Allergic Rhinitis

1. Allergic Rhinitis Henry J. Kanarek, MD Adult/Pediatric Allergy & Asthma Overland Park, Kansas www.kallergy.com Speakers Bureaus Alcon Laboratories, Glaxo Smith Kline, Schering Plough, Aventis Sanofi, Inspire Pharmaceuticals, Ivax Pharmaceuticals, Astra Zeneca

2. Definition and Prevalence of Allergic Rhinitis Rhinitis • Group of nasal disorders characterized by 1 or more symptoms1 • Sneezing – Nasal itching • Rhinorrhea – Nasal congestion • Allergic rhinitis • Most common type of chronic rhinitis (inflammation of the nasal mucous membranes) • Affects up to 40 million Americans2 • Remains constant in young adults but gradually declines in later years3 1. Dykewicz MS. J Allergy Clin Immunol. 2003;111(2 Suppl):S520–S529. 2. Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81(5 Pt 2):478–518. 3. Fireman P. In: Atlas of Allergies. Philadelphia, PA: JB Lippincott Co; 1991:9.2–9.18.

3. Allergic Rhinitis is Principally Seasonal • Tree pollen: March 1 – June 30 • Grass pollen: April 15 – August 15 • Weed pollen: August 15- Oct 30 • Ragweed

4. Perennial Allergens • Molds • Dust mite • Cockroach • Cat • Dog

5. Early-Phase Reaction Mast Cell Response Late-Phase Reaction Cellular Infiltration/Inflammation Eosinophil • Histamine • Proteases CysLTs, GM-CSF, TNF-, IL-1, IL-3, PAF, ECP, MBP Degranulation Allergen Basophil Chemotactic Factors (CysLTs, PAF, IL-5) Histamine, CysLTs,TNF-, IL-4 to 6 Mast Cell • CysLTs • Prostaglandins • PAF • Bradykinin • Interleukins • TNF- • GM-CSF Neosynthesis Monocyte CysLTs, TNF-, PAF, IL-1 Lymphocyte IL-4, IL-13, IL-5, IL-3, GM-CSF Natural History of Allergic Rhinitis

6. Human Mast Cells • Type I hypersensitivity response • IgE-mediated degranulation • Release of histamine, leukotrienes, cytokines

7. The Allergic Response

9. Early Phase

10. Histamine Is a Potent Mediator of the Allergic Response Histamine • Nasal responses • Itchiness • Sneezing • Rhinorrhea • Nasal congestion • Other responses • Itchy, watery, or red eyes • Itchy palate or throat • Skin responses • Pruritus • Erythema • Edema Allergic Rhinitis Urticaria Source:American Academy of Allergy, Asthma, and Immunology. The Allergy Report. Vols 2 and 3.

11. Effect of Antihistamines on Allergic Rhinitis Antihistamines Inhibit nasal responses Inhibit other responses • Itching • Itchy/watery/red eyes • Sneezing • Runny nose • Itchy palate/throat Sources: Dykewicz MS et al. Ann Allergy Asthma Immunol. 1998; Howarth PH. In: Simons FER, ed. Histamine and H1-Antihistamines in Allergic Disease. 2nd ed. 2002.

12. Histamine Tryptase Chymase Heparin NCF Prostaglandins Thromboxanes Leukotrienes Histamine - Very Important, But Not the Whole Story Pre-formed in Granules Newly formed whenMast Cell is stimulated

13. Late Phase

14. Nasal Congestion Runny Nose 40% Itchy Eyes 28% Sneezing 26% Itchy Palate 21% Watery Eyes 22% Itchy Ears 20% Itchy Nose 18% 13% Severity of Nasal Symptoms in Sufferers With Allergic Rhinitis* % reporting symptoms as severe† Based on a nationwide survey of 2002 self-reported adult allergic rhinitis sufferers with nasal congestion or parents of a child with allergic rhinitis with nasal congestion. Data on file, Schering Corporation. *Among those who experience symptoms †9, 10 is most severe based on a 10 point scale Data on file, Schering Corporation, Kenilworth, NJ.

15. SAR Symptoms occur or increase at certain seasons and correlate with presence of seasonal allergens Watery rhinorrhea – Pruritus of eyes, nose, Nasal congestion ears, throat Repetitive sneezing – Watery eyes Patients may not present with all symptoms Clinical Features That Distinguish Seasonal and Perennial Allergic Rhinitis (SAR and PAR) The Allergy Report, 2000, Vol. 2

16. PAR Symptoms are intermittent or continuous throughout year Prominent and severe nasal blockage/congestion Postnasal discharge Clear rhinorrhea, sneezing less prominent than in SAR Pruritus of eyes and throat less frequent than in SAR Perennial symptoms may also be accompanied by seasonal exacerbations Clinical Features That Distinguish Seasonal and Perennial Allergic Rhinitis (SAR and PAR) The Allergy Report, 2000, Vol. 2 Skoner D. J Allergy Clin Immunol. 2001;108:S2-S8.

25. ARIA Guidelines Antihistamines as a Recommended Treatment for the Management of Allergic Rhinitis MODERATE/ SEVERE PERSISTENT MILD PERSISTENT MODERATE/ SEVERE INTERMITTENT MILD INTERMITTENT Allergen and irritant avoidance Intranasal decongestant (<5 days) or oral decongestant Intranasal or oral nonsedating antihistamine Intranasal steroid Immunotherapy Adapted from Bousquet J et al. Allergy. 2008;63(Suppl 86):8-160.

26. WHAT TO DO: • Diagnose and treat correctly • Learn the formularies • Recommend the correct over the counter meds • Learn the costs of the over the counter meds • Educate your patient to maximize med. benefit

27. WHAT NOT TO DO: • Order a RAST (BLOOD TEST) • Prescribe expensive meds • Recommend expensive O.T.C. • mucinex • Prescribe Singulair

28. DIAGNOSE PROPERLY • HISTORY • SKIN TEST

29. TREATMENT using OTC • Loratadine • Ceterizine • Sudafed • Phenylephrine • Ketotifen

30. Immunotherapy (allergy shots) • Injections consist of what you are allergic to • Weekly for 6 months, then every other week, and continue to spread frequency • Injections are received for 5 years • Improvement can be seen in 3 months • After 5 years 90% adults are allergy free for life • Can reduce the affects of allergy on asthma • Will improve most aspects of allergy, eyes, fatigue, and in some cases eczema. Medications will rarely be needed • Need to be given in a doctors office due to systemic reactions

31. Decongestants • Pseudoephedrine: -agonist  vasoconstriction • No effect on itching, sneezing, or nasal secretion • Adverse reactions • Insomnia • Loss of appetite • Nervousness/jitteriness • Urinary retention in benign prostatic hyperplasia • Potential for rebound congestion with topicals ALLEGRA-D® [package insert]. Kansas City, MO: Aventis Pharmaceuticals Inc. Corey JP, et al. Ear Nose Throat J. 2000;79:690–693, 696, 698 passim. Dykewicz M. J Allergy Clin Immunol. 2003;111:S520–S529. ZYRTEC-D 12-HOUR® [package insert]. New York, NY: Pfizer Inc.

32. Methods for Evaluating Sedation • Subjective • Drowsiness • Somnolence • Loss of alertness • Decreased concentration • Objective (Impairment) • Attention • Memory • Coordination • Psychomotor performance Sources: Hindmarch I et al. Clin Exp Allergy. 1999; Passalacqua G et al. Allergol Immunopathol (Madr). 1993.

33. Fexofenadine HCl Does Not Displace 11C-Doxepin on PET Images • At baseline, PET images show radiolabeled doxepin bound to CNS H1-receptors • If antihistamine crosses the blood-brain barrier, the 11C-doxepin is displaced from the H1 receptors, and the color intensity on the PET image is attenuated • Baseline With Radiolabeled 11C-Doxepin (Binds to H1-Receptors) PET images shown are from a single patient, and follow-up images with fexofenadine or diphenhydramine were taken at 90 minutes after drug administration (at peak plasma levels) • After Fexofenadine 360 mg • 11C-Doxepin Not Displaced • After Diphenhydramine 50 mg • 11C-Doxepin Displaced Sources: Data on file, Aventis Pharmaceuticals; Dogan AS et al. J Nucl Med. 2001.

34. States With DUI Laws Concerning Any Drugs • In 32 states and the District of Columbia, it is illegal to drive while impaired by medications* *Definition of impairment varies by state—laws are written broadly and cover medications that are not specifically identified. Sources: National Highway Traffic Safety Administration. Digest of State Alcohol-Highway Safety Related Legislation.2002.

35. Use of Fexofenadine HCl Authorized for Pilots and Air Traffic Controllers • The US Air Force and US Navy have authorized the use of fexofenadine HCl by pilots and naval aviators, with the appropriate waiver • The FAA has, under special conditions, medically qualified pilots and air traffic controllers who use fexofenadine HCl Source: Data on file, Aventis Pharmaceuticals.

36. Assessing Self-Awareness of Impairment • Patients who are impaired by older antihistamines may not even know it, increasing the risk of an accident • Subjective ratings of impairment are often unreliable, because sedation by its own nature can influence self-evaluation of awareness Sources: Hindmarch I et al. Br J Clin Pharmacol. 1999; Mansfield L et al. Ann Allergy Asthma Immunol. 2003.