1. Allergic Rhinitis in Children Alfred Tam MBBS(HK), FRCP(Edin., London, Glasg.) FHKCPaed, FHKAM(Paediatrics) Department of Paediatrics and Adolescent Medicine, University of Hong Kong

2. Allergic Rhinitis in Children What is allergic rhinitis? Diagnosis and differential diagnosis Assessment and classification of AR What can make AR worse or better? Health effects of AR What can we do to make AR better?

3. What is allergic rhinitis? Rhinorhoea Nasal blockage Postnasal drip Itchiness Sneezing Associated health effects ‼IgE mediated

4. Allergic rhinitis is increasing Lee SL et al. Pediatr Allergy Immunol 2004; 15: 72-8.

5. AR prevalence varies in different cities Wong G et al. Clin Exp Allergy 2001; 31: 1225. Past 12 mths %(95%CI) HKBJGZ Numbers311042273565 Wheeze5.8(5.0-6.7)3.8(3.3-4.4)3.4(2.8-4.1) Rhinoconjunctivitis15.0(13.9-16.4)6.7(5.9-7.5)7.4(6.6-8.3) Flexural eczema3.8(3.1-4.5)2.2(1.8-2.7)1.8(1.4-2.3)

6. Atopic sensitization is not that different! Wong G et al. BMJ 2004; 329:486-9. %(95%CI)HKBJGZ Numbers134110441098 Atopic41.2(38.5-43.8)23.9(21.3-26.4)30.8(28.1-33.5) D. pter34.1(31.5-36.6)7.5(5.9-9.1)20.0(17.6-22.4) D. far25.9(23.5-28.2)5.7(4.3-7.1)17.9(15.6-20.2) Cat3.7(2.7-4.7)5.6(4.2-6.9)4.3(3.1-5.5) Cockroach11.5(9.8-13.2)13.3(11.3-15.4)17.8(14.8-19.2)

7. Allergic Rhinitis in Hanoi Nguyen et al. Pediatr Allergy Immunol 2003; 14:272-9. Symptoms%n Ever allergic rhinitis34.9338 Allergic rhinitis in past 12 months27.6267 Allergic rhinoconjunctivitis in past 12 months10.7104 AR limiting activities17165 Ever hay fever7.876 Doctor diagnosed hay fever11.2109

9. Diagnosis of Allergic Rhinitis 1.Clinical symptoms of recurrent or persistent rhinitis and/or associated health effects 2.Signs of atopy and recurrent or persistent rhinitis 3.Demonstration of IgE allergy 4.Exclusion of other causes of rhinitis

10. Diagnosis of Allergic Rhinitis 1.Clinical symptoms of recurrent or persistent rhinitis and/or associated health effects –Rhinorhoea –Nasal blockage –Postnasal drip –Itchiness –Sneezing –Others: conjunctivitis, eczema, asthma, chronic rhinosinusitis, otitis media with effusion, sleep obstruction…

11. Diagnosis of Allergic Rhinitis 2.Signs of atopy and recurrent or persistent rhinitis

12. Diagnosis in Primary Care Setting

13. Diagnosis of Allergic Rhinitis 3.Demonstration of IgE allergy

14. Immunoassay Not influenced by medication Not influenced by skin disease Does not require expertise Quality control possible Expensive Skin test Higher sensitivity Immediate results Requires expertise Cheaper Immunoassay vs Skin Test for Diagnosis of Allergy

15. Other Causes of Rhinitis in Children Infection –Viral, bacterial, –Rhinosinusitis Foreign body in the nose Rhinitis associated with physical or chemical factors Drug, food induced rhinitis NARES, aspirin sensitivity Vasomotor rhinitis

16. Health Effects of Allergic Rhinitis Social inconvenience Sleep disturbances/obstruction Learning difficulties Impaired maxillary growth Dental problems Infection: nose and sinuses Co-morbidities: conjunctivitis, asthma, rhinosinusitis, otitis media

17. Adapted from Meltzer EO et al. J Allergy Clin Immunol. 1997;99:S815 Short Form Health Survey (SF-36) Profiles of Patients with Allergic Rhinitis * * * * * * 50 55 60 65 70 75 80 85 90 Physical Functioning Role– Physical Bodily Pain General Health VitalitySocial Functioning Role– Emotional Mental Health Change in Health allergic rhinitis (n=312) controls (n=139) † Declining health status Domains scale: 0 to 100

19. Perennial Rhinitis: an Independent Risk Factor for Asthma (European Community Respiratory Health Survey) Adapted from Leynaert B et al. J Allergy Clin Immunol 1999; 104:301 Asthma (%) Atopic Non atopic no rhinitis, N=5198 rhinitis, N=1412 OR=11 OR=17 0 5 10 15 20 25

20. Looking for asthma…

21. In Patients with Rhinitis: Routinely ask for symptoms suggestive of asthma Perform chest examination Consider lung function testing Consider tests for bronchial hyperresponsiveness in selected cases

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

24. sneezingrhinorrheanasalnasal eyeobstructionitch symptoms H1-antihistamines oral++++++0 to ++++++ intranasal++++++++0 intraocular0000 +++ Corticosteroids+++++++++++ Cromones intranasal ++++0 intraocular0000++ Decongestants intranasal00++00 oral00+00 Anti-cholinergics0+++000 Anti-leukotrienes0+++0++ Medications for Allergic Rhinitis - ARIA

25. Oral Antihistamines First generation agents Chlorpheniramine Brompheniramine Diphenydramine Promethazine Tripolidine Hydroxyzine Azatadine Newer agents Acrivastine Azelastine Cetirizine Desloratadine Fexofenadine Levocetirizine Loratadine Mizolastine

26. Nasal Antihistamines Azelastine Levocabastine Olopatadine

27. Bachert C et al. J Allergy Clin Immunol 2004:114:838 Efficacy of an Antihistamine over 6 Months in Persistent Allergic Rhinitis SneezingRhinorrheaPruritus NosePruritus EyesCongestion * * * * * * * * * * * * * 1.0 0.8 0.6 0.4 0.2 0 1 wk 4 wk 6 mo1 wk 4 wk 6 mo1 wk 4 wk 6 mo1 wk 4 wk 6 mo1 wk 4 wk 6 mo mean Individual symptom score improvement * P<0.05 Levocetirizine, 5 mg, N = 276 Placebo, N = 271 Baseline total symptom score: 8.95

28. Efficacy of an Antihistamine in the Treatment of Allergic Rhinitis with Perennial Symptoms (n= 337) (n= 339) Simons FER et al., J Allergy Clin Immunol 2003;111:617

29. Newer Generation Oral Antihistamines Somnolence/Drowsiness ActivePlaceboData Source Cetirizine 10 mg qd 13.7%6.3% www.PDR.net Desloratadine 5 mg qd 2.1%1.8% www.PDR.net Fexofenadine 60 mg bid 1.3%0.9% www.PDR.net Levocetirizine 5 mg qd 6.8%1.8% Bachert et al JACI 2004;114:838 Loratadine 10 mg qd 8%6% www.PDR.net

30. First line treatment for mild allergic rhinitis Effective for –Rhinorrhea –Nasal pruritus –Sneezing Less effective for –Nasal blockage Possible additional anti-allergic and anti-inflammatory effect In-vitro effect > in-vivo effect Minimal or no sedative effects Once daily administration Rapid onset and 24 hour duration of action Newer Generation Oral Antihistamines

31. Decongestants: Alpha-2 Adrenergic Agonists Oral Pseudoephedrine Nasal Phenylephrine Oxymetazoline Xylometazoline

32. vasoconstriction Decongestants: Alpha-2 Adrenergic Agonists nasal airway lumen nasal turbinates nasal septum

33. Decongestants EFFICACY: Oral decongestants: moderate Nasal decongestants: high ADVERSE EFFECTS: Oral decongestants: insomnia, tachycardia, hyperkinesia tremor, increased blood pressure, stroke (?) Nasal decongestants: tachyphylaxis, rebound congestion, nasal hyperresponsiveness, rhinitis medicamentosa

34. nucleus cytosolic phospholipase A 2 arachidonic acid 5-lipoxygenase activating protein leukotriene A 4 5-lipoxygenase leukotriene C 4 synthase leukotriene C 4 leukotriene D 4 leukotriene E 4 CysLT1 receptor mast cells basophils eosinophils macrophages + Cysteinyl-Leukotriene Production and the CysLT1 Receptor

35. Daytime Nasal Symptoms Score (0-3 point scale) -0.6 -0.4 -0.2 0 Adapted from Nayak, et al. Ann Allergy Asthma Immunol. 2002;88: 592 Change from baseline (mean, 95% CI) mean baseline=2.0 * * placebo, N=149 montelukast, N=155 loratadine, N=301 *p<0.01 vs placebo Efficacy of a CysLT1 Receptor Antagonist in Allergic Rhinitis with Seasonal Symptoms

36. Anti-Leukotriene Treatment in Allergic Rhinitis Efficacy Equipotent to H1 receptor antagonists but with onset of action after 2 days Reduce nasal and systemic eosinophilia May be used for simultaneous treatment of allergic rhinitis and asthma Safety Dyspepsia (approx. 2%)

37. Nasal Corticosteroids Beclomethasone dipropionate Budesonide Ciclesonide* Flunisolide Fluticasone propionate Mometasone furoate Triamcinolone acetonide * Currently only approved for asthma

38. Nasal Corticosteroids reduction of symptoms and exacerbations reduction of mucosal inflammation reduction of late phase reactions priming nasal hyperresponsiveness 1 reduction of mucosal mast cells reduction of acute allergic reactions 2 suppression of glandular activity and vascular leakage induction of vasoconstriction 3

39. Meltzer E. et al. J Allergy Clin Immunol. 1999;104:107. Efficacy of Nasal Corticosteroid Sprays in Children with Allergic Rhinitis and Seasonal Symptoms

40. Mandl M. et al. Ann Allergy Asthma Immunol 1997;79:370 Comparative Efficacy of Nasal Corticosteroids

41. Nasal Corticosteroids Most potent anti-inflammatory agents Effective in treatment of all nasal symptoms including obstruction Superior to anti-histamines and anti-leukotienes First line pharmacotherapy for persistent allergic rhinitis

42. Nasal Corticosteroids Overall safe to use Adverse Effects –Nasal irritation –Epistaxis –Septal perforation (extremely rare) –HPA axis suppression (inconsistent and not clinically significant) –Suppressed growth (only in one study with beclomethasone)

43. Adapted from Galant, S. P. et al. Pediatrics 2003;112:96 Nasal Corticosteroid vs Placebo: Effects on 12-Hour Urinary Free Cortisol in 2-3 Year-Old Children 6-week treatment 0.98 SE=1.14 N=31 0.94 SE=1.15 N=29 Adjusted Geometric Mean of the Change from Baseline 1.0 0.8 0.6 0.4 0.2 0 Fluticasone Proprionate Nasal Spray 200 µg daily Placebo Value of 1 indicates no change from baseline

44. Other Management Aspects Manage other co-morbidities: –Allergic conjunctivitis –Asthma –Sinusitis… Environmental manipulations: –allergen avoidance –Pollution treatment Nutritional support Activities and sports

45. Environmental Control House dust mites Pets Cockroaches Molds Pollen 1. Allergens 2. Pollutants and Irritants

46. House dust mite allergen avoidance –Provide adequate ventilation to decrease humidity –Wash bedding regularly at 60°C –Encase pillow, mattress and quilt in allergen impermeable covers –Use vacuum cleaner with HEPA filter –Dispose of feather bedding –Remove carpets –Remove curtains, pets and stuffed toys from bedroom

47. Allergen Avoidance Pets Remove pets from bedrooms and, even better, from the entire home Vacuum carpets, mattresses and upholstery regularly Wash pets regularly (±) Molds Ensure dry indoor conditions Use ammonia to remove mold from bathrooms and other wet spaces Cockroaches Eradicate cockroaches with appropriate gel-type, non-volatile, insecticides Eliminate dampness, cracks in floors, ceilings, cover food; wash surfaces, fabrics to remove allergen Pollen Remain indoors with windows closed at peak pollen times Wear sunglasses Use air-conditioning, where possible Install car pollen filter

48. To Conclude… Allergic rhinitis is very common and causes considerable morbidity Adequate and appropriate treatment leads to significant improvement in quality of life Co-morbid conditions are common and warrants special attention and treatment for optimal results Environmental manipulations is also important in the control of disease

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