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
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