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Are rhinitis and asthma two manifestations of one disease? Stephen R. Durham

Are rhinitis and asthma two manifestations of one disease? Stephen R. Durham Allergy and Clinical Immunology Royal Brompton Hospital and Imperial College London. WAO Cancun Dec 7 th 2011. Relationship between rhinitis and asthma – implications for treatment.

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Are rhinitis and asthma two manifestations of one disease? Stephen R. Durham

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  1. Are rhinitis and asthma two manifestations of one disease? Stephen R. Durham Allergy and Clinical Immunology Royal Brompton Hospital and Imperial College London WAO Cancun Dec 7th 2011

  2. Relationship between rhinitis and asthma – implications for treatment Is there a relationship between rhinitis and asthma ? Is the relationship causal ? Does treating rhinitis improve asthma?

  3. Jarvis D et al Allergy 2011 Nov 4. [Epub ahead of print]Asthma in adults and its association with chronic rhinosinusitis: The GA(2)LEN survey in Europe. 52,000 adults (18 -75 yr) 19 centres,12 countries. Strong association of asthma with CRS (adjusted OR: 3.47; 95% CI: 3.20-3.76). Association stronger in those with CRS and allergic rhinitis (adjusted OR: 11.85; 95% CI: 10.57-13.17).

  4. Allergic rhinitis is a risk factor for asthma Allergic rhinitis increased the risk of asthma ~3-fold 12 10 8 6 4 2 0 p<0.002 10.5 % of patients who developed asthma 3.6 No allergic rhinitisat baseline(n=528) Allergic rhinitisat baseline(n=162) 23-year follow-up of college freshmen undergoing allergy testing; data based on 738 individuals (69% male) with average age of 40 years. Settipane RJ et al Allergy Proc 1994;15:21-25.

  5. The nose is that part of the lung which is accessible to the finger

  6. Rhinitis / Asthma : Similarities • Frequently coexist • Respiratory pseudostratified epithelium • IgE-dependent mechanisms • Th2 T lymphocyte activation • Eosinophil rcruitment • Mast cell / basophil activation and transepithelial migration

  7. Epithelium intact Basement membrane normal No airway smooth muscle Venous sinusoids Submucosal glands prominent Remodelling absent Antihistamines effective 2-agonists ineffective Epithelium disrupted Basement membrane abnormal Bronchial smooth muscle No venous sinusoids Submucosal glands few Remodelling present Antihistamines ineffective (?) 2-agonists effective Rhinitis / Asthma: Differences Rhinitis Asthma

  8. Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways. Braunstahl G-J, Overbeek SE, KleinJan A, Prins J-B, Hoogsteden HC, Fokkens WJ. J Allergy Clin Immunol 2001;107:469-76.

  9. Study design

  10. Nasal Ag provocation Nasal Ag provocation Ag

  11. Nasal mucosa Bronchial mucosa ICAM-1 VCAM-1 ICAM-1 VCAM-1 T 0h T 24h

  12. 0 0 0 0 0 0 24 24 24 24 24 24 Allergic Rhinitis ELAM-1/CD31 ICAM-1/CD31 VCAM-1/CD31 Influence of nasal challenge on expression of adhesion molecules on blood vessels in the nasal ( ) and bronchial ( ) mucosa 100 100 100 * 80 80 80 Nose * * Bronchus 60 60 60 * * Percent positive * * p<0.05 40 40 40 20 20 20 0 0 0 Controls (n=9) ELAM-1/CD31 ICAM-1/CD31 VCAM-1/CD31 100 100 100 80 80 80 Nose Bronchus 60 60 60 Percent positive 40 40 40 20 20 20 0 0 0

  13. moderate severe persistent mild persistent moderate severe intermittent mild intermittent Intra-nasal steroid (+/- antileukotriene) Oral or topical antihistamine Allergen and irritant avoidance Immunotherapy Treatment of allergic rhinitis http://www.whiar.org/

  14. Does treating hayfever help patients with asthma? • Antihistamines • Leukotriene antagonists • Nasal corticosteroids • Allergen immunotherapy

  15. High-dose H1 receptor antagonist treatment in persistent asthma Simons FER. Clin Exp Allergy 1999; 29: S98–104

  16. Effect of cetirizine in patients with seasonal rhinitis and concomitant asthma 10 8 Mean total rhinitis score 6 4 2 0 Study week 8 6 Mean total asthma score 4 2 0 1 1 2 2 3 3 4 4 5 5 6 6 Study week placebo cetirizine Grant et al. J Allergy Clin Immmunol 1995; 97: 923–732

  17. Does treating hayfever help patients with asthma? • Antihistamines • Leukotriene antagonists • Nasal corticosteroids • Allergen immunotherapy

  18. Philip G. Curr Med Res Opin. 2004 Oct;20(10):1549-58.

  19. Montelukast: Effect on hayfever in patients with asthma (n=631) * p < 0.001 compared with placebo Philip G. Curr Med Res Opin. 2004 Oct;20(10):1549-58.

  20. Montelukast: Effect on hayfever in patients with asthma (n=631) Philip G. Curr Med Res Opin. 2004 Oct;20(10):1549-58.

  21. Does treating hayfever help patients with asthma? • Antihistamines • Leukotriene antagonists • Nasal corticosteroids • Allergen immunotherapy

  22. Welsh PW, Stricker WE, Chu CP, Naessens JM, Reese ME, Reed CE and Marcoux. Efficacy of beclomethasone nasal solution flunisolide, and cromolyn in relieving symptoms of ragweed allergy. Mayo Clin Proc.1987;62:125-34. All three treatments superior to placebo (p< 0.001). Glucocorticoids more effective than cromolyn (p<0.001). All 3 intranasal treatments ALSO reduced seasonal asthma. Study randomised but NOT blinded:

  23. Nasalide Beconase aqueous Nasalcrom Placebo 100 80 60 40 20 0 Treatment Mean weekly hay fever raw score 7.11 7.24 8.7 8.21 9.4 1984 7.17 7.31 8.14 8.28 9.11 9.18 Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed rhinitis Welsh PW. Mayo Clinic Proceedings 1987; 62: 125-34.

  24. Nasalide Beconase aqueous Nasalcrom Placebo Treatment 15 10 5 0 -5 Asthma score mean weekly difference from baseline Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed asthma Welsh PW. Mayo Clinic Proceedings 1987; 62: 125-34.

  25. Dahl R. Allergy 2005: 60: 875–881 • DBPC double-dummy study in seasonal rhinitis and asthma • no effect of intranasal steroids on asthma outcomes • no effect of inhaled steroids on nasal outcomes • but ? too mild disease to show an effect

  26. Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma Geometric mean PD20 methacholine measured at baseline () and after 4 weeks treatment () (*** p < 0.001 IHFP ± INFP vs INFP or placebo). INFP, fluticasone proprionate nasal spray; IHFP, inhaled fluticasone propionate. Dahl R. Allergy 2005: 60: 875–881

  27. Does treating hayfever help patients with asthma? • Antihistamines • Leukotriene antagonists • Nasal corticosteroids • Allergen immunotherapy

  28. Grass Birch Mites Cat Allergens of Proven Efficacy in Double-Blind Placebo-Controlled Studies

  29. Walker SM. J Allergy Clin Immunol 2001; 107: 87-93

  30. Subcutaneous immunotherapy for hayfever:effect on symptoms and rescue medication Symptoms Medication 0 Immunotherapy group -50 Placebo group P = .01 P = .007 -100 % reduction from baseline (1998/1996) 50% decrease in nasal Symptoms 85% decrease in asthma symptoms Walker SM et al JACI 2001; 107: 87-93

  31. P = .04 P = .01 P = ns >16.0 16.0 8.0 4.0 2.0 1.0 Methacholine PC20,mg/mL Placebo Immunotherapy Winter Summer Summer 1996 1996 1998 Winter Summer Summer 1996 1996 1998 Effect of immunotherapy on airway responsiveness to methacholine Walker SM. J Allergy Clin Immunol 2001; 107: 87-93

  32. Does treating hayfever help patients with asthma? • Antihistamines • Leukotriene antagonists • Nasal corticosteroids • Allergen immunotherapy

  33. Adams RJ et al. J Allergy Clin Immunol 2002; 109: 636-42.

  34. Retrospective study of 13,844 asthmatics 1031 had emergency dept visit (7.4%) Relative risk-INS 1/yr = 0.7, >3/yr = 0.5 RR anti-histamine = 0.9 Effect of rhinitis treatment on asthmaexacerbations Adams RJ et al. J Allergy Clin Immunol 2002; 109: 636-42.

  35. Corren J. J Allergy Clin Immunol 2004; 113: 415-9.

  36. Rhinitis therapy and the prevention of hospital care for asthma: A case-control study Adjusted odds ratios for asthma-related hospital care in relation to intranasal corticosteroid and second generation antihistamine use during 1-year period before the index date Corren J. J Allergy Clin Immunol 2004; 113: 415-9.

  37. Is there a relationship between rhinitis and asthma ? Yes Is the relationship causal ? Yes Does treating rhinitis Maybe improve asthma? Relationship between rhinitis and asthma – implications for treatment

  38. Patients with rhinitis should be evaluated for asthma Patients with asthma should be evaluated for rhinitis A strategy should combine the treatment of upper and lower airways in terms of efficacy and safety Recommendations

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