WHO INITIATIVE WHO INITIATIVE ALLERGIC RHINITIS AND ITS IMPACT IN ASTHMAALLERGIC RHINITIS AND ITS IMPACT IN ASTHMA

( ARIA )( ARIA )

ARIF DERMAWAN

Faculty of Medicine Padjadjaran University

Dr. Hasan Sadikin General Hospital

Bandung

Preface

Allergic rhinitis (AR): a symptomatic disorder of the nose, induced after allergen exposure, by an IgE-mediated inflammation of the nasal membranes

Allergic 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 productivity• The costs of incurred by rhinitis are substantial • Asthma and rhinitis are common co-morbidities “ one airway one disease “ • Maxillary sinusitis is the common complication

• AR represent a global health problem• 10 - 25% population• The prevalence is increasing• Alter the social life of patients: school performance/work productivity• The costs of incurred by rhinitis are substantial • Asthma and rhinitis are common co-morbidities “ one airway one disease “ • Maxillary sinusitis is the common complication

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ARIA classification of Allergic Rhinitis

Moderate-severeModerate-severeone or more itemsone or more items

• abnormal sleepabnormal sleep• impairment of daily activities, impairment of daily activities,

sport, leisuresport, leisure• abnormal work and schoolabnormal work and school• troublesome symptomstroublesome symptoms

PersistentPersistent SymptomsSymptoms

• > 4 days per week> 4 days per week

• andand > 4 weeks > 4 weeks

MildMild• normal sleepnormal sleep• no impairment of dailyno impairment of daily activities, activities,

sport, leisuresport, leisure• normal work andnormal work and

schoolschool• no troublesome symptomsno troublesome symptoms

IntermittentIntermittent SymptomsSymptoms

• << 4 days per week 4 days per week• oror << 4 weeks 4 weeks

6(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 sleep• Normal daily activities, sport, leisure• Normal work and school• No troublesome symptoms

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Moderate-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 symptoms

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

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Mild-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 Rhinitis

Allergens Aeroallergens

mites, pollens, animal danders, insects, plant origin, moulds

Food allergens Occupational rhinitis Latex allergy

Pollutants Indoor air pollution

domestic allergens, indoor gas pollutants (tobacco smoke)

Outdoors air pollution Automobile pollution

Pathophysiology of Allergic InflammationPathophysiology of Allergic Inflammation

Three phases :

Sensitization phase

Early Phase Allergic Reaction

Late Phase Allergic Reaction

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Pathophysiology of Allergic InflammationPathophysiology 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 systemic

Asthma

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Clinical assessment and classification of rhinitisHistory• nasal discharge• blockage• sneeze / itch

2 or moresymptoms for > 1 hr

on most days

Sneezers and runners Blockers Sneezing

Rhinorrhea

Itching

Nasal blockage

Diurnal rhythm

Conjunctivitis

Especially paroxysmal

Watery

anterior and posterior

Yes

Variable

Worse during day, improving at night

Often present

Little or none

Thick mucus

more posterior

No

Often severe

Constant, day and night, may be worse at night

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.

Diagnostic Allergic Rhinitis

Typical History General ENT examination Diagnostic Test

• Skin tests • Allergen-specific IgE

Endoscopy Cytology Nasal challenge test Imaging

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(ARIA WHO Consensus 2001)

1. Allergen avoidance2. Medications ( Pharmacotherapy )3. Specific Immunotherapy 4. Education Improving The Physical Fitness

1. Allergen avoidance2. Medications ( Pharmacotherapy )3. Specific Immunotherapy 4. Education Improving The Physical Fitness

5. Optional therapy: Other medications and/or surgery for complications5. Optional therapy: Other medications and/or surgery for complications

Managements

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Allergen avoidance

indicated when possible

Patient education

always indicated

Pharmacotherapysafety

effectivenesseasy administration

Immunotherapyeffectiveness

specialist prescriptionmay alter the naturalcourse of the disease

Therapeutic considerations

Costs

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Allergen avoidance

Avoidance 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 possible

Avoidance 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 possible

Improving The Physical Fitness:•Induce the Th1 on anti inflammatory cytokines production•Improve adrenaline production by cortex adrenal

Improving The Physical Fitness:•Induce the Th1 on anti inflammatory cytokines production•Improve adrenaline production by cortex adrenal

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Ideal Antihistamine: Anti-inflammatory Profile

Should inhibits: Histamine release from basophils TNF release from mast cells PGD2, LTC4 release from FcERI positive cells IL-6/IL-8 release from endothelial cells Histamine-induced P-selectin expression TNF-induced RANTES release IL-4/IL-13 release from human basophils Superoxide-synthesis from eosinophils PAF-induced chemotaxis of eosinophils Adhesion to endothelial cells ICAM-1 expression

Should inhibits: Histamine release from basophils TNF release from mast cells PGD2, LTC4 release from FcERI positive cells IL-6/IL-8 release from endothelial cells Histamine-induced P-selectin expression TNF-induced RANTES release IL-4/IL-13 release from human basophils Superoxide-synthesis from eosinophils PAF-induced chemotaxis of eosinophils Adhesion to endothelial cells ICAM-1 expression

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(ARIA WHO Consensus 2001)

Topical decongestant :Rebound effect (Rhinitis medicamentosa)

if used >7-10 days; Need a steroid therapy use it < twice/month

Topical decongestant :Rebound effect (Rhinitis medicamentosa)

if used >7-10 days; Need a steroid therapy use it < twice/month

Oral decongestant :Very effective (especially for nasal congestion)

Combined with antihistamine more effective

than alone

Oral decongestant :Very effective (especially for nasal congestion)

Combined with antihistamine more effective

than alone

Decongestan

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Topical Steroid

IL-5 dan GM-CSF mRNA expression T cells

Inhibition of IL-5 secretion from blood peripher T cells

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

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

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sneezing rhinorrhea Nasal

obstruction

Nasal

itch

Eye symptoms

H1-antihistamines

oral

intranasal

intraocular

Corticosteroids

intranasal

Chromones

intranasal

intraocular

Decongestants

intranasal

oral

Anti-cholinergics

Anti-leukotrienes

++

++

0

+++

+

0

0

0

0

0

++

++

0

+++

+

0

0

0

++

+

+

+

0

+++

+

0

++++

+

0

++

+++

++

0

++

+

0

0

0

0

0

++

0

+++

++

0

++

0

0

0

++

Pharmacological Managements of AR Effect of therapies on rhinitis symptomps

Adapted 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.

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Allergen specific immunotherapy

Allergen specific immunotherapy:Has a place in selected patient with demonstrable

IgE-mediated diseases: • who either have a long duration of symptoms, or• in whom insufficiently controlled by conventional

pharmacotherapy, or • in whom pharmacotherapy produce undisirable

side effect, or• in patients who do not wish to be on

pharmacotherapy, or• in 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-γ Ratio

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Treat AR in a Stepwise Approach (adolescent and adults)

If + Conjunctivitis add:• Oral H-1-blocker• or Intraocular H1-blocker• or Intraocular Chromone• (or saline)

If + Conjunctivitis add:• Oral H-1-blocker• or Intraocular H1-blocker• or Intraocular Chromone• (or saline)

Not in preferred order• Oral H-1-blocker• Intranasal-H1-blocker• and/or decongestant

In persistent rhinitis review the patient after 2-4 weeks

If failure: step-up

and/or

If improved: continue for 1 monthand/or

Not in preferred order• Oral H-1-blocker• Intranasal-H1-blocker• and/or decongestant• Intranasal CS• (Chromone)

Consider Specific Immunotherapy Consider Specific Immunotherapy

Mild

Diagnosis of allergic rhinitis (history + skin prick tests or serum specific IgE)

Allergen avoidance

Persistent symptomsIntermittent symptoms

MildModerate-severe Moderate-severe

Increase intranasalCS dose and/or

Intranasal CS

Review the patient after 2-4 weeks

FailureImproved

Review diagnosisReview compliance

Query infections or other causes

Step-down andcontinue treatment

for 1 month

Itch sneeze:add H1 blocker

Rhinorrhea:add ipratropium

and/or

Blockage: add decongestant, or oral

CS (short term)

Failure:Surgical refferal

(ARIA WHO Consensus 2002)

immunotherapy

allergen and irritant avoidance

intra-nasal decongestant (<10 days) or oral decongestant

local cromone

oral or local non-sedative H1-blocker

intra-nasal steroidmild

intermittent

moderatesevere

intermittent

mildpersistent

moderatesevere

persistent

Treatment of Allergic Rhinitis Allergic Rhinitis and its Impact on Asthma

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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 treatment

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mildintermittent

moderatesevere

intermittent

mildpersistent

moderatesevere

persistent

Oral H1- AH NasalBeclomethasone

high dose(300-400 μg

/daily)

Oral H1-AH

Oral CS

Oral H1-AH

NasalBeclomethasone

low dose(100-200 μg

/daily)

add

and / or

or

NasalBeclomethasone

high dose(300-400 μg /daily)

add

Oral H1-AH

Oral CSand / or

If needed after 1 week treat

Severe symptoms

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

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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

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TTHANK YOU