Module 1:

Allergic Rhinitis
an educational program of:

Updated: June 2011

Global Resources in Allergy

(GLORIA)
Global Resources In Allergy (GLORIA) is the
flagship program of the World Allergy
Organization (WAO). Its curriculum educates
medical professionals worldwide through
regional and national presentations. GLORIA
modules are created from established guidelines
and recommendations to address different
aspects of allergy-related patient care.

World Allergy Organization (WAO)

The World Allergy Organization is an
international coalition of 89 regional and
national allergy and clinical immunology
societies.

WAOs Mission
WAOs mission is to be a global resource
and advocate in the field of allergy,
advancing excellence in clinical care,
education, research and training through a
world-wide alliance of allergy and clinical
immunology societies

Module 1: Allergic Rhinitis

Revised in 2007 by:
Omer Kalayci, MD
Ankara, Turkey
Alkis Togias, MD
Bethesda, MD, USA

The full GLORIA Module on Allergic Rhinitis

consists of 105 slides.
The WAO GLORIA presenter will select
slides
from this set for presentation today.
These slides will be available for download for
your own teaching
at: www.worldallergy.org/gloria

GLORIA resource documents

Allergic Rhinitis and Its Impact on Asthma
(ARIA): JACI 2001:56: 813-824
Contemporary Approaches to Ocular Allergy
Management: American College of Allergy,
Asthma and Immunology, 1998.
Consensus Statement on the Treatment of
Allergic Rhinitis. Allergy 2000: 55: 116-134
World Allergy Forum program series: WAO
2000-2003

 Rhinitis: Symptomatic disorder of the nose

characterized by itching, nasal discharge,
sneezing and nasal airway obstruction
Allergic rhinitis: Induction of rhinitis symptoms
after allergen exposure by an IgE-mediated
immune reaction; accompanied by inflammation
of the nasal mucosa and nasal airway
hyperreactivity.

Rhinitis phenotypes
most common forms
Allergic
Infectious: Viral (acute), bacterial, fungal
Non-Allergic, Non-Infectious, Rhinitis
Non-Allergic Rhinitis with Eosinophilia Syndrome (NARES)
Chronic Rhinosinusitis with or without Polyps: Hypertrophic,
inflammatory disorder that can affect allergic or non-allergic
individuals

Rhinitis phenotypes
less common forms
Occupational: May be allergic or non-allergic
Drug-induced: Aspirin, some vasodilators
Hormonal: Pregnancy, menstruation, hormonal
contraceptives, thyroid disorders
Food-induced (gustatory)

Cold air-induced (skiers nose)

Atrophic (rhinitis of the elderly)

Conditions that mimic rhinitis

Cystic fibrosis
Mucociliary defects
Cerebrospinal rhinorrhoea

Anatomic abnormalities
Foreign bodies
Tumors
Granulomas: Sarcoid, Wegeners, Midline Granuloma

Non-allergic,
non-infectious rhinitis
(a poorly-defined phenotype)

Pathophysiologic hypotheses
Non-inflammatory (vasomotor)
Sensorineural hyperresponsiveness
Hyperesthesia
Dysautonomia

Local allergic reaction

Non-inflammatory rhinitis
1

*
0.75

Ratio of
eosinophils/
epithelial
cells
in mucosal
scrapings

0.5

0.25

0
Healthy
Controls
N = 25
Numata T et al:Int Arch Allergy Immunol 1999;119:304-313
S. Karger AG, Basel

Non-allergic
Rhinitis
N = 18

Allergic
Rhinitis
N = 25

Local allergic reaction

(nasal challenges with allergen in non-allergic rhinitics)

Copyright permission for reproduction pending

Carney et al. Clin Exp Allergy 2002;32:1436

IgE can be produced in the nasal mucosa

In situ hybridization for I mRNA - tissue obtained from subjects with alleric rhinitis

Not exposed to
ragweed

I RNA+ cells
(germline
transcript)

Cameron et al J Immunol 2003;171:3816

Exposed to
ragweed

Prevalence of rhinitis in adults

AUTHOR

YEAR

AGE RANGE

NUMBER OF
SUBJECTS

COUNTRY

PREVALENCE

Droste

1996

20-70

2,167

Netherlands

29.5%

Sakurai

1998

19-65 (males)

2,307

Japan

35.5%

Ng

1994

20-74

2,868

Singapore

10.8%

Bachert

2006

> 15

4,959

Belgium

39.3%

Dinmezel

2005

20-44

995

Turkey

27.7%

Sibbald

1991

16-65

2,969

United
Kingdom

24%

Turkeltaub

1991

12-74

12,742

United States

30.5%

Allergic vs. nonallergic rhinitis

N = 10,854; >12 years old; NHANES II data (USA, 1976-80)
Positive skin tests

AGE
Seasonal symptoms
or
Diagnosis of hay fever
(9.8%)

12-24
25-49

Perennial symptoms
and no
Diagnosis of hay fever
(20.4%)

12-24
25-49

Negative (or equivocal) skin tests

50-74

50-74

25

Adapted from Gergen and Turkeltaub Arch Int Med 1991;151:487

Copyright 1991, American Medical Association

50
75
% of subjects in each group

100

Current Prevalence of Allergic

Rhinoconjunctivitis
ISAAC phase 1 & 3 (7 years apart)
Age: 6-7 years

Copyright permission for reproduction pending

Adapted from Lancet 2006;368:733-743

Current Prevalence of Allergic

Rhinoconjunctivitis
ISAAC phase 1 & 3 (7 years apart)
Age: 13-14 years

Copyright permission for reproduction pending

Adapted from Lancet 2006;368:733-743

Allergic rhinitis: impact

High prevalence
Impaired quality of life
Work and school absence
Impaired learning

Impaired sleeping
Associated asthma, sinusitis, otitis

Short form health survey (SF-36)

profiles of patients with allergic rhinitis
controls (n=139)

90

allergic rhinitis (n=312)

85

scale: 0 to 100

80

Declining
health
status

75

70

*
*

65
60

55
50
Physical
Functioning

Role
Physical

Bodily
Pain

General
Health

Vitality

Domains

Adapted from Meltzer EO et al. J Allergy Clin Immunol. 1997;99:S815

Social
Functioning

Role
Emotional

Mental
Health

Change in
Health

Impairment due to allergic rhinitis:

work productivity and activity impairment questionnaire

Copyright permission for reproduction pending

Tanner LA et al. Am J Managed Care 1999;5(Suppl):S235

Allergic rhinitis co-morbidities

Conjunctivitis
Sinusitis

Otitis Media
Cough
Asthma

Co-existence of allergic conjunctivitis

with other allergic diseases
p=0.006

45
40
35
30
% with
conjunctivitis

25
20
15
10
5
0

All rhinitis
n=316

Asthma
n= 324

Eczema
n=149

Adapted from Gradman J and Wolthers OD Pediatr Allergy Immunol. 2006;17:524-6

All rhinitis + asthma

n=203

Presence of sinus disease based on CT findings in

patients with allergic rhinitis and controls
Total
With positive sinus CT
40

p=0.017

35
30
25

Number of subjects

67.5%

20
15
10

33.4%

5
0

Allergic rhinitis

Berrettini et al., Allergy. 1999;54:242-8.

Controls

Allergic rhinitis as a risk factor for chronic sinusitis

Ear Nose Throat-related flight disqualifying events that developed over a 5year period in Naval Flight Personnel with only allergic rhinitis (N=465)
versus controls (N=12,628)

Relative Risk

95% CI

Chonic Sinusitis

4.5

(1.7-11.6)

Alternobaric Disease

1.6

(0.4-6.6)

Polyposis

1.2

(0.2-8.7)

Conductive Hearing
Loss

0.9

(0.1-6.6)

Requirement for ENT

Surgery

3.4

(0.4-27.1)

Walker C. et al. Aviat Space Environ Med. 1998; 69:952

Allergic rhinitis: the basis of

co-morbidity with otitis media
with effusion
Copyright permission for reproduction pending

Adapted from Sobotta, Atlas der Anatomie des Menschen. Bd. 1, 21; 2000.

Risk factors for otitis media in children

O: otitis media with effusion (N=172)
C: controls (N=200 )

Copyright permission for reproduction pending

Adapted form Caffarelli et al., Clin Exp Allergy 1998;28:591-596

Risk factors for otitis media in children

Multivariate logistic regression for risk of OME

Case-control study in children 1-7 years (N=88 cases, N=88 controls)

Chantzi FM et al. Allergy 2006;61:332

Nasal treatment improves cough

in patients with seasonal allergic rhinitis
(15-day treatment)
1.0
0.8

Mean improvement
from baseline
in the cough
symptom score

0.6
0.4
0.2
0.0

Adapted from Gawchik S et al. Ann Allergy Asthma Immunol 2003;90:416

Mean baseline score: 2.3

Mometasone, N=122
Placebo, N=123

ALLERGIC RHINITIS AND ITS

IMPACT ON ASTHMA
ARIA

JACI 2001:56: 813-824

Perennial rhinitis: an independent risk

factor for asthma
(European Community Respiratory Health Survey)
25

20

OR=11

no rhinitis, N=5198
rhinitis, N=1412

15

Asthma (%)

OR=17

10

5
0

Atopic
Adapted from Leynaert B et al. J Allergy Clin Immunol 1999; 104:301

Non atopic

Association of rhinitis with incident asthma

in an adult cohort
(173 incident cases and 2,177 controls; approx. 10-yr follow-up)

odds ratio
for the
association
with asthma

Test for trend, p < 0.001

3
1

rhinitis

Guerra S et al. J Allergy Clin Immunol 2002;109:419

Test for trend, p < 0.001

In patients with rhinitis:

Routinely query for symptoms suggestive of asthma

Perform chest examination

Consider lung function testing
Consider tests for bronchial hyperresponsiveness in
selected cases

Allergic rhinitis classification

Intermittent
Symptoms
< 4 days / week
or < 4 weeks

Mild
Sleep: normal
Daily activities (incl. sports):
normal
Work-school activities: normal
Severe symptoms: no

Persistent

Symptoms
> 4 days / week
or > 4 weeks

Moderate- severe
Sleep: disturbed
Daily activities: Restricted
Work and school activities:
disrupted
Severe symptoms: yes

Seasonal allergic rhinitis intermittent

perennial allergic rhinitis persistent
Intermittent

Persistent

Seasonal
Allergic
Rhinitis (n=193)

133

60

Perennial
Allergic
Rhinitis (n=208)

151

57

Bauchau, V. & Durham, S. R. Allergy 2005; 60 (3), 350-353.

Globally important sources of allergens

House dust mites
Grass, tree and weed
pollen
Pets
Cockroaches
Molds

Diagnosis of allergic rhinitis

Detailed personal and family allergic history

Intranasal examination anterior rhinoscopy
Symptoms of other allergic diseases
Allergy skin tests
and/or
In vitro specific IgE tests

Allergy skin prick testing

Skin prick test / positive result

Concept of In Vitro IgE assays

Substrate
Enzyme

Secondary Ab
Sample to be
measured
Primary Ab

In Vitro specific IgE assay (standard curve)

spectrophotometric outcome (OD)

4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
0

200

400

600
IgE IU/ml

800

1000

1200

Immunoassay vs skin test for diagnosis

of allergy
Immunoassay
Not influenced by
medication
Not influenced by skin
disease
Does not require expertise
Quality control possible
Expensive

Skin test

Higher sensitivity
Immediate results
Requires expertise
Cheaper

Other diagnostic tests

Nasal secretion / scraping cytology

Nasal allergen challenge
Nasal endoscopy
CT scan
anatomic abnormalities
concomitant presence of sinusitis

The nasal allergic response

allergen
IgE

preformed &
newly formed
mediators/cytokines

cytokines
chemokines

Endothelial
cell activation

mast cell

allergen
dendritic cell

Leukocyte
infiltration and activation
(lymphocytes, eosinophils, basophils)

IL-4
IL-13

T-lymphocyte

B-lymphocyte

IMMEDIATE (early)
RESPONSE
Sneezing
Pruritus
Rhinorrhea
Nasal obstruction
Ocular symptoms

LATE-PHASE
RESPONSES
Nasal obstruction
Rhinorrhea

Nasal
hyperresponsiveness

To allergens
(priming)

To irritants and to
atmospheric changes

IgE

The immediate (early phase) allergic

reaction in the nose
brain

PRURITUS

sensory
nerves
epithelium
glands (mucous)

SNEEZING

blood vessels

OBSTRUCTION
RHINORRHEA

histamine
sulfidopeptide leukotrienes

Cellular infiltration and activation at the site of

an allergic reaction

Busse WW, Lemanske RF Jr. N Engl J Med. 2001;344:350-62.

Nasal hyperresponsiveness in allergic rhinitis

7
6
5
Sneezes
induced by
histamine*

4
3

p<0.0001

N = 25

2
1
* same dose in both groups

N = 18
0
Perennial
Allergic
Rhinitis

Sanico AM et al:Int Arch Allergy Immunol 1999;118:154-158

S. Karger AG, Basel

Healthy

Nasal priming in the natural

presentation of seasonal allergic rhinitis

The ratio of symptoms

to pollen counts almost
doubles between the
beginning to the end
of the pollen season

Norman P. J Allergy 1969;44:129

MANAGEMENT OF

ALLERGIC RHINITIS

Management of
Allergic Rhinitis: ARIA Guidelines

mild
intermittent

moderate
severe
intermittent

mild
persistent

moderate
severe
persistent

intranasal steroid

oral or local nonsedative H1-blocker

intranasal decongestant (<10 days) or oral decongestant
leukotriene receptor antagonists
avoidance of allergens, irritant and pollutants
immunotherapy

Modified from Bousquet J et al. J Allergy Clin Immunol. 2001;108:S147.

Stepwise management of allergic rhinitis

Copyright permission for reproduction pending

Modified from ARIA workshop, 2001

Environmental control
1. Allergens
House dust mites
Pets
Cockroaches
Molds
Pollen
2. Pollutants and Irritants

Allergen avoidance

Pets
Remove pets from bedrooms and, even better, from the entire home
Vacuum carpets, mattresses and upholstery regularly

Wash pets regularly ()

Molds
Ensure dry indoor conditions
Use ammonia to remove mold from bathrooms and other wet spaces

Cockroaches
Eradicate cockroaches with appropriate gel-type, non-volatile, insecticides
Eliminate dampness, cracks in floors, ceilings, cover food; wash surfaces, fabrics to remove
allergen

Pollen
Remain indoors with windows closed at peak pollen times
Wear sunglasses
Use air-conditioning, where possible
Install car pollen filter

House dust mite allergen avoidance

Provide adequate ventilation to decrease humidity
Wash bedding regularly at 60C
Encase pillow, mattress and quilt in allergen impermeable
covers
Use vacuum cleaner with HEPA filter
Dispose of feather bedding
Remove carpets
Remove curtains, pets and stuffed toys from bedroom

2003;349:237

Bed covers in persistent

allergic rhinitis

Der p1 and Der f1 in mattress (g/g of dust)

No. of patients

79

87

Base-line concentration

4.12 (2.93-5.79)

5.91 (4.00-8.73)

0.18

12-Mo concentration

1.29 (0.95-1.75)

4.84 (3.62-6.47)

<0.001

Mean change (95%Cl)

P value

.31 (0.21 to 0.46)

<0.001

0.82 (0.58 to 1.15)

0.25

Difference between changes

(95%Cl)
Terreehorst et al. N Engl J Med. 2003;349:237

0.38 (0.23 to 0.64)

<0.001

Bed covers in persistent allergic rhinitis

Variable

Impermeable-Cover
Group

Control Group

P
Value

No. of patients

114

118

Base-line score

52.18+2.79

49.82+2.76

0.56

12-Mo score

42.35+2.79

38.96+2.68

0.38

-9.83 (-15.28 to-4.39)

<0.001

-10.86 (-16.64 to-5.09)

<0.001

Primary end point

Rhinitis-spcific visual-analogue scale

Mean change (95%Cl)

P value
Difference between changes (95%Cl)

Terreehorst et al. N Engl J Med. 2003;349:237

1.03 (-6.87 to 8.94)

0.80

2004;351:1068-80

Environmental intervention in urban US

children with asthma
937 subjects
randomized

469 assigned
to environmental
intervention

444 included in
Year 2 analyses

407 included in
Year 2 analyses

Adapted from Morgan WJ et al. New Engl J Med 2004;351:1068-80

468 assigned
to control

425 included in
Year 1 analyses

414 included in
Year 2 analyses

Environmental intervention in urban

US children with asthma
Tailored to
Skin test profile
Environmental exposure
Caretakers report

House dust mite

Passive smoking

Adapted from Morgan WJ et al. New Engl J Med 2004;351:1068-80

Cockroaches
Pets
Rodents
Mold

Environmental intervention in urban

US children with asthma

The difference
between treatment
arms was
statistically
significant
(p<0.001) in both
phases of the study

Morgan WJ et al. New Engl J Med 2004;351:1068-80

Environmental control
The most logical strategy for disease that relates
to the indoor environment
Effectiveness requires comprehensive and
multifaceted measures
More studies are needed to also address the role
of indoor pollutants (e.g. NO2, PMs, tobacco
smoke, endotoxin)

PHARMACOTHERAPY OF
ALLERGIC RHINITIS

Agents and actions

Oral
antihistam
ines

Nasal
antihistam
ines

Cys-LT1
receptor
antagonists

Nasal
steroids

Nasal
decongest
ants

Oral
decongest
ants

Nasal
ipratropium

Nasal
cromones

Rhinorrhea

++

++

++

+++

+++

Congestion

+++

++++

++

Sneezing

++

++

++

+++

Pruritus

++

++

+++

Ocular symptoms

++

++

++

Onset of action

1 hr

15 min

48 hr

12 hr

5-15 min

1 hr

15-30 min

Duration

12-24 hr

6-12 hr

24 hr

12-48 hr

3-6 hr

12-24 hr

4-12 hr

2-6 hr

Modified from van Cauwenberge P Allergy 2000;55:116-134

Oral antihistamines
First generation agents

Newer agents

Chlorpheniramine

Acrivastine

Brompheniramine

Azelastine

Diphenydramine

Cetirizine

Promethazine

Desloratadine Fexofenadine

Tripolidine

Levocetirizine Loratadine

Hydroxyzine

Mizolastine

Azatadine

Nasal antihistamines
Azelastine
Levocabastine
Olopatadine

Simplified two-state model of the

histamine H1-receptor
Copyright permission for reproduction pending

Simons, F. E. R. N Engl J Med 2004;351:2203

Efficacy of an antihistamine over 6 months in

persistent allergic rhinitis
Sneezing

0.8

Pruritus Nose

1.0

mean
Individual
symptom
score
improvement

Rhinorrhea

0.6

Congestion

Pruritus Eyes

0.4

0.2

* P<0.05

1 wk

6 mo

1 wk

4 wk

6 mo
4 wk

1 wk

6 mo
4 wk

1 wk

6 mo
4 wk

1 wk

6 mo
4 wk

Baseline total symptom score: 8.95

Levocetirizine, 5 mg, N = 276
Placebo, N = 271

Bachert C et al. J Allergy Clin Immunol 2004:114:838

Efficacy of an antihistamine in the treatment of

allergic rhinitis with perennial symptoms

(n= 337)
(n= 339)

Simons FER et al., J Allergy Clin Immunol 2003;111:617

Newer antihistamines are equally effective

in the treatment of allergic rhinitis
0

Placebo
N =201

-0.5

Change from
baseline in
total symptom
score
(AM, instantaneous,
trough)

Fexofenadine 120 mg
N =211

-1.0
-1.5

Fexofenadine 180 mg
N =202

-2.0
-2.5
-3.0

*: <0.05 compared to placebo

Howarth P et al. J Allergy Clin Immunol 1999;104:927

Cetirizine 10 mg
N =207

*
Baseline symptoms
Study duration

Effectiveness of a nasal antihistamine in

allergic rhinitis with seasonal symptoms

Copyright permission for reproduction pending

Storms WW et al. Ear Nose Throat J. 1994;73:382.

Newer generation oral antihistamines

somnolence/drowsiness
Active

Placebo

Data Source

Cetirizine
10 mg qd

13.7%

6.3%

www.PDR.net

Desloratadine
5 mg qd

2.1%

1.8%

www.PDR.net

Fexofenadine
60 mg bid

1.3%

0.9%

www.PDR.net

Levocetirizine
5 mg qd

6.8%

1.8%

Bachert et al
JACI 2004;114:838

Loratadine
10 mg qd

8%

6%

www.PDR.net

Newer generation oral antihistamines

First line treatment for mild allergic rhinitis

Effective for
Rhinorrhea
Nasal pruritus
Sneezing

Less effective for

Nasal blockage

Possible additional anti-allergic and anti-inflammatory effect

In-vitro effect > in-vivo effect

Minimal or no sedative effects

Once daily administration

Rapid onset and 24 hour duration of action

Decongestants: alpha-2
adrenergic agonists
Oral

Pseudoephedrine

Nasal

Phenylephrine
Oxymetazoline
Xylometazoline

Decongestants: alpha-2
adrenergic agonists
nasal septum

nasal
turbinates

nasal airway lumen

vasoconstriction

Effect of a nasal decongestant under MRI imaging

Copyright permission for reproduction pending

Adapted from Ng BA et al. Ear, Nose and Throat J 1999;78:159

Efficacy of pseudoephedrine in
seasonal allergic rhinitis
Pseudoephedrine 120 mg twice daily, N=211

Placebo, N=212

1.0

0.8

*
Mean reduction
in nasal stuffiness score
from baseline

0.6

0.4

0.2

0.0
Day 4
Adapted from Bronsky E. et al. J Allergy Clin Immunol 1995;96:139

Endpoint

Overall
(15 days)

Nasal obstruction: antihistamine vs decongestant vs

vombination in allergic rhinitis with perennial symptoms
Cetirizine 5mg twice daily, N=70
Pseudoephedrine 120 mg twice daily , N=70

2.1

Combination, N=70
1.7

Nasal
obstruction
severity score
(scale: 0-3)

1.3
0.9
0.5
0

10

Day

Bertrand et al. Rhinology 1996;34:91

12

14

16

18

20

21

Decongestants
EFFICACY:

Oral decongestants: moderate

Nasal decongestants: high

ADVERSE EFFECTS:

Oral decongestants: insomnia, tachycardia, hyperkinesia

tremor, increased blood pressure, stroke (?)

Nasal decongestants: tachyphylaxis, rebound congestion, nasal

hyperresponsiveness, rhinitis medicamentosa

Mechanism of action of ipratropium bromide

indirect effect:
cholinergic

Acetylcholine
on
muscarinic
receptors

brain
sensory
nerves

vidian nerve

epithelium

RHINORRHEA

submucosal glands

direct effect of mediators:

not cholinergic

Efficacy of ipratropium bromide against

rhinorrhea in allergic rhinitis with perennial symptoms
6.0

3.0

5.0

2.5

4.0

Mean Duration
(hours/day)

*
*

3.0

*
2.0

Mean Severity
1.5
Score
(scale: 0-5)

2.0

1.0

1.0

0.5

0
Baseline Wk 1

Wk 2

Wk 3

Wk 4

Baseline Wk 1

Wk 2

Wk 3

Ipratropium, 42 g/nostril three times daily, N=42

Ipratropium, 21 g/nostril three times daily, N=39
Placebo, N=42
* p<0.05 against Placebo

Adapted from Meltzer E at al. J Allergy Clin Immunol 1992;90:242

Wk 4

Anticholinergic treatment:
ipratropium bromide
Nasal glands are activated by muscarinic, cholinergic receptors

Ipratropium bromide is a nonselective muscarinic receptor antagonist

Ipratropium bromide applied intranasally blocks rhinorrhea induced by

cholinergic stimulation
Ipratropium bromide has negligent systemic anticholinergic activity

Topical adverse effects: excessive dryness, epistaxis

Anti-leukotriene agents
CysLT1 Receptor

5-Lipoxygenase

Antagonists

Inhibitors

Montelukast *

Zileuton

Pranlukast *

Zafirlukast
* Approved for allergic rhinitis

Cysteinyl-leukotriene production and

the CysLT1 receptor
CysLT1
receptor

cytosolic
phospholipase A2
leukotriene C4
arachidonic
nucleus
acid
+
5-lipoxygenase
activating
protein
5-lipoxygenase
leukotriene A4

leukotriene C4

leukotriene D4
leukotriene E4

leukotriene C4
synthase

mast cells
basophils
eosinophils
macrophages

Efficacy of a CysLT1 receptor antagonist

in allergic rhinitis with seasonal symptoms
Daytime Nasal Symptoms Score
(0-3 point scale)
0

Change from
baseline
(mean, 95% CI)

-0.2

-0.4
-0.6

*
placebo, N=149
montelukast, N=155

mean baseline=2.0
*p<0.01 vs placebo
Adapted from Nayak, et al. Ann Allergy Asthma Immunol. 2002;88: 592

loratadine, N=301

Additive effects of CysLT1 receptor antagonists and

H1 receptor antagonists in allergic rhinitis ?
improvement

no change

worsening

70
60

50

% of
subjects

40
30
20
10
0

placebo

montelukast
10 mg

montelukast
20 mg

Adapted from Meltzer EO, et al. J Allergy Clin Immunol. 2000;105:917

loratadine
10 mg

montelukast
10 mg
+
loratadine
10 mg

Equipotency of CysLT1 receptor antagonist/antihistamine and

decongestant/antihistamine
on nasal peak inspiratory flow
230
220
210

200
Liters/min

190
180
170

Fexofenadine/Pseudoephedrine, N = 34

160

Loratadine/Montelukast, N = 34

150
B

Treatment Days
Adapted from Moinuddin R et al. Ann Allergy Asthma Immunol 2004;92:73

10

11

12

Anti-leukotriene treatment in
allergic rhinitis
Efficacy

Equipotent to H1 receptor antagonists but with onset of

action after 2 days
Reduce nasal and systemic eosinophilia
May be used for simultaneous treatment of allergic rhinitis and
asthma

Safety

Dyspepsia (approx. 2%)

Nasal vorticosteroids
Beclomethasone dipropionate
Budesonide
Ciclesonide*

Flunisolide
Fluticasone propionate
Mometasone furoate
Triamcinolone acetonide

* Currently only approved for asthma

Molecular effects of corticosteroids

Copyright permission for reproduction pending

Adapted from Barnes PJ. Eur J Pharmacol. 2006;533:2

Nasal corticosteroids
1

reduction of
mucosal mast cells

reduction of
mucosal inflammation

reduction of
late phase reactions
priming
nasal hyperresponsiveness

reduction of
acute allergic reactions

reduction of
symptoms and exacerbations

suppression of

glandular activity
and vascular leakage
induction of
vasoconstriction

Efficacy of nasal corticosteroid sprays in children with

allergic rhinitis and seasonal symptoms

Meltzer E. et al. J Allergy Clin Immunol. 1999;104:107.

Onset of action of intranasal budesonide Against

allergen exposure
(controlled environmental exposure - peak nasal inspiratory flow)

Day JH. et al. J Allergy Clin Immunol. 2000;105:489.

Comparative efficacy of
nasal corticosteroids

Mandl M. et al. Ann Allergy Asthma Immunol 1997;79:370

Various treatment combinations in

seasonal allergic rhinitis
Nasal congestion score, Scale: 0-3

Copyright permission for reproduction pending

Adapted from Di Lorenzo et al. Clin Exp Allergy 2004;934:259

Various treatment combinations in

seasonal allergic rhinitis
total symptom score
Scale: 0-12

Copyright permission for reproduction pending

Adapted from Di Lorenzo et al. Clin Exp Allergy 2004;934:259

Nasal corticosteroids
Most potent anti-inflammatory agents
Effective in treatment of all nasal symptoms including
obstruction
Superior to anti-histamines and anti-leukotienes
First line pharmacotherapy for persistent allergic
rhinitis

Nasal corticosteroids
Overall safe to use
Adverse Effects
Nasal irritation
Epistaxis
Septal perforation (extremely rare)
HPA axis suppression (inconsistent and not clinically
significant)
Suppressed growth (only in one study with
beclomethasone)

Nasal corticosteroid vs placebo: effects on 12-hour

urinary free Cortisol in 2-3 year-old children
6-week treatment

Value of 1 indicates
no change from baseline

1.0
0.8

Adjusted Geometric Mean 0.6

of the Change from Baseline 0.4

0.98

0.94

SE=1.14

SE=1.15

N=31

N=29

Fluticasone
Proprionate
Nasal Spray
200 g daily

Placebo

0.2

Adapted from Galant, S. P. et al. Pediatrics 2003;112:96

Allergen immunotherapy
(vaccines)
Subcutaneous

Sublingual

Nasal

Possible mechanisms of immune response

regulation by allergen immunotherapy

Th1

Treg-lymphocyte

DC

Th0-lymphocyte

Th2

Possible mechanism: allergen immunotherapy

induces regulatory T-lymphocytes
B
lymphocyte

interleukin 10
TGF
IgG4

Treg
lymphocyte

interleukin 10
TGF

TH2
lymphocyte

Subcutaneous immunotherapy:
effect on serum specific IgE
Initiation of
immunotherapy
70
60

August
November

50

Anti - ragweed
40
IgE
(ng/ml)
30
20
10
baseline

year 1

Adapted from: Peng et al. J Allergy Clin Immunol 1992;89:519

year 2

year 6

year 7

year 8

Long-term efficacy of subcutaneous immunotherapy

Copyright permission for reproduction pending

Durham et al. N Eng J Med 1999;341:468

Sublingual immunotherapy in
grass pollen-induced allergic rhinitis
SLIT, N=316
Placebo, N=318

Need:
Overall p value

Dahl R et al., J Allergy Clin Immunol. 2006;118:434.

Treatment: grass allergen

tablets
Dose?
Frequency?
Started how long before season?

Humanized monoclonal
anti-IgE antibody: omalizumab
IgE
Omalizumab
C3
region

Efficacy of omalizumab in seasonal allergic rhinitis

(ragweed pollen season)
1.4
SQ

treatments every 3-4 weeks x 3-4

First dose prior to the pollen season

1.2
1.0

Average
weekly
symptom
score

0.8

Placebo, N=136

0.6

Omalizumab
50mg, N=137
150mg, N=134
300mg. N=129

0.4
0.2
0.0
4

13 20 27

Aug

10

Casale T, et al. JAMA 2001;286:2956

Copyright 2001 American Medical Association. All Rights reserved

17 24

Sep

15 22 29

Oct

Omalizumab and subcutaneous

immunotherapy in children: study design
SIT (birch) + placebo

SIT (birch) + omalizumab

n = 54

n = 55

Prescreening
Randomization
SIT (grass) + omalizumab

n = 59

SIT (grass) + placebo

n = 53

SIT titration

Week 0
Kuehr J et al. J Allergy Clin Immunol 2002;109:274

Week 12

SIT maintenance + study drug

Week 36

Omalizumab and subcutaneous

immunotherapy in children: symptom load
(rescue medications + symptom severity scores)
grass pollen season

Copyright permission for reproduction pending

Kuehr J et al. J Allergy Clin Immunol 2002;109:274

Anti IgE - omalizumab

Not licensed to treat allergic rhinitis
Could be considered in severe cases
unresponsive to conventional treatment
Could be an adjunct to immunotherapy in severe
cases

World Allergy Organization (WAO)

For more information on the World Allergy
Organization (WAO), please visit
www.worldallery.org or contact the:
WAO Secretariat
555 East Wells Street, Suite 1100
Milwaukee, WI 53202
United States
Tel: +1 414 276 1791
Fax: +1 414 276 3349
Email: info@worldallergy.org