Good updated guidelines for Allergy

1. In collaboration with the World Health Organization

2. 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)

3. 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.

5. 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

7. 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal
inflammation
4- Treatment based on evidence
5- Impact of rhinitis on asthma

8. Prevalence of hay fever: 13-14 yr olds - ISAAC
Strachan et al, Pediatr Allergy Immunology 1997
≥20%
10-20%
<10%

9. Asthma - ISAAC (1997-8)
Source: N Aït Khaled, IUATLD
Morocco
Casablanca:12%
Rabat: 6.6%
Marrakech: 17%
Algeria
Algiers West: 4.8%
Algiers Centre: 6.6%
Tunisia
Sousse15.2%
Ethiopia
Addis Ababa: 2.8%
Jima: 2.2 %
Conakry
Guinea
10.3%
Abidjan
Ivory Coast
11.8%
Kenya
Nairobi: 15.4%
Eldoret: 6.8%
Nigeria
Ibadan: 18.4%
South Africa
Cape Town: 13.1%

10. “Hay fever ever” - ISAAC (1997-8)
Source: N Aït Khaled, IUATLD
Morocco
Casablanca: 27%
Rabat: 18%
Marrakech: 21%
Algeria
Algiers West: 13%
Algiers Centre: 24%
Tunisia
Sousse:15.2%
Ethiopia:2%
Guinea
Conakry:48%
Ivory Coast
Abidjan: 49%
Kenya: 12%
Nigeria
Ibadan: 40%
South Africa 15%

11. 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

12. SF-36 in seasonal and perennial rhinitis
Bousquet, Burtin et al J Allergy Clin Immunol 1994
Ciprandi et al, Allergy 2002
100
controls
Mean score
perennial rhinitis
75
pollen rhinitis
50
25
0
PF
SF
PA
SA
MH
EF
BP
GH

13. 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

14. 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.

15. 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

16. 1- Why ARIA ?
2- New classification of rhinitis

17. ARIA
The classification "seasonal" and
"perennial" allergic rhinitis
has been changed to
"intermittent" and "persistent"
allergic rhinitis

18. Pollen season in Montpellier (1990)
6000
grass
cypress
pollens/m
3
air
.
5000
4000
3000
2000
1000
0
0
10
20
weeks
30
40
threshold level
for symptoms

19. 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
for symptoms
1
0,1
0
2
minimal
persistent
symptoms inflammation
inflammation
4
6
8
10
12 Months

20. ARIA Classification
Intermittent
Persistent
. < 4 days per week
. or < 4 weeks
. ≥ 4 days per week
. and ≥ 4 weeks
Mild
Moderate-severe
normal sleep
& no impairment of daily
activities, sport,
leisure
& normal work and
school
& no troublesome
symptoms
in untreated patients
one or more items
. abnormal sleep
. impairment of daily
activities, sport, leisure
. abnormal work and
school
. troublesome symptoms

21. 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal inflammation

22. Persistent rhinitis
histamine

23. 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal inflammation
4- Treatment based on evidence

24. allergen
allergen
avoidance
avoidance
indicated
indicated
when possible
when possible
pharmacotherapy
pharmacotherapy
safety
safety
effectiveness
effectiveness
easily administered
easily administered
costs
patient
patient
education
education
always indicated
always indicated
immunotherapy
immunotherapy
effectiveness
effectiveness
specialist prescription
specialist prescription
may alter the natural
may alter the natural
course of the disease
course of the disease

25. Statement of evidence: Strength of evidence
Shekelle et al, BMJ 1999
A directly based on randomized controlled trials
and meta-analyses
B
C
evidence from at least one controlled study without
randomization or
extrapolated recommendation from
category A evidence
evidence from at least one other type of quasiexperimental 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

26. Strength of evidence for treatment of rhinitis
ARIA
intervention
SAR
adult
PAR
children adult
children
oral anti-H1
intranasal anti-H1
intranasal CS
intranasal chromone
anti-leukotriene
subcutaneous SIT
sublingual / nasal SIT
allergen avoidance
A
A
A
A
A
A
A
D
A
A
A
A
A
A
A
D
A
A
A
A
A
A
A
A
A
A
D
A
D

27. Medications of allergic rhinitis
ARIA
sneezing
H1-antihistamines
oral
intranasal
intraocular
Corticosteroids
Chromones
intranasal
intraocular
Decongestants
intranasal
oral
Anti-cholinergics
Anti-leukotrienes
rhinorrhea
nasal
obstruction
nasal
itch
eye
symptoms
+++
++
0
+++
+++
+++
0
+++
0 to +
+
0
++
+++
++
0
++
++
0
+++
+
+
0
+
0
+
0
+
0
0
++
0
0
0
+
0
0
+++
++
++
+
0
++
0
0
0
?
0
0
0
++

28. Mild intermittent rhinitis
ARIA
Options (not in preferred order)
- oral or intranasal anti-H1
- intranasal decongestants
- oral decongestants (not in children)

29. 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

30. 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

31. 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

32. Treatment of allergic rhinitis (ARIA)
Allergic Rhinitis and its Impact on Asthma
mild
intermittent
moderate
severe
intermittent
mild
persistent
moderate
severe
persistent
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

33. 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

34. 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)

35. 1- Why ARIA ?
2- New classification of rhinitis
3- Importance of nasal inflammation
4- Treatment based on evidence
5- Impact of rhinitis on asthma

36. 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"

37. 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

38. Perennial rhinitis: an independent risk factor
for asthma
Leynaert et al, J Allergy Clin Immunol 1999
% subjects with asthma
25
controls
20
rhinitis
15
10
5
0
atopic
non-atopic

39. Frequency of asthma related to allergens
Frequency of asthma related
to allergens (%)
Linneberg et al, Respir Med 2001
60
50
no rhinitis
rhinitis
40
"allergy"
assessed by
questionnair
e
30
20
10
0
pollen
animal dander
allergy
mite

40. Early allergic rhinitis as a risk factor for
asthma
Wright et al, Pediatrics 1994
children with symptoms (%)
80
60
cough, wheeze
asthma
40
20
0
rhinitis allergic allergic non-allergic none
ND
in prick test
pos.
neg.
ND
ND
neg.

41. Bronchial hyperreactivity in ECHRS patients
Leynaert, Bousquet, Neukirch, Am J Respir Crit Care
Med 1997
80
- Paris + MPL
% subjects
60
- 821 adults
- 20-44 yr
40
- PC20 methacholine
≤4mg
20
0
controls seasonal perennial seasonal asthma
rhinitis
rhinitis + perennial
rhinitis
non-asthmatic
without wheeze

43. Eosinophils (EG2+ cells)
in biopsies of asthmatics
Bronchial mucosa
Bousquet J et al. N Engl J Med 1990
Nasal mucosa
Chanez P et al. Am J Respir Crit Care Med 1999

52. nose
allergens
noxious agents
epithelial
mesenchymal
trophic
unit
bronchus
allergens
noxious agents
epithelial
mesenchymal
muscular
trophic
unit

53. 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
Mean score
50
allergic rhinitis (N=297)
asthma + AR (N=76)
40
30
20
10
0
controls (N=448)
Physical Summary
Mental summary
score

55. 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.

56. 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

57. 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