What is Happening in the Schools?

Updates from the School
Inner-City Asthma Study:
Working with the Community
to Make a Difference
Wanda Phipatanakul, M.D., M.S.
asthma@childrens.harvard.edu
Associate Professor of Pediatrics
Boston Children’s Hospital
Johnston Professorship October 3, 2014
HARVARD
MEDICAL SCHOOL
Disclosures
• NIH funding to Institution
HOME Allergen Exposure and
Asthma Morbidity in Inner City Children
Hospitalizations
p=0.001
0.3
0.2
0.1
Change in Care Giver’s Plans
Days With Changed
Plans in Past Year
p<0.001
2
1
0
0
20
3
No. of Visits in
Past Year
Hospitalizations
in Past Year
0.4
Unscheduled Medical Visits
p=0.006
15
neg skin test, low allergen exposure
neg skin test, high allergen exposure*
pos skin test, low allergen exposure
pos skin test, high allergen exposure*
10
5
0
Rosenstreich et al., N Eng J Med, 336: 1356-1363, 1997
* Bla g 1 > 8 U/gram
Inner City Asthma Study HOME
Intervention Reduces Asthma Morbidity
Reductions in cockroach and dust mite allergens highly
correlated with reduced asthma morbidity
Morgan et al., N Eng J Med, 351: 1068-1080, 2004
Background
• Indoor allergen exposure is a known
trigger that increases asthma morbidity
• NIH funded Inner-City Asthma studies
have established that unique urban
exposures are associated with asthma
morbidity
• Most indoor allergen studies have
targeted the home/bedroom (Considered
primary exposure site)
• Children spend the majority of their day in
schools
• Little is known about the role of
school/classroom specific environmental
exposure and asthma
• First US study to fully evaluate
school/classroom specific environmental risk
factors and asthma morbidity, adjusting for
home(R01-AI073964-Phipatanakul)
School Inner-City Asthma Study Repeating
Annual Schema
Class
Sampling
Spring Summer
Screening
& Recruitment
8-10 schools
75 Students/yr
Fall
Baseline
Phenotype
Survey
Spirometry
Skin testing
Blood/Nasal
Winter
Class
Sampling
Spring
3, 6, 9 ,12 months
Follow-up Health Outcomes
Linked to Sampling
Spirometry, FeNO, Nasal
SICAS Methods – skin
testing
• Children skin tested to:
– Molds (aspergillus, cladosporium,
alternaria, penicillium)
– Indoor allergens (cat, dog, dust
mite, roach, mouse, rat)
– Outdoor allergens (grass, pollen,
ragweed)
Dust/Air Home/School Environmental
Sample Testing
 Multiplex array for indoor allergens (MARIA™)
 Dust/Air Samples analyzed for common indoor
allergens
▪ Cockroach – Bla g 2
▪ Dust Mite – Der f 1, Der p 1
▪ Cat – Fel d 1
▪ Dog – Can f 1
▪ Mouse – Mus m 1
▪ Rat- Rat n 1
▪ Alt-a 1 (mold)
Classroom Mold Sampling
Methods
• Airborne fungal
spores were
collected by Burkard samplers from
inner-city elementary schools twice
during the academic school year
– Slides were analyzed at 1000X
magnification
– A segment representing the school day
(8a-4p) was scanned and all fungal
spores were counted and identified
– Results were reported as spores per
cubic meter of air (spores/m3) for the
8-hour school day
Air Pollution Sampling
• Fastened to Air
Samplers to
collect pollutants
passively
• Particulate
Matter black
boxes correlated
with area
samplers NIEHS
School Sampling Visits- Want to Sign
Up for This Study?
•
•
•
•
•
•
•
8 Air Samplers
2-3 Vacuums/ Dust Samplers
4 Burkard Mold Samplers
8 Pollution Particle Box Samplers
8 NO2 Samplers
3-4 Staff
Not During MCAS
1-2 Cars
(State Testing) please
What We Do in 10 Minutes at School
FeNOmeasurements
Nasal swabs
Spirometry/Piko
School Vs. Home Allergen Levels
Sheehan WJ, Phipatanakul W Ann Allergy Asthma Immunol. 2009;102:125-30
Permaul P, Phipatanakul W Peds Allergy Immunol. 2012 ;23(6):543-9
Classroom Airborne vs. Settled Dust
Mouse Levels
3
Classroom Airborne Mus m 1
(log -10)
N=180
r=0.48, p < 0.0001
2.5
2
1.5
1
0.5
0
-4
-3
-2
-1
-0.5 0
1
2
-1
-1.5
-2
Classroom Settled Dust Mus m 1 (log -10)
Permaul P, Phipatanakul W Peds Allergy Immunol. 2012 ;23(6):543-9
3
Relation of Visible Mouse
and Classroom Expoosure
Visible Classroom Mouse Droppings
p=0.07
Settled Mus m 1 Dust Levels (µg/g)
7
6
p=0.002
6.11
NO
YES
(n=20)
5
4
p<0.001
p=0.12
3
2.22
(n=21)
2
1.21
(n=162)
1
0.45
(n=166)
0
FALL
SPRING
Permaul , Phipatanakul Annals Allergy 2013;111(4):299301.
Sample
Preschool Table Wipes
Fel d 1
ng/wipe
Can f 1
ng/wipe
Mus m 1
ng/wipe
Endotoxin
EU/wipe
1
18.87
17.55
14.67
70975.97
2
<0.20
<0.60
2.40
70559.92
3
1.40
<0.60
2.90
264741.54
4
0.40
<0.60
0.40
909595.44
5
6
7
8
2.50
1.95
4.60
1.35
0.90
2.00
<0.60
<0.60
2.23
5.40
11.20
2.13
435147.87
9778.22
683.38
6162.44
9
0.60
<0.60
3.13
132757.71
10
0.40
<0.60
15.17
1393106.74
11
0.30
1.50
1.53
220012.49
<0.02
<0.06
<0.01
<0.25
LLOD ng/ml
Kanchongkittiphon, Sheehan, Phipatanakul Allergy 2014; 69(7):960-3
Home/School Endotoxin Exposure in
Children with Asthma
• Endotoxins are part of the outer membrane of
Gram Negative Bacteria
• Shed into the environment after bacteria die
• Endotoxins are potent stimulators of the immune
system
• Endotoxins are active for much longer than the life
of bacteria
Classroom vs. Bedroom Endotoxin
Levels for Children with Asthma
Endotoxin Level (EU/g)
20,000
15,000
10,000
Median
5,000
0
CLASSROOM (n=104)
BEDROOM (n=104)
Sheehan WJ, Phipatanakul Ann Allergy
2012;108(6):418-222.
Increased Morbidity in Subjects
with Multiple Food Allergies
>3 days of asthma
symptoms, past 2 weeks
Use of asthma controller
medication
Mean # of clinic or ED
visits for asthma, past
12 months
Mean # of missed school
days for asthma, past 12
months
Multiple
Food
Allergies
(N=36)
No Food
Allergies
(N=227)
Odds Ratio
(CI)
P value
42%
22%
2.60 (1.3 – 5.4)
.009
78%
59%
2.47 (1.1 – 5.7)
.029
5.81
4.09
n/a
.008
8.08
5.84
n/a
.086
Friedlander JL, Phipatanakul W J Allergy Clin Immunol : In Practice 2013;1:
479-84
Neighborhood Safety and Asthma
Control
Kopel/ Phipatanakul 2014, Peds Pulmonol (In Press)
ADB2 Methylation Associated with
fewer symptoms/better control
Methylati
on SITE
PValu
e
0.00
2
Outcome
(4 week)
Effect
Daytime
2.06 (1.31 CPG8
control
3.23)
rescue
1.46 (1.02 control
2.07)
0.04
Daytime
2.27 (1.33 - 0.00
3.87)
3
CPG9
control
Daytime
2.74 (1.22 CPG10
control
6.17)
0.02
adjusted for age, race, gender, preterm birth, family history of asthma and
diagnosis of eczema, unless otherwise noted
**adjusted for age, race gender and preterm birth
Gaffin, Phipatanakul, Clin Exp Allergy 2014;44(5):681-9
25
SICAS-2 Next Phase
• School/classroom environment
important
• We can utilize strategies known to work
in home and school environments
(IPM/Air filters/Purifiers
• School-based intervention could
efficiently and effectively benefit a
community of children as opposed to
home intervention which benefits only
single child or family in a home
• Community trust vital sustainable, policy
changing school-based interventions in
the future- Stay Tuned
Questions?
asthma@childrens.harvard.edu
857-218-5336
Acknowledgements
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Diane Gold, MD, MPH
Petros Koustrakis, PhD
Carter Petty, MS
Brent Coull, PhD
Andrea Baccarelli, MD, PhD
Sachin Baxi, MD
Perdita Permaul, MD (AAP/NIH)
Michael Muilenberg, MS
Michelle Fox, MD,
Lisa Bartnikas, MD (NIH LRP)
Margee Louisias, MD (Public Health
Services Award)
Lakeia Wright, MD F32 HL124919
Bridget Hron, MD F32 HL122080
William Sheehan, MD K23 AI104780
Peggy Lai, MD, MPH, K23ES023700
Jon Gaffin, MD, MMSc K23AI106945
David Kantor, MD, PhD K12 HD 047349
Critical Care Scholars
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NIH/ NIAID/NHLBI
ALA/AAAAI/Noonan (Phipatanakul)
Aeorcrine/ATS/Glaxo Fellow Awards
ACAAI/Von Clements/AAP ATS Minority
Award/Bates
SICAS- Ann Bailey/ACRC Staff
Lincoln Diagnostics/Greer
CTSU-NIH/Harvard Catalyst
Community/Schools/Principals/
Collaborations- Community/ER/Pulm
R01 AI073964 (Phipatanakul)
ARRA AI073964 Suppl (Phipatanakul)
K24 AI 106822 (Phipatanakul)
Research Scholarship from Ramathibodi
Hospital ( Champ Kanchokittiphon, MD,
PhD)
Marissa Hauptman, MD, MPH
Amanda Green, PhD ©
SICAS References
• Phipatanakul W, Bailey A, Hoffman EB, Sheehan WJ, Lane JP, Baxi S, Rao D,
Permaul P, Gaffin JM, Rogers CA, Muilenberg M, and Gold DR. The School
Inner-City Asthma Study (SICAS): Design, Methods, and Lessons Learned
2011 J Asthma 2011; 48:1007-14.
• Baxi SN, Sheehan WJ, Gaffin JM, Yodying J, Panupattanapong S, Lane JP, Fu
C, Hoffman EB, Gold DR, Phipatanakul W. Agreement between Parent and
Student Responses to an Asthma and Allergy Questionnaire in a Diverse
Inner City Elementary School Population.” Annals Allergy, Asthma, and
Immunology 2011;107 : 371-3.
• Sheehan WJ, Hoffman EB, Fu C, Baxi S, Bailey A, King EM, Chapman MD,
Lane JP, Gaffin JM, Permaul P, Gold DR, Phipatanakul, W. Endotoxin
Exposure in Inner-City Schools and Homes of Children with Asthma Annals
of Allergy, Asthma, and Immunology 2012;108(6):418-222.
SICAS References
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Permaul P, Sheehan WJ, Baxi SN, Gaffin JM, Fu C, Petty CR, Gold DR, Phipatanakul
W. Predictors of Indoor Exposure to Mouse Allergen in Inner-City Elementary
Schools. Annals Allergy, Asthma, Immunol 2013;111(4):299-301.
Baxi SN, Muilenberg M, Rogers CA, Sheehan WJ, Gaffin JM, Permaul P, Kopel L, Lai
P, Lane JP, Bailey A, Petty C, Fu Chunxia, Gold DR, Phipatanakul W. Exposures to
Molds in School Classrooms of Children with Asthma. Peds Allergy and Immunolgy
2013; 24: 697-703
Kanchongkittiphon W. Sheehan WJ, Friedlander J, Chapman MD, King EM ,
Martirosyan K, Baxi SN, Permaul P, Gaffin JM , Kopel L, Bailey A, Fu C, Petty CR,
Gold DR ,and Phipatanakul W Allergen Exposure on Desktop Surfaces in Preschools
and Elementary Schools of Urban Children with Asthma. Allergy 2014; 69(7):960-3
SICAS References
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Friedlander J, Sheehan WJ, Hoffman EB, Fu C, Gold DR,
Phipatanakul W. Food allergy and increased asthma
morbidity in a school inner-city asthma study. J Allergy
Clin Immunol : In Practice 2013;1: 479-84.
Gaffin JM, Raby B, Petty C, Hoffman E, Gold DR,
Phipatanakul W. B2 adrenergic receptor gene
methylation is associated with decreased asthma
severity, Clinical Experimental Allergy 2014; 44(5):681-9
Kopel LS, Gaffin JM, Rao DR, Sheehan WJ, Friedlander JL,
Hoffman EB, Fu C, Subramanian SV, Gold DR, and
Phipatanakul W. Perceived Neighborhood Safety and
Asthma Morbidity in a School-Based Inner-City Asthma
Study . Pediatric Pulmonology 2015;Jan;50(1):17-24.
References
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Phipatanakul W, Matsui E, Portnoy J, Williams PB, Barnes C,
Kennedy K, Bernstein D, Blessing-Moore J, Cox L, Khan D,
Lang D, Nicklas R, Oppenheimer J, Randolph C, Schuller D,
Spector S, Tilles SA, Wallace D, Sublett J, Bernstein J, Grimes
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Rodent Parameters Ann Allergy Asthma Immunol. 2012
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Sheehan WJ, Rangsithienchai PA, Wood RA, Rivard D,
Chinratanapisit S, Persanowski MS, Chew GL, Seltzer JM,
Matsui EC and Phipatanakul W. “Pest and Allergen
Exposure and Abatement in Inner-City Asthma: A Work
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& Immunology Indoor Allergy/Air Pollution
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W. Michael Foster and Daniel L. Costa.
Health Effects of Air Pollution Rostrum. J Allergy
Clinical Immunology 2004;114:1116-23.
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