes after
removal of a cat
Wood et al JACI 83:730,1989
Effect of Air Filters and Pet Washing
Air filters
• The clinical effects of home air filtration in homes where the
cat remains has been mixed
• Wood et al. found no clinical effect on symptoms or peak
flow for young adult asthmatics
• Van der Heide et al. found a reduction in bronchial hyperreactivity for asthmatic children when air filters were
placed in the living and bed rooms.
Washing cats and dogs
• Washing cats and dogs can significantly reduced airborne
cat allergen, but the decrease is not maintained for more
than a few days.
Wood et al , AJRCCM 1998;158:115-20]
Van der Heide et al. , JACI 1999;104:447-51]
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Cat and Dog Allergens - Summary
• Direct and indirect cat exposure associated with asthma
symptoms and morbidity
• The association between pet ownership and the
development of sensitization and asthma is mixed in the
literature, with increased, decreased and no risk reported.
• Cat removal is effective in lowering cat allergen levels over
months and improving asthma outcomes
• Results of studies of air filters are mixed
• Pet washing only reduces allergen temporarily
Portnoy J, Kennedy K, Sublett J. Environmental assessment and exposure control: a practice
parameter – furry animals. Ann Allergy 2012; 108:223-e1-223-e15.
Mouse Allergen: Characteristics
• Mus m 1
•
•
Molecular weight 19 kD
Found in hair follicles, dander and
urine
• 4 times higher in male mice than in
females
• Mus m 2
• Molecular weight 16 kD
• Found in hair, dander, but not urine
• Albumin is allergenic in about 30% of
mice-sensitive individuals.
• ~90% of Mus m 1 found on particles
≤10 microns
Price et al. Clin Exp Allergy 1990,20: 71-77
Prevalence of Mouse Allergen
Cohort
NCICAS
Phipatanakul et al., JACI,
2000;106:1070-4
NY, NY
Chew et al., EHP, 2003; 111:1348–1351
Baltimore
Matsui et al.,JACI,2005;115:358-363
United States
Cohn et al., JACI, 2004;113: 1167-1171
Suburban Maryland
Matsui et al., JACI, 2004; 113:910-5
Popul’n
Room
% detectable
608
children
kitchen, BR,
or LR
95%
221
mothers
kitchen
100
children
kitchen
831
housing
units
kitchen, BR,
or LR
335
children
kitchen
57- 66%
100%
82%
75%
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Sensitization to Mouse
Prevalence Rates of Skin Test Sensitivity
Study
Population
+ mouse
SPT/IgE (%)
Occupational
Matsui Annals 2004
151 adults
20
NCICAS
Phipatanakul JACI 2000
499 children
18
ICAS
Gruchalla JACI 2005; Pongracic Annals 2008
937 children
22
Baltimore
Matsui Annals 2006
150 children
26
West Virginia
Welch Annals 2003
209 children
12
Suburban Maryland
Matsui JACI 2004
335 children
13
Gergen et al., JACI, 2009, 124: 447-453)
Mouse Sensitization/Exposure and Morbidity
Mouse sensitized
and exposed
urban children
with asthma are at
greater risk for
asthma morbidity
than nonsensitized or nonexposed children
7
OR
OR (95%
(95% CI)CI)
6
5
4
3
2
1
0
UD Visit
•
•
•
ED Visit
ORs for unscheduled doctor visit (UD) and ED visit for
mouse sensitized and exposed children compared to
non-sensitized or non-exposed children
Adjusted for age, sex, atopy, cockroach sensitization
and exposure, public health insurance, and study visit
Hospitalization, adjusted OR: 69.9 (5.8-838.9)
Matsui et al Ann Allergy Asthma Immunol. 2006;97:514-520
Rat Allergen
• Urine, saliva, hair, and dander
• Rat n 1A MW = 20 to 21 kD
• Rat n 1B MW = 16 to 17 kD
• Rat fur contains 5 allergens
• Salivary glands demonstrate
at least five other allergens
• Rat-specific IgE found in 1.2%
US population
• 24% of rat allergic individuals show
sensitivity to rat albumin
• Remains airborne ≥60 minutes after disturbance
Bayard et al Biochem Biophys Acta 1996, 1290: 129-134,
Gordon et al. Allergy 2001, 56: 563-756
Gergen et al. J Allergy Clin Immunol 2009, 124: 447-453
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Rat Allergen and Asthma
Morbidity
National Cooperative Inner-city Asthma Study
School age inner-city children with asthma
Perry, et al JACI 2003;112:346-52
Mouse & Rat Allergens - Summary
• Mouse allergen is widespread in occupation and home
settings, with higher levels occurring in urban areas and low
income, multi-family dwellings
• Mouse sensitization is more common in minority race/ethnicity
and lower socioeconomic groups
• Exposure to high levels of mouse/rat allergen is associated
with excess asthma morbidity in inner city children who are
sensitive to mouse/rat allergen
• Effective mouse allergen mitigation involves basic principles of
integrated pest management (IPM)
• Reductions in mouse allergen in inner city
asthmatic children may improve asthma
symptoms
Phipatanakul W, Matsui E, Portnoy J, et al. Environmental assessment and exposure
reduction of rodents: a practice parameter. Ann Allergy Asthma Immunol 109;
2012:375-387.
Fungi grown from house dust
Definition of Mold
• Mold is not a scientific term.
It stems from old English for earth.
The term, also often called “mildew”, refers to the fuzzy
growth found indoors and outdoors composed of bundles
of hyphae which form a mycelium (pleural = mycelia).
• The kingdom of Fungi encompasses both the single
celled yeasts and the multi-celled molds.
• The fungi are eukaryotes like animals and plants, but are
a separate kingdom. Most exist as masses of filaments,
living off of dead or decaying organic matter, and
reproducing sexually and/or asexually by spores.
Alternaria
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Fungi and Allergy/Asthma are Linked
by Much Anecdotal Evidence
• The association of fungal spore exposure and
respiratory disease is historically appreciated
• Charles Blackley (1820-1900) recorded that he
suffered for days from “aphonia and bronchael
distress” after inhaling Penicillium spores.
• Bouts of asthma have been associated with cool
mist humidifiers when they emit high levels of
fungal propagules.
• Solomon linked asthma attacks with spore
release from cool mist humidifiers.
Penicillium
Blackley C. Experimental researches on the causes and nature of catarrher
aestirus (Hay fever and Hay asthma) London 1873, Balliere, Tindall and
Cox
Solomon W R 1975. Assessing fungus prevalence in domestic interiors. J
.Allergy Clin. Immunol. 56:235-242
Solomon WR 1974. Fungus aerosols arizing from cold-mist vaporizers. J
Allergy 54:222-8
Association Between Spore Peaks
and Asthma Hospitalizations
•First documented by Salvaggio 1971
Spores
25
20000
ER Visits
20
15000
15
10
Salvaggio et al. JACI.
48:96, 1971
25000
10000
5000
0
0
• Data
from
Kansas
City
1995
4
4 / /1 /1
1 9
4 / 0 /1 9 5
1 9
4 / 9 /1 9 5
30 99
5 /19 5
5 / /9 /1 9 5
21 99
5 / /1 5
3 9
6 / 1 /1 9 5
1 9
6 / 1 /1 9 5
20 99
7 /19 5
7 / /1 /1 9 5
1 9
7 / 1 /1 9 5
2 9
7 / 2 /1 9 5
31 99
8 /19 5
8 / /9 /1 9 5
2 9
8 / 0 /1 9 5
29 99
9/ /19 5
9 / 9 /1 9 5
1 9
9 / 8 /1 9 5
2 9
1 0 7 /1 9 5
/8 9 9
/1 5
99
5
5
Spores per Cubic Meter of Air
ER Visits
30
Sensitization and Exposure to Common
Fungi is Associated with Asthma
• A case report of a patient with IgE-mediated sensitivity to
Alternaria describes a life-threatening asthma attack
during peak Alternaria season
• Exposure to Alternaria is a risk factor for respiratory arrest.
10 of 11 asthma patients with RA were skin test positive
for Alternaria, compared to 31% of controls (p < 0.001)
• In the NHANES, asthma was associated with skin prick
test reactivity to Alternaria (OR, 5.1; 95% CI: 2.9-8.9)
• Sensitization to Alternaria, Aspergillus, Penicillium, or
Cladosporium is associated with a higher number of
symptom days among inner-city children with asthma
Bush RK et al. J Allergy Clin Immunol. 2004; 113: 227-234.
O’Hollaren MT et al. N Engl J Med. 1991; 324: 359-363.
Gergen PJ et al. J Allergy Clin Immunol. 1992; 90: 579-588.
Pongracic J et al. J Allergy Clin Immunol. 2010; 125: 593-9.
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Exposure to A alternata in US Homes is
Associated with Active Asthma
The National
Survey of Lead
and Allergens in
Housing (831 units
from 75 locations)
found increasing
Alternaria levels
correlated with
asthma.
Salo PM et al. J Allergy Clin Immunol. 2005; 116:623-629.
Salo PM et al. J Allergy Clin Immunol. 2006; 118: 892-898.
There is an Association Between Damp Indoor
Environments and Poor Respiratory Health
• An IOM expert panel reviewed the relationship between
damp or moldy environments and adverse health effects.
• They reported an epidemiologic association between damp
indoor environments or indoor mold or other agents and:
– upper respiratory tract symptoms
– cough
– wheeze
– hypersensitivity pneumonitis
– asthma sxs in sensitized asthmatic persons
2007 NAEPP Guidelines Recommend
Controlling Dampness and Mold
• Mold growth indoors can be inhibited by reducing
moisture and humidity.
• Proper building maintenance, dehumidification, air
conditioning, and increased ventilation are all
helpful.
• Humidifiers and vaporizers increase indoor humidity
and can become contaminated with mold and
should not be used in homes of asthmatics.
Expert panel report 3: guidelines for the diagnosis and management of asthma. National
Institutes of Health, National Asthma Education and Prevention Program; Bethesda MD:
2007 [Accessed September 3, 2010]. NIH Publication No. 08-4051. Available from
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf
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Indoor Allergens and Patient Care:
NAEPP Guidelines
• Assess exposures
• Patient’s history may help identify relevant allergen
exposures
• Assess sensitization
• Use skin testing or in vitro testing to determine
sensitivity to perennial indoor inhalant allergens,
including common molds
• Consider testing for seasonal allergens if suggested by
patient history
• Assess the significance of positive tests in the context of
the patient’s medical history.
Expert Panel Report 3 (EPR3):
Guidelines for the Diagnosis and Management of Asthma
Indoor Allergens and Patient
Care: NAEPP Guidelines (cont)
• Patients who have asthma at any level of
severity should:
• Reduce, if possible, exposure to allergens to
which the patient is sensitized
• Effective allergen avoidance requires a
multifaceted, comprehensive approach
Expert Panel Report 3 (EPR3):
Guidelines for the Diagnosis and Management of Asthma
Resources
•
•
•
•
www.epa.gov
www.aaaai.org
www.acaai.org
Health Canada www.hc-sc.gc.ca/ewhsemt/air/index-eng.php
• Air Pollutants and the Respiratory Tract 2nd
Ed. Eds. W. Michael Foster and Daniel L.
Costa.
• Health Effects of Air Pollution Rostrum. J
Allergy Clinical Immunology 2004;114:111623.
25