Dennis R. Ownby, M.D.Dennis R. Ownby, M.D.Betty B. Wray Professor of PediatricsBetty B. Wray Professor of Pediatrics

Georgia Health Sciences University, Augusta, Georgia Health Sciences University, Augusta, Georgia, USAGeorgia, USA

The Link Between Pets and The Link Between Pets and Reduced Risk of Allergic DiseaseReduced Risk of Allergic Disease

Disclosures• In the past year I have been:

– A consultant to CarboNix, LLC– Advisory board, Merck Childhood Asthma

Network• No discussion of off label drug use• Research Support: National Institutes of

Health• Legal Fees: None• Gifts: None

Ideas to explore• Consistency of observations about animal

exposure and risk of allergic disease• Other environmental exposures related to

risk of allergic disease• Pets and home microbiomes• How much dirt and house dust do children

normally eat• What links these observations together

Animal Exposure and Allergy Risk

• Cross-sectional survey of rural areas in Austria, Germany, Switzerland (only nationals analyzed)

• 2618/3504 (78%) of 6-13 year old children interviewed about allergic diseases - ISAAC

• Measurement of allergen specific IgE antibodies (n=901)

Riedler J, et al. Lancet 2001;358:1129-33

Farm Animal Exposure And Allergy Risk

Drawn from Riedler J, et al. Lancet 2001;358:1129-33, table 2.

Stables & Farm Milk < 1 yr

Stables, No Farm Milk < 1 yr

Farm Milk, No Stables < 1 yr

Stables &/or Farm Milk > 1 yr

Neither Stables nor Farm Milk

Detroit Childhood Allergy Study: CAS

• Birth cohort of 835 middle-class children living in suburbs

• Yearly questionnaires concerning home environments plus home visits at 2&4 years

• Evaluation between 6 and 8 years for asthma and allergy

Ownby DR et al JAMA 2002;288:963-972

First Year Pet Exposure And Allergic Sensitivity: CAS

Ownby DR et al JAMA 2002;288:963-972

Per

cent

of C

hild

ren

P = .04P = .02

P = .003P = .005

Lung Function And First Year Pet Exposure: CAS P

erce

nt o

f Chi

ldre

n

Ownby DR et al JAMA 2002;288:963-972

P = .01

P = .03P = NS

P = NS

Pet Exposure and Total IgE at 18 Years of Age: CAS

All Participants Allergen Sensitized Participants

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p = .053, p trend = .017

n=314 165 86n=176 96 40

p = .029, p trend = .007

Wegienka G et al. J Allergy Clin Immunol 2010;126:274-279

• Wayne County Health Environment Allergy and Asthma Longitudinal Study = WHEALS

• Geographically based birth cohort– not selected for risk

• Detailed examination of pet effect on allergy risk especially– 1st year of life– Endotoxin– Antibiotics

• Diverse cohort by SES, race and urban versus suburban residence

WHEALS Birth Cohort

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Trajectory of Total Serum IgE by Prenatal Pet Exposure in WHEALS

Havstad S et al. J Allergy Clin Immunol 2011;128:880-885

On average, IgE was 28% lower, over time, for children in pet homes(p<0.001), as comparedto children in pet-free homes

On average, IgE was 28% lower, over time, for children in pet homes(p<0.001), as comparedto children in pet-free homes

n=1187African American = 62.5%≥1 indoor pet = 35.4%

12Havstad S et al. J Allergy Clin Immunol 2011;128:880-885

Trajectory of Total Serum IgE by Prenatal Pet Exposure in WHEALS

n=1187African American = 62.5%≥1 indoor pet = 35.4%

Farm Environment and Juvenile Inflammatory Bowel Disease

• Case-control study, 13 children’s hospitals• All 6 to 18 years of age• 444 cases of Crohn disease• 304 cases of ulcerative colitis• 1481 controls, strabismus surgery• Regular contact with pets or farm animals in first

year of life

Radon K, et al. Pediatrics 2007;120:354-361

Farm Environment And Juvenile Inflammatory Bowel Disease

Radon K, et al. Pediatrics 2007;120:354-361

Animal contact

Crohn DiseaseFully adjusted*

Ulcerative colitisFully adjusted*

House pets 1.0 (0.8 – 1.3) 0.9 (0.6 – 1.2)

Farm animals 0.5 (0.3 – 0.9) 0.4 (0.2 – 0.8)

*adjusted for age, gender, region, parental education, birth weight, maternalsmoking in pregnancy, older siblings, allergic rhinitis, parental IBD and other variables

Farm Animal Farm Animal Exposure?Exposure?

Pet Exposure?Pet Exposure?

or

Meta-analysis of Farm or Pet Exposure and Allergy Risk

Tse K, Horner AJ. Seminar Immunopath 2008;30:53-62

Role of Unpasteurized Milk

• Multi-center European study (PARSIFAL)• 14,893 children 5-13 years-of-age• Farm milk inversely associated with asthma,

adjOR = 0.74 (95% CI 0.61-0.88)• Rhinoconjunctivitis, sensitization to pollen and

food mixes also significantly inversely associated with farm milk

Waser M, et al. Clinical Exp Allergy 2006;37:661-670

Drinking Water Microbes and Atopy

• 563 children, 7-16 years, living in Finnish- and Russian-Karelia

• Skin prick tested with 14 common allergens and foods

• Finnish children significantly more sensitization – 48% vs 16%

• Multivariable analysis – sex, cat < 1 yr, density of microbes in water

Von Hertzen L, et al. Allergy 2007;62:288-292

Microbiota Hypothesis• Most consistent feature of hygiene hypothesis is

intensity of exposure to microbes, especially soil microbes via the gut

• Endotoxin – primarily surrogate marker of bacterial exposure

• Factors influencing the development of the microbiota of the gut– Maternal microbiota– Ingested bacteria– Diet composition– Antibiotics

• Evidence favors the - “Microbiota Hypothesis”

Penders J, et al. Allergy 2007;62:1223-1236

Common Features of Published Studies

• Exposure impact of animals only in 1st year of life• Farm animals and household pets have similar

effects• Reduced risk is not allergen specific• Animal exposure alters risk of other diseases of

immune dysregulation e.g. Th1 diseases – IBD

Common Features of Published Studies

• Impact does not correlate well with – Animal allergen concentration– Endotoxin concentration– Muramic acid concentration

• Effects of C-section versus vaginal delivery– Exposure to maternal microbiota

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Do Infants Ingest Bacteria from House Dust

• Hand-to-mouth activity in all children

• Well studied by toxicologists

• Studies demonstrate that hand-to-mouth activity relates dust and child concentrations of toxins

Soil and House Dust Ingestion by Children

• Soil and dust ingestion directly related to hand to mouth and object to mouth activity in children

• Hand to mouth activity is highly variable in children and varies indoors and outdoors

• Average dust ingestion is 30–100 mg/day for children 6 months – 11 years of age

• Pica (ingestion of large quantities of soil ~5 gm/day) is relatively common in children

U.S. EPA. Child Specific Exposure Factors Handbook 2008

Estimated Bacterial Ingestion from House Dust

• qPCR estimated bacterial load of house dust• 7.2 x 105 cells/mg of dust• Numbers of bacteria ingested by normal

children– 30 mg = 2.2 x 107 bacteria/day– 100 mg = 7.2 x 107 bacteria/day

• Probiotic trials commonly use a dose of - 5 x 109 bacteria/day

• Pets in the home alter house dust microbiota

Karkkainen PM, et al. J Environ Monit 2010;12:759-768

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MicrobialCommunity Composition In Home

HouseholdCharacteristics

PET

PrenatalImmune Status

Early Immune Response & Development

PersistentImmune ResponsePhenotype

AllergicAsthma

Baby/Child’s Gut Microbial Community Composition

Baby’s Genotype,Season, SES, Upper Resp Infect, Antibiotics, Diet, Activity, Pets, Other Children, Pollutants, Stress

Our Conceptual Model of How Pets Influence Allergic DiseaseOur Conceptual Model of How Pets Influence Allergic Disease

WHEALS InvestigatorsHenry Ford Hospital Kevin Bobbitt PhD Christine Cole Johnson PhD MPH Suzanne Havstad, M.A. Al Levin PhD Edward L. Peterson PhD Ganesa Wegienka PhD, MS Kim Woodcroft PhD, MPH Edward M. Zoratti MDGeorgia Health Sciences University Dennis R. Ownby MD

University of California-San Francisco Homer Boushey MD Susan Lynch PhDUniversity of Michigan Nicholas Lukacs PhD

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