Prof. Tara Dean on allergies - Cafe Scientifique Isle of Wight

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Prof. Tara Dean on allergies - Cafe Scientifique Isle of Wight

  1. 1. Research Training at the University of PortsmouthAllergiesProfessor Tara DeanCafé Scientifiq​ue I.O.W.10th June 2013
  2. 2. Allergic diseases include• Asthma• Atopic dermatitis (eczema)• Urticaria• Occupational allergy• Allergic conjunctivitis• Allergic rhinitis (hay fever)• Insect/sting allergy• Drug allergy• Food allergyAtopic individuals are more at risk of developing allergies.Atopy is a state (hereditary disposition) that makes a personmore likely to develop allergic reactions of any type
  3. 3. 64321680 1 2 4IncidenceAge (years)AsthmaRhinitisEczemaFoodallergyAtopic MarchRedrawn from Durham SR & Church MK, Allergy 2nd edition, 2001, Mosby
  4. 4. • Allergic disease is the 5th leading chronic diseaseamong all ages• 3rd common chronic disease among children under18 years old• Trends indicate that by 2015, half of all Europeansmay be suffering from an allergyWAO, 2007
  5. 5. Allergic diseases• Some allergies may be fatal• Impose significant burdens on societies• Are becoming more important from a financial andhealthcare perspective• Seriously compromise the quality of life
  6. 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 havehad allergy training
  7. 7. Allergic diseases include• Asthma• Atopic dermatitis (eczema)• Urticaria• Occupational allergy• Allergic conjunctivitis• Allergic rhinitis (hay fever)• Insect/sting allergy• Drug allergy• Food allergyAtopic individuals are more at risk of developing allergies.Atopy is a state (hereditary disposition) that makes a personmore likely to develop allergic reactions of any type
  8. 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 withwidespread, but variable, airflow obstructionwithin the lung that is often reversible eitherspontaneously or with treatment.
  9. 9. Pathologyof AsthmaSource: “What You and Your Family Can Do About Asthma”by the Global Initiative For Asthma Created and funded by NIH/NHLBI, 1995Normal AsthmaAsthma involvesinflammation ofthe airways
  10. 10. Child and Adult Asthma Prevalence, US, 1980-200702468101214Prevalence(%)Year12-MonthLifetime• Child AdultSource: National Health Interview Survey; CDC National Center for Health StatisticsCurrent
  11. 11. Risk Factors for Developing Asthma• Genetic characteristics• Occupational exposures• Environmental exposures
  12. 12. Clearing the Air:Indoor Air Exposures & Asthma DevelopmentBiological Agents• Sufficient evidence of causalrelationship– House dust mite• Sufficient evidence of association– None found• Limited or suggestive evidence ofassociation– Cockroach (among pre-school agedchildren)– Respiratory syncytial virus (RSV)Chemical Agents• Sufficient evidence of causalrelationship– None found• Sufficient evidence of association– Environmental Tobacco Smoke(among pre-school aged children)• Limited or suggestive evidence ofassociation– None found
  13. 13. Clearing the Air:Indoor Air Exposures & Asthma ExacerbationBiological Agents– Sufficient evidence of causalrelationship• Cat• Cockroach• House dust mite– Sufficient evidence of an association• Dog• Fungus/Molds• Rhinovirus– Limited or suggestive evidence ofassociation• Domestic birds• Chlamydia and Mycoplasma pneumonia• RSVChemical Agents• Sufficient evidence of causalrelationship– Environmental tobacco smoke(among pre-school aged children)• Sufficient evidence of association– NO2, NOX (high levels)• Limited or suggestive evidence ofassociation– Environmental Tobacco Smoke(among school-aged, olderchildren, and adults)– Formaldehyde– Fragrances
  14. 14. • In general, higher ratesin developed countries• Some hypotheses• “Hygiene hypothesis”• Environmental exposures• Diet• Physical activity/lifestyleISAAC (1998), Lancet 351:1225-32.Between-population disparities
  15. 15. “Hygiene Hypothesis”• Studies in the late 1980s and 1990s in the UKand reunified Germany suggested that highersanitation increased risks of these healthconditions• Reduction/lack of in infections and microbialexposures early in life may be associated withincreased risk of allergy, asthma andautoimmune 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. 16. Allergic disease(Th2)Helminth Infection(Th2)Microbial Infection(Th1)The relationship between infection and allergic diseaseHygiene HypothesisIn developed countries:High incidence ofallergic diseaseLow incidence ofinfectious diseases (Th1)Low infection withworms (helminths)In developing countries:Low incidence ofallergic diseaseHigh incidence ofinfectious diseases (Th1)High infection withworms (helminths)
  17. 17. Allergic diseases include• Asthma• Atopic dermatitis (eczema)• Urticaria• Occupational allergy• Allergic conjunctivitis• Allergic rhinitis (hay fever)• Insect/sting allergy• Drug allergy• Food allergyAtopic individuals are more at risk of developing allergies.Atopy is a state (hereditary disposition) that makes a personmore likely to develop allergic reactions of any type
  18. 18. European Academy of Allergy and Clinical ImmunologyFoodHypersensitivityFood AllergyIgE mediatedfood allergyNon-IgEmediated foodallergyNon-allergicFHS18ImmunesysteminvolvedDoes notinvolveimmunesystem
  19. 19. European Academy of Allergy and Clinical ImmunologyFoodHypersensitivityFood AllergyIgE mediatedfood allergyNon-IgEmediated foodallergyNon-allergicFHS19ImmunesysteminvolvedDoes notinvolveimmunesystem
  20. 20. • IgE is an antibody (alsocalled immunoglobulin)made in the body againstallergens.
  21. 21. • IgE antibodiescirculate in thebloodstream and bindto receptors on mastcells• Binding of a foodprotein to theantibodies triggersrelease of mediators(e.g., histamine)causing symptoms
  22. 22. 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
  23. 23. Geographical variation• Fish in Norway• Rice in Japan• Peanuts in USA andUK• Peach and celery inGermany• Olives in Greece
  24. 24. 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
  25. 25. • Milk allergens - casein, lactoglobulins,lactoalbumins– No reduction by pasteurization, condensation,evaporation, and drying• High degree of cross-reactivity with sheep andgoat’s milk
  26. 26. Potential for Allergic ReactionImmune SystemProtein size and AllergenicityHigh Molecular Weight Low Molecular Weight
  27. 27. Hydrolysed ProteinHydrolysisHydrolysed proteins have a lower chance ofinducing sensitisation
  28. 28. Hydrolysis Can Reduce Allergenicity of Cows Milk ProteinsMedian Molecular Weight of Infant Formulas
  29. 29. The case of peanuts
  30. 30. Anaesthetic20%Antibiotic12%Contrast6%Otheriatrogenic9%Venom25%Nuts18%Other food10%Nearly all deaths from food allergy occur in brittle asthmatics.UK deaths from anaphylaxis 94-98
  31. 31. Clinical characteristics• 1/250 of a peanut is enough to trigger areaction (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 severereactions.• Unpredictability of reactions
  32. 32. 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 developrespiratory allergies
  33. 33. Symptoms of a Food-Allergic Reaction• Allergy to food is not a stand alonedisease• Multi organ systems• Multiple symptoms
  34. 34. Symptoms of a Food-Allergic ReactionRespiratory tract:Mild:Itchy, watery eyes, running or stuffy nose,sneezing, cough, itching or swelling of the lips,wheezingSevere:shortness of breath, difficulty swallowing, chesttightness, tingling of the mouth, itching orswelling of the throat,
  35. 35. Symptoms of a Food-Allergic ReactionGI tract:–abdominal cramps, nausea, vomiting,diarrheaSkin:–hives, eczema, itchy red rash, Urticaria
  36. 36. Symptoms of a Food-Allergic ReactionCardiovascular– Drop in blood pressure, loss ofconsciousness/fainting, dizziness, faintness,heart irregularities, shock– Anaphylaxis: sudden, severe, potentiallyfatal, systemic allergic reaction
  37. 37. 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
  38. 38. Allergy Diagnosis• Clinical History• Physical examination• Allergy testing:– Skin Tests– Specific IgE tests• Food challenges
  39. 39. Allergy Skin tests• Prick – most common technique,introduces allergen into the verysuperficial skin usually flexor surface offorearm, sometimes on back
  40. 40. Skin prick testingHistamine HazelMilkPeanutAlmondSalineSoyaBrazil
  41. 41. Management of food allergy
  42. 42. • Currently there is no cure– Avoidance– Avoidance– Avoidance• Cross contamination• Cross-reactivity• Meticulous attention to labels• Education on sources of “hidden foods”
  43. 43. Unexpected food sources of common allergenFood IngredientSoy sauce WheatPeanut Butter SoyCamembert WheatHamburger SoyHam/Sausages Milk
  44. 44. Treatment of allergic reactions• Epinephrine (Adrenalin)• Emergency ward treatment• Oral/parenteral antihistamines• Corticosteroids
  45. 45. Epinephrine• It quickly constricts blood vessels, raisingblood pressure• It relaxes smooth muscles in the lungs toimprove breathing• It stimulates the heart beat• It works to reverse the hives and swellingaround the face and lips
  46. 46. • Epinephrine is available in an auto injectorcalled an EpiPen• The EpiPen is administered into the large outerthigh muscles
  47. 47. Food Allergy Research• Prolific rise of research evidence between1980s to 2000• However the big basic questions were still nottackled– What is the prevalence of food allergy– Who is at risk– What is its natural history
  48. 48. FSA’s research requirement (2001-2002)identified the need for better prevalenceand 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!!!
  49. 49. Food Allergy & Intolerance Research (FAIR) projectFAIR projectProspective Study of a birth cohortto establish the incidence data duringearly childhoodWhole population cohortsto establish prevalence at6, 11 and 15 years of ageBirth Cohort School Cohorts
  50. 50. FAIR studyDetailed history regarding food related problems were obtainedAll children were clinically examined and skin prick testedThose with a positive skin prick test that had never knowingly had thefood or large amounts of the food previously, and those who indicateda previous adverse reaction to foods (regardless of their SPT data)were invited for food challengesChallenges were performed following an algorithm adhering to thehistory in terms of dose and timing when availableAll foods for challenges were freshly prepared for each individualchild, taking into consideration the range of food each infant wouldprefer
  51. 51. Total number of children approached was 5647, of which 3221(57.0%) were recruited into the study3 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)
  52. 52. Symptoms reportedRate of parental reported FHS:Symptoms of FHS were reported by 352/3221 (10.9%) parents andchildren.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 duringthe 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%)
  53. 53. Sensitisation status2690 (83.5%) were skin prick tested (642, 700, 699 and 649of 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 foodallergens (milk, egg, fish, peanut, sesame and wheat) was4.4% (117/2690, 95%CI: 3.6 to 5.2)
  54. 54. Food allergen sensitisation051015202530egg peanut milk fish sesame wheat3 yrs6 yrs11 yrs15 yrsnumbersThe rate of sensitisation to any of the predefined food allergens wasAt 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%
  55. 55. United Kingdom – Birth cohortBased on DBPCFC:• Three years: 2.9% FHS,– milk, peanuts, egg, treenuts, 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, greenbeans, and kiwi• Fifteen years: 2.1%– peanut, tree nuts, wheat, gluten, shell fish, egg andmilk19 %confirmed14%confirmed12%confirmed17%confirmed

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