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MANAGEMENT OF THE PATIENT WITH RHINITIS AND ASTHMA Giovanni Passalacqua

Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2011 libra. Le ricordiamo che questo materiale è di proprietà dell’autore e fornito come supporto didattico per uso personale. MANAGEMENT OF THE PATIENT WITH RHINITIS AND ASTHMA Giovanni Passalacqua.

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MANAGEMENT OF THE PATIENT WITH RHINITIS AND ASTHMA Giovanni Passalacqua

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  1. Grazie per aver scelto di utilizzare a scopo didattico questo materiale delle Guidelines 2011 libra.Le ricordiamo che questo materiale è di proprietà dell’autore e fornito come supporto didattico per uso personale.

  2. MANAGEMENT OF THE PATIENT WITH RHINITIS AND ASTHMA Giovanni Passalacqua Allergy & Respiratory Diseases Dept.Internal Medicine- University of Genoa ITALY

  3. ALTERNATIVE: VAS X No symptoms Untolerable symptoms ARIA Classification Intermittent . < 4 days/week . or < 4 weeks Persistent . > 4 days/week . AND > 4 weeks • MILD • All the following • No sleep disturbance • No daily activity • limitations • normal work/school Activity • No bothersome symptom • Moderate-severe • One or more: • . No sleep disturbances • daily activity limitations • impaired work or school activity • bothersome symptoms

  4. Diagnostic tools. The problem Differently from asthma, there is no reliable or Standardized objective measurement. No objective evaluation of severity No tool is capable to discriminate allergic and nonallergic rhinitis. No tool is capable to discriminate healthy and rhinitics

  5. PERSPECTIVES: Phenotypes of rhinitis? OCCUPATIONAL IgE PURE SEASONAL (hayfever) POLYPS NARES NA-NI NARESMA VASOMOTOR HORMONAL PERSISTENT LOCAL RESPONSE NON IgE

  6. SLEEPDISORDERS RHINOSINUSITIS polyps OTITIS CONJUNCTIVITIS Rhinitis: comorbidities ASTHMA RHINITIS

  7. Allergic rhinobronchitis: the asthma-allergic rhinitis link. Simons FERJ Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):534-40. Linking upper and lower respiratory airways. Aubier M. J Allergy Clin Immunol 1999; 83: 431-434. United airways disease: therapeutic aspects. Passalacqua G, Ciprandi G, Canonica GWThorax. 2000 Oct;55 Suppl 2:S26-7.

  8. UNITED AIRWAYS EPIDEMIOLOGY Comorbidity rhinitis asthma Natural history Rhinitis as risk factor for asthma

  9. STUDY LOCUS SUBJECTS % ASTHMA rhin. 13.4 no rhin. 3.8 rhin. 22.5 no rhin. 4 rhin. 32 no rhin. 5 rhin. 10.5 no rhin. 3.6 SAR. 23 PAR 26 both 43 Pariente Leynaert Wright Settipane Sibbad France ECRHS Tucson Providence England adults adults children adolesc adults 1367 262 129 162 319 Leynaert et al. JACI 2000 93% of asthmatics have concomitant rhinitis Kapsali T et al, JACI 1998

  10. Prevalence of asthma (physician diagnosed) in rhinitis Bousquet, CEA 2005 35 30 25 20 % pazienti 15 % subjects • 591 patients • 502 controls • allergic to pollens, mite, • epithelia 10 5 0 contr mild severe mild severe persistent intermittent

  11. Shaaban, Lancet 2008

  12. Allergic rhinitis as a predictor for wheezing onset in school-aged children. Rochat et al, JACI 2010 Cohort of 1,314 children followed from birth to 13 yrs

  13. UNITED AIRWAYS IMMUNOLOGY Allergic inflammation Bone marrow response Neuroinflammation PATHOPHYSIOLOGY Naso-broncghial reflex Physical filter Nonspecific hyperresponsiveness

  14. Same inflammation Bronchial biopsioes after Specific provocation in patients with rhinitis or asthma ASTHMA Crimi E et al, JAP 2001 RHINITIS ALONE

  15. Nasal allergen challenge Increases bronchial reactivity Induces bronchial inflammation Littell NT, Changes in airways resistance following nasal provocation. Am Rev Respir Dis 1990 Corren J Changes in bronchial responsiveness following nasal provocation with allergens. JACI 1992 Small P ET AL The effects of allergen-induced nasal provocation on pulmonary function in patients with perennial allergic rhinitis. Am J Rhinol 1989

  16. Induces nasal inflammation Bronchial endoscopic challenge With allergen

  17. The nose-lung interaction in allergic rhinitis and asthma: united airways disease G.Passalacqua, G.Ciprandi & G.W.Canonica 2004 Asthma and rhinitis as different Aspects of a sinlge disorder

  18. Perennial rhinitis: independent factor for developing asthma Leynaert et al, J Allergy Clin Immunol 1999 25 controls 20 rhnitis 15 % pazienti asmatici 10 5 0 atopic non-atopic

  19. Children with allergic and nonallergic rhinitis have a similar risk of asthma. Chawes et al JACI 2010

  20. naso-bronchial reflex nose physical filter function allergen adhesion molecules INFLAMMATION viral infection cytokines bone marrow bronchial hyperreactivity bronchi

  21. PATIENTS WITH PERSISTENT RHINITIS MUST BE ASSESSED FOR THE POSSIBILITY OF ASTHMA HISTORY/EXAMINATION Do you have recurrent wheezing? Do you have dry cough? Do you experience cough after exercise? Do you have chest tightness? IF POSITIVE Spirometry normal obstruction Assess reversibility Nonspecific Bronchial provocation

  22. UNITED AIRWAYS THERAPY Immunotherapy Nasal steroids Antihistamines Combination therapy

  23. TREATMENT OF ALLERGIC RHINITIS ARIA -Allergic Rhinitis and its Impact on Asthma Moderate- severe persistent Moderate- severe intermittent Mild persistent mild intermittent Antileukotrienes(if asthma) Nasal steroid Cromones 2nd Generation antihistamine Decongestant (<10 days) Allergen avoidance Immunotherapy

  24. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. Journal of Allergy and Clinical Immunology 2010; 126: 466-476 69 CLINICAL QUESTIONS ON THE TREATMENT RECOMMENDATION: CONDITIONAL/STRONG LEVEL OF EVIDENCE: HIGH/MODERATE/LOW/VERY LOW

  25. high Weak: 84% Strenght of recommendation moderate Very low low Grade of evidence

  26. BASIC QUESTIONS: Does the treatment of rhinitis affect comorbid asthma? Any effect on the natural history?

  27. Cruz, Allergy 2008

  28. asthma Asthma + rhinitis Untreated rhinitis increases the risk of asthma attacks. Bousquet, Clin Exp Allergy 2005

  29. Mean % reduction of AM instantaneous asthma score Safety and efficacy of desloratadine 5 mg in asthma patients with seasonal allergic rhinitis and nasal congestion. Berger et al. Ann Allergy Asthma Immunol 2002 14 8 2 Mean % reduction of AM/PM asthma score 30 * * 15 5 WKS 1-2 WKS 1-4

  30. Taramarcaz, Cochrane 2008

  31. Effects of mometasone furoate on the Quality of Life: a randomised placebo controlled trial in persistent allergic rhinitis and intermittent asthma using the Rhinasthma questionnaire Ilaria Baiardini1, Elisa Villa1, Anthi Rogkakou1, Sara Pellegrini1, Micaela Bacic1, Enrico Compalati1, Fulvio Braido1, Cristina Le Grazie2, Giorgio Walter Canonica1, Giovanni Passalacqua1 Clin Exp Allergy 2011

  32. MFNS N= 26 52 Placebo N= 26 Run in 1 sett V1 V2 V3

  33. Primary outcome: Global Summary (GS) of Rhinasthma, Changes at 2 and 4 weeks versus baseline • Secondary outcomes: • Changes vs baseline in the 3 domains of Rhinasthma • Upper airways (UA) • Lower airways (LA) • Respiratory Allergy Impact (RAI) • Nasal symptom score • Nasal + asthma scores

  34. Enrolled n = 57 Screening failures n = 5 Entry criteria not satisfied, n = 1 Refused to continue for reason unrelated to study drug, n=2; Privacy Form not signed, n = 2 Randomized n = 52 Mometasone n = 26 Placebo n = 26 Discontinuations n = 4 Adverse event, n = 1 Consent withdrawn, n = 2 Treatment failure, n = 1 Discontinuations n = 1 Consent withdrawn Completed n = 25 Completed n = 22

  35. Primary endpoint: Rhinasthma Global Score ITT Population Mean changes from baseline (V2) to endpoint (V4) MFNS Placebo p<0.001 2 0,4 0 - 2 - 4 Mean change vs baseline - 6 - 8 - 10 10,3 - - 12

  36. Rhinasthma global summary MFNS Placebo <.001 <.001 30 25 20 15 Rhinasthma GS mean 10 5 baseline week 2 week 4

  37. MFNS 40 <.001 <.001 Placebo 35 30 <.001 <.001 25 20 15 10 5 baseline week 2 week 4 baseline week 2 week 4 baseline week 2 week 4 LAS RAI UAS

  38. Global Symptom Score (GSS) Weekly score 12 10 8 Mean score * * 6 GSS Placebo 4 GSS MFNS 2 0 basale 1 2 3 4

  39. Conclusions • Treating persistent rhinitis with mometasone furoate nasal spray resulted in a significant improvement in QoL for both upper and lower respiratory tract domains • There was a significant improvement of the global symptom scores (rhinitis + asthma) • No significant change in rhinitis symptoms when analyzed separately (trial powered on the basis of the primary outcome) • Good safety profile

  40. SPECIFIC IMMUNOTHERAPY IN ASTHMA AND RHINITIS

  41. Meta-analysis of the efficacy of sublingual immunotherapy in allergic asthma in pediatric patients, 3 to 18 years of age. M Penagos, G Passalacqua, E Compalati, C Baena-Cagnani, S Orozco, A Pedroza GW Canonica SYMPTOMS MEDICATIONS

  42. MEDICATIONS SYMPTOM DETERIORATION ASTHMA SYMPTOMS Abramson, Puy, Weiner Cochrane 2010

  43. Effect of specific immunotherapy added to pharmacologic treatment and allergen avoidance in asthmatic patients allergic to house dust mite Maestrelli et al, JACI 2004

  44. Effect of SLIT to Parietaria on seasonal BHR in children NS 0.001 NS Pajno GB & Passalacqua G, Allergy 2004 0.008 0.005 0.005 10 SLIT PLACEBO PC20 mgmL 5 WINTER 99 SPRING 99 SPRING 01 WINTER 99 SPRING 99 SPRING 01

  45. CONCLUSIONS Based on the literature, SIT is effective in allergic asthma associated with rhinitis, and should be used in association with standard medications SIT reduces bronchial hyperresponsiveness, that is an indirect marker of bronchial inflammation.

  46. RISK FACTORS Based on nonfatal reactions Uncontrolled asthma Severe asthma Use of betablockers Rush immunotherapy Use of new vials Technical errors Based on fatal reactions Uncontrolled asthma Severe asthma Use of betablockers Rush immunotherapy Build-up phase Use of new vials Technical errors Estimated incidence of fatalities < 1/2.000.000 injections

  47. BHR/ ASTHMA RHINITIS POLY- SENSITIZATION MONO- SENSITIZATION

  48. Allergic rhinitis as a predictor for wheezing onset in school-aged children. Rochat et al, JACI 2010 Cohort of 1,314 children followed from birth to 13 yrs

  49. MARTINEZ,PEDERSEN Long-Term Inhaled Corticosteroids in Preschool Children at High Risk for Asthma Guilbert T, NEJM 2006

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