2/19/2016. Hoffman TILT Project Department of Family and Community Medicine University of Texas School of Medicine at San Antonio

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TILT Objectives Explain evidence for human exposures Describe major populations affected by TILT Describe preliminary biomarkers Discuss recommendations on minimizing TILT triggers Describe

10 Americans Study Environmental Working Group 10 Americans Study EWG randomly selected 10 US citizens Tested for ~ 400 synthetic chemicals Discovered 280 toxic synthetic chemicals 3,079

, 2013; photo: Heather West) Urinary Metabolites of OP Pesticide in US population (ug/l) by age (CDC: NHANES 1999-2010) Survey years Geometric mean (95% conf. interval) Age group 6-11 yr 99-00 2.

1 TILT Objectives Explain evidence for human exposures Describe major populations affected by TILT Describe preliminary biomarkers Discuss recommendations on minimizing TILT triggers Describe components of an environmental house call Hoffman TILT Project Department of Family and Community Medicine University of Texas School of Medicine at San Antonio Environmental Working Group (EWG) 10 Americans Study Environmental Working Group 10 Americans Study EWG randomly selected 10 US citizens Tested for ~ 400 synthetic chemicals Discovered 280 toxic synthetic chemicals 3,079 metabolites detected in urine 2,282 come from diet, drugs, cosmetics, fragrances and environmental exposures (Wishart et al., 2013; photo: Heather West) Urinary Metabolites of OP Pesticide in US population (ug/l) by age (CDC: NHANES ) Survey years Geometric mean (95% conf. interval) Age group 6-11 yr ( ) ( ) ( ) ( ) yr ( ) ( ) ( ) ( ) years ( ) ( ) ( ) ( ) 1

Acetaminophen, pesticide and diethylhexyl phthalate metabolites,

of perinatal exposure. Camann DE et al. 2013.

Subjects with Concentration (ng/g) Analyte (parent) QL ng/g detections

3 Ibuprofen 98 1 < 98 < 98 111 TCPy (chlorpyrifos) 5.6 2* < 5.6 3.

9 181 2460 Recovery of equilibrated acetaminophen-d 4 ranged from 30%

a Estimated value below quantitation limit (QL) * 2 children with

treatments Chemicals Detected in 6-yr old boy with ADHD, dyslexia,

2 Acetaminophen, pesticide and diethylhexyl phthalate metabolites, anandamide, and fatty acids in deciduous molars: potential biomarkers of perinatal exposure. Camann DE et al J Expo Sci Environ Epidemiol. 23: Subjects with Concentration (ng/g) Analyte (parent) QL ng/g detections P 50 P 95 Maximum Acetaminophen < Ibuprofen 98 1 < 98 < TCPy (chlorpyrifos) 5.6 2* < a 46 IMPy (diazinon) < MEHP (DEHP) < Recovery of equilibrated acetaminophen-d 4 ranged from 30% to 106% in 25 molars from 21 subjects. a Estimated value below quantitation limit (QL) * 2 children with AD/HD, one who has severe DCD from home with quarterly exterminator treatments Chemicals Detected in 6-yr old boy with ADHD, dyslexia, auditory processing disorder 2D View (6 year old boy) naphthalene dibutyl phthalate 100 s more to be identified BHT Case Study II Case Study II Claudia Miller, MD Little Teeth. Big Impact teeth and counting 2

Claudia Miller, MD CI Screener (4 questions) Masking QEESI available at: https://redcap.uthscsa.edu/redcap/surveys/?

exposures in patients w/high CI scores Major populations affected by TILT Veterans with TILT 1.

9/11 World Trade Center 1 st responders (toxic fumes) 4. Flight attendants/pilots (TCP: fume events) 5.

Individuals (remodeling, pesticides, cleaning products) CW agent-filled weapons destroyed Gulf War Veterans 25-33% are ill

reports of ill veterans/burn pits VA establishes a burn pit registry COPD, Bronchiolitis, TILT, rashes, muscle pain Insomnia, liver

3 Claudia Miller, MD CI Screener (4 questions) Masking QEESI available at: NLAN8XTP Chemical and Other intolerances Scales patients aware Masking/Unmasking use Masking Index to determine/eliminate exposures in patients w/high CI scores Major populations affected by TILT Veterans with TILT 1. Gulf War and Iraq/Afghanistan veterans (CWA, burn pits) 2. EPA staff scientists (remodeling) 3. 9/11 World Trade Center 1 st responders (toxic fumes) 4. Flight attendants/pilots (TCP: fume events) 5. Other occupational exposures (e.g. hairdressers; janitors) 6. Individuals (remodeling, pesticides, cleaning products) CW agent-filled weapons destroyed Gulf War Veterans 25-33% are ill (>200,000) Robert Haley, UT SW Medical Center in Dallas, 2013 CW bunkers Khamisiyah, Iraq Veterans with TILT Iraq and Afghanistan reports of ill veterans/burn pits VA establishes a burn pit registry COPD, Bronchiolitis, TILT, rashes, muscle pain Insomnia, liver conditions, decreased physical function, chronic multi-symptom illnesses (Military Times, July 2015) Disinfectant Exposure 13-year old girl was cleaning pantry floor with disinfectant Reacted initially with mild cough, tearing Delayed onset anaphylaxis Treated w/ epinephrine Developed intolerances to fragrances and cleaning agents 3

4 18-yr old male Pesticide/Remodeling Exposure Previous history of viral illness age 11 (6 weeks) Dx: Chronic fatigue age 14, recovered age 16 Exposed to Diazinon at work age 18 Sx: bloody nose, difficulty breathing, confusion, shaking uncontrollably Fatigue so severe, wheelchair bound for several months Pesticide/Remodeling Exposure Exposed to polyurethane from refinished hardwood floors the following spring Parents realized that son was chemically sensitized from his severe reaction to floors Recalled that the owners of the pizza place mixed their own diazinon Tested negative for Lupus, MS Elevated liver enzymes (temporary); swollen visible lymph nodes Pesticide/Remodeling Exposure Dx: IBS Developed multiple intolerances to fragrances, cleaning agents Alcohol, dairy, wheat, sugar intolerant Successful wood working business using a respirator Mold triggers symptoms Periods of wellness, followed by illness when exposed to low level chemicals or foods that are problematic Preliminary Evidence for TILT Results CYP p450 polymorphisms; CYP activities and expression levels Chemical oxidative stress: Nitrates/nitrites, multiple inflammatory markers Our results suggest that serious and multiple dysfunctions of chemical defensive system are found in these patients. Elevated proinflammatory markers CI individuals displayed a distinct systemic immune mediator profile with low-grade systemic inflammation, not involving IGEmediated mechanisms Refs Deluca et al. 2010, 2013 (CI) Dantoft et al (CI) Preliminary Evidence for TILT American College of Obstetrics and Gynecology 2013 Report Results SOD2 polymorphisms (primary mitochondrial antioxidant) related to high CI scores OR of 4.30 (95% CI, ) Ala/Ala +Ala/Val vs. Val/Val Refs Katoh et al (Pulp plant-males only) fmri differences in thalamus and caudate Calley et al (GWV) Autonomic regulatory disruption in cerebral perfusion Bunegin et al (GWV) Autonomic Nervous System dysfunction Haley et al (GWV) Chemicals Perchlorate PFOAs Flame retardants BPA Formaldehyde Reproductive/ Developmental effects Altered thyroid function Birth weight; ADHD Impaired neurodevelopment, stillbirth, LBW, prematurity Recurrent miscarriage, aggression, hyperactivity Spontaneous abortion, LBW ( Detected in teeth) 4

Chemicals American College of Obstetrics and Gynecology 2013 Report Reproductive/ Developmental effects Poor Populations Disproportionately Exposed Pesticides Solvents Phthalates PCBs Air pollutants

5 Chemicals American College of Obstetrics and Gynecology 2013 Report Reproductive/ Developmental effects Poor Populations Disproportionately Exposed Pesticides Solvents Phthalates PCBs Air pollutants Impaired neurodevelopment and fetal growth; childhood cancer Fetal loss, miscarriage, birth weight, congenital malformations Masculine play & anogenital distance; preterm birth, impaired mental develop, BMI ADHD, IQ, BMI LBW, birth defects, autism ( Detected in teeth) Mexican Americans and African Americans were 2-6 times more likely than whites to have highest concentrations of the toilet block/air freshener chemical 4.7 times more likely to have the highest levels of the insecticide chemical. (Xiaoyun et al. 2014) The Precautionary Principle Instead of Try this Spraying pesticides Baits, traps, and food containers Scented products Fragrance-free products Strong cleaners Elbow grease, soap and water, baking soda and vinegar Regular paint No-VOC paint, less pigments Particle board furnishings Solid wood or metal furniture or items that have out-gassed (no odor) New carpet, vinyl, laminate Solid wood or tile with washable rugs Instead of The Precautionary Principle in the Kitchen Plastic, Styrofoam Teflon cookware Canned/processed foods Conventional produce Try this Glass, stainless steel Stainless steel or cast iron Fresh or frozen, w/o artificial dyes, preservatives Organic; Clean 15/Dirty Dozen Environmental Working Group Organic foods-clean 15/dirty dozen* (APA recommendations) Cosmetics, personal care products Skin Deep APP Sunscreens Household cleaners Water filter information **Pesticide metabolite levels dropped below detection limits within 5 days after switching children from a conventional to organic diet (Lu et al. 2008) Hoffman TILT Research and Education Project Education (physicians, allied health, nurses) Research -Biomarkers (CYPs & Cytokines, methylation) -EHC (environmental sampling &education) 5

Environmental House Call (EHC) 5 Total Home visits over approximately 10 12

samples 2 nd Visit: Walk through assessment, photo documentation of known and

Environmental sampling 2 nd and 4 th visits (6 to 8 months apart) EHC Sampling

monitoring badge (worn for 8 hours) EHC Sampling (Cont d) Mold (inside and

samples Humidity, temperature, CO and CO2 EHC Sampling (Cont d) EHC Sampling

6 Environmental House Call (EHC) 5 Total Home visits over approximately months 1 st Visit: Consent, QEESI, Exposure History, Buccal Swab and/or blood samples 2 nd Visit: Walk through assessment, photo documentation of known and potential triggers/irritants. Environmental sampling 2 nd and 4 th visits (6 to 8 months apart) EHC Sampling Volatile Organic Compounds(VOCs) Total VOC count & specific levels Personal air monitoring badge (worn for 8 hours) EHC Sampling (Cont d) Mold (inside and outdoors): Buck BioAire sampler using Air-O-Cell Cassettes ERMI using dust samples Humidity, temperature, CO and CO2 EHC Sampling (Cont d) EHC Sampling (Cont d) Particulates: ultrafine (UFP) and coarse ( µm) Environmental Allergens: Dust sample (dog, cat, mouse, rat, cockroach, dust mite) 6

7 3rd Visit: TILT Pre Questionnaire, TILT Education, discussion of Environmental House Call results and TILT Action Plan; Teach about alternative cleaning supplies 4th Visit: Repeat all sampling, walk through assessment; Photo documentation of changes made in the home; TILT post questionnaire; follow up QEESI Indoor Air Quality (IAQ) Sampling Demonstration 5th Visit: Provide participant with overall evaluation of TILT home intervention; provide results of genetic testing and question and answer session with participant Questions? Funding for the TILT Education & Research Program made possible by the Marilyn B. Hoffman Foundation 7

Claudia S. Miller, MD, MS Professor, Occupational and Environmental Medicine University of Texas School of Medicine at San Antonio

Claudia S. Miller, MD, MS Professor, Occupational and Environmental Medicine University of Texas School of Medicine at San Antonio November 15, 2011 Autism Prevalence rate/10,000 Autism rates over 12 years