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Prevention of chronic respiratory
diseases in childhood and its impact
             later in life
               Nikos Papadopoulos
Allergy Dpt, 2nd Pediatric Clinic,University of Athens,

              EAACI Secretary General
The high burden of chronic respiratory
           diseases (CRD)




   www.who.int/respiratory/
Asthma starts early in life
The Melbourne cohort




Am J Respir Crit Care Med. 2000 Dec;162(6):2177-81
Aim:
To predict and prevent any
     long-term effects
Understanding mechanisms




               Papadopoulos et al. Allergy (2007)
Asthma starts with an infection
   • In 140 children, 47 of which were hospitalized for RSV bronchiolitis.
   • Asthma outcome at 7.5 years higher in cases

             35
                               30%
             30
Children
   with
             25
 asthma
  at age     20
7.5 years
             15
   (%)
             10


              5                                                         3%


              0
                              RSV                                   Control
                             (n=47)                                  (n=93)
                                       Sigurs N et al. Am J Respir Crit Care Med 2000;161:1501-1507
12 month follow-up: Persistence (>= 2
   additional episodes of wheeze)


                                    35           15 (42%)
                                   RSV (+)          Relapses


          64                        24           21 (87%)
   Bronchiolitis cases             RV (+)           Relapses


                                     5           5 (100%)
                                  RSV-RV(+)         Relapses

                                              Controls:
                                              5/52 (9.6%)
Papadopoulos et al. unpublished               3/5 were RV(+)
Asthma is an allergic disease
 Allergen

Dendritic cell

               IL-1                                MBP ECP             LTs
                               IgE                                     PGs
    Th0-cell                                                           PAF
                                              B-cell           Eosinophil                  Mast cell
                              IL-4    IL-13
                 IL-10                                 Eotaxin IL-5
                                                         RANTES
               IFN-
                                                                                histamin
  Th1-cell               Th2-cell
                                     VCAM-1 ICAM-1 E-
                                         selectin


                                                                      Systemic
                                                                      circulation
Asthma persists in allergic children




                        Illi et al. Lancet 2006
Mechanisms of interaction
Synergy between virus & allergen
 exposure in hospital admissions
       25

       20

       15
Risk
       10

        5

        0




                          Murray et al. Thorax (2005)
The PreDicta hypothesis

                  (Atopy &
 Infection        other risk       Infection     Asthma
                   factors)

                                               ‘Blocked’ state
   Possibly         Increased      Repeated
 bronchiolitis    susceptibility                     of
                                    events     hyperreactivity



www.predicta.eu
Other contributors
•   Weather
•   Pollution
•   Stress
•   Tobacco smoke
How can we prevent childhood
           CRD?

    Early pharmacological treatment
            Infection control
           Allergen avoidance
              ETS avoidance
Early treatment in school-age children

                            12
  Yearly change of FEV1 %




                            10
                                                                          P = 0.02
                            8

                            6

                            4

                            2

                            0
                                      <2           2–3           3–5            >5
                                Asthma duration at the beginning of therapy with budesonide


                                                            Agertoft and Pedersen, Respir Med 1994
Intervention effects
• No long-term effect in fluticasone-treated
  children




Guilbert et al. (2006) NEJM 354:19
J Allergy Clin Immunol 2010;126:256-62
Is a rhinovirus vaccine possible ?




Niespodziana, Papadopoulos, Valenta et al. FASEB J 2012
Allergen avoidance
• Only thorough allergen
  avoidance may have results
   – Allergen testing
     required
Allergen-specific Immunotherapy may
     prevent disease progression




              Jacobsen et al. Allergy 62:943-948.
Effects of passive exposure to ETS
                                                                     Doctor
                                                           Current   diagnosed
                                        Ever wheeze wheeze           asthma
                                        1.31 **            1.21
    Either parent smoking                                            1.53 **


    Father current smoker               1.21#              1.16      1.50 *


    mother current smoker               1.26 *             1.18      1.24
    Active smoking during
    pregnancy                           1.55 **            1.40 **   1.56*

    passive exposure to ETS
    during pregnancy                    1.22 #             1.31 *    1.36 #
Xepapadaki, Papadopoulos et al. Ped Allergy Immunol 2009
Conclusions
• Chronic respiratory diseases, including
  asthma, place a high burden on public health
• Asthma, the most frequent chronic disease in
  children, starts early in life, with a respiratory
  infection
• Interactions between allergy and infection
  lead to chronic persistent disease
Conclusions
• Early treatment, allergen avoidance, infection
  control and environmental tobacco avoidance
  may alleviate the long-term impact
• Allergen-specific immunotherapy may prevent
  disease progression
Call for action
Public Health:
  1. Facilitate allergen immunotherapy
      • Awareness campaigns
      • Monitoring
      • Updating of National healthcare policies
  2. Drastically reduce ETS exposure
Research:
  3. Focus on infection-related consequences
Prevention of Chronic Respiratory Diseases in Childhood and its Impact Later in Life

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Prevention of Chronic Respiratory Diseases in Childhood and its Impact Later in Life

  • 1. Prevention of chronic respiratory diseases in childhood and its impact later in life Nikos Papadopoulos Allergy Dpt, 2nd Pediatric Clinic,University of Athens, EAACI Secretary General
  • 2. The high burden of chronic respiratory diseases (CRD) www.who.int/respiratory/
  • 3.
  • 5. The Melbourne cohort Am J Respir Crit Care Med. 2000 Dec;162(6):2177-81
  • 6. Aim: To predict and prevent any long-term effects
  • 7. Understanding mechanisms Papadopoulos et al. Allergy (2007)
  • 8. Asthma starts with an infection • In 140 children, 47 of which were hospitalized for RSV bronchiolitis. • Asthma outcome at 7.5 years higher in cases 35 30% 30 Children with 25 asthma at age 20 7.5 years 15 (%) 10 5 3% 0 RSV Control (n=47) (n=93) Sigurs N et al. Am J Respir Crit Care Med 2000;161:1501-1507
  • 9. 12 month follow-up: Persistence (>= 2 additional episodes of wheeze) 35 15 (42%) RSV (+) Relapses 64 24 21 (87%) Bronchiolitis cases RV (+) Relapses 5 5 (100%) RSV-RV(+) Relapses Controls: 5/52 (9.6%) Papadopoulos et al. unpublished 3/5 were RV(+)
  • 10. Asthma is an allergic disease Allergen Dendritic cell IL-1 MBP ECP LTs IgE PGs Th0-cell PAF B-cell Eosinophil Mast cell IL-4 IL-13 IL-10 Eotaxin IL-5 RANTES IFN- histamin Th1-cell Th2-cell VCAM-1 ICAM-1 E- selectin Systemic circulation
  • 11. Asthma persists in allergic children Illi et al. Lancet 2006
  • 13. Synergy between virus & allergen exposure in hospital admissions 25 20 15 Risk 10 5 0 Murray et al. Thorax (2005)
  • 14. The PreDicta hypothesis (Atopy & Infection other risk Infection Asthma factors) ‘Blocked’ state Possibly Increased Repeated bronchiolitis susceptibility of events hyperreactivity www.predicta.eu
  • 15. Other contributors • Weather • Pollution • Stress • Tobacco smoke
  • 16. How can we prevent childhood CRD? Early pharmacological treatment Infection control Allergen avoidance ETS avoidance
  • 17. Early treatment in school-age children 12 Yearly change of FEV1 % 10 P = 0.02 8 6 4 2 0 <2 2–3 3–5 >5 Asthma duration at the beginning of therapy with budesonide Agertoft and Pedersen, Respir Med 1994
  • 18. Intervention effects • No long-term effect in fluticasone-treated children Guilbert et al. (2006) NEJM 354:19
  • 19. J Allergy Clin Immunol 2010;126:256-62
  • 20. Is a rhinovirus vaccine possible ? Niespodziana, Papadopoulos, Valenta et al. FASEB J 2012
  • 21. Allergen avoidance • Only thorough allergen avoidance may have results – Allergen testing required
  • 22. Allergen-specific Immunotherapy may prevent disease progression Jacobsen et al. Allergy 62:943-948.
  • 23.
  • 24. Effects of passive exposure to ETS Doctor Current diagnosed Ever wheeze wheeze asthma 1.31 ** 1.21 Either parent smoking 1.53 ** Father current smoker 1.21# 1.16 1.50 * mother current smoker 1.26 * 1.18 1.24 Active smoking during pregnancy 1.55 ** 1.40 ** 1.56* passive exposure to ETS during pregnancy 1.22 # 1.31 * 1.36 # Xepapadaki, Papadopoulos et al. Ped Allergy Immunol 2009
  • 25. Conclusions • Chronic respiratory diseases, including asthma, place a high burden on public health • Asthma, the most frequent chronic disease in children, starts early in life, with a respiratory infection • Interactions between allergy and infection lead to chronic persistent disease
  • 26. Conclusions • Early treatment, allergen avoidance, infection control and environmental tobacco avoidance may alleviate the long-term impact • Allergen-specific immunotherapy may prevent disease progression
  • 27. Call for action Public Health: 1. Facilitate allergen immunotherapy • Awareness campaigns • Monitoring • Updating of National healthcare policies 2. Drastically reduce ETS exposure Research: 3. Focus on infection-related consequences

Hinweis der Redaktion

  1. 1. ston 1o xrono follow up 5/52 controls emfanisan vrogxiolitida gia thn opoia noshleuthkan - oi 3/5 htan RV positive2. persistence of wheeze thewrhsame oti parathroume se paidia pou parousiasan 2 or kai perissotera epeisodia syrigmou pou ta enoxlouse se tetoio vathmo wste na xreiastoun na epikoinwnhsoun h na episkeftoun ton paidiatro tous ( ta enoxlouse ston ypno, sto paixnidi, sto faghto )- h farmakeutikh agwgh den htan krithrio gia to an ypotropiasan h oxi- wstoso, ola phran farmakeutikh agwgh (toulaxiston gia 5 hmeres)
  2. 10-year follow-up of the PAT studyThe percentage of children with and without asthma 7 years after termination (10-year follow-up) of specific immunotherapy. Based on the patients without asthma before treatment (n = 117). The absolute number of children is shown above the bars.Background: 3-year subcutaneous specific immunotherapy (SIT) in children withseasonal allergic rhinoconjunctivitis reduced the risk of developing asthmaduring treatment and 2 years after discontinuation of SIT (5-year follow-up)indicating long-term preventive effect of SIT.Objective: We evaluated the long-term clinical effect and the preventive effect ofdeveloping asthma 7-years after termination of SIT.Methods: One hundred and forty-seven subjects, aged 16–25 years with grassand/or birch pollen allergy was investigated 10 years after initiation of a 3-yearcourse of SIT with standardized allergen extracts of grass and/or birch or no SITrespectively. Conjunctival provocations were performed outside the season andmethacholine bronchial provocations were performed during the season andwinter. Asthma was assessed by clinical evaluation.Results: The significant improvements in rhinoconjunctivitis and conjunctivalsensitivity persisted at the 10-year follow-up. Significantly less actively treatedsubjects had developed asthma at 10-year follow-up as evaluated by clinicalsymptoms [odds ratio 2.5 (1.1–5.9)]. Patients who developed asthma amongcontrols were 24/53 and in the SIT group 16/64. The longitudinal treatmenteffect when adjusted for bronchial hyper-responsiveness and asthma status atbaseline including all observations at 3, 5 and 10 years follow-up (children withor without asthma at baseline, n = 189; 511 observations) was statisticallysignificant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5–13.7) in favor of SIT.Conclusion: A 3-year course of SIT with standardized allergen extracts hasshown long-term clinical effects and the potential of preventing developmentof asthma in children with allergic rhinoconjunctivitis up to 7 years aftertreatment.Clinical implication: Specific immunotherapy has long-term clinical effects andthe potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment termination.
  3. Background: Environmental tobacco smoke (ETS) is a significant risk factor for the presence and increased severity of asthma and allergy-related symptoms in children. Smoking during pregnancy has detrimental effects on asthma-associated outcomes in childhood. Whether passive exposure of pregnant women to ETS may also lead to asthma in their offspring, is not known. The aim of our study was to investigate the association of passive exposure of pregnant women to ETS and asthma and / or allergy-related symptoms in preschool children.Methods: Cross-sectional data were collected with questionnaires from 2374 preschool children, recruited from public and private nurseries and day-care centres.Results: Parental smoking was significantly associated with wheezing symptoms in their children. Mother’s active smoking during pregnancy, significantly increased the risk for occurrence of asthma symptoms and /or medically diagnosed asthma in preschool children in a dose – dependent manner. Passive exposure to ETS, mainly during the 3rd trimester of pregnancy, was significantly associated with asthma and allergy – related symptoms after adjusting for several confounders in a multivariate analysis (current wheeze: OR=1.42, 95%CI=1.06-1.91, pruritic rash ever: OR= 1.45, 95%CI= 1.01-2.08).Conclusions: Passive exposure of pregnant women to ETS during the 3rd trimester is positively associated with asthma and allergy-related symptoms in their preschool age children. Public health policies should be oriented not only towards smoking cessation but also reinforce elimination of ETS exposure of pregnant women.