WHO INITIATIVE ALLERGIC RHINITIS AND ITS IMPACT IN ASTHMA( ARIA )ARIF DERMAWANFaculty of Medicine Padjadjaran University Dr. Hasan Sadikin General HospitalBandung

PrefaceAllergic rhinitis (AR): a symptomatic disorder of the nose, induced after allergen exposure, by an IgE-mediated inflammation of the nasal membranes AR represent a global health problem 10 - 25% population The prevalence is increasing Alter the social life of patients: school performance/work productivityThe costs of incurred by rhinitis are substantial Asthma and rhinitis are common co-morbidities one airway one disease Maxillary sinusitis is the common complication 2

ARIA classification of Allergic RhinitisModerate-severe one or more itemsabnormal sleepimpairment of daily activities, sport, leisureabnormal work and schooltroublesome symptomsPersistent Symptoms > 4 days per week and > 4 weeksMildnormal sleepno impairment of daily activities, sport, leisurenormal work and schoolno troublesome symptomsIntermittent Symptoms < 4 days per week or < 4 weeks6(ARIA WHO Consensus 2001)

ARIA WHO classification based on the severity of AR symptoms and quality of life Mild-Intermittent AR

Symptoms: < 4 days a week or < 4 weeks

Quality of Life (QOL):

Normal sleepNormal daily activities, sport, leisureNormal work and schoolNo troublesome symptoms

7Moderate-severe Intermittent AR

Symptoms: < 4 days a week or < 4 weeks

QOL: One or more items of: Abnormal sleep Impairment daily activities, sport, leisure Impairment of work or school

Troublesome symptoms

Moderate-severe Persistent AR

Symptoms: > 4 days a week and for > 4 weeks

QOL: One or more items of: Abnormal sleep Impairment daily activities, sport, leisure Impairment of work or school Troublesome symptomsARIA WHO classification based on the severity of AR symptoms and quality of life 8Mild-Persistent AR

Symptoms: > 4 days a week and for > 4 weeks

Quality of Life (QOL): Normal sleep Normal daily activities, sport, leisure Normal work or school No troublesome symptoms

Trigger of Allergic RhinitisAllergens Aeroallergens mites, pollens, animal danders, insects, plant origin, moulds Food allergens Occupational rhinitis Latex allergyPollutants Indoor air pollution domestic allergens, indoor gas pollutants (tobacco smoke) Outdoors air pollution Automobile pollution

Pathophysiology of Allergic Inflammation

Three phases : Sensitization phase Early Phase Allergic Reaction Late Phase Allergic Reaction 10

Pathophysiology of Allergic Inflammation

Co-morbidities The nasal and bronchial mucosa have many similarities Epidemiological co-exist in the same patients Most px allergic and non allergic asthma have rhinitis Many px with rhinitis have asthma Allergic rhinitis is associated with and also constitutes a risk factors for asthma Many px with allergic rhinitis have increased non-specific bronchial hyper reactivity Pathophysiological studies suggest that a strong relationship exits between rhinitis and asthma Allergic diseases may be systemicAsthma14

Clinical assessment and classification of rhinitisHistory nasal discharge blockage sneeze / itch2 or moresymptoms for > 1 hron most days

Sneezers and runnersBlockers Lund, V.J.,et al., International Consensus Report on the Diagnosis and Management of Rhinitis.International Rhinitis Management Working Group. Allergy, 1994;49(Suppl 19):1-34.

SneezingRhinorrhea

ItchingNasal blockageDiurnal rhythm

ConjunctivitisEspecially paroxysmalWatery anterior and posteriorYesVariableWorse during day, improving at night

Often presentLittle or noneThick mucus more posteriorNoOften severeConstant, day and night, may be worse at night

Diagnostic Allergic Rhinitis Typical History General ENT examination Diagnostic Test Skin tests Allergen-specific IgE Endoscopy Cytology Nasal challenge test Imaging16(ARIA WHO Consensus 2001)

Allergen avoidanceMedications ( Pharmacotherapy )Specific Immunotherapy 4. Education Improving The Physical Fitness 5. Optional therapy: Other medications and/or surgery for complications

Managements 17

Allergen avoidanceindicated when possiblePatient educationalways indicated Pharmacotherapysafety effectivenesseasy administrationImmunotherapyeffectiveness specialist prescriptionmay alter the naturalcourse of the diseaseTherapeutic considerations Costs18

Allergen avoidanceAvoidance of allergen and trigger factors:Although there is no definite demonstration that allergen avoidance measures are effective in the treatment of AR, it is indicated when possibleImproving The Physical Fitness:Induce the Th1 on anti inflammatory cytokines productionImprove adrenaline production by cortex adrenal19

Ideal Antihistamine: Anti-inflammatory Profile Should inhibits:Histamine release from basophilsTNF release from mast cellsPGD2, LTC4 release from FcERI positive cellsIL-6/IL-8 release from endothelial cellsHistamine-induced P-selectin expressionTNF-induced RANTES releaseIL-4/IL-13 release from human basophilsSuperoxide-synthesis from eosinophilsPAF-induced chemotaxis of eosinophilsAdhesion to endothelial cells ICAM-1 expression

20(ARIA WHO Consensus 2001)

Decongestan 21

Topical Steroid IL-5 dan GM-CSF mRNA expression T cells Inhibition of IL-5 secretion from blood peripher T cells AR clinical symptoms Eosinophilia (EG2+) (nasal epithelium and submucous) through product inhibition of IL-5 by T cells CD3+ T CD3+ submucous number or not increasing 22

Pharmacological Managements of AR Effect of therapies on rhinitis symptompsAdapted from van Cauwenberge, P., et al., Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy, 2000; 55(2):p.116-34. 23

sneezingrhinorrheaNasal obstructionNasal itchEye symptomsH1-antihistamines oral intranasal intraocularCorticosteroids intranasalChromones intranasal intraocularDecongestants intranasal oralAnti-cholinergicsAnti-leukotrienes++++0

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Allergen specific immunotherapyAllergen specific immunotherapy:Has a place in selected patient with demonstrable IgE-mediated diseases: who either have a long duration of symptoms, orin whom insufficiently controlled by conventional pharmacotherapy, or in whom pharmacotherapy produce undisirable side effect, orin patients who do not wish to be on pharmacotherapy, orin patients who do not want to receive long-term pharmacological treatment 24

The hypothesis of immunotherapy mechanism TH1 response changes which occurred either as a consequently of decreasing of regulation TH2 response (anergy), or immune deviation be influenced by IL-12. (Adapted from Durham and Till, 1998)IL-4 / IFN- Ratio25

Treat AR in a Stepwise Approach (adolescent and adults)Consider Specific Immunotherapy (ARIA WHO Consensus 2002)

immunotherapy Treatment of Allergic Rhinitis Allergic Rhinitis and its Impact on Asthma 27

Stepwise treatment proposed Mild intermitten AR : oral H1-antihistamines Moderate severe Intermittent AR :intra nasal topical steroid (high dose) + if needed: oral H-1 antihistamine and/or oral steroid (short term course) Mild persistent AR :oral H-1 Antihistamine, orlow dose intra nasal topical steroid Moderate-severe persistent AR :High dose intra nasal topical steroid If symptoms are severe : add oral H-1 Antihistamine, and or short course of oral corticosteroid at beginning of the treatment28

Stepwise treatment proposed

Allergic rhinitis is IgE mediated hypersensitivity, starting by sensitization phase, followed by EPR and LPR During LPR : inflammatory cells accumulation followed by mediators, cytokines, chemokines release (including adhesion molecules and chemotactic factors)Conclusion Well understanding of AR pathophysiology is important for selecting either rational present diagnosis or treatment strategies 30

The WHO initiative ARIA has lay down the rational concept of diagnotic strategies: the routine tests and the optional tests. Conclusion The choice of treatment approach used, includes:Allergen(s) avoidance and prevention against inducing factors, andMedications (pharmacological treatment), and/orSpecific immunotherapy, andPatient education, andSurgery as adjunctive intervention if necessary 31

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