Post on 26-Dec-2015
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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
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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