1. Research Training at the University of Portsmouth
Allergies
Professor Tara Dean
Café Scientifiq​ue I.O.W.
10th June 2013

2. Allergic diseases include
• Asthma
• Atopic dermatitis (eczema)
• Urticaria
• Occupational allergy
• Allergic conjunctivitis
• Allergic rhinitis (hay fever)
• Insect/sting allergy
• Drug allergy
• Food allergy
Atopic individuals are more at risk of developing allergies.
Atopy is a state (hereditary disposition) that makes a person
more likely to develop allergic reactions of any type

3. 64321680 1 2 4
Incidence
Age (years)
Asthma
Rhinitis
Eczema
Food
allergy
Atopic March
Redrawn from Durham SR & Church MK, Allergy 2nd edition, 2001, Mosby

4. • Allergic disease is the 5th leading chronic disease
among all ages
• 3rd common chronic disease among children under
18 years old
• Trends indicate that by 2015, half of all Europeans
may be suffering from an allergy
WAO, 2007

5. Allergic diseases
• Some allergies may be fatal
• Impose significant burdens on societies
• Are becoming more important from a financial and
healthcare perspective
• Seriously compromise the quality of life

6. Allergic diseases
• 3 million GP consultations pa
– £210-£311 million
• 70,000 admissions pa
– £56-£83 million
• 72.6 million prescriptions
– £900 million
– 11% of NHS drug budget
• Only 10% of GPs ,17% of practice nurses have
had allergy training

7. Allergic diseases include
• Asthma
• Atopic dermatitis (eczema)
• Urticaria
• Occupational allergy
• Allergic conjunctivitis
• Allergic rhinitis (hay fever)
• Insect/sting allergy
• Drug allergy
• Food allergy
Atopic individuals are more at risk of developing allergies.
Atopy is a state (hereditary disposition) that makes a person
more likely to develop allergic reactions of any type

8. What is Asthma?
• Chronic disease of the airways that may cause
• Wheezing
• Breathlessness
• Chest tightness
• Nighttime or early morning coughing
• Episodes are usually associated with
widespread, but variable, airflow obstruction
within the lung that is often reversible either
spontaneously or with treatment.

9. Pathology
of Asthma
Source: “What You and Your Family Can Do About Asthma”
by the Global Initiative For Asthma Created and funded by NIH/NHLBI, 1995
Normal Asthma
Asthma involves
inflammation of
the airways

10. Child and Adult Asthma Prevalence, US, 1980-2007
0
2
4
6
8
10
12
14
Prevalence(%)
Year
12-Month
Lifetime• Child
 Adult
Source: National Health Interview Survey; CDC National Center for Health Statistics
Current

11. Risk Factors for Developing Asthma
• Genetic characteristics
• Occupational exposures
• Environmental exposures

12. Clearing the Air:
Indoor Air Exposures & Asthma Development
Biological Agents
• Sufficient evidence of causal
relationship
– House dust mite
• Sufficient evidence of association
– None found
• Limited or suggestive evidence of
association
– Cockroach (among pre-school aged
children)
– Respiratory syncytial virus (RSV)
Chemical Agents
• Sufficient evidence of causal
relationship
– None found
• Sufficient evidence of association
– Environmental Tobacco Smoke
(among pre-school aged children)
• Limited or suggestive evidence of
association
– None found

13. Clearing the Air:
Indoor Air Exposures & Asthma Exacerbation
Biological Agents
– Sufficient evidence of causal
relationship
• Cat
• Cockroach
• House dust mite
– Sufficient evidence of an association
• Dog
• Fungus/Molds
• Rhinovirus
– Limited or suggestive evidence of
association
• Domestic birds
• Chlamydia and Mycoplasma pneumonia
• RSV
Chemical Agents
• Sufficient evidence of causal
relationship
– Environmental tobacco smoke
(among pre-school aged children)
• Sufficient evidence of association
– NO2, NOX (high levels)
• Limited or suggestive evidence of
association
– Environmental Tobacco Smoke
(among school-aged, older
children, and adults)
– Formaldehyde
– Fragrances

14. • In general, higher rates
in developed countries
• Some hypotheses
• “Hygiene hypothesis”
• Environmental exposures
• Diet
• Physical activity/lifestyle
ISAAC (1998), Lancet 351:1225-32.
Between-population disparities

15. “Hygiene Hypothesis”
• Studies in the late 1980s and 1990s in the UK
and reunified Germany suggested that higher
sanitation increased risks of these health
conditions
• Reduction/lack of in infections and microbial
exposures early in life may be associated with
increased risk of allergy, asthma and
autoimmune diseases
• Based on observations and speculation on:
– Urban/rural differences
– Farming/non-farming differences
– Birth order / small families / day care
– Early exposure to parasites, allergens, viruses, etc.

16. Allergic disease
(Th2)
Helminth Infection
(Th2)
Microbial Infection
(Th1)
The relationship between infection and allergic disease
Hygiene Hypothesis
In developed countries:
High incidence of
allergic disease
Low incidence of
infectious diseases (Th1)
Low infection with
worms (helminths)
In developing countries:
Low incidence of
allergic disease
High incidence of
infectious diseases (Th1)
High infection with
worms (helminths)

17. Allergic diseases include
• Asthma
• Atopic dermatitis (eczema)
• Urticaria
• Occupational allergy
• Allergic conjunctivitis
• Allergic rhinitis (hay fever)
• Insect/sting allergy
• Drug allergy
• Food allergy
Atopic individuals are more at risk of developing allergies.
Atopy is a state (hereditary disposition) that makes a person
more likely to develop allergic reactions of any type

18. European Academy of Allergy and Clinical Immunology
Food
Hypersensitivity
Food Allergy
IgE mediated
food allergy
Non-IgE
mediated food
allergy
Non-allergic
FHS
1
8
Immune
system
involved
Does not
involve
immune
system

19. European Academy of Allergy and Clinical Immunology
Food
Hypersensitivity
Food Allergy
IgE mediated
food allergy
Non-IgE
mediated food
allergy
Non-allergic
FHS
1
9
Immune
system
involved
Does not
involve
immune
system

21. • IgE is an antibody (also
called immunoglobulin)
made in the body against
allergens.

22. • IgE antibodies
circulate in the
bloodstream and bind
to receptors on mast
cells
• Binding of a food
protein to the
antibodies triggers
release of mediators
(e.g., histamine)
causing symptoms

23. 8 foods accounts for most food allergies
(The big eight)
• Milk
• Eggs
• Tree nuts (such as almonds)
• Fish (such as cod)
• Shellfish (such as crab, lobster, prawns)
• Soy
• Wheat
• Peanuts

24. Geographical variation
• Fish in Norway
• Rice in Japan
• Peanuts in USA and
UK
• Peach and celery in
Germany
• Olives in Greece

25. 8 foods accounts for most food allergies
(The big eight)
• Milk
• Eggs
• Tree nuts (such as almonds)
• Fish (such as cod)
• Shellfish (such as crab)
• Soy
• Wheat
• Peanuts

26. • Milk allergens - casein, lactoglobulins,
lactoalbumins
– No reduction by pasteurization, condensation,
evaporation, and drying
• High degree of cross-reactivity with sheep and
goat’s milk

27. Potential for Allergic Reaction
Immune System
Protein size and Allergenicity
High Molecular Weight Low Molecular Weight

28. Hydrolysed Protein
Hydrolysis
Hydrolysed proteins have a lower chance of
inducing sensitisation

29. Hydrolysis Can Reduce Allergenicity of Cows Milk Proteins
Median Molecular Weight of Infant Formulas

30. The case of peanuts

31. Anaesthetic
20%
Antibiotic
12%
Contrast
6%
Otheriatrogenic
9%
Venom
25%
Nuts
18%
Other food
10%
Nearly all deaths from food allergy occur in brittle asthmatics.
UK deaths from anaphylaxis 94-98

32. Clinical characteristics
• 1/250 of a peanut is enough to trigger a
reaction (cutting a peanut in half 125 times!)
• Severe allergies are typically life-long
• High cross-reactivity with tree nuts (almonds,
walnuts, etc.)
• Peanut allergies tend to cause the most severe
reactions.
• Unpredictability of reactions

33. Prognosis
• Resolve: Cow’s milk, Egg, Soya, Wheat
– By 5 years age, tolerance in
• 85% of CMA children
• 66% of egg allergic children
• Persist: Peanut, Tree nut, Fish & Shellfish
– However, around 20% of PA will resolve
• Youngest patients
• Low specific IgE
• Mild reaction at presentation
• About 25% of allergic children develop
respiratory allergies

34. Symptoms of a Food-Allergic Reaction
• Allergy to food is not a stand alone
disease
• Multi organ systems
• Multiple symptoms

35. Symptoms of a Food-Allergic Reaction
Respiratory tract:
Mild:
Itchy, watery eyes, running or stuffy nose,
sneezing, cough, itching or swelling of the lips,
wheezing
Severe:
shortness of breath, difficulty swallowing, chest
tightness, tingling of the mouth, itching or
swelling of the throat,

37. Symptoms of a Food-Allergic Reaction
GI tract:
–abdominal cramps, nausea, vomiting,
diarrhea
Skin:
–hives, eczema, itchy red rash, Urticaria

39. Symptoms of a Food-Allergic Reaction
Cardiovascular
– Drop in blood pressure, loss of
consciousness/fainting, dizziness, faintness,
heart irregularities, shock
– Anaphylaxis: sudden, severe, potentially
fatal, systemic allergic reaction

40. What a child says:
• I think I am going to throw up
• My mouth/tongue itches
• My chest feels tight
• I feel itchy
• My tongue feels hot/burning/tingling/heavy
• There’s something in my throat
• My lips feel tight
• My tongue feels like there is hair on it
• Feels like bugs are in my ears

41. Allergy Diagnosis
• Clinical History
• Physical examination
• Allergy testing:
– Skin Tests
– Specific IgE tests
• Food challenges

42. Allergy Skin tests
• Prick – most common technique,
introduces allergen into the very
superficial skin usually flexor surface of
forearm, sometimes on back

43. Skin prick testing
Histamine HazelMilk
PeanutAlmondSaline
Soya
Brazil

44. Management of food allergy

45. • Currently there is no cure
– Avoidance
– Avoidance
– Avoidance
• Cross contamination
• Cross-reactivity
• Meticulous attention to labels
• Education on sources of “hidden foods”

46. Unexpected food sources of common allergen
Food Ingredient
Soy sauce Wheat
Peanut Butter Soy
Camembert Wheat
Hamburger Soy
Ham/Sausages Milk

47. Treatment of allergic reactions
• Epinephrine (Adrenalin)
• Emergency ward treatment
• Oral/parenteral antihistamines
• Corticosteroids

48. Epinephrine
• It quickly constricts blood vessels, raising
blood pressure
• It relaxes smooth muscles in the lungs to
improve breathing
• It stimulates the heart beat
• It works to reverse the hives and swelling
around the face and lips

49. • Epinephrine is available in an auto injector
called an EpiPen
• The EpiPen is administered into the large outer
thigh muscles

50. Food Allergy Research
• Prolific rise of research evidence between
1980s to 2000
• However the big basic questions were still not
tackled
– What is the prevalence of food allergy
– Who is at risk
– What is its natural history

51. FSA’s research requirement (2001-2002)
identified the need for better prevalence
and incidence data in UK
• One population based study: Young et al, Lancet, 1994: 1127
• Population prevalence rate: 1.4-1.8%
• Screening phase included adult and children
• Food challenges used a mixture of processed food
• No children at challenge stage!!!

52. Food Allergy & Intolerance Research (FAIR) project
FAIR project
Prospective Study of a birth cohort
to establish the incidence data during
early childhood
Whole population cohorts
to establish prevalence at
6, 11 and 15 years of age
Birth Cohort School Cohorts

53. FAIR study
Detailed history regarding food related problems were obtained
All children were clinically examined and skin prick tested
Those with a positive skin prick test that had never knowingly had the
food or large amounts of the food previously, and those who indicated
a previous adverse reaction to foods (regardless of their SPT data)
were invited for food challenges
Challenges were performed following an algorithm adhering to the
history in terms of dose and timing when available
All foods for challenges were freshly prepared for each individual
child, taking into consideration the range of food each infant would
prefer

55. Total number of children approached was 5647, of which 3221
(57.0%) were recruited into the study
3 year olds: 891 (m=499)
6 yr olds: 798 children (M=403)
11 yr olds: 775 children (M=388)
15 yr olds: 757 children (M=379)

56. Symptoms reported
Rate of parental reported FHS:
Symptoms of FHS were reported by 352/3221 (10.9%) parents and
children.
At 3 years of age: 74/891 (8.3%)
At 6 years of age: 94/798 (11.8%)
At 11 years of age: 90/775 (11.6%)
At 15 years of age: 94/757 (12.4%)
Rate of food avoidance:
In total, 727/3221 (23.5%) children were avoiding some foods during
the study.
At 3 years of age: 286/891 (32.1%)
At 6 years of age: 177/798 (14.6%)
At 11 years of age: 122/775 (15.7%)
At 15 years of age: 142/757 (18.8%)

57. Sensitisation status
2690 (83.5%) were skin prick tested (642, 700, 699 and 649
of 3, 6, 11 and 15 year olds)
The rate of sensitisation to the predefined aero-allergens
(house dust mite, cat and grass) was 20.1%
(541/2690, 95%CI: 18.6 to 21.7)
The rate of sensitisation to any of the predefined food
allergens (milk, egg, fish, peanut, sesame and wheat) was
4.4% (117/2690, 95%CI: 3.6 to 5.2)

58. Food allergen sensitisation
0
5
10
15
20
25
30
egg peanut milk fish sesame wheat
3 yrs
6 yrs
11 yrs
15 yrs
numbers
The rate of sensitisation to any of the predefined food allergens was
At 3 years of age: 4.5% At 11 years of age: 5.2%
At 6 years of age: 3.6% At 15 years of age: 4.9%

59. United Kingdom – Birth cohort
Based on DBPCFC:
• Three years: 2.9% FHS,
– milk, peanuts, egg, tree
nuts, wheat, gluten, salicylate and sesame
• Six years:1.6%
– milk, peanut and tree nuts, wheat, sesame, banana
• Eleven years: 1.4%
– peanuts, tree nuts, egg, milk, shell fish, gluten, green
beans, and kiwi
• Fifteen years: 2.1%
– peanut, tree nuts, wheat, gluten, shell fish, egg and
milk
19 %
confirmed
14%
confirmed
12%
confirmed
17%
confirmed