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Prof. Dr. U. Wahn

Prof. Dr. U. Wahn. Prevention of asthma in childhood. Ulrich Wahn Department of Pediatric Pneumology and Immunology. Possible opportunities. Allergen avoidance Preventative Pharmakotherapy in high risk groups a) Cetirizin/Levocetiricin b) Desloratadin c) Pimecrolimus

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Prof. Dr. U. Wahn

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  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/Levocetiricinb) Desloratadinc) 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

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

  5. Early sensitization and allergenexposure to perennial allergens* andlung function at school age Not sensitized Sensitized/low exposure Sensitized/high exposure Mean±SD 160 140 120 100 80 60 40 20 0 p=0.003 p=0.020 p=0.018 p=0.001 p<0.001 p=0.003 p=0.025 FEV1(% FVC) FEV1(% predicted) MEF75(% predicted) MEF50(% predicted) MEF25(% predicted) FEV1 = 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

  6. Parental smoking and sensitization 27,7 Adj. OR and 95%CI No atopic parents 1 atopic parent 2 atopic parents No atopic parents 1 atopic parent 2 atopic parents No atopic parents 1 atopic parent 2 atopic parents Mother smoked regularly Only father smoked Mother smoked irregularly T. Keil et al, Allergy Allergy. 2010 Apr;65(4):482-90

  7. Laminar airflow systems

  8. Pharmacotherapeutic attempts • Cetiricin/Levocetericin • Desloratadin • Pimecrolimus

  9. Placebo (n=252) Levocetirizine (n=252) EPAAC™ : Percentage of Subjects Who Developed Asthma at the end of the 18 Month Treatment Period 100 No significant differences between treatments 80 60 % of subjects who developed asthma 40 36.5% 37.3% 20 0

  10. Specific Immunotherapy in pollen allergic children

  11. 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)

  12. Probability of New Onset of Wheeze in children with and without atopy Rochat et al, JACI 2010; 126: 1170-1175

  13. The PAT study

  14. PAT Study Period Maintenance dose: Grass: 20 µg Phl p5 Birch: 13 µg Bet v1 Follow up Follow up SIT AAAAI, 2006 In print, Allergy 2006 Möller et al. J Allergy Clin.Immunol. 2002;109:251-6.

  15. All included No asthma Asthma *** Number 208 (205)* 163 42 Mean age (range) 10.7 (6 - 15) 10.7 (6 - 15) 10.6 (6 - 14) Sex M/F 138/70 (137/68)* 108/55 29/13 Mean years with 4.7(1 - 15)** 4.6(1 - 15)** 4.9(1 - 9)** hay fever (range) N=171 N=137 N=34 Demographic data at inclusion Methacholin e PC 20 Mean (range) 10.8 (0.03 - 16) 12.2 (0.16 - 16) 5.1 (0.03 - 16) 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 information’s included ***Mild seasonal asthma during first season before randomization

  16. Patient flow Patients included 205 SIT group 103 Control group 102 Asthma: 42 Continued for 3 years as controls 94 Continued for 3 years on SIT 97 Asthma: 40 Follow up at 5 years 83 Follow up at5 years 95 Asthma: 36 Follow up at10 years 68 Follow up at 10 years 79 Asthma: 30 Total follow up at 10 years: 147

  17. Conjunctival provocation test 3 P<0.001 P<0.001 P<0.001 P<0.001 P<0.05 2,5 2 Control 1,5 Change from baseline (2 x log SQ) Active 1 0,5 0 1 2 3 5 10 Year

  18. Rhinitis: Change from baseline (Visual analogue scores) 30 P=0.01 P<0.001 P<0.0001 P<0.0001 P<0.05 15 Control 0 Mean VAS Score Active -15 -30 1 2 3 5 10 Year Means adjusted for baseline difference

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

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

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

  22. GAP-Study

  23. Sublingual allergen application

  24. SLIT in high risk infants

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

  26. Onset pre-clinical early late clinical Number of Phl pmolecules recognized by IgE in 79 children with SAR by time from the onset of symptoms Onset = 2,575 mol Years/mol = 4,1 confidential 10-15 kU/l IgE to g6 2.5 – 3 molecules to be adjusted by AGE AT ONSET!!! Component Resolved Prophylaxis CRP early simplified (es-CRT) (too) complex late CRT 1,4 2,1 3,0 4,0 4,2

  27. 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

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

  29. The child at risk for asthma Parental Phenotypes Atopy/Asthma Atopy/Asthma Filaggrin Mutation Filaggrin Mutation AD Wheeze InfantilePhenotypes Food Sensitization Food Sensitization Perennial aero-sensitization Perennial aero-sensitization Persistent asthmain adolescene

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

  31. Primary prevention by modifcation of infant nutrition

  32. 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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