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Common Allergy Update 2001

Common Allergy Update 2001

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Common Allergy Update 2001

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  1. Common Allergy Update 2001 Asst. Prof. Kiat Ruxrungtham, M.D.Division of Allergy and Clinical ImmunologyDepartment of MedicineFaculty of MedicineChulalongkorn University

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

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

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

  5. Mediators of Mast Cells and Allergy Urticaria, Angioedema Laryngeal edema, Shock Blood Vessels 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 • 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 % no Asthma 79 % no AR 86 % 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 AsthmaUpper-Lower Airway Linked Placebo Welsh et al. Mayo Clin Proc 1987;62:125-34

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

  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; 100:781-788

  13. Safety No CNS toxicity No cardiotoxicity 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 Ideal Antihistamines 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 16-24 1-2 h 3-4 h 8-12 h Astemizole Liver 9.5 days 2 day 9-12d weeks Loratadine Liver 17-24 >1 h 4-8 h 24 h Cetirizine no (Kidney) 25 1 h 4-8 h 24 h Fexofenadine minimal 14.4 1 h 2-3 h 24 h Kaliner M. Clin Geriatrics 1997; Simons FE, NEJM 1994 AllergyChula

  15. H1-Antagonists and Drug Interaction First-generation H1-Antagonists • Potentiation of Sedation : Alcohol, sedative agents, hypnotics, antidepressants • Potentiation of anticholinergiceffect: 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

  16. 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

  17. Treatment of Allergic Rhinitis in Adults Allergy Immunol Clinic 2000

  18. เยื่อจมูกบวมใน โรคภูมิแพ้ทางจมูก Allergy Chula 1999

  19. 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

  20. Adverse Effects of H1-Antagonists Adverse EffectsCPM HZ TF ASZ LD CZFX Sedation+ ++ - - - -/+ - Appetite stim.- -/+ - -/++ - -/+ - Weight gain- -/+ - -/++ - -/+ - Dry mouth ++ + - - - -/+ - Prolong QTc -/ ? -/ ? +* +* - - - Torsade de Points - - +* +* - -- AllergyChula

  21. Effects of fexofenadine, diphenhydramine, and alcohol on driving performance: in the Iowa driving simulator Weiler JM et al. Ann Intern Med 2000 Mar 7;132(5):354-63 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

  22. Mann RD, et al. BMJ 2000 Apr 29;320(7243):1184-1187 Sedation with "non-sedating” antihistamines: four prescription-event monitoring studies in general practice N= a total of 43 363 patients: Drowsiness The Odd RatioP value (versusLoratadine) Fexofenadine 0.63 (0.36-1.11) 0.1 Acrivastine 2.79 (1.69-4.58) <0.0001 Cetirizine 3.53 (2.07-5.42) <0.0001 No increased risk of accident or injury was evident with any of the four drugs.

  23. 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

  24. 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

  25. GINA guidelines 1998Focus 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

  26. 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

  27. 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)

  28. Theophylline as an Add On Regimen (2) Ukena et al Eur Respir J 1997; 10:2754-60 P<0.01 P=ns P<0.01 N= 69 N= 64

  29. Pathogenesis of Allergy and Asthma and Potential Novel Therapy B Cells T-Helper Cells Th2 IL-4 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

  30. Future Options Phosphodiesterase 4 (PDE-4) inhibitors • Theophyllineis 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

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

  32. การจัดห้องนอนให้ปลอดไรฝุ่นการจัดห้องนอนให้ปลอดไรฝุ่น เฟอร์นิเจอร์ มีเฟอร์นิเจอร์เท่าที่จำเป็น ควรใช้วัสดุที่ทำความสะอาดง่าย เช่น ไม้ บุหนังแท้หรือเทียม ไม่ควรบุผ้า พื้นห้อง ไม่ควรปูพรม ม่านไม่ควรใช้ผ้าม่านเพราะกักฝุ่น ควรใช้มู่ลี่แทน เพราะทำความสะอาดง่าย หมอนควรใช้ใยสังเคราะห์ และหุ้มด้วยผ้าไวนิลหรือ ผ้าใยสังเคราะห์พิเศษ และไม่ใช้นุ่น หรือขนนก ตากแดดทุก 1-2 สัปดาห์ ที่นอน ควรหุ้มด้วยผ้าสังเคราะห์ที่ป้องกันไรฝุ่นได้ ตากแดด ทุก 1-2 สัปดาห์ ผ้าห่มควรทำจากใยสังเคราะห์หรือผ้าแพร การทำความสะอาดซักเครื่องนอนต่างๆด้วยน้ำอุ่น (550C) ทุก 1-2 สัปดาห์

  33. ควันบุหรี่ ควันธูป

  34. Principles of Allergen Immunotherapy Induction Maintenance Phase AllergyChula

  35. Allergen IT: Literature Searchedby Tittle Words in IGM (31 Oct 1998) AllergyChula

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

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

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

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

  40. Pathogenesis of Allergy and Asthma and Potential Novel Therapy B Cells T-Helper Cells Th2 IL-4 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

  41. Factors Affecting Clinical Outcomesof 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 Severe Moderate AllergyChula