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Farm studies in allergy and

their potential connection to

auto immune diseases.

Erika von Mutius

Professor of Pediatrics

University Childrens Hospital Munich, Germany

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PrevalencePrevalence ofofasthmaasthma,, hayhay feverfeverandand

atopyatopy amongamong farmersfarmers'' childrenchildren inin thetheALEXALEX StudyStudy..

%

0

510

15

20

25

30

35

40

Asthma

diagnosis

Asthma

symptoms

Hay fever

diagnosis

Hay fever

symptoms

Atopy

Non-Farmers (n=493)

Farmers (n=319)

* * **

*

* p< 0.05

Riedler et al. Lancet 2001

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FarmFarm effectseffects onon asthmaasthma,, hayhay feverfever, atopic, atopic eczemaeczema

and atopy atand atopy at schoolschool age in PARSIFALage in PARSIFAL (N=8,263/2,086).(N=8,263/2,086).

Asthma Hay fever

Spec. IgEEczema

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No relation between

farm exposures and

type 1 diabetes in a

German case control

study (n=466).

Radon et al, Diabetes 2005

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ExposureExposure toto stablesstables and/and/ororfarmfarmmilkmilkinin thethe 1.1. yearyearof life.of life.

11.8

1.4

14.8

2.8

16

3.2

19.8

5.1

32.9

12.4

0

5

10

15

20

25

30

35

Asthma

diagnosis

Asthma

symptoms

Hay fever

diagnosis

Hay fever

symptoms

Atopy

No exposure

Milk only

Stable only

Stable and milk

%

ALEX-StudyRiedler et al. Lancet 2001

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Atopy and maternal exposures in pregnancyin the PARSIFAL Study (N=8,263/2,086).

0.87

(0.64-1.19)

0.76

(0.54-1.07)

0.78

(0.44-1.38)

0.77

(0.52-1.14)

0.56

(0.38-0.83)**

Stable

exposure in

pregnancy

Diagnosis of

asthma

Wheeze 12

months

Diagnosis of

hay fever

Hay fever

symptoms

Atopic

sensitization

Adjusted for current farm exposure, contact to farm animals ever and farm milk

consumption ever, age, sex, family history of atopy, parental education,

environmental tobacco smoking, maternal smoking during pregnancy,

number of older siblings, contact to pets ever, study center. Ege, Bieli et al JACI 2006

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Maternal exposure in pregnancyand expression of

genes of innate immunityat schoolage in the Swiss

PARSIFAL sample (n=322).

1.52 (1.11-2.08) **1.30 (1.01-1.67) *1.39 (1.04-1.87) *Stableexposure in

pregnancy

CD14TLR4TLR2

p< 0.05; ** p

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Number of animal species the mother has

encountered in her pregnancy and expressionof genes of innate immunity in the offspring at

school age (Swiss PARSIFAL sample).

p = 0.00043

Number of different farm animal species the mother had contact to during pregnancy

Ege, Bieli et al JACI 2006

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School age: Independent effects of farm characteristics

and childrens activities on asthma, wheeze and atopy.

Exposures mutually adjusted by backward logistic regression analysis.

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TLRTLRss andandNODNODss

Strober et al, Nature Rev Immunol 2006

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OnlyOnly childrenchildren withwith TTTT genotypegenotype at NOD1/-21596at NOD1/-21596 areare

protectedprotected fromfrom allergyallergy in ain a farmingfarming environmentenvironment..

0

2

4

6

8

10

12

14

16

Hay fever Atop asthma Pollen sens Mite sens

CC/CT

TT

Eder et al,

Allergy 2006

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Gene Environment Interactions

Endotoxin exposure TLR4 - atopy

Farm exposure TLR 2 asthma/atopy

Farm exposure NOD 1 atopy

Farm animal exposure CD14 - atopy

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Conclusions:

In a farming environment the protection from

asthma and allergies is likely to start in utero.

The effects are attributable to a number ofprotective exposures which counterbalance the

effects of risk factors.

An increasing number of protective exposures islikely to activate the innate immune responses

through a number of different receptors.

A number of gene*environment interactions havebeen identified for various farming exposures and

various allergic outcomes.

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PASTURE PARSIFAL ALEX

Switzerland: Charlotte Braun-Fahrlnder, Roger Lauener.

Germany: Erika von Mutius, Harald Renz, Otto Holst, Albrecht

Bufe.

Austria: Josef Riedler, Waltraud Eder.

The Netherlands: Bert Brunekreef, Rob van Strien, Dieneke Schram.

Sweden: Gran Pershagen, Marianne van Hage, Annika Scheynius.France: Jean-Charles Dalphin, Dominique Vuitton.

USA: Fernando Martinez, Donata Vercelli