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Allergic RhinitisUpdate 2008

Prof. Ralph Mösges

Otorhinolaryngologist and Allergologist

University Hospital of Cologne

An atopic family

Augustus Claudius Britanicus

Allergic Rhinitis Update 2008

• Epidemiology

• Etiology

• Mechanisms

• Management

C. von Pirquet

Are we trading oneepidemic against anotherone?

Asthma prevalence,children and young adults

%

0.01

100

1.0

10

0.1

1920 1940 1960 1980 2000 2020

Year1930 1950 1970 1990 2010

Courtesy SGO Johansson

The problem

Prevalence of atopic conditions in 12-13 year olds1973* / 1988* / 1996**

30

25

20

15

10

5

0Asthma Rhinitis

%

Doubling every 8 years* Burr et al 1989 Arch Dis Child 64: 1452**Kaur et al 1997 Brit Med J

Allergy is more present in the medical field

Rhinitis prevalencein the east of Germany

0,0%

0,5%

1,0%

1,5%

2,0%

2,5%

3,0%

3,5%

91-93 94-96 96-98

doubling every 3 years

1920 1960 2000

The cohort effect„allergy decreases with age“

When does Allergy begin?

25%

Allergy is an transmissible disease!

Riskfactor spouse/husband

The Causes of Allergic Rhinitis

The Causes of allergic rhinitis

• Genes

• Hygene

• Environmental exposure

• Vaccination studies!

The mechanisms

Some mediators of allergy

SerotoninSerotoninAdenosineAdenosineNitric oxideNitric oxideSuperoxideSuperoxidePeroxynitritePeroxynitrite

PGEPGE22PGIPGI22PGFPGF22ααPGDPGD22TxATxA22LTDLTD44HPETEsHPETEsdidi--HETESHETESLipoxinsLipoxinsPAF PAF

AChAChSPSPNKANKANPKNPKCGRPCGRPVIPVIPGalGalNPYNPY

EndothelinsEndothelinsBradykininBradykininKallidinKallidinC5aC5aC3aC3a

ILIL--11ββILIL--22ILIL--33ILIL--44ILIL--55ILIL--66ILIL--77ILIL--99ILIL--1010ILIL--1111ILIL--1212ILIL--1313ILIL--1515ILIL--1616ILIL--1717ILIL--1818ILIL--nnnn

TNFTNF--ααGMGM--CSFCSFSCFSCFIFNIFN--γγOncostatinOncostatinLIFLIF

ILIL--88RANTESRANTESEotaxinEotaxin--11EotaxinEotaxin--22EotaxinEotaxin--33MIPMIP--11ααMCPMCP--11MCPMCP--22MCPMCP--33MCPMCP--44MDCMDCSDFSDF--11αα//ββTARCTARC

PDGFPDGFFGFFGFTGFTGF--ββEGFEGFVEGFVEGFBMPBMPIGFIGF

TryptaseTryptaseChymaseChymasehNEhNEMMPMMP--22MMPMMP--99

HistamineHistamine

Barnes PJ et al. Pharmacol Rev 1998

The mechanisms

• Dendritic cells

• T-reg cells

• Cytokines

• Chemokines

• Mediators

The management of AR

• Diagnosis

• Prevention

• Therapy

Diagnostics

• Anamnesis

• Skin test

• NPT / CPT

• Lab Test– IgE

–Basophils

Diagnostics

• Micro-Array-Technology

Prevalence of Allergies is Increasing

• >80 million people in Europe have some form of allergy1

• Research worldwide shows a steep rise in prevalence of asthma and allergic rhinitis (AR)2

• Allergic rhinoconjunctivitis affects about 20% of the population globally3

• New sensitisations / Onset of allergic diseases also in elder patients

1. EFA. http://www.efanet.org/allergy/index.htnl;2. Green RJ. Current Allergy & Clinical Immunology 2003;

3. World Allergy Organization. http://www.worldallergy.org/media/globalstatistics.shtml

Exposure to Novel Outdoor Allergensis also Increasing

• Spread of invasive, non-native plant species has increased

– increase in ragweed and birch pollen allergen in Europe1, 2, 3

1.1. AseroAsero R. Allergy 2002 R. Allergy 2002

2.2. LaaidiLaaidi M. et al. Ann M. et al. Ann Allergy Asthma Allergy Asthma ImmunolImmunol20032003

3.3. KlimekKlimek L. et al. HNO 2006L. et al. HNO 2006

Evolution of Ambrosia pollen concentrations

1989 1997

20082008

Exposure to Novel Outdoor Allergens - Consequences

• Previously non-allergic individuals may develop allergies

• Previously allergic individuals may become polysensitised

Allergic Rhinitis is often causedby polysensitisation

05

1015202530354045

1 2 3 4 5+number of triggers

% p

atie

nts

Valovirta E. Curr Opinion Allergy Immunol; in press

Moderate-severeone or more items

. abnormal sleep

. impairment of daily activities, sport, leisure

. abnormal work

Persistent . > 4 days per week. and > 4 weeks

Mildnormal sleep

& no impairment of daily activities, sport, leisure

& normal work and school

& no troublesomesymptoms

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

ARIA Classification

in untreated patients

Allergic rhinitis complaintsARIA Classification

Persistent Mild5.35%

Intermittent Mild22.9%

Persistent Moderate/severe

30.79%

Intermittent Moderate/severe

40.96%

Bachert C, Belgian Survey 2004

What is today‘s situation?

40%

Take your patient seriously!Among the 295 matched patient-physicianrecords, the physicians rated 4.8% of the patientsas having severe allergic rhinitis, while 14.8% of the patients gave themselves such a rating. Thephysicians gave a rating of mild to 43.5% of patients, while 31.3% of patients self-rated theirdisease as mild. Moderate ratings were given by51.7% of physicians and 54.0% of patients. Physicians reported sleep disturbance in 23.4%,compared with such reports by 47.2% of patients.

Today’s Allergies RequireNew Treatment Strategies

PollutionPollution↑↑ SensitisationSensitisation↑↑ ResponsivenessResponsiveness↑↑ AllergenicityAllergenicity

Indoor lifestyle / Indoor lifestyle / Novel AllergensNovel AllergensPerennial exposurePerennial exposurePolysensitisationPolysensitisation

NeuroimmunologicalNeuroimmunologicalfactorsfactors

↑↑ SensitisationSensitisation↑↑ ManifestationManifestation

Severe symptomsSevere symptoms Persistent symptomsPersistent symptoms

Need for new treatment strategiesNeed for new treatment strategies

Therapy

Leuko-trienreceptor-antagonists

Dekongestants

Allergen-specific

Immunotherapy

Cromones

Antihistamines

Glukocortico-steroids

Drug-therapy

Anti-IgE

Treatment of allergic rhinitis (ARIA)

Allergen and irritant avoidanceAllergen and irritant avoidance

ImmunotherapyImmunotherapy

Intra-nasal decongestant (< 10 days) or oral decongestantIntra-nasal decongestant (< 10 days) or oral decongestant

Local cromoneLocal cromone

Oral or local non-sedative H1-blockerOral or local non-sedative H1-blocker

Intra-nasal steroidIntra-nasal steroid

Mildintermittent

Mildintermittent

Moderatesevere

intermittent

Moderatesevere

intermittent

Mildpersistent

Mildpersistent

Moderatesevere

persistent

Moderatesevere

persistent

ARIA guidelines

New ARIA Guideline

Meta-Analysis of placebo-controlled clinical trials

-0,7

-0,6

-0,5

-0,4

-0,3

-0,2

-0,1

0

0,1

Fexofenadin Cetirizin Levocetirizin Ebastin Rupatadin Mizolastin Desloratadin Loratadin

Antihistaminikum

Effe

ktm

aß

no comedicationcomedication

Monotherapy

0,00 1,00 2,00 3,00 4,00 5,00 6,00 7,00 8,00 9,00

Baselinevalue nasal sum score

0,00

2,00

4,00

6,00

Mea

n im

prov

emen

t of n

asal

sum

sco

re

p < 0.001

Monotherapy

0,00

1,00

2,00

3,00

Mea

n im

prov

emen

t of n

asal

sum

sco

re

n=12708

3,69

n=1820

3,31

no comedication comedication

0,001,00

Spray or steroid

0 1 2 3

n=3405

0,76

n=75

0,44

n=4381

1,45

n=156

0,97

n=2592

2,13

n=210

1,79

n=2686

-0,03

n=29

-0,10

Mea

n im

prov

emen

t of c

onge

stio

n

2,00

1,50

1,00

0,50

0,00

Congestion

Prophylactic treatmentim

pairm

ent

5%

30%

37%

7-10%

16-20%

Anti leucotriens

Local steroids

Anti H1SLIT Tablets

SIT vs symptomatic drugsEfficacy of symptomatic drugs in rhinitis(improvement vs placebo)

SCIT

Source : Wilson study quoted by S. Duhram ( JACI 2006)

0

10

20

30

40

50

60

Durham et al,75.000 SQ-T

Dahl et al,75.000 SQ-T

Mösges et al,300 IR

Didier, 300 IR

Red

uktio

n im

Ver

glei

ch z

u P

lace

bo (%

) SymptomscoreMedikationsscore

1. Dahl R, Kapp A, Colombo G, Monchy J, Rak S, Emminger W, Rivas MF, Ribel M, Durham SR (2006) Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 118:434-440

2. Didier A (2006) Randomised, double-blind, placebo-controlled, multinational, multi-centre, Phase IIb/III study of the efficacy and safetyof three doses of sublingual immunotherapy (SLIT) administered as tablets* once daily to patients suffering from grass pollen rhinoconjunctivitis. In: XXV EAACI Congress Vienna

3. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S (2006) Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 117:802-809

4. Mösges et al.: Eigene Auswertung

73%

Most frequent related adverse events (AE)Incidence of at least 5 % (safety population)

0

10

20

30

40

50

60

70

80

90

100

Ear pruritus Oedema mouth Oral pruritus Tongue oedema Throat irritation

% o

f pat

ient

s

Placebo 100 IR 300 IR 500 IRN=156 N=157 N=155 N=160

38%

• No serious AE were related to treatment

Intra-lymphnodal-IT

• Randomized controlled study

• n=154

• 3 injections à 1000 SQas efficient as

• 3 years with injections of 4.000.000 SQ

• Less side effects

10 points to remember1. Allergic rhinitis is a major chronic respiratory disease due to its:

prevalenceimpact on quality of lifeimpact on work/school performance and productivityeconomic burdenlinks with asthma

2. In addition, allergic rhinitis is associated with sinusitis and other co-morbidities such as conjunctivitis

3. Allergic rhinitis should be considered as a risk factor for asthma alongwith other known risk factors

4. A new subdivision of allergic rhinitis has been proposed:Intermittent – persistent

5. The severity of allergic rhinitis has been classified as mild ormoderate/severe depending on the severity of symptoms and quality

of life outcomes

10 points to remember6. Depending on the subdivision and severity of allergic rhinitis, a stepwise

therapeutic approach has been proposed

7. The treatment of allergic rhinitis combines:allergen avoidance (when possible)pharmacotherapyimmunotherapyEducation

8. Patients with persistent allergic rhinitis should be evaluated for asthmaby history, chest examination and, if possible and when necessary, theassessment of airflow obstruction before and after bronchodilator

9. Patients with asthma should be appropriately evaluated (history and physical examination) for rhinitis

10. A combined strategy should ideally be used to treat the upper and lowerairway diseases in terms of efficacy and safety

5 points to remember• Think of allergy in sinusitis patients

• Longer treatment duration• Continuous treatment

• Avoid combinations, they reduce patients‘compliance

• Use potent compounds

KISS –KeepItSimple &Small

Allergic RhinitisUpdate 2008

Prof. Ralph Mösges

Otorhinolaryngologist and Allergologist

University Hospital of Cologne