Transcript Combating Allergy and Asthma in Europe: Issues and Perspectives.

Combating Allergy and Asthma in
Europe: Issues and Perspectives.
Erika von Mutius MD MSc
Professor of Pediatrics
University Children‘s Hospital
Munich, Germany
WROCŁAW
Atopic sensitisation in Sobotka and surrounding villages.
UK-type
prevalence
40
Sobotka
villages
30
% 20
10
lowest prevalence
in Europe
0
5-10
11-20
21-30
31-40
41-50
51-60
61+
age
Sozanska et al, Allergy 2007
Lifetime residence and atopy.
35
Never village
30
Moved between town
and village
Always village
25
20
15
10
5
0
5-20 yrs
21-40 yrs
41-60 yrs
Sozanska et al, Allergy 2007
Prevalence of atopy in Karelian children.
%
45
Finnish
40
35
Russian
30
25
20
z
15
10
5
0
Asthma
Hay fever Skin test
positive
von Hertzen et al, JACI 2006
Microbial exposures
in Finnish and Russian
Karelian homes.
Pakarinen et al,
Environ Microbiology 2008
Allergy protection from exposures to stables,
farm milk and barns (ALEX Study).
OR
1
No exposure
One exposure
At least 2 exposures
All 3 exposures
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
Asthma
Wheeze
Hay fever Hay fever
diagnosis symptoms
Atopy
mattress
dust
DNA
extraction
amplification
of the bacterial
16S rRNA gene
gel-electrophoresis
under non-denaturing
conditions
scanning gel and
transformation into
density values
ds DNA
exonuclease
digestion
denaturation
of DNA
ss DNA
statistical analysis for significant
associations with health outcomes
or farm-related exposures
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.
GABRIEL Advanced Surveys
Population
Children 6-12 years
Alpine regions and Poland
Parental questionnaire
Phenotypes
Lung function
Genetics
Blood sampling:
Allergy test, DNA/RNA
Exposure
Nasal and throat swabs
Indoor and outdoor dust
Milk samples
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