WHO INITIATIVE

ALLERGIC RHINITIS AND ITS IMPACT IN ASTHMA

( 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 IgEmediated 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
2

ARIA classification of
Allergic Rhinitis
Intermittent

Persistent

Symptoms

Symptoms

< 4 days per week

or < 4 weeks

Moderate-severe

Mild

normal sleep
no impairment of daily activities,
sport, leisure
normal work and
school
no troublesome symptoms

> 4 days per week

and > 4 weeks

one or more items

abnormal sleep
impairment of daily activities,
sport, leisure
abnormal work and school
troublesome symptoms
(ARIA WHO Consensus 2001)
6

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

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
7

ARIA WHO classification

based on the severity of AR symptoms and quality of life

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

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
8

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 Inflammation

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

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Pathophysiology of Allergic Inflammation

Co-morbidities
Asthma
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
14

Clinical assessment and

classification of rhinitis
History
nasal discharge
blockage
sneeze / itch

2 or more
symptoms for > 1 hr
on most days

Sneezers and runners

Sneezing
Rhinorrhea

Especially paroxysmal
Watery
anterior and posterior
Itching
Yes
Nasal blockage Variable
Diurnal rhythm Worse during day, improving at night
Conjunctivitis

Blockers
Little or none
Thick mucus
more posterior
No
Often severe
Constant, day and night,
may be worse at night

Often present

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
(ARIA WHO Consensus 2001)

16

Managements
1.
2.
3.
4.

Allergen avoidance
Medications ( Pharmacotherapy )
Specific Immunotherapy
Education
Improving The Physical Fitness

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

17

Therapeutic considerations
Allergen
avoidance
indicated when
possible

Pharmacotherapy
safety
effectiveness
easy administration

Immunotherapy

Costs

effectiveness
specialist prescription
may alter the natural
course of the disease

Patient
education
always indicated
18

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

Improving The Physical Fitness:

Induce the Th1 on anti inflammatory cytokines production
Improve adrenaline production by cortex adrenal

19

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

(ARIA WHO Consensus 2001)

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Decongestan
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
21

Topical Steroid
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

IL-5 dan GM-CSF mRNA expression T cells

Inhibition of IL-5 secretion from blood peripher T cells

22

Pharmacological Managements of AR
Effect of therapies on rhinitis symptomps

H1-antihistamines
oral
intranasal
intraocular
Corticosteroids
intranasal
Chromones
intranasal
intraocular
Decongestants
intranasal
oral
Anti-cholinergics
Anti-leukotrienes

sneezing

rhinorrhea

Nasal
obstruction

Nasal
itch

Eye
symptoms

++
++
0

++
++
0

+
+
0

+++
++
0

++
0
+++

+++

+++

+++

++

++

+
0

+
0

+
0

+
0

0
++

0
0
0
0

0
0
++
+

++++
+
0
++

0
0
0
0

0
0
0
++

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

IL-4 / IFN- Ratio

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)

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Treat AR in a Stepwise Approach (adolescent and adults)

Diagnosis of allergic rhinitis (history + skin prick tests or serum specific IgE)
Allergen avoidance
Intermittent symptoms

Mild
Not in preferred order
Oral H-1-blocker
Intranasal-H1-blocker
and/or decongestant
If + Conjunctivitis add:
Oral H-1-blocker
or Intraocular H1-blocker
or Intraocular Chromone
(or saline)

Persistent symptoms

Moderate-severe

Not in preferred order

Oral H-1-blocker
Intranasal-H1-blocker
and/or decongestant
Intranasal CS
(Chromone)
In persistent rhinitis review
the patient after 2-4 weeks

If improved: continue for 1 month

and/or

Moderate-severe

Mild

If failure: stepup
and/or

Intranasal CS
Review the patient after 2-4 weeks
Improved

Failure

Step-down and
continue treatment
for 1 month

Increase
intranasal
CS dose
and/or

Review diagnosis
Review compliance
Query infections or other causes

Rhinorrhea:
add ipratropium
and/or

Blockage: add
decongestant, or oral
CS (short term)

Itch sneeze:
add H1 blocker

(ARIA WHO Consensus 2002)

Consider Specific Immunotherapy

Failure:
Surgical refferal

Treatment of Allergic Rhinitis

Allergic Rhinitis and its Impact on Asthma

moderate
severe

mild

mild

persistent

moderate
severe
persistent

intermittent

intermittent intra-nasal steroid

local cromone

oral or local non-sedative H1-blocker

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

allergen and irritant avoidance

immunotherapy
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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, or
low 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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Stepwise treatment proposed

mild

intermittent
Oral H1- AH

moderate
severe

intermittent
Nasal
Beclomethasone
high dose
(300-400 g /daily)

If needed after
1 week treat

add
Oral H1-AH
and / or
Oral CS

mild
persistent
Oral H1-AH
or
Nasal
Beclomethasone
low dose
(100-200 g /daily)

moderate
severe
persistent
Nasal
Beclomethasone
high dose
(300-400 g /daily)

Severe
symptoms

add
Oral H1-AH
and / or
Oral CS

Conclusion
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)
Well understanding of AR pathophysiology is
important for selecting either rational present
diagnosis or treatment strategies
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Conclusion
The WHO initiative ARIA has lay down
the rational concept of diagnotic strategies: the
routine tests and the optional tests.
The choice of treatment approach used, includes:
Allergen(s) avoidance and prevention against inducing
factors, and
Medications (pharmacological treatment), and/or
Specific immunotherapy, and
Patient education, and
Surgery as adjunctive intervention if necessary

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THANK YOU
T