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