Allergic Rhinitis Update Prof. Ralph Mösges Otorhinolaryngologist and Allergologist University Hospital of Cologne

Transcription

1 Allergic Rhinitis Update 2008 Prof. Ralph Mösges Otorhinolaryngologist and Allergologist University Hospital of Cologne

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3 Augustus Claudius Britanicus An atopic family

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6 Allergic Rhinitis Update 2008 Epidemiology Etiology Mechanisms Management

7 C. von Pirquet

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11 Are we trading one epidemic against another one?

12 Asthma prevalence, children and young adults % Year Courtesy SGO Johansson

13 The problem

14 Prevalence of atopic conditions in year olds 1973* / 1988* / 1996** * Burr et al 1989 Arch Dis Child 64: 1452 **Kaur et al 1997 Brit Med J % Asthma Rhinitis Doubling every 8 years

15 Allergy is more present in the medical field

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17 Rhinitis prevalence in the east of Germany 3,5% 3,0% 2,5% 2,0% 1,5% 1,0% 0,5% 0,0% doubling every 3 years

18 The cohort effect allergy decreases with age

19 When does Allergy begin? 25%

20 Allergy is an transmissible disease!

21 Riskfactor spouse/husband

22 The Causes of Allergic Rhinitis

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24 The Causes of allergic rhinitis Genes Hygene Environmental exposure Vaccination studies!

25 The mechanisms

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28 Some mediators of allergy Histamine Serotonin Adenosine Nitric oxide Superoxide Peroxynitrite PGE 2 PGI 2 PGF 2α PGD 2 TxA 2 LTD 4 HPETEs di-hetes Lipoxins PAF ACh SP NKA NPK CGRP VIP Gal NPY Endothelins Bradykinin Kallidin C5a C3a Barnes PJ et al. Pharmacol Rev 1998 IL-1β IL-2 IL-3 IL-4 IL-5 IL-6 IL-7 IL-9 IL-10 IL-11 IL-12 IL-13 IL-15 IL-16 IL-17 IL-18 IL-nn nn TNF-α GM-CSF SCF IFN-γ Oncostatin LIF IL-8 RANTES Eotaxin-1 Eotaxin-2 Eotaxin-3 MIP-1α MCP-1 MCP-2 MCP-3 MCP-4 MDC SDF-1α/β TARC PDGF FGF TGF-β EGF VEGF BMP IGF Tryptase Chymase hne MMP-2 MMP-9

29 The mechanisms Dendritic cells T-reg cells Cytokines Chemokines Mediators

30 The management of AR Diagnosis Prevention Therapy

31 Diagnostics Anamnesis Skin test NPT / CPT Lab Test IgE Basophils

32 Diagnostics Micro-Array-Technology

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34 Prevalence of Allergies is Increasing >80 million people in Europe have some form of allergy 1 Research worldwide shows a steep rise in prevalence of asthma and allergic rhinitis (AR) 2 Allergic rhinoconjunctivitis affects about 20% of the population globally 3 New sensitisations / Onset of allergic diseases also in elder patients 1. EFA Green RJ. Current Allergy & Clinical Immunology 2003; 3. World Allergy Organization.

35 Exposure to Novel Outdoor Allergens is also Increasing Spread of invasive, non-native plant species has increased increase in ragweed and birch pollen allergen in Europe 1, 2, 3 1. Asero R. Allergy Laaidi M. et al. Ann Allergy Asthma Immunol Klimek L. et al. HNO 2006

36 Evolution of Ambrosia pollen concentrations

37 Exposure to Novel Outdoor Allergens - Consequences Previously non-allergic individuals may develop allergies Previously allergic individuals may become polysensitised

38 Allergic Rhinitis is often caused by polysensitisation % patients number of triggers Valovirta E. Curr Opinion Allergy Immunol; in press

39 ARIA Classification Intermittent. 4 days per week. or 4 weeks Mild normal sleep & no impairment of daily activities, sport, leisure & normal work and school & no troublesome symptoms in untreated patients Persistent. > 4 days per week. and > 4 weeks Moderate-severe one or more items. abnormal sleep. impairment of daily activities, sport, leisure. abnormal work

40 Allergic rhinitis complaints ARIA Classification Intermittent Mild 22.9% Persistent Mild 5.35% Intermittent Moderate/severe 40.96% Persistent Moderate/severe 30.79% Bachert C, Belgian Survey 2004

41 What is today s situation?

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46 Take your patient seriously! Among the 295 matched patient-physician records, the physicians rated 4.8% of the patients as having severe allergic rhinitis, while 14.8% of the patients gave themselves such a rating. The physicians gave a rating of mild to 43.5% of patients, while 31.3% of patients self-rated their disease as mild. Moderate ratings were given by 51.7% of physicians and 54.0% of patients. Physicians reported sleep disturbance in 23.4%, compared with such reports by 47.2% of patients.

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56 Today s Allergies Require New Treatment Strategies Pollution Sensitisation Responsiveness Allergenicity Indoor lifestyle / Novel Allergens Perennial exposure Polysensitisation Neuroimmunological factors Sensitisation Manifestation Severe symptoms Persistent symptoms Need for new treatment strategies

57 Therapy

58 Anti-IgE Cromones Leukotrienreceptorantagonists Allergenspecific Immunotherapy Antihistamines Dekongestants Glukocorticosteroids Drugtherapy

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60 Treatment of allergic rhinitis (ARIA) Mild intermittent Moderate severe intermittent Intra-nasal steroid Local cromone 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 ARIA guidelines

61 New ARIA Guideline

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63 Meta-Analysis of placebo-controlled clinical trials 0,1 0-0,1 Fexofenadin Cetirizin Levocetirizin Ebastin Rupatadin Mizolastin Desloratadin Loratadin Effektmaß -0,2-0,3-0,4-0,5-0,6-0,7 Antihistaminikum

64 Mean improvement of nasal sum score 6,00 Monotherapy no comedication comedication 4,00 2,00 p < Mean improvement of nasal sum score 3,00 0,00 0,00 1,00 2,00 3,00 4,00 5,00 6,00 7,00 8,00 9,00 Baselinevalue nasal sum score 2,00 1,00 3,69 n= ,31 n=1820 0,00 no comedication Monotherapy comedication

65 2,00 Spray or steroid 0,00 1,00 Mean improvement of congestion 1,50 1,00 0,50 0,76 0,44 1,45 0,97 2,13 1,79 0,00 n=2686 n=29 n=3405 n=75 n=4381 n=156 n=2592 n=210-0,03-0, Congestion

66 impairment Prophylactic treatment

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69 SIT vs symptomatic drugs Efficacy of symptomatic drugs in rhinitis (improvement vs placebo) 30% 37% 16-20% 5% 7-10% Anti leucotriens Anti H1 Local steroids SCIT SLIT Tablets Source : Wilson study quoted by S. Duhram ( JACI 2006)

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75 Reduktion im Vergleich zu Placebo (%) Symptomscore Medikationsscore Durham et al, SQ-T Dahl et al, SQ-T Mösges et al, 300 IR Didier, 300 IR 1. Dahl R, Kapp A, Colombo G, Monchy J, Rak S, Emminger W, Rivas MF, Ribel M, Durham SR (2006) Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 118: Didier A (2006) Randomised, double-blind, placebo-controlled, multinational, multi-centre, Phase IIb/III study of the efficacy and safety of three doses of sublingual immunotherapy (SLIT) administered as tablets* once daily to patients suffering from grass pollen rhinoconjunctivitis. In: XXV EAACI Congress Vienna 3. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S (2006) Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 117: Mösges et al.: Eigene Auswertung

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77 No serious AE were related to treatment Most frequent related adverse events (AE) Incidence of at least 5 % (safety population) % % of patients Ear pruritus Oedema mouth Oral pruritus Tongue oedema Throat irritation Placebo 100 IR 300 IR 500 IR N=156 N=157 N=155 N=160

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81 Intra-lymphnodal-IT Randomizedcontrolledstudy n=154 3 injections à 1000 SQ as efficient as 3 years with injections of SQ Less side effects

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83 10 points to remember 1. Allergic rhinitis is a major chronic respiratory disease due to its: prevalence impact on quality of life impact on work/school performance and productivity economic burden links with asthma 2. In addition, allergic rhinitis is associated with sinusitis and other comorbidities such as conjunctivitis 3. Allergic rhinitis should be considered as a risk factor for asthma along with other known risk factors 4. A new subdivision of allergic rhinitis has been proposed: Intermittent persistent 5. The severity of allergic rhinitis has been classified as mild or moderate/severe depending on the severity of symptoms and quality of life outcomes

84 10 points to remember 6. Depending on the subdivision and severity of allergic rhinitis, a stepwise therapeutic approach has been proposed 7. The treatment of allergic rhinitis combines: allergen avoidance (when possible) pharmacotherapy immunotherapy Education 8. Patients with persistent allergic rhinitis should be evaluated for asthma by history, chest examination and, if possible and when necessary, the assessment of airflow obstruction before and after bronchodilator 9. Patients with asthma should be appropriately evaluated (history and physical examination) for rhinitis 10. A combined strategy should ideally be used to treat the upper and lower airway diseases in terms of efficacy and safety

85 5 points to remember Think of allergy in sinusitis patients Longertreatment duration Continuous treatment Avoid combinations, they reduce patients compliance Use potent compounds

86 KISS Keep It Simple & Small

87 Allergic Rhinitis Update 2008 Prof. Ralph Mösges Otorhinolaryngologist and Allergologist University Hospital of Cologne

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