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 At 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%

Nigeria Ibadan: 18.4%

Kenya Nairobi: 15.4% Eldoret: 6.8%

South Africa Cape Town: 13.1%

Hay fever ever - ISAAC (1997-8)

Source: N At 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% Nigeria Ibadan: 40% Kenya: 12%

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 Mean score 75 pollen rhinitis

50

25

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

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

3 pollens/m

air

5000 4000 3000 2000 1000 0 0 10 20 weeks 30 40 threshold level for symptoms

Concept of "minimal persistent inflammation"

Mec hanisms of house dust mite induced rhinitis
mite allergen (g/g of dust)
100
10
.

Ciprandi et al, J Allergy Clin Immunol 1996

theshold level for symptoms

0 2 4 6 8 10 12 Months

0,1

minimal persistent symptoms inflammation inflammation

ARIA Classification

Intermittent
. < 4 days per week . or < 4 weeks

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 in untreated patients

Moderate-severe
one or more items . abnormal sleep . impairment of daily activities, sport, leisure . abnormal work and school . troublesome symptoms

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 avoidance
indicated when possible

pharmacotherapy
safety effectiveness easily administered

costs

immunotherapy
effectiveness specialist prescription may alter the natural course of the disease

patient education
always 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 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

Strength of evidence for treatment of rhinitis ARIA

intervention oral anti-H1 intranasal anti-H1 intranasal CS SAR adult A A A PAR children adult children A A A A A A A A A

intranasal chromone anti-leukotriene

subcutaneous SIT sublingual / nasal SIT allergen avoidance

A A
A A D

A A
A A D

A
A A D

A
A D

Medications of allergic rhinitis

ARIA
sneezing rhinorrhea nasal obstruction nasal itch eye symptoms

H1-antihistamines oral intranasal intraocular Corticosteroids Chromones intranasal intraocular Decongestants intranasal +++ ++ 0 +++ + 0 0 +++ +++ 0 +++ + 0 0 0 to + + 0 ++ + 0 ++ +++ ++ 0 ++ + 0 0 ++ 0 +++ + 0 ++ 0

oral Anti-cholinergics Anti-leukotrienes

0 0 +

0 +++ ++

+ 0 ++

0 0 ?

0 0 ++

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

mild intermittent

moderate severe intermittent

local chromone

mild persistent

moderate severe persistent

intra-nasal steroid

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 % subjects with asthma 20 15 10 5 0

controls
rhinitis

atopic

non-atopic

Frequency of asthma related to allergens

Linneberg et al, Respir Med 2001
Frequency of asthma related to allergens (%) 60 50 40 30 20 10 0 "allergy" assessed by questionnaire

no rhinitis
rhinitis

pollen

animal dander allergy

mite

Early allergic rhinitis as a risk factor for asthma

Wright et al, Pediatrics 1994
80 children with symptoms (%) cough, wheeze asthma 40

60

20

0 rhinitis allergic skin prick test pos.

allergic non-allergic none neg. ND ND

ND neg.

Bronchial hyperreactivity in ECHRS patients

Leynaert, Bousquet, Neukirch, Am J Respir Crit Care Med 1997
80 60 % subjects 40 20 0 - Paris + MPL - 821 adults - 20-44 yr - PC20 methacholine 4mg

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
allergens noxious agents

bronchus
allergens noxious agents

epithelial mesenchymal trophic unit

epithelial mesenchymal muscular trophic unit

QOL in a population-based study (ECRHS)

Leynaert et al, Am J Respir Crit Care Med 2000
60 50 Mean score 40 30 20 10 0
p<0.001 p<0.001 p<0.001 p<0.001

controls (N=448) allergic rhinitis (N=297) asthma + AR (N=76)

Physical Summary
score

Mental summary

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