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

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

6. 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

7. Early sensitization and allergen exposure to perennial allergens
Early sensitization and allergen exposure to perennial allergens* and lung function at school age
Not sensitized
Sensitized/ low exposure
Sensitized/ high exposure
Mean±SD
160
140
120
100 80 60 40 20
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

12. 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
Only father smoked
Mother smoked irregularly
Mother smoked regularly
T. Keil et al, Allergy Allergy Apr;65(4):482-90

13. Laminar airflow systems
Cancun Prevention of asthma in childhood

14. Pharmacotherapeutic attempts
Cetiricin/Levocetericin
Desloratadin
Pimecrolimus

15. 36.5% 37.3% EPAAC™ : Percentage of Subjects Who Developed Asthma
at the end of the 18 Month Treatment Period
Levocetirizine (n=252)
Placebo (n=252)
100
No significant differences between treatments 80 60
% of subjects who developed asthma
At the end of the 18 month treatment period evaluation of the asthma development showed no significant difference in the % of subjects developing asthma between the two study groups. 40
36.5%
37.3% 20
Cancun Prevention of asthma in childhood 15

17. Specific Immunotherapy in pollen allergic children

18. Clinical efficacy of immunotherapy
Early effect
reduction in symptoms/need for medication
Progressive effect
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)
Cancun Prevention of asthma in childhood

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

20. The PAT study
Cancun Prevention of asthma in childhood

21. PAT Study Period SIT Follow up Follow up 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.
Cancun Prevention of asthma in childhood

22. Demographic data at inclusion
All included
No asthma
Asthma ***
Number
208 (205)*
163 42
Mean age (range)
10.7 (6 -
15)
10.6 (6
14)
Sex M/F
138/70 (137/68)*
108/55
29/13
Mean years with
hay fever (range)
4.7(1
15)**
N=171
4.6(1
N=137
4.9(1
9)**
N=34
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
Cancun Prevention of asthma in childhood

23. Patient flow Patients included 205 Control group 102 SIT group 103
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 at 5 years 95
Asthma: 36
Follow up at 10 years 68
Follow up at 10 years 79
Asthma: 30
Total follow up at 10 years: 147

24. Conjunctival provocation test3
P<0.001
P<0.001
P<0.001
P<0.001
P<0.05
2,5 2
Control
Change from baseline
1,5
(2 x log SQ)
Active 1
0,5 1 2 3 5 10
Year

25. 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
Mean VAS Score
Active
-15
-30 1 2 3 5 10
Year
Means adjusted for baseline difference

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

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

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

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. Onset pre-clinical early late clinical
Number of Phl p molecules 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

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
Cancun Prevention of asthma in childhood

35. 12 months of oral application
Study Design
Allergens
(Cat, house dust mites, grass)
Endpoint Assessment
(ITT/ PP)
Randomisation
(n=200)
(age 12 – 30 month)
Enrolment
Patient fulfilling the inclusion criteria were randomly assigned to one of the 4 treatment arms (SIT birch, SIT grass, Xolair+SIT birch or Xolair+SIT grass)
Each patients randomly received active treatment i.e. SIT birch or grass
In addition each patient randomly received Xolair or Xolair-placebo.
The SIT titration was performed in accordance to ALK guidelines for 12 weeks followed by 24 weeks of combined treatment SIT+Xolair during both pollen seasons.
Start of SIT treatement was weeks prior to the expected start of birch pollen season.
Start of Xolair treatment was scheduled weeks prior to to the expected start of birch pollen season.
Duration of birch + grass pollen season was expected to be 24 weeks in total.
Placebo
Follow-up
12 months of oral application
Cancun Prevention of asthma in childhood

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

37. 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

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
Cancun Prevention of asthma in childhood