Transcript Link Pets Allergic Disease HO

The Link Between Pets and
Reduced Risk of Allergic Disease
Dennis R. Ownby, M.D.
Betty B. Wray Professor of Pediatrics
Georgia Health Sciences University, Augusta,
Georgia, USA
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
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
Drawn from Riedler J, et al. Lancet 2001;358:1129-33, table 2.
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
Percent of Children
P = .003
P = .005
P = .04
P = .02
Ownby DR et al JAMA 2002;288:963-972
Lung Function And First Year Pet Exposure: CAS
P = .01
Percent of Children
P = NS
Ownby DR et al JAMA 2002;288:963-972
P = NS
P = .03
Pet Exposure and Total IgE at 18 Years of Age:
CAS
Allergen Sensitized Participants
Total Serum IgE (95% CI)
All Participants
n=314
165
86
p = .053, p trend = .017
n=176
96
40
p = .029, p trend = .007
Wegienka G et al. J Allergy Clin Immunol 2010;126:274-279
9
WHEALS Birth Cohort
• 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
Trajectory of Total Serum IgE by Prenatal
Pet Exposure in WHEALS
On average, IgE was
28% lower, over time,
for children in pet homes
(p<0.001), as compared
to children in pet-free homes
n=1187
African American = 62.5%
≥1 indoor pet = 35.4%
Havstad S et al. J Allergy Clin Immunol 2011;128:880-885
11
Trajectory of Total Serum IgE by Prenatal
Pet Exposure in WHEALS
n=1187
African American = 62.5%
≥1 indoor pet = 35.4%
Havstad S et al. J Allergy Clin Immunol 2011;128:880-885
12
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
Animal contact
House pets
Crohn Disease
Fully adjusted*
1.0 (0.8 – 1.3)
Ulcerative colitis
Fully adjusted*
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, maternal
smoking in pregnancy, older siblings, allergic rhinitis, parental IBD and other
variables
Radon K, et al. Pediatrics 2007;120:354-361
Farm Animal
Exposure?
or
Pet Exposure?
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
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
22
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
Our Conceptual Model of How Pets
Influence Allergic Disease
Baby’s Genotype,
Season, SES, Upper Resp Infect,
Antibiotics, Diet, Activity,
Pets, Other Children,
Pollutants, Stress
Prenatal
Immune Status
Household
Characteristics
Microbial
Community
Composition
In Home
PET
Early Immune
Response &
Development
Baby/Child’s Gut
Microbial Community
Composition
Persistent
Immune
Response
Phenotype
Allergic
Asthma
25
WHEALS Investigators
Henry 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 MD
Georgia Health Sciences University
Dennis R. Ownby MD
University of California-San Francisco
Homer Boushey MD
Susan Lynch PhD
University of Michigan
Nicholas Lukacs PhD
26