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Prof. Dr. U. Wahn Prevention of asthma in childhood Ulrich Wahn Department of Pediatric Pneumology and Immunology.

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Presentation on theme: "Prof. Dr. U. Wahn Prevention of asthma in childhood Ulrich Wahn Department of Pediatric Pneumology and Immunology."— Presentation transcript:

1 Prof. Dr. U. Wahn Prevention of asthma in childhood Ulrich Wahn Department of Pediatric Pneumology and Immunology

2 Possible opportunities Allergen avoidance Preventative Pharmakotherapy in high risk groups a) Cetirizin/Levocetiricin b) Desloratadin c) Pimecrolimus Spec. Immunotherapy in pollen allergic children SLIT in high risk infants Primary prevention by modification of infant nutrition

3 Allergen avoidace Dust mites Pets Novel tools

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6 Prevalence of current wheeze from birth to age 13 years Age (years) Wheezing at school age (5–7 years) Illi S, et al. Lancet 2006 Non-atopicAtopic

7 Early sensitization and allergen exposure to perennial allergens* and lung function at school age p=0.020 p=0.003 FEV 1 (% FVC) p=0.018 p=0.003 p=0.001 p=0.025 p<0.001 Not sensitizedSensitized/ low exposure Sensitized/ high exposure Mean±SD FEV 1 (% predicted) MEF 75 (% predicted) MEF 50 (% predicted) MEF 25 (% predicted) FEV 1 = forced expiratory volume in 1 second; FVC = forced vital capacity; MEF = maximal expiratory flow *Sensitization/exposure to mites and/or cats up to the age of 3 years Illi S, et al. Lancet 2006

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12 Parental smoking and sensitization 27,7 Mother smoked regularly Mother smoked irregularly Only father smoked Adj. OR and 95%CI 1 atopic parent No atopic parents 2 atopic parents 1 atopic parent No atopic parents 2 atopic parents 1 atopic parent No atopic parents 2 atopic parents T. Keil et al, Allergy Allergy Apr;65(4):482-90

13 Laminar airflow systems

14 Pharmacotherapeutic attempts Cetiricin/Levocetericin Desloratadin Pimecrolimus

15 EPAAC : Percentage of Subjects Who Developed Asthma at the end of the 18 Month Treatment Period % of subjects who developed asthma Placebo (n=252)Levocetirizine (n=252) No significant differences between treatments 37.3%36.5%

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17 Specific Immunotherapy in pollen allergic children

18 Clinical efficacy of immunotherapy Early effect –reduction in symptoms/need for medication Progressive effect –reduction in symptoms/need for medication –reduction in hyperresponsiveness/late phase response Persistent effect –long-term reduced symptoms/need for medication –long-term reduced hyperresponsiveness/late phase response Preventive effect –prevention of new sensitivities and exacerbation of disease (rhinitis into asthma)

19 Probability of New Onset of Wheeze in children with and without atopy Rochat et al, JACI 2010; 126:

20 The PAT study

21 SIT Follow up Möller et al. J Allergy Clin.Immunol. 2002;109: Maintenance dose: Grass: 20 µg Phl p5 Birch: 13 µg Bet v1 PAT Study Period In print, Allergy 2006 AAAAI, 2006

22 Demographic data at inclusion Methacholine PC 20 Mean (range) 10.8 ( ) 12.2 ( ) 5.1 ( ) Control/SIT f. 3 years 94/97 72/79 22/18 * Three patients dropped out of before baseline monitoring season (0 – season) ** Only patients with reliable informations included ***Mild seasonal asthma during first season before randomization

23 Patients included 205 Control group 102 SIT group 103 Continued for 3 years as controls 94 Continued for 3 years on SIT 97 Patient flow Follow up at 5 years 83 Follow up at 5 years 95 Follow up at 10 years 68 Follow up at 10 years 79 Asthma: 42 Asthma: 40 Asthma: 36 Asthma: 30 Total follow up at 10 years: 147

24 P< Conjunctival provocation test Change from baseline (2 x log SQ) P< ,5 1 1,5 2 2,5 3 Year Control Active

25 Rhinitis: Change from baseline (Visual analogue scores) P=0.01P<0.001P< P<0.05 Means adjusted for baseline difference Year Mean VAS Score Control Active

26 Development of asthma at 3 years N=151 (patients without asthma in season one) N=60 N=19 N=40 N=32 Odds-ratio = 2.52 (1.3 – 5.1)

27 N=60 N=15 N=38 N=29 Odds-ratio = 2.68 (1.3 – 5.7) Development of asthma at 5 years N=142 (patients without asthma in season one)

28 N=48 N=16 N=29 N=24 Odds-ratio = 2.48 (1.2 – 5.4) Development of asthma at 10 years N=117 (patients without asthma in season one)

29 GAP-Study

30 Sublingual allergen application

31 SLIT in high risk infants

32 Recent evidence from high dose SLIT trials opens new avenues for early intervention studies in infants and young children

33 3,04,04,22,11,4 Onset = 2,575 mol Years/mol = 4,1 to be adjusted by AGE AT ONSET!!! Number of Phl p molecules recognized by IgE in 79 children with SAR by time from the onset of symptoms pre-clinical clinicallateearly Onset Component Resolved Prophylaxis CRP early simplified (es-CRT) (too) complex late CRT confidential kU/l IgE to g6 2.5 – 3 molecules

34 Prophylaxis of atopy and asthma in children (ITN) Inclusion criteria: Children 12 – 30 months of age (n=200) Atopic dermatitis, sensitisation to food No sensitisation to aeroallergens Positive family history for atopy/asthma Primary end points: Allergic sensitisation Secondary end points: Current asthma 3 years after the end of intervention

35 Enrolment Randomisation (n=200) (age 12 – 30 month) (Cat, house dust mites, grass) Allergens Placebo Endpoint Assessment (ITT/ PP) 12 months of oral application Follow-up Study Design

36 Parental Phenotypes Infantile Phenotypes Atopy/Asthma ADWheeze Food Sensitization Perennial aero- sensitization Food Sensitization Perennial aero- sensitization Persistent asthma in adolescene Filaggrin Mutation The child at risk for asthma

37 What are the studies we need? 1.Allergen-specific SLIT in young children at high risk for asthma with established sensitization to house dust mite 2.Allergen-specific mucosal tolerance induction at high risk for asthma prior to aeroallergen sensitization 3.Asthma prevention studies in established disease of the upper airways

38 Primary prevention by modifcation of infant nutrition

39 Conclusion Asthma prevention: challenge for pediatric allergist Asthma prediction in high risk infants possible Results of allergen avoidance strategies and pharmacotherapeutic interventions not very encouraging Primary prevention in infance not sucessful Immunotherapeutic interventions probably more promissing


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