In collaboration with the World Health Organization

The ARIA initiative was developed

as a state-of-the-art for the specialist, the general
practitioner and for health care workers:
• to update their knowledge of allergic rhinitis,
• to highlight the impact of allergic rhinitis on asthma,
• to provide an evidence-based documented revision on
the diagnosis methods,
• to provide an evidence-based revision on the
treatments available,
• to propose a stepwise approach to the management of
the disease,
• to assess the magnitude of the problem in developing
countries and to implement guidelines (with IUATLD)
 ARIA program
First phase:
• Development of evidence-based guidelines
during a workshop held at WHO in December
1999 (J Allergy Clin Immunol, suppl, Nov 2001).
• Document has been endorsed by several allergy,
respiratory, ENT and paediatric associations.
 ARIA program
First phase:
• Development of evidence-based guidelines during a workshop held
at WHO in December 1999 (J Allergy Clin Immunol, suppl, Nov 2001).
• Document has been endorsed by several allergy, respiratory, ENT
and pediatric associations.

Second phase:
• To produce materials to help improve delivery of
care to those with rhinitis. In particular a pocket
guide
• To implement ARIA guidelines
• To update the workshop report
 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal
inflammation
4- Treatment based on evidence
5- Impact of rhinitis on asthma
Prevalence of hay fever: 13-14 yr olds - ISAAC
Strachan et al, Pediatr Allergy Immunology 1997

≥20%
10-20%
<10%
 Asthma - ISAAC (1997-8)
Source: N Aït Khaled, IUATLD
Morocco
Casablanca:12% Algeria
Rabat: 6.6% Algiers West: 4.8%
Marrakech: 17% Algiers Centre: 6.6%

Tunisia
Sousse15.2%
Ethiopia
Addis Ababa: 2.8%
Jima: 2.2 %

Conakry
Guinea
10.3%

Abidjan Kenya
Ivory Coast Nairobi: 15.4%
11.8% Eldoret: 6.8%
Nigeria
Ibadan: 18.4%

South Africa
Cape Town: 13.1%
 “Hay fever ever” - ISAAC (1997-8)
Source: N Aït Khaled, IUATLD
Morocco Algeria
Casablanca: 27% Algiers West: 13%
Rabat: 18% Algiers Centre: 24%
Marrakech: 21%
Tunisia
Sousse:15.2%

Ethiopia:2%

Guinea
Conakry:48%

Ivory Coast Kenya: 12%

Abidjan: 49%

Nigeria
Ibadan: 40%

South Africa 15%

 Increase in prevalence of rhinitis with age in
Denmark
- Study 1: children 7-17 yrs studied at 6 yr intervals
Ulrik et al, Allergy 2000
- rhinitis increased from 15 to 22%
- often linked with IgE sensitization
- Study 2: adults 15-41s yr studied at 8 yr intervals
Linneberg et al, J Allergy Clin Immunol 2000
- rhinitis increased from 25 to 32%
- often linked with IgE sensitization
 SF-36 in seasonal and perennial rhinitis
Bousquet, Burtin et al J Allergy Clin Immunol 1994
Ciprandi et al, Allergy 2002
100
controls
perennial rhinitis
75 pollen rhinitis
Mean score

50

25

0
PF SF PA SA MH EF BP GH
 Needs for new guidelines in the
management of allergic rhinitis
• The International Consensus on Rhinitis was a
major step forward and was recently validated for
the treatment of seasonal allergic rhinitis.
• However,
• it was not evidence-based
• new drugs have been available since 1995.
• it was mainly applicable to developed countries.
• Moreover, the ARIA guidelines are targeting the
patient globally instead of treating each target
organ individually
Needs for guidelines in the management of
allergic rhinitis
• Allergic rhinitis is a global health problem
affecting 5 to 50 % of the population
• Its prevalence is increasing.
• Although it is not usually a severe disease,
rhinitis alters social life and affects school
performance and work productivity.
• Costs incurred by rhinitis are substantial.
• Implementation of guidelines improves the
condition of patients with allergic rhinitis.
Needs for guidelines in the management of
allergic rhinitis in developing countries
• ISAAC study: seasonal allergic rhinitis (hay
fever) affects up to 50% of adolescents in certain
developing countries: Guinea (Conakry), Ivory
Coast (Abidjan) or Nigeria (Lagos).
• However, the validity of the questionnaire used
should be checked in these countries
• Rhinitis may be a problem in some parts of
developing countries only
• Risk factors should be understood for
preventive measures
 1- Why ARIA ?
2- New classification of rhinitis
 ARIA

The classification "seasonal" and

"perennial" allergic rhinitis

has been changed to

"intermittent" and "persistent"

allergic rhinitis
 Pollen season in Montpellier (1990)

6000 grass
.
cypress
5000
air
3

4000
pollens/m

3000

2000

1000
threshold level
0 for symptoms
0 10 20 30 40
weeks
 Concept of "minimal persistent inflammation"
Ciprandi et al, J Allergy Clin Immunol 1996
mite allergen (µg/g of dust) Mechanisms of house dust mite induced rhinitis

100

10 .

theshold level
1
for symptoms

0,1
0 2 4 6 8 10 12 Months

minimal
persistent
symptoms inflammation
inflammation
 ARIA Classification
Intermittent Persistent
. < 4 days per week . ≥ 4 days per week
. or < 4 weeks . and ≥ 4 weeks

Mild Moderate-severe
normal sleep one or more items
& no impairment of daily . abnormal sleep
activities, sport, . impairment of daily
leisure activities, sport, leisure
& normal work and . abnormal work and
school school
& no troublesome . troublesome symptoms
symptoms
in untreated patients
 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal inflammation
Persistent rhinitis

histamine
 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal inflammation
4- Treatment based on evidence
 allergen
allergen
avoidance
avoidance
indicated
indicated
when
whenpossible
possible

pharmacotherapy
pharmacotherapy immunotherapy
immunotherapy
safety
safety
effectiveness
effectiveness
costs effectiveness
effectiveness
specialist
specialistprescription
prescription
easily may
mayalter
alterthe
thenatural
natural
easilyadministered
administered course
courseofofthe
thedisease
disease

patient
patient
education
education
always
alwaysindicated
indicated
Statement of evidence: Strength of evidence
Shekelle et al, BMJ 1999

A directly based on randomized controlled trials

and meta-analyses
B evidence from at least one controlled study without
randomization or extrapolated recommendation from
category A evidence
C evidence from at least one other type of quasi-
experimental study or extrapolated recommendation from
category A or B evidence

D evidence from expert committee reports or

opinions or clinical experience of respected
authorities, or both
 Strength of evidence for treatment of rhinitis
ARIA
intervention SAR PAR adult
children adult children
oral anti-H1 A A A A
intranasal anti-H1 A A A A
intranasal CS A A A A
intranasal chromone A A A A
anti-leukotriene A A
subcutaneous SIT A A A A
sublingual / nasal SIT A A A
allergen avoidance D D D D
 Medications of allergic rhinitis
ARIA
sneezing rhinorrhea nasal nasal eye obstruction
itch symptoms
H1-antihistamines
oral +++ +++ 0 to + +++ ++
intranasal ++ +++ + ++ 0
intraocular 0 0 0 0 +++
Corticosteroids +++ +++ ++ ++ +
Chromones
intranasal + + + + 0
intraocular 0 0 0 0 ++
Decongestants
intranasal 0 0 ++ 0 0
oral 0 0 + 0 0
Anti-cholinergics 0 +++ 0 0 0
Anti-leukotrienes + ++ ++ ? ++
 Mild intermittent rhinitis
ARIA
Options (not in preferred order)
- oral or intranasal anti-H1
- intranasal decongestants
- oral decongestants (not in children)
 Moderate-severe intermittent rhinitis
Mild persistent rhinitis
ARIA
Options (not in preferred order)
- oral or intranasal anti-H1
- oral anti-H1 + decongestant
- intranasal CS
- (chromones)
Patient should be re-assessed after 2-4 wks
 Moderate-severe persistent rhinitis
ARIA
Step-wise approach
- intranasal CS as a first line treatment
- if major blockage: add short course of oral CS
or decongestant
Re-assess after 2-4 weeks
- if symptoms present add:
- oral anti-H1 (± decongestants)
- ipratropium
 Conjunctivitis rhinitis
ARIA
Options (not in preferred order)
- oral or ocular anti-H1
- ocular chromones
- saline
Do not use ocular CS without care and eye
examination
 Treatment of allergic rhinitis (ARIA)
Allergic Rhinitis and its Impact on Asthma

moderate
severe
mild persistent
moderate persistent
severe
mild intermittent
intermittent intra-nasal steroid
local chromone
oral or local non-sedative H1-blocker
intra-nasal decongestant (<10 days) or oral decongestant
allergen and irritant avoidance
immunotherapy
 ARIA in low-income countries
• The rationale for treatment choice in
developing countries is based upon:
• level of efficacy
• low drug cost affordable for the majority
of patients
• inclusion in the WHO essential list of drugs:
only chlorpeniramine and BDP are listed
• It is hoped that new drugs will be available on
this list
 ARIA in low-income countries
Stepwise treatment proposed
• Mild intermittent rhinitis: oral antihistamine
• Moderate/severe intermittent rhinitis: BDP low
dose ± oral antihistamine
• Mild persistent rhinitis: oral antihistamine
or low dose BDP
• Moderate/severe persistent rhinitis: high dose
BDP. Consider adding oral antihistamine ± oral
steroids (short course)
 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal inflammation
4- Treatment based on evidence
5- Impact of rhinitis on asthma
First description of hay fever
John Bostock, Med Chir Trans, 1819; 10: 161

"About the beginning or middle of

June in every year …..
…. A sensation of heat and fulness is
experienced in the eyes ….
…. To this succeeds irritation of the
nose producing sneezing ….
…. To the sneezings are added a
further sensation of tightness of the
chest, and a difficulty of breathing"
 Links between rhinitis and asthma:
Epidemiologic evidence
1- Asthma prevalence is increased in allergic and
non-allergic rhinitis
2- Rhinitis is almost always present in asthma
3- Rhinitis may be a risk factor for asthma
4- Non-specific bronchial hyperreactivity is
increased in persistent rhinitis
Perennial rhinitis: an independent risk factor
for asthma
Leynaert et al, J Allergy Clin Immunol 1999

25

controls
% subjects with asthma

20
rhinitis
15

10

0
atopic non-atopic
 Frequency of asthma related to allergens
Linneberg et al, Respir Med 2001

60
Frequency of asthma related

50 no rhinitis
rhinitis
to allergens (%)

40
"allergy"
30 assessed by
questionnaire
20

10

0
pollen animal dander mite
allergy
 Early allergic rhinitis as a risk factor for asthma
Wright et al, Pediatrics 1994

80
children with symptoms (%)

cough, wheeze
60
asthma

40

20

0
rhinitis allergic allergic non-allergic none ND
skin prick test pos. neg. ND ND neg.
 Bronchial hyperreactivity in ECHRS patients
Leynaert, Bousquet, Neukirch, Am J Respir Crit Care Med 1997

80

60 - Paris + MPL
- 821 adults
% subjects

40 - 20-44 yr
- PC20 methacholine
≤4mg
20

0
controls seasonal perennial seasonal asthma
rhinitis rhinitis + perennial
rhinitis
non-asthmatic
without wheeze
 Eosinophils (EG2+ cells)
in biopsies of asthmatics

Bronchial mucosa Nasal mucosa

Bousquet J et al. N Engl J Med 1990 Chanez P et al. Am J Respir Crit Care Med 1999
 nose bronchus
allergens allergens
noxious agents noxious agents

epithelial epithelial
mesenchymal mesenchymal
trophic muscular
unit trophic
unit
 QOL in a population-based study (ECRHS)
Leynaert et al, Am J Respir Crit Care Med 2000

60
p<0.001 p<0.001
p<0.001 p<0.001 controls (N=448)
50
allergic rhinitis (N=297)
asthma + AR (N=76)
40
Mean score

30

20

10

0
Physical Summary Mental summary
score
 ARIA program
• Guideline implementation in low income
developing countries in collaboration with
IUATLD
• need of adaptation to the local situation as
well as to social and cultural barriers.
• A joined ARIA-IUATLD program started to
assess the magnitude of allergic rhinitis in
these countries to confirm the results of the
ISAAC study using a more detailed
questionnaire.
• Then, a pocket guide specifically devoted to
low income countries will be developed.
 Ultimate goals of ARIA
• To translate evolving science on rhinitis into
recommendations for the management and
prevention of the disease
• To better assess the interactions between
rhinitis and asthma
• To increase awareness of rhinitis and its
public health consequences
• To make the effective treatment of rhinitis
available and affordable for every patient in
the world
 Recommendations
1- Patients with persistent rhinitis should be
evaluated for asthma
2- Patients with persistent asthma should be
evaluated for rhinitis
3- A strategy should combine the treatment of
upper and lower airways in terms of
efficacy and safety