8/21/13

Key Content:

Impact of allergic rhinitis on asthma

Optimizing Management of
Allergic Rhinitis

Diagnosis in children and adults

Treatment of allergic rhinitis

- ARIA guideline
Orapan Pochanukoon, MD.
Associate Professor of Allergy and Immunology
Thammasat University

- Co-morbidities: ARC, RS

3. Thailand
(46.4%)

Prevalence of allergic diseases in Thailand

(6-7 years old)

Pediatr Allergy Immunol 2008.

5. Japan
(43.3%)
11. China
(38.6%)

Chiangmai
Asthma 7.8%
Allergic Rhinitis 23.5%
Atopic dermatitis 16.3%

27. USA
(30.25%)

Bangkok

Worldwide time trends for Allergic rhinitis

Asthma 15%
Allergic Rhinitis 43.2%
Atopic dermatitis 13.3%

Khonkaen
Asthma 10.5%
Allergic Rhinitis 29.3%
Atopic dermatitis 13.5%

Asthma, allergic rhinitis and rhinosinusitis

50. Sweden
(20%)
54. Albania
(14.2%)

The link between upper to lower airways disease

- 60-80% of asthma patients had allergic rhinitis.

- The younger patients with asthma had a higher co-morbid rate of rhinitis.

Sinusitus

Asthma

Central
Sensitization and
NasopharyngoBronchial reflexes

Dripping and
Aspiration of
Inflammatory
materail

Systemic
Propagation of
(para)nasal
inflammation

Allergic
Rhini2s

WAO Journal 2012; 5:S212S217

Lower airways disease

published data on the role of respiratory virus on the inception of

AR or long-term rhinitis symptoms. Regardless, the same set of
viruses suggested related to asthma, such as human rhinovirus,
respiratory synctitial virus, human parainfluenza virus, human
influenza virus and human coronavirus, have been detected in
infants with upper respiratory tract infection and rhinorrhea [40].
Since respiratory viruses have been shown to cause inflammatory
changes in the upper airway as has been seen in the lower airway
[41], it is plausible for respiratory virus infections to play a role in
Percentage
distribution
of rhinitis
according
to study in
the development
of AR
or NAR. severity
An ongoing
birth cohort
the severity of coexistent asthma.
Singapore (GUSTO; http://www.gusto.sg/) will focus on this role
of early respiratory viruses infections in development of rhinitis
including AR.
Burden and co-morbidities
Besides its direct effect on the quality of life, rhinitis has
significant co-morbid disorders (summarised in Fig. 3). The ARIA
recommendations
emphasizes
the concept of treating upper and
Intermi9ent
Mild
Moderate
Severe
asthma
Persistent
Persistent
Persistent
lower airway
airway, one disease which includes
asthma disorders
asthma as one
asthma
association was found between severity of rhinitis and severity of coexisting asthma (P= NS)
aNoholistic
approach towards the management of co-morbidities
apallergy.org

30% of patients had asthma

90

% of patients

Fig. 3. Relationship of rhinitis and its co-morbidities. Asia Pacific Allergy 2011.

119

http://dx.doi.org/10.5415/apallergy.2011.1.3.115

Allergic Rhini2s symptoms in Children and Adults

100

mometasone diproprionate have age limit approval from 2

years and above (with the exception for EMEA for mometasone
diproprionate where approval is for 6 years and above). Intranasal
application of medications may also be challenging in terms of 8/21/13
the childs co-operation with the application. In a recent study
in Singaporean children about a quarter of children prescribed
topical nasal medications refused to comply with therapy [47].
Montelukast is an additional anti-inflammatory agent that is
approved for use for AR in children above the age of 6 months.
Relationship of rhinitis and its co-morbidies

80
70
60

8 2



PE: swelling of turbinate, clear discharge
PEFR-normal

50

Adult

40

Children

30
20
10
0
Itching

Sneezing Rhinorrhea Obstruction

1. Bunnag C. APJAI 2000

Eye
symptoms

a. Asthma
b. Rhinosinusitis
c. Acute bronchitis
d. Allergic rhinoconjuntivitis
e. Nonallergic rhinitis

2. Poachanukoon O, et al. APJAI 2008.

Case

Sinusitis and chronic cough in children

admit
ICS

PE: no dyspnea, swelling of turbinate with clear D/C

86 patients, cough > 4 weeks, mean age 5 yr.

65% of children had positive films sinus
Symptoms of purulent rhinorrhea, inflamed

mucosa, PND and post-tussis emesis:

associate with abnormal sinus x-rays.

Wilson NM et al. Journal of Asthma and Allergy 2012; 5: 27-32.

8/21/13

Symptoms between ARS and CRS

Poachanukoon et al. APJAI 2012

rhinorrhea, cough, congestion

periorbital pain, sleep apnea

ARS

CRS
International
Immunopharmacology 2011

Symptoms of Patients with AR

100
90

"

"

"

"

//

"

"

Percent

80
70
60
50

Adult

40

Children

30
20
10
0
Itching

Sneezing

Rhinorrhea ObstrucJon

1. Bunnag C. APJAI 2000

Eye
symptoms

2. Poachanukoon O, et al. APJAI 2008.

5
6

8/21/13

Classification of AR symptoms
Symptom

Sneezers and runners

Blockers

Sneezing
Rhinorrhea

Paroxysmal
Always present: anterior
and posterior
Yes, often
Variable
Worsen on awakening,
improve during the day
Often present

Little or none
Vairable, can be thick
mucus and posterior
No
Often, severe
Constant day and night,
worsen at night
none

Nasal itching
Nasal blocker
Diurnal rhythm
conjunctivitis

Blocker Type

Scadding GK et al. Fast Facts: Rhinitis 2007

Linkage between upper and lower airways

Rhini2s

25-70 %

Sinusi2s/Polyps
30 million cases/year

Upper Airway
Obstruc2on
PNDS

86%

Asthma
Cough

OSA

GERD
NERD

Obesity



Mild
Normal sleep; no
Impairment of daily,
leisure, or sport activities;
Normal work or school; no
troublesome symptoms

Intermittent
AR

<4day/week
or <4 weeks

Symptoms
Rhinorrhea
Blocked nose
Itchy nose
Sneezing
Itchy eyes

4
/
4

>4day/week
and >4 weeks

Persistent
AR

Moderate-severe
One or more of the
Following: abnormal sleep;
Impairment of daily,
Leisure, or sport activities;
Abnormal work or school;
Troublesome symptoms

Intermittent
symptoms

Persistent
symptoms

8/21/13



Intermittent

- Antileukotrienes*

- Antileukotrienes*
2 - 4

*
antileukotrienes

Mild intermittent: ATH, LTRA ( AS)

-
-
- 1 ipratropium bromide
-

- 2

- *

- Antileukotrienes*
2 - 4

Persistent

12 2

CPM

Mod. to severe intermittent/mild persistent:

ATH, INS, LTRA ( AS)

Mod. to severe persistent: INS, ATH, LTRA

()

F/U at 2-4 weeks

a. INS
b. 2 generation ATH + pseudoephidrine
c. ATH + LTRA
d. ATH + intraocular mast cell stabilizer

Check asthma in severe or persistent AR

Intranasal corticosteroid
Beclomethasone dipropionate (BDP)
Budesonide (BUD)
Triamcinolone acetonide (TA)
Fluticasone propionate (FP)
Mometasone furoate (MF)
Fluticasone furoate (FF)

Dosage of INS in AR
Drugs

Recommended
dose

Beclomethosone (Beconase)

6-12 yr: 1 bid

> 12 yr: 1-2 bid

Budesonide (Rhinocort)

6-12 yr: 1 OD
> 12 yr: 1-2 OD

Fluticosone propionate (Flixonase)

> 4 yr: 1 OD
Adult 2 OD

Triamcinolone (Nasacort)

2-12 yr: 1 OD
> 12 yr: 2 OD

Mometasone (Nasonex)

2-12 yr: 1 OD
> 12 yr: 2 OD

Fluticasone furoate (Avamyst)

2-12 yr: 1 OD
> 12 yr: 2 OD

8/21/13

Correlation of binding of glucocorticoid to human

nasal tissue with RRA

Fluticasone furoate: low bioavailability

Bioavailability of currently used INS

3.5

FF

3.0

MF

FP

2.5

25

% bioavailability

Tissue binding (ng/mg)

4.0

2.0
1.5
1.0

R = 0.9423

Bud

0.5

11%
10

500

1000

1500

2000

2500

3000

3500

The correlaJon between nasal Jssue binding and relaJve aniJes to the human
glucocorJcoid receptor was high, with a coecient of correlaJon of
r = 0.971 (P<0.01)
Baumann D. Bachert C. Hogger P. et al. DissoluJon in nasal uid, retenJon and anJ-inammatory acJvity of uJcasone furoate in human nasal
Jssue ex vivo. Clinical & Experimental Allergy 2009; 39: 15401550

Fu2casone
furoate
(FF)

1)Nasal
symptom
(SAR &
PAR)
Indica2ons
2)Ocular
symptom
(SAR)

Flu2casone
propionate
(FP)

Beclo-
methasone
dipropionate

Budesonide
(BUD)

1)prophylaxis
1)Allergic
and
RhiniJs
1)Prophylaxis
Treatment SAR and
(SAR& PAR)
& PAR
treatment of 2)Nasal polyp
2)Hay fever
PAR & SAR 3)PrevenJon of
2)Vasomotor
3) Sinus
nasal polyp
pain and
acer
rhiniJs.
pressure
polypectomy

Mometasone
furoate
(MF)

0.5%

0.5%

Fluticasone
propionate

Mometasone
furoate

Budesonide

Flunisolide

Bryson HM, Faulds D. Drugs 1992;43:76075.

Daley-Yates PT, Baker RC. Br J Clin Pharmacol 2001;51:1035.
Daley-Yates PT et al. Eur J Clin Pharmacol 2004;60:2658.
Allen A et al. Clin Ther 2007;29:141520.

Triam-
cinolone
Acetonide

1)Allergic
RhiniJs (SAR
+ PAR)
Nasal
2)AdjuncJve
symptom
Acute
(SAR & PAR)
RhinosinusiJs
1)Nasal Polyp

2 years
Thailand

4 years
Thailand

6 years
Thailand

6 years
Thailand

3 years
Thailand

2 years
Thailand

Onset

8 hrs

12 hrs

3 days-3 weeks

4-48 hrs

12-72 hrs

24 hrs

NLED

Yes
( )

Yes
( )

Yes
( )

Yes
( )

Product informaJon




KaJal RK. Allergy Asthma Proc 2009:30:595-604.

0.5%

Fluticasone
furoate

Rela2ve receptor anity (RRA)

Prescribe
age

15

TCA

0.0

Generic
name

20%

20

12 2

CPM

*Approved indicaJon in adult

Potential side effects of INS

Local

Systemic

Dryness
Burning
Epistaxis

HPA axis suppression

Growth issues in children
Ocular changes-increase
intraocular pressure

Nasal septal perforation

15

76
70
48
80

NO evidence of damaging to nasal mucosa or growth

suppression in studies up to 1 year.
Blaiss MS. Allergy Asthma Proc 2011.

N= 260

8/21/13

12 2

CPM

A[tudes of nasal steroid

Questionnaires

% of
patients

Do you know anything about INS?

-Ive heard of them, but dont know much
-Effective/important drugs
-Dangerous drugs
Would you use INS if they were
prescribe?
-I would use them
-First, I would check the risk factors
-I would check with another doctor
-I would not use them

31
19
36

a. Add oral prednisolone (short course)

b. Double dose ATH

47
28
13
12

c. Add oral decongestant

d. Add LTRAs

Cingi C et al. Eur Arch Otorhinolaryngol 2010; 267: 725-30.

Stepwise algorithm for treatment of AR

add LTRA

Allergen avoidance

Oral antihistamines

a. Add systemic steroids

Intranasal corticosteroids

b. Add intranasal ephedrine

c. Add first generation ATH

Leukotriene receptor antigonists

d. immunotherapy

Allergen immunotherapy
Small and Kim Allergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S3.

Allergen-specific immunotherapy:
indication in respiratory allergy

Saline irrigation in upper respiratory conditions

Patient with allergic rhinitis/conjunctivitis and /or allergic asthma

who have evidence of specific IgE Ab:

-do not achieve control of symptoms with

avoidance and pharmacotherapy
-do not want ongoing or long-term pharmacotherapy
-experience undesirable side effects with pharmacotherapy

Allergen immunotherapy: Practice parameter. J Allergy Clin Immunol 2011.

Key clinical recommendation

Evidence
rating

Effective adjunctive treatment for CRS

Effective adjunctive treatment for AR, irritant

rhinitis, viral URI congestion, post-op FESS

Mild to moderate rhinitis of pregnancy, ARS

Side effect, mild, self-limited

Am Fam Physician 2009: 1117-9.

8/21/13

QoL, satisfaction and effectiveness at 2,4 weeks

Nasal Saline douches

Parameters

2nd visit (2 weeks)

3rd visit (4 weeks)

BHS

NSS

BHS

NSS

QOL

42.26.3+

48.914.4*+

43.09.2#

47.611.4#

Satisfaction

6.01.6

5.91.2

5.81.3

6.11.1

Medication use

11 (44%)

17 (73.9%)*

14 (56%)

14 (66.7%)

Episode URI

NA

NA

4 (16%)

6 (28.6%)

24 (96%)

22 (95.7%)

22 (88%)

20 (95.2%)

Side effect, no

* p< 0.05 compare between group in the same period

+ p < 0.05 in the same group (compare before and after treatment)
Satdhabudha A, Pochanukoon O .
Int J Pediatr Rhino Otolaryngol 2012.

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Control in rhinitis and rhinosinusitis

Treatment of AR relation to control (adapted from ARIA)

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8/21/13

12 2
AR SPT
positive to HDM
INS ATH 3

Strategies and Evidence for step up/down

Moderate to severe symptoms:

antihistamines + intranasal corticosteroids

INS

ATH

For resistant nasal symptoms: add LTRAs

ATH+INS 3-6

After control of symptoms with combination therapy,

(influence different pathogenic mechanism)

discontinue add on medications

NEJM 2005; 353: 1934-44.

Minimal Persistent Inflammation

Continuous or on-demand therapy

Symptoms

Mild intermittent: on demand treatment

Mod. to severe intermittent: continuous to prevent

development of persistent rhinitis

ALLERGENS

Persistent: continuous treatment

No symptoms

ATH and INCs are more effective if continuous

Inflammation

Laekeman et al. Respiratory Medicine 2010; 104: 615-625.

Particular situations in which MPI should be present

Polysensitized patients
Occupational/personal exposure to the allergen
Perennial allergen (HDM)
Exposure to allergen with prolonged pollination periods
Environmental pollution: ozone, NO2, diesel exhaust

particles

Summary and Conclusions

INSs have potent anti-inflammatory effects and

effectively treat the associated consequences of ARC

and RS
Long term medication should be recommended in a

patients with moderate to severe persistent.

Lack of improvement with INS, adherence and spray

technique should be assessed.

Montoro J et al. J Investig Allergol Clin Immunol 2007.

8/21/13

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