Βρογχικό άσθμα : Χρόνια φαρμακευτική αγωγή ή απευαισθητοποίηση. Απευαισθητοποίηση

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1 9o Παμπελοποννησιακό Συνέδριο Στρογγυλό τραπέζι Βρογχικό άσθμα : Χρόνια φαρμακευτική αγωγή ή απευαισθητοποίηση Απευαισθητοποίηση Μήκος Νικόλαος Αλλεργιολόγος Λαϊκό Νοσοκομείο Αθηνών

2 SIT SLIT

6 Subcutaneous immunotherapy: effect on serum specific IgE 70 Initiation of immunotherapy Anti - ragweed IgE (ng/ml) August November baseline year 1 year 2 year 6 year 7 year 8 Adapted from: Peng et al. J Allergy Clin Immunol 1992;89:519

30 20 10 August November baseline year 1 year 2 year 6 year 7

9 Studies Defining Benefit of Immunotherapy for Allergic Rhinitis No Efficacy Low Efficacy Medium Efficacy High Efficacy Malling HJ Allergy 1998; 53:

0 No Efficacy Low Efficacy Medium Efficacy

10 Treatment of allergic rhinitis (ARIA) Allergic Rhinitis and its Impact on Asthma mild intermittent moderate severe intermittent intra-nasal steroid local chromone mild persistent moderate severe persistent oral or local non-sedative H1-blocker intra-nasal decongestant (<10 days) or oral decongestant allergen and irritant avoidance immunotherapy

persistent moderate severe persistent oral or local non-sedative H1-blocker

13 Πριν την ΑΝΘ Μετά την ΑΝΘ

18 Nasal inflammation and BHR 20 Nasal eosinophil number 10 0 PD20 22 absent 3 low 11 moderate 12 high methacholine Ciprandi G. et al, Int Arch Allergy Immunol 2004

22 Asthma symptom score Asthma medication score

23 Πνευμονική λειτουργία

24 Meta-Analysis of Immunotherapy for (Abramson et al. AARD 1995;151) Asthma Mites Smith (n=22) Maunsell (n=34) Werner (n=51) D Souza (n=91) Pauli (n=18) Newton (n=14) BTA (n=56) Other Allergens Frankland (n=57) Ohman (n=17) Sundin (n=39) Valovirta (n=27) Mites Combined (n=286) Other Allergens (n=140) All Studies (n=426)

27 Injection allergen immunotherapy for asthma Abramson MJ, Puy RM, Weiner JM Search strategy We searched the Cochrane Airways Group Trials Register up to 2005, This version first published online: July Last assessed as up-to-date: April Authors' conclusions Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.

29 Γιατί αυτή η σχέση ρινίτιδας/άσθματος είναι σημαντική;;

30 Επιδημιολογικά δεδομένα 80-95% ασθματικών ασθενών, έχουν ρινίτιδα 76% ασθματικών ασθενών, αναφέρουν παρουσία ρινίτιδας πριν από την εμφάνιση του άσθματος Η εμφάνιση του άσθματος συσχετίζεται με την διάρκεια και την σοβαρότητα της ρινίτιδας Leynaert, J Allergy Clin Immunol 2004

32 Perennial rhinitis: an independent risk factor for asthma Leynaert et al, J Allergy Clin Immunol % subjects with asthma controls rhinitis 0 atopic non-atopic

35 Επεισόδια άσθματος % untreated AR p = treated AR Crystal-Peters, J Allergy Clin Immunol 2002

36 Prevention of Asthma by Immunotherapy 5-Year Follow-Up Do not develop Asthma Develop Asthma asthma asthma Immunotherapy 30 9 Control Number 10 of patients Number of Patients Jacobsen L Ann Allergy Asthma Immunol 2001; 87:

37 7-13 ετών, χωρίς άσθμα ΑΝΘ 3 χρόνια Επανεκτίμηση άσθματος 7 χρόνια μετά την διακοπή ΑΝΘ Conclusion: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis. J Allergy Clin Immunol 2002;109:251-6

41 SLIT is certainly indicated in allergic rhinitis in both adults and children SLIT may exert a preventative effect on the development of asthma SLIT can be used also when asthma is associated to rhinitis, whereas it is not the first choice for the treatment of isolated asthma

42 Σε ποιους ασθενείς

43 Σε ποιους ασθενείς Σε αλλεργικούς που το αλλεργιογόνο τους σχετίζεται με τα συμπτώματα Σε μονοευαισθησίες Σε ασθενείς με αλλεργική μετρία-σοβαρή ρινίτιδα και ήπιο-σοβαρό άσθμα Σε FEV1>70% Όχι σε μη-ελεγχόμενο άσθμα

44 Η ανοσοθεραπεία είναι η μόνη ανοσορυθμιστική θεραπεία που μπορεί να αναστείλει την φυσική πορεία των αλλεργικών παθήσεων (ρινίτιδα-άσθμα )

46 Ανοσοθεραπεία Ρινίτιδα Αποτελεσματική Ένα και ορισμένα αλλεργιογόνα Σε κάθε ηλικία ασφάλεια Άσθμα Αποτελεσματική;;; Ένα και ορισμένα αλλεργιογόνα Ηλικία;;; Ασφάλεια;;;

47 Ανοσοθεραπεία Ρινίτιδα Αποτελεσματική Ένα και ορισμένα αλλεργιογόνα Σε κάθε ηλικία ασφάλεια Άσθμα Αποτελεσματική;;; Ένα και ορισμένα αλλεργιογόνα Ηλικία;;; Ασφάλεια;;;

49 Σας ευχαριστώ

62 Improvement in Medication Requirements and Symptom Scores After Immunotherapy Outcome measure Symptom Improvement Reduction in medication Decreased bronchial hyperresponsive ness Dust mite (Odds Ratio) Other allergens (pollen, mold,dander) (Odds Ratio) 2.7 ( ) 4.8 ( ) 4.2 ( ) ND 13.7 (3.8-50) 5.5 ( ) Abramson MJ, Puy RM, Weiner JM Am J Respir Crit Care Med 1995; 151:

63 100 % of patients N=60 Odds-ratio = 2.52 N=19 N=40 N= SIT No asthma Asthma Control

64 Long-Term Clinical Efficacy of Grass-Pollen Immunotherapy Initial Placebo Trial Current Trial Symptom Score Pollen Count (grains/m 3 ) Study group Immunotherapy Placebo Immunotherapy Maintenance Discontinuation None (control) May June July Aug. May June July Aug. May June July Aug. May June July Aug. Durham SR et al N Engl J Med 1999; 341:

65 rhinitis asthma Disease severity time Togias, Allergy 1999

66 THE SAFETY OF SUBLINGUAL IMMUNOTHERAPY WITH ONE OR MULTIPLE ALLERGENS IN CHILDREN Fabio Agostinis 1, Carlo Foglia 1, Marcello Cottini 2, Giorgio Walter Canonica 3, Giovanni Passalacqua 3 Table 2. Summary of the reported side effects. Oral itching/burning Single allergen 16,744 doses 36 mild 4 moderate Multiple allergens 22,666 doses 48 mild 5 moderate Oral/tongue swelling 8 mild 11 mild 1 moderate Rhinitis/ear itching 3 mild 2 mild Troath irritation 12 mild 1 moderate 22 mild 2 moderate Nausea/abdominal pain 3 mild 4 mild Vomiting/diarrhea - - Cough 5 mild 7 mild Asthma - - Generalized urticaria - - Anaphylaxis - - TOTAL 72 episodes 44,44% patients 4,3/1000 doses 102 episodes 40,32% patients 4,5/1000 doses

67 Authors' conclusions Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. ( One trial found that the size of the benefit is possibly comparable to inhaled steroids.) * The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered. * ( Immunotherapy May Beat Corticosteroids in Dust Mite-Sensitive Kids With Asthma Dr. Aarif O. Eifan, of Marmara University Medical Faculty, Istanbul )

68 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Evidence for long-term prevention Moller C, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002; 109: children aged 6 to 14 years; SIT for 3 years Niggemann B, Jacobsen L, Dreborg S, et al. Five-year follow up on the PAT study: specific immunotherapy and long-termprevention of asthma in children. Allergy 2006; 61: Jacobsen L, Niggemann B, et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow up on the PAT study. Allergy 2007; 62: Significant improvements in rhinoconjunctivitis persisted Less treated subjects had developed asthma [odds ratio 2.5]

69 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Evidence for prevention of asthma The experimental evidence for prevention of asthma in patients with allergic rhinitis.. is Ib for allergen SIT and SLIT Together with the long-term clinical experience available, we regard SIT as an important treatment for the prevention of asthma in patients with allergic rhinitis. Ib evidence from at least 1 randomised controlled trial

70 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Evidence for long-term prevention Moller C, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002; 109: children aged 6 to 14 years; SIT for 3 years Niggemann B, Jacobsen L, Dreborg S, et al. Five-year follow up on the PAT study: specific immunotherapy and long-termprevention of asthma in children. Allergy 2006; 61: Significant improvement in hay fever Treated children had less asthma (OR = 2.68; P<0.01)

71 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Evidence for the prevention of new allergies Johnstone DE, Crump L. Value of hyposensitization therapy for perennial bronchial asthma in children. Pediatrics 1961; 61: year course of high-dose SCIT; new IgE sensitivities: 0 treated vs 25% in the control group. Des Roches A, et al. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children. J Allergy Clin Immunol 1997; 99: children with allergy to HDM; monosensitized; 3 years SIT New sensitivity 55% (IT-treated group) vs 100% (control group)

72 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Evidence for prevention of asthma Moller C, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol 2002; 109: SCIT for 3 years; 208 children, 6-14 years; grass and/or birch pollen allergy the group treated with SIT had significantly less asthma as evaluated by clinical symptoms (OR = 2.52; P<0.001) Novembre E, et al. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 2004; 114: children (5-14 years) treated with SLIT for 3 consecutive years (4 months every year) 8/45 treated vs 18/44 controls developed asthma; OR 3.80

73 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Evidence for prevention of asthma Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children a 14-year study. Pediatrics 1968; 42: year follow-up study in children 22% of the placebo-treated children free of asthma compared with 72% of the SCIT-treated children. Bauer CP. Study of preventing the development of asthma during specific immunotherapy in children Allergologie 1993; 11:468. children with allergy to grass and allergic rhinitis reduced development of seasonal BHR to histamine after 2 years

74 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Recent findings: long-term follow-up on IT studies demonstrates that: SIT for 3 years shows persistent long-term effects on clinical symptoms after termination of treatment and preventive effects on later development of asthma in children with seasonal rhinoconjunctivitis. IT seems to reduce the development of new allergic sensitivities

75 L. B. Bacharier, A. Boner, et al (16), The European Pediatric Asthma Group Review article Allergy 2008: 63: 5 34 Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report IMMUNOTHERAPY: is the only way of permanently redirecting the disease process of allergic (atopic) asthma. Pajno GB. Clin Exp Allergy 2005;35: Preventive effect Can prevent sensitization to other allergens, Des Roches A, et al. J Allergy Clin Immunol 1997;99: can improve asthma, prevent progression from allergic rhinitis to asthma Niggemann B, et al. Allergy 2006;61: reduce the development of asthma in children with seasonal allergies Novembre E, et al. J Allergy Clin Immunol 2004;114: , (the PATstudy) J Allergy Clin Immunol 2002;109. The effect appears to continue after treatment has stopped Durham et al. N Engl J Med 1999;341:

76 L. B. Bacharier, A. Boner, et al (16), The European Pediatric Asthma Group Review article Allergy 2008: 63: 5 34 Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report IMMUNOTHERAPY: is the only way of permanently redirecting the disease process of allergic (atopic) asthma. Pajno GB. Clin Exp Allergy 2005;35: Preventive effect Can prevent sensitization to other allergens, Des Roches A, et al. J Allergy Clin Immunol 1997;99: can improve asthma, prevent progression from allergic rhinitis to asthma Niggemann B, et al. Allergy 2006;61: reduce the development of asthma in children with seasonal allergies Novembre E, et al. J Allergy Clin Immunol 2004;114: , (the PATstudy) J Allergy Clin Immunol 2002;109. The effect appears to continue after treatment has stopped Durham et al. N Engl J Med 1999;341:

77 How strong is the evidence that immunotherapy in children prevents the progression of allergy and asthma? Lars Jacobsen and Erkka Valovirta Current Opinion in Allergy and Clinical Immunology 2007, 7: Evidence for long-term prevention The category of evidence for the long-term effect of SIT is Ib for SCIT Since BHR in children with seasonal allergic rhinitis is significantly related to an increased risk for later development of asthma it could be considered to include evaluation of BHR in the indication of immunotherapy. Ib evidence from at least 1 randomised controlled trial

78 Preventative Therapy in Children Odds ratio of developing asthma in those without immunotherapy at 5 years was 2.68 ( ) 80 SIT; Control; 60 % Patients No Asthma Asthma 10 0 SIT Control Moller C et al J Allergy Clin Immunol 2002; 109:

80 Bronchial hyperreactivity in ECHRS patients Leynaert, Bousquet, Neukirch, Am J Respir Crit Care Med Paris + MPL % subjects adults yr 40 - PC20 methacholine 4mg 20 0 controls seasonal perennial seasonal asthma rhinitis rhinitis + perennial rhinitis non-asthmatic without wheeze

81 Frequency of asthma related to allergens Frequency of asthma related to allergens (%) Linneberg et al, Respir Med no rhinitis rhinitis 40 "allergy" assessed by questionnaire pollen animal dander allergy mite

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