What is Happening in the Schools?
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. [email protected] 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? [email protected] 857-218-5336 Acknowledgements • • • • • • • • • • • • • • • • • 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 • • • • • • • • • • • • • • • 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 • • • • • 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 • • • • 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 • • • • • • 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 C, Miller JD, Seltzer J. Rodent Parameters Ann Allergy Asthma Immunol. 2012 Dec;109(6):375-87. 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 Group Report of the American Academy of Allergy, Asthma & Immunology Indoor Allergy/Air Pollution Committee.” Journal of Allergy and Clinical Immunology 2010;125(3):575-81 www.epa.gov , 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;114:1116-23. References • • • • • Lodrup Carlsen KC, Roll S, Carlsen KH, Mowinckel P, Wijga AH, Brunekreef B, et al. Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts. PLoS One. 2012;7(8):e43214. Konradsen JR, Nordlund B, Nilsson OB, van Hage M, Nopp A, Hedlin G, et al. High basophil allergen sensitivity (CD-sens) is associated with severe allergic asthma in children. Pediatric Allergy and Immunology. 2012;23(4):376-84. Brauner EV, Loft S, Raaschou-Nielsen O, Vogel U, Andersen PS, Sorensen M. Effects of a 17q21 chromosome gene variant, tobacco smoke and furred pets on infant wheeze. Genes Immun. 2012;13(1):94-7. Delfino RJ, Staimer N, Tjoa T. Personal endotoxin exposure in a panel study of school children with asthma. Environ Health. 2011;10:69. Pa¨ ivi M. Salo, PhD, Michelle L. Sever, MSPH, and Darryl C. Zeldin, Indoor allergens in school and day care environments. J Allergy Clin Immunol 2009;124:185-92