combating allergy and asthma in europe: issues and perspectives. erika von mutius md msc professor...

Combating Allergy and Asthma in

Europe: Issues and Perspectives.

Erika von Mutius MD MSc

Professor of PediatricsUniversity Children‘s Hospital

Munich, Germany

WROCŁAW

0

10

20

30

40

5-10 11-20 21-30 31-40 41-50 51-60 61+

age

%

Sobotka

villages

lowest prevalencein Europe

UK-type prevalence

Atopic sensitisation in Sobotka and surrounding villages.

Sozanska et al, Allergy 2007

Lifetime residence and atopy.

0

5

10

15

20

25

30

35

5-20 yrs 21-40 yrs 41-60 yrs

Never village

Moved between townand village

Always village

Sozanska et al, Allergy 2007

Prevalence of atopy in Karelian children.

0

5

10

15

20

25

30

35

40

45

Asthma Hay fever Skin testpositive

Finnish

Russian

z

von Hertzen et al, JACI 2006

%

Pakarinen et al, Environ Microbiology 2008

Microbial exposures

in Finnish and Russian

Karelian homes.

Allergy protection from exposures to stables,

farm milk and barns (ALEX Study).

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

Asthma Wheeze Hay feverdiagnosis

Hay feversymptoms

Atopy

No exposureOne exposureAt least 2 exposuresAll 3 exposures

OR

DNAextraction

denaturationof DNA

amplificationof the bacterial16S rRNA gene

ds DNA

exonucleasedigestion

ss DNA

statistical analysis for significantassociations with health outcomes

or farm-related exposuresscanning gel and

transformation intodensity values

mattressdust

gel-electrophoresis

under non-denaturing conditions

Study the Microbiome in Environmental Samples by Pyrosequencing.

• The ‚New Age of Molecular Diagnostics for Microbial Agents‘ (R. Whitley in NEJM March 2008).

• The most comprehensive

method to detect bacteria, viruses, fungi of all known and unknown species.

• Will identify the most solid, so far unexplored, candidates.

Margulies et al, Nature 2005; Whitley NEJM 2008, Palacios et al, NEJM 2008.

Children 6-12 years Alpine regions and

PolandParental questionnaire

Blood sampling:Allergy test, DNA/RNA

Indoor and outdoor dust

Milk samples

Phenotypes

Population

Exposure

Genetics

Nasal and throat swabs

Lung function

GABRIEL Advanced Surveys

GABRIEL Advanced Survey Design

• Stage I: Recruitment in alpine areas– Recruitment questionnaire to large populations (N=135,359).

Participation rate: 80.7%. • Randomisation: Random sample of full consent group

• Stage II: Main study– Comprehensive questionnaire, blood samples (IgE, genetics),

dust samples, nasal swabs (n=9,668)• Randomisation: Random sample in area with strongest effects

(Germany)

• Stage III: In depth environmental exposure– Collection of multiple dust samples, milk samples, throat swabs

and measurement of lung function (n=895)

GABRIEL exposure assessment.

• Because of restricted funding only possible in 225 subjects (26.2% of subjects in Stage III)– Bacterial exposure by 16 sRNA– Viable bacteria– Endotoxin– Muramic acid– CpG DNA– Fungal exposure by 16 sRNA

Vision for FP7:

• Comprehensive characterisation of allergy protective environments (Alpine Areas, Eastern Europe, China).

• Test identified allergy protective microbes / compounds in experimental studies.

• Develop novel prevention strategies