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Common Allergy Update 2001 Asst. Prof. Kiat Ruxrungtham, M.D. Division of Allergy and Clinical Immunology Department of Medicine Faculty of Medicine Chulalongkorn.

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Presentation on theme: "Common Allergy Update 2001 Asst. Prof. Kiat Ruxrungtham, M.D. Division of Allergy and Clinical Immunology Department of Medicine Faculty of Medicine Chulalongkorn."— Presentation transcript:

1 Common Allergy Update 2001 Asst. Prof. Kiat Ruxrungtham, M.D. Division of Allergy and Clinical Immunology Department of Medicine Faculty of Medicine Chulalongkorn University

2 โรคภูมิแพ้ที่พบบ่อย โรคภูมิแพ้ทางจมูก Allergic Rhinitis
โรคหืดจากภูมิแพ้ Allergic Asthma โรคภูมิแพ้ทางผิวหนัง Atopic Dermatitis โรคลมพิษ Urticaria โรคแพ้อาหาร Food Allergy การแพ้ยา Drug Allergy Allergy Chula 1999

3 Epidemiology of Allergic Diseases in Thai Children
พยนต์ บุญญฤทธิพงษ์ และมนตรี ตู้จินดา 2533; ปกิต วิชยานนท์ และคณะ 2541

4 Mediators of Mast Cells and Basophils
Secondary Mediators Primary Mediators Prostaglandins Leukotrienes PAF Histamine RFs IL-3, 4, 5, 6, 7, 8 GM-CSF, TNFa Chemokines -MCP1, MIP1 Oxygen radicals Histamine Tryptase Chymotryptase Heparin/Chondroitin Kininogenase Chemotactic Factors AllergyChula Sim TC, Grant JA 1996

5 Mediators of Mast Cells and Allergy
Blood Vessels Urticaria, Angioedema Laryngeal edema, Shock H, PGD2, LTs, PAF bradykinin Bronchospasm Abd. pain, Vomiting Smooth Muscles H, PGD2, LTs, PAF Diarrhea, Rhinorhea Bronchial secretion Mucus Glands H Mast Cell Basophil Sensory Nerves Itching LTB4 PAF IL3, IL5 Chemokines Leukocytes Inflammation - LPAR AllergyChula

6 Pathogenesis of Allergic Disease
Genetic Susceptibility Adjuvant factors: Tobacco smoke Air pollutants Lack of protective factors: Infection ? Immunization ? Nutrition ? Allergic Sensitzation Allergen Exposure Upper/lower airway or Skin hyperresponsiveness Pollutants Infection Excercise Allergic Diseases Vary in spectrum and severity Modified from Ulrich Wahn 1998

7 Principle Pathogenesis of Allergic Diseases
Durham and Till 1998, Lu 1998, Drazen 1996 Allergen APC CD4+ T-cell IL-12 Allergen Th-1 Th-2 IL-4 IgE IFN-g IL-5 IL-3 GM-CSF B-cell B-cell CD8+ cell IgG Mast cell IL-5 Other cells _ + Eosonophil MBP ECP, LTs Late Phase Reaction Tryptase, LTs AllergyChula

8 The Respiratory Tract Upper Respiratory Tract Lower Respiratory Tract
Structures - Nose —> trachea - Sinuses, eustachian tubes - Ciliated mucosal lining Functions - Conditioning the air - Defense Filtration Inflammatory reaction Immune reaction - Smell - Voice Lower Respiratory Tract Structures - Trachea —> alveoli Functions - Inhalation-exhalation - Gas exchange - Acid-base balance

9 Co-existence of Asthma and AR
23-Years Follow-up Study of Former Brown University Students (N=738) 21 % Asthma no 79 % no 86 % AR 306 former students with Allergic Rhinitis 84 former students with Asthma Greisner WA et al Allergy Asthma Proc 1998; 19:185-8

10 Ragweed Hay Fever with Seasonal Asthma Upper-Lower Airway Linked
Placebo Welsh et al. Mayo Clin Proc 1987;62:125-34

11 Watson WTA et al J Allergy Clin Immunol 1993; 91:97-101
AR in Patients with Mild Asthma Treatment with intranasal corticosteroids : Effect on lower airway responsiveness P =0.04 Watson WTA et al J Allergy Clin Immunol 1993; 91:97-101 AllergyChula

12 Mean Changes in FEV1 (Litre) in Treated AR with Mild Asthma
Morning (AM) * P=0.01 *<0.05 * * * * Corren J, et al J Allergy Clin Immuno 1997; 100:

13 Ideal Antihistamines Safety Pharmacology Specific H1 receptor blockade
Additional potent anti-allergic/anti-inflammatory effects Rapid onset of action Long-acting No-tachyphylaxis No drug interaction No dose-adjustment required in special-risk groups Safety No CNS toxicity No cardiotoxicity Simons FE EAACI 1998 AllergyChula

14 PK and PD : Second-Third generation Antihistamines
Inhibition of Histamine-wheal/flare Drug Metabolism T1/2 (h)* Onset Peak Duration Terfenadine Liver h h h Astemizole Liver days day d weeks Loratadine Liver >1 h h h Cetirizine no (Kidney) h h h Fexofenadine minimal h h h Kaliner M. Clin Geriatrics 1997; Simons FE, NEJM 1994 AllergyChula

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17 H1-Antagonists and Drug Interaction
First-generation H1-Antagonists Potentiation of Sedation : Alcohol, sedative agents, hypnotics, antidepressants Potentiation of anticholinergic effect: Antidepressants Second-generation H1-Antagonists (Terfenadine, astemizole, ebastine-animal model , but not loratadine) Decrease hepatic metabolism and increase risk of cardiotoxicity: Drugs that inhibit cytochrome p450 : Ketoconazole, macrolides-erythromycin, other azoles- itraconazole Drugs that prolong QT : quinidine Third-generation H1-Antagonists (Cetirizine, Fexofenadine) No clinical significant in drug interaction AllergyChula

18 Antihistamines in Elderly
Drawsiness, fatigue and may increase risk falling or accident The first-generation H1 antagonist should be avoided in patient with glaucoma The first-generation H1 antagonist should also be avoided in patient with prostrate hypertrophy Be aware of cardiotoxic risk; terfenadine, astemizole should be used with caution AllergyChula

19 Treatment of Allergic Rhinitis in Adults
Allergy Immunol Clinic 2000

20 เยื่อจมูกบวมใน โรคภูมิแพ้ทางจมูก
Allergy Chula 1999

21 Characteristics of Antihistamines
Characteristics First Second/Third Generation H1 Antagonist Anticholinergic (Cetirizine -dry mouth) Sedation / (Cetirizine +/-) Duration of Action / /+++ (Astemizole-longest) Antiallergic / /++ (Azelastine) Antiinflammatory /+ (Clinical ?) (Citirizine, Loratadine Fexofenadine) AllergyChula

22 Adverse Effects of H1-Antagonists
Adverse Effects CPM HZ TF ASZ LD CZ FX Sedation /+ - Appetite stim / / /+ - Weight gain / / /+ - Dry mouth /+ - Prolong QTc / ? / ? * * Torsade de Points * * AllergyChula

23 Overall driving performance Fexofenadine = placebo Alcohol >placebo
Weiler JM et al. Ann Intern Med 2000 Mar 7;132(5):354-63 Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: in the Iowa driving simulator Overall driving performance Fexofenadine = placebo Alcohol >placebo Diphenhydramine > alcohol Drowsiness ratings were not a good predictor of impairment suggesting: drivers cannot use drowsiness to indicate when they should not drive. AllergyChula

24 N= a total of 43 363 patients: Drowsiness The Odd Ratio P value
Mann RD, et al. BMJ 2000 Apr 29;320(7243): Sedation with "non-sedating” antihistamines: four prescription-event monitoring studies in general practice N= a total of patients: Drowsiness The Odd Ratio P value (versus Loratadine) Fexofenadine 0.63 ( ) 0.1 Acrivastine ( ) <0.0001 Cetirizine ( ) <0.0001 No increased risk of accident or injury was evident with any of the four drugs.

25 Antihistamines in Elderly
Drawsiness, fatigue and may increase risk falling or accident The first-generation H1 antagonist should be avoided in patient with glaucoma The first-generation H1 antagonist should also be avoided in patient with prostrate hypertrophy Be aware of cardiotoxic risk; terfenadine, astemizole should be used with caution AllergyChula

26 Anti-H1 and Anti-inflammation
Antihistamine Evidence-based In Vitro In Vivo (DPCT) (positive results/total) Loratadine yes 1/3 Cetirizine yes 3/5 Terfenadine yes 1/1 Fexofenadine yes nd AllergyChula

27 GINA guidelines 1998 Focus on ICS and ß2-agonists
Severe persistent Moderate persistent Mild persistent Intermittent Short-acting ß2 prn Inhaled corticosteroids Long-acting ß2 J Bousquet Berlin 1999

28 Theophylline: Plasma concentrations
Clinical Efficacy in Chronic Asthma as a monotherapy : 10-20 mg/ml Anti-inflammatory, Immunomodulatory : >5-10 mg/ml Food and Drug Interaction Increase clearance: anticonvalsants (phenobarbital, phynytoin,carbamazepine), rifampicin Decrease clearnace: alcohol, antibiotics (erythromycin, clarithromycin, ciprofloxacin), cimetidine AllergyChula

29 Theophylline as an Add On Regimen (1)
Evans DJ, et al N Engl J Med 1997; 13:1412-8 *Median serum Theophylline =8.7 mg/ml NS N=31 per group Budesonide: Low dose =400, High dose=800 BID** (**Decreased cortisol level) Theophylline: Low dose =250 mg BID (BW<80 kg) or =375 mg BID (BW>80)

30 Theophylline as an Add On Regimen (2)
Ukena et al Eur Respir J 1997; 10: P<0.01 P=ns P<0.01 N= 69 N= 64

31 Pathogenesis of Allergy and Asthma and Potential Novel Therapy
B Cells IL-4 T-Helper Cells Th2 Anti--IL-4 Ab IFNg (Th1) IFNg (Th1 switch) IgE Leukotrienes PGD2 Histamine IL-5 Anti--IL-5 Ab Eosinophil Recruitment and Production Anti--leukotrienes Zileuton Zafirlukast Montelukast Mast cell Eosinophil Bronchoconstriction and Mucus Secretion Chemotaxis Tryptase PAF Inflammation Eotaxin RANTES MCP4 Airway Hyperreactivity Tryptase inhibitor Anti-PAF

32 Future Options Phosphodiesterase 4 (PDE-4) inhibitors
Theophylline is a non-selective PDE-4 inhibitor Selective inhibitors: CDP840, KF 19514, CP80, 633 Increase intracellular c-AMP Decreased eosinophil survival (IL-5 induced) Decreeased IL-4, IL-13 production Momose T 1998, Faissier L 1996, Shichijo M 1997

33 สิ่งเหล่านี้มีอยู่รอบตัวเรา มีทั้งในบ้านและนอกบ้าน
สิ่งแวดล้อม กับ โรคภูมิแพ้ ฝุ่นบ้าน ฝุ่นบี่นอน สัตว์เลี้ยง เชื้อรา เกสร ตัวไร่ฝุ่น ที่กักฝุ่น อาหาร สิ่งเหล่านี้มีอยู่รอบตัวเรา มีทั้งในบ้านและนอกบ้าน แต่มีหลายอย่างที่เราหลีกเลี่ยงได้ หากเรารู้วิธีที่ถูกต้อง

34 การจัดห้องนอนให้ปลอดไรฝุ่น
เฟอร์นิเจอร์ มีเฟอร์นิเจอร์เท่าที่จำเป็น ควรใช้วัสดุที่ทำความสะอาดง่าย เช่น ไม้ บุหนังแท้หรือเทียม ไม่ควรบุผ้า พื้นห้อง ไม่ควรปูพรม ม่าน ไม่ควรใช้ผ้าม่านเพราะกักฝุ่น ควรใช้มู่ลี่แทน เพราะทำความสะอาดง่าย หมอน ควรใช้ใยสังเคราะห์ และหุ้มด้วยผ้าไวนิลหรือ ผ้าใยสังเคราะห์พิเศษ และไม่ใช้นุ่น หรือขนนก ตากแดดทุก 1-2 สัปดาห์ ที่นอน ควรหุ้มด้วยผ้าสังเคราะห์ที่ป้องกันไรฝุ่นได้ ตากแดด ทุก 1-2 สัปดาห์ ผ้าห่ม ควรทำจากใยสังเคราะห์หรือผ้าแพร การทำความสะอาด ซักเครื่องนอนต่างๆด้วยน้ำอุ่น (550C) ทุก 1-2 สัปดาห์

35 ควันบุหรี่ ควันธูป

36 Principles of Allergen Immunotherapy
Induction Maintenance Phase AllergyChula

37 Allergen IT: Literature Searched by Tittle Words in IGM (31 Oct 1998)
AllergyChula

38 Efficacy of Venom Immunotherapy (VIT) (Protection from systemic reaction to the insect stings)
% Efficcacy AllergyChula

39 Clinical Efficacy of AIT in Allergic Rhinitis (41 DBPC trials as by October 1998)
AllergyChula

40 Indications of Allergen Immunotherapy
Insect sting allergy Systemic reaction (absolute indication) Allergic rhinitis* Allergic asthma* (PFT >70% pred. value) *Dissatisfactory with avoidance + pharmacotherapy AllergyChula

41 Allergen Immunotherapy not proven effective in:
Atopic Dermatitis Food Allergy Chronic Urticaria AllergyChula

42 Pathogenesis of Allergy and Asthma and Potential Novel Therapy
B Cells IL-4 T-Helper Cells Th2 Anti--IL-4 Ab IFNg (Th1) IFNg (Th1 switch) IgE Leukotrienes PGD2 Histamine IL-5 Anti--IL-5 Ab Eosinophil Recruitment and Production Anti--leukotrienes Zileuton Zafirlukast Montelukast Mast cell Eosinophil Bronchoconstriction and Mucus Secretion Chemotaxis Tryptase PAF Inflammation Eotaxin RANTES MCP4 Airway Hyperreactivity Tryptase inhibitor Anti-PAF

43 Factors Affecting Clinical Outcomes of Allergic Diseases
Treatment Anti-inflammatory Anti-allergic Relievers Enivronmental Allergens Irritants Westernization Genetic Degree of atopy Compliance Avoidance Medication uses Infection Viral Bacterial Allergen Immunotherapy Allergic Diseases Future Therapy Remission Mild Moderate Severe AllergyChula


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