Food allergy Dual –allergen exposure hypothesis ... - Helsedirektoratet

Primærforebyggende /ltak –
myter for fall?
Primary preven/on;
myths and reali/es
Karin C. Lødrup Carlsen
Professor MD, Head of research
Women and Children’s division, Oslo University Hospital
Faculty of Medicine, University of Oslo,
Norway
ORAACLE
Oslo Research group for Asthma, Allergy in Childhood; the Lung and Environment

Health: a fine tuned balanced between man and environment
First line of defence DisrupJon in host: eg
www.humanillnesses.com
InfecJons Allergy

Primary prevention
• Is primary prevention possible?
• Prevention for all or some?
• What’s good for some may be bad for others… or?
• Avoidance vs exposure
• Allergy vs tolerance (natural or induced)

• Risk factors
– Asthma
– Allergic rhiniJs / RhinoconjuncJviJs (AR)
– Atopic Eczema / atopic dermaJJs (AD)
– Food allergy
• From risk factor to intervenJon
• RecommendaJons
• Basis for recommendaJons
• Myths or realiJes?
• Way forward?
Asthma
“Allergy”

Advice today
Environment
Tobacco
Indoor dampnesss
Pets
Other
Food and nutrients: (briefly)
Breast feeding
Vitamines
Pro-pre and synbiotics
Allergens

Indoor environment

1. Tobacco smoke exposure
Unngå røyking innendørs.
Dersom du røyker ute, bør du vente minst e[
minu[ e[er røyking før du går inn, så
lungene kan tømmes for røyk.
Barn er spesielt utsa[ for helseskadelige
effekter av tobakksrøyk i omgivelsene.
De skadelige parJklene I røyken spres i huset
og er kra]ig lu]veisirriterende.
Do not smoke indoors!
Proven beyond doubt for asthma, lung funcJon
development, secretory oJJs media, perinatal
complicaJons, less clear for allergic sensiJsaJon

2. ’Home dampness / humidity problems’
• Significant risk factor for cough, wheeze and
asthma (Bornehag et al, 2001)
• Risk of asthma (age 2) (Wickman et al, 2003)
• wheezing or bronchial obstruction (2-6 years)
(Nafstad et al, 1998, Belager et al, 2003, Jaakkola et
al, 2005)
Mechanisms unknown
Sufficient data support maintaining advice on eliminaJon

3. Pet keeping
Pet keeping is discussed in terms of increasing or reducing allergy, but unJl further
clarity; avoid pets in the child’s room.
Families with asthma or allergy should consider carefully prior to acquiring pet(s)
Birds indoors spread a lot and strongly allergenic parJcles

Cats in the homes and
sensitisation to cat
Non-­‐linear dose
relaJonship exposure in
homes to cat and allergic
sensiJsaJon
Allergens many places
Hertzen et al, Allergy 2009
24 European
Birth Cohorts on
Asthma and
Allergy

Pet
Allergic asthma Non-­‐Allergic asthma
ownership
Cat, dog, birds or rodents
not asscoiated with non-­‐
allergic asthma.
Pet ownership in early life did not appear to either increase or reduce the risk of asthma or
allergic rhini/s symptoms in children aged 6–10.
Advice from health care pracJJoners to avoid or to specifically acquire pets for primary
prevenJon of asthma or allergic rhiniJs in children should not be given.
PLoS ONE 7(8): e43214. doi:10.1371

4. Pollens, plants and allergy
Careful planning of a green environment is important for all, also for
environmental handicapped (asthmaJcs, allergics and persons with
hypersensiJvity) -­‐ parJcularly in children’s environments.
A good green environment promotes health, and is important for
growth and development.
1. Alternative to grass
Grass lawns in the kindergarden and schools are not good for allergic
children. Gravel, sand, tree and stones are good alternatives
2. A “green wall” of trees/shrubs adjacent to roads with traffic can filter
dust and polluJon.
Alder, Hazel, Selje and parJcularly birch must be removed not to be re-­‐
planted.

”Karelia surprise:”
Sensitisation to birch:
2 % in Russia
14 % in Finland
Allergy 2007
PARSIFAL & GABRIELA: farm-living
protected for asthma: wider range of
microbial exposures, Could not
identify specific microbes that may
confer protection, environment.

Microbiota
Documentation
INHALED
• Farming environments
• Karelia studies
ORAL
• (Caecarian section)
• GIT microbiota diversity
• RCT pro/pre-biotics, synbiotics

Food introduction
Helsedirektoratet ; Mat for spedbarn 2011

235 children with a 5 yrs of follow-­‐up.
% with wheezing 4-­‐12 mo
Rapid early weight gain is a risk factor for clinically relevant
wheezing illnesses in the first years of life and lower lung
function in childhood
One-­‐point z-­‐score increase in
weight gain
Gave a 37% increase in days
with wheeze

Food/ nutrition
• Supplement (enough of good things)
• Avoidance (remove problematic items)
ADVICE:
1) the commencement of complementary foods in general
2) avoidance or exposure to specific ‘allergenic’ foods
3) the use of modified allergens, such as the hydrolysed
proteins found in some hypoallergenic formulas.

5. Breast feeding
Infant:
should be exclusively breasCed for
6 months, conJnue for 12 months
PotenJal benefit;
Development of food allergy and
atopic eczema my be postponed if
the baby is breasqed for 4-­‐6
months
Helsedirektoratet ; Mat for spedbarn 2011

Food allergy Dual –allergen exposure hypothesis
AD develops as a result of
• Altered barrier skin function
• Abnormal immune reactivity
• Environmental factors
Allergen exposure
Too much vs too li[le
Both hi’ and lo’ exposure é� risk
of allergy
Oral vs Non-­‐oral route
Hudson Nature geneTcs 2006
Lack. G JACI 2012;129:1187-­‐97

Food allergy Dual –allergen exposure hypothesis
Lack. G JACI 2012;129:1187-­‐97
???
Exposure to food
allergen proteins
may require opJmal
microbioJc
environment in GIT
for tolerance
development

8. Allergen avoidance
Children with high risk of allergy should have completely
hydrolysed formula from the pharmacy unJl the child is
at least 4 months old
Helsedirektoratet ; Mat for spedbarn 2011

From 6 months
Germ-­‐free mice do
not develop oral
allergen tolerance
Helsedirektoratet ; Mat for spedbarn 2011
Breast feeding is
recommended beyond 6
months to prevent reacJons in
the child to other foods
?
Tolerance may depend on > one factor; ie
Early allergen exposure may require also breast milk, which may provide
opJmal immunomodulatory factors to induce tolerance
Lack JACI 2012

Use of hydrolysed formulas in infants at hi’ risk of allergy if
breasqeeding is not possible
most allergy prevention guidelines recommend the use of hydrolysed
formulas in infants at high risk of allergy if breastfeeding is not possible,
based on the earlier Cochrane meta-analysis.
However, preliminary report on the revised meta-analysis from these
authors indicates that of the 16 studies now eligible, there is no
significant difference in any allergy outcomes (eczema, food
allergy, asthma or rhinitis) with the use of hydrolysed formulas, either
overall or in subgroup analysis of infants at high risk of allergy.
Pending a more detailed report, allergy prevenJon guidelines are likely to
be revised on this point and we anJcipate that this aspect of early feeding
will be discussed in more detail elsewhere in the near future
Palmer & PrescoWCurr All Asthma Rep (2012) 12:321–331

6. Vit D and fatty acids
No differences in
allergic outcomes at 12
months of age:
• any allergic
• disease,
• overall sensitization,
• Specific
sensitization
• eczema,
• food allergy
Fish oil supplementaJon0-­‐6 months modestly (sign) elevated n-­‐3 LCPUFA levels and
reduced n-­‐6 AA levels at6 months. However, breast milk LCPUFA levels were another
major determinant of infant PUFA status at this age.
The primary analysis revealed no significant effect of the intervenJon on infant
allergic outcomes at 12 months of age.
D’vas Pediatrics 2012

Nutrients and vitamines: Primary prevention of asthma and
allergic disorders in children
no published experimental studies invesJgaJng the role of nutrients and foods
epidemiologic evidence for nutrients & dietary factors are weak, but suggesJve:
• vitamins A, D, and E; zinc;
• fruits and vegetables;
• Mediterranean diet parJcularly in relaJon to asthma outcomes
• less encouraging in relaJon to vitamin C and selenium
need for well designed randomized controlled trials of vitamins A, D, and E; zinc;
fruits and vegetables; and Mediterranean diet.
Need to prioriJze vit. D and E trials for the primary prevenJon of asthma
The exisJng level of evidence adds to the exisJng public health messages on a
balanced healthy diet in relaJon to a Mediterranean diet and fruits and vegetables
Numatov et al JACI 2012

a significant proportion of infants have already established food sensitisation
and clinical reactivity (including anaphylaxis) prior to the ‘first’ introduction of
foods at 4–6 months of age
…the processes leading to sensitisation are already strongly established by
this age in many infants
….even earlier preventive interventions will ultimately be required
Palmer & PrescoW Curr All Asthma Rep (2012) 12:321–331

Pro- Pre- Syn- and postbiotics
Probio/cs: ‘live microorganisms that, when administered in adequate amounts,
confer a health benefit on the host’
Prebio/cs: are selecJvely fermented ingredients that allow changes in the
composiJon and/or acJvity of gastrointesJnal microbiota that confer benefits
upon host well being
Synbio/c: combinaJons of probioJcs and prebioJcs.
Postbio/cs: probioJc fermentaJon products such as short-­‐chain fa[y acids

7. Pre-probiotica (review 2008)
• …. theoreJcally pro-­‐, pre and synbioJcs are promising candidates to prevent
or treat AD, results of the clinical trials pt. are not conclusive.
• PrevenJon trials show promising, but heterogenic results.
• …at present not evidence to support the use of pro-­‐pre-­‐ or synbioJcs for
prevenJon of AD in clinical pracJce.
• Results of treatment trials are not very convincing,
• Prevent food allergy: few trials, not support the use of probioJcs
• Clinical and immunological effects of different probioJc strains, prebioJcs or
combinaJons of need well-­‐designed randomized controlled trials before they
can be recommended for prevenJon or treatment of AD or food allergy
Van der Aa PAI 2008

Pro-synbiotics
Model: esJmate health economic impact of prebioJc prevenJve disease management of
atopic dermaJJs.
Data sources: published clinical trials and official price/tariff lists and naJonal populaJon
staJsJcs.
Comparator: no supplementaJon with prebioJcs.
Primary perspec/ve: based on the situaJon in The Netherlands in 2009
..favourable health benefit of a specific mixture of prebioJcs results in posiJve
short-­‐ and long-­‐term health economic benefits.
…the use of infant formula with a specific mixture of prebioJcs is a highly cost-­‐
effecJve way of prevenJng atopic dermaJJs in The Netherlands.
Lenoir-­‐Wijnkoop Eur J Health Econ (2012) 13:101–110

Jarvinen, Immunol Allergy Clin N Am 32 (2012) 51–65

“Myths” or realities 1. prevention of asthma and/or allergies
Environment
Tobacco smoke avoidance ✓ yes
House dampness repair ✓ yes
Pet keeping avoidance ✓ no
“Myth” “True” Advice in 2013 comments
Plants outdoor environment no ? 2ry prevenJon vs
tolerance inducJon
Food/Nutrients
Exclusive breast feeding 6 m. ✓ no
Breast feeding a]er 4 m ✓ yes
Vit D ✓ Probably ? For allergy
Pre-­‐/Pro/-­‐SynbioJcs Possibly food allergy only?
Fruits/vegetables ✓ yes
Delay food allergen introd. ✓ ? possibly

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