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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 programFirst 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 programFirst 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
≥20%10-20%<10%
Prevalence of hay fever: 13-14 yr olds - ISAACStrachan et al, Pediatr Allergy Immunology 1997
Asthma - ISAAC (1997-8)Source: N Aït Khaled, IUATLD
Conakry Guinea10.3%
TunisiaSousse15.2%
AbidjanIvory Coast11.8%
AlgeriaAlgiers West: 4.8%Algiers Centre: 6.6%
MoroccoCasablanca:12%Rabat: 6.6%Marrakech: 17%
KenyaNairobi: 15.4% Eldoret: 6.8%
EthiopiaAddis Ababa: 2.8%Jima: 2.2 %
NigeriaIbadan: 18.4%
South AfricaCape Town: 13.1%
“Hay fever ever” - ISAAC (1997-8)Source: N Aït Khaled, IUATLD
TunisiaSousse:15.2%
Morocco Casablanca: 27%Rabat: 18%Marrakech: 21%
Ivory CoastAbidjan: 49%
GuineaConakry:48%
AlgeriaAlgiers West: 13%Algiers Centre: 24%
NigeriaIbadan: 40%
Kenya: 12%
South Africa 15%
Ethiopia:2%
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
0
25
50
75
100
Mea
n sc
ore
PF SF PA SA MH EF BP GH
pollen rhinitis
perennial rhinitis
controls
SF-36 in seasonal and perennial rhinitisBousquet, Burtin et al J Allergy Clin Immunol 1994
Ciprandi et al, Allergy 2002
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)
.
4030201000
1000
2000
3000
4000
5000
6000 grasscypress
weeks
polle
ns/m
3 a
ir
threshold levelfor symptoms
.
0,1
1
10
100
0 2 4 6 8 10 12 Months
symptoms
inflammation
minimalpersistent
inflammation
theshold levelfor symptoms
Mechanisms of house dust mite induced rhinitism
ite a
llerg
en (
µg/
g of
dus
t)
Concept of "minimal persistent inflammation"Ciprandi et al, J Allergy Clin Immunol 1996
Moderate-severeone or more items
. abnormal sleep
. impairment of daily activities, sport, leisure
. abnormal work and school
. troublesome symptoms
Persistent . ≥ 4 days per week . and ≥ 4 weeks
Mild normal sleep& no impairment of daily
activities, sport, leisure
& normal work and school
& no troublesome symptoms
Intermittent
. < 4 days per week
. or < 4 weeks
ARIA Classification
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
allergenavoidance
indicated when possible
allergenavoidance
indicated when possible
pharmacotherapysafety
effectivenesseasily administered
pharmacotherapysafety
effectivenesseasily administered
immunotherapyeffectiveness
specialist prescription may alter the natural course of the disease
immunotherapyeffectiveness
specialist prescription may alter the natural course of the disease
patienteducation
always indicated
patienteducation
always indicated
costs
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
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 + ++ ++ ? ++
Medications of allergic rhinitis ARIA
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
mildintermittent
mildpersistentmoderate
severeintermittent
moderatesevere
persistent
allergen and irritant avoidance
immunotherapy
intra-nasal decongestant (<10 days) or oral decongestant
local chromone intra-nasal steroid
oral or local non-sedative H1-blocker
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
"About the beginning or middle of
June in every year …..
…. A sensation of heat and fulness is
experienced in the eyes ….
First description of hay feverJohn Bostock, Med Chir Trans, 1819; 10: 161
…. 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
0
5
10
15
20
25%
sub
ject
s w
ith a
sthm
a
atopic non-atopic
rhinitis
controls
Frequency of asthma related to allergens
Linneberg et al, Respir Med 2001
"allergy" assessed by questionnaire
0
10
20
30
40
50
60
Fre
qu
ency
of
asth
ma
rela
ted
to
alle
rgen
s (%
)
pollen animal dander mite
allergy
rhinitis
no rhinitis
0
20
40
60
80
child
ren
with
sym
ptom
s (%
)
allergic allergic non-allergic none ND
asthma
rhinitisskin prick test pos. neg. ND ND neg.
Early allergic rhinitis as a risk factor for asthma
Wright et al, Pediatrics 1994
cough, wheeze
Bronchial hyperreactivity in ECHRS patientsLeynaert, Bousquet, Neukirch, Am J Respir Crit Care Med 1997
0
20
40
60
80
% s
ubje
cts
controls seasonalrhinitis
perennialrhinitis
seasonal+ perennial
rhinitis
asthma
- Paris + MPL
- 821 adults
- 20-44 yr
- PC20 methacholine ≤4mg
non-asthmatic without wheeze
Eosinophils (EG2+ cells) in biopsies of asthmatics
Bousquet J et al. N Engl J Med 1990
Bronchial mucosa
Chanez P et al. Am J Respir Crit Care Med 1999
Nasal mucosa
epithelialmesenchymal
trophicunit
allergens noxious agents
allergens noxious agents
nose bronchus
epithelialmesenchymalmusculartrophicunit
QOL in a population-based study (ECRHS)Leynaert et al, Am J Respir Crit Care Med 2000
p<0.001
p<0.001
p<0.001p<0.001
0
10
20
30
40
50
60
Mea
n sc
ore
Physical Summary Mental summary
score
asthma + AR (N=76)
allergic rhinitis (N=297)
controls (N=448)
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