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Orapan Pochanukoon, MD. Associate Professor of Allergy and Immunology

Thammasat University

Optimizing Management of Allergic Rhinitis

Impact of allergic rhinitis on asthma

Diagnosis in children and adults

Treatment of allergic rhinitis

- ARIA guideline

- Co-morbidities: ARC, RS

Key Content:

ChiangmaiAsthma 7.8% Allergic Rhinitis 23.5% Atopic dermatitis 16.3%

Prevalence of allergic diseases in Thailand

BangkokAsthma 15% Allergic Rhinitis 43.2% Atopic dermatitis 13.3%

KhonkaenAsthma 10.5% Allergic Rhinitis 29.3% Atopic dermatitis 13.5%

(6-7 years old)

Pediatr Allergy Immunol 2008.

3. Thailand (46.4%)

5. Japan (43.3%)

27. USA (30.25%)

11. China (38.6%)

50. Sweden (20%)

54. Albania (14.2%)

Worldwide time trends for Allergic rhinitis

- 60-80% of asthma patients had allergic rhinitis. - The younger patients with asthma had a higher co-morbid rate of rhinitis.

WAO Journal 2012; 5:S212S217

Sinusitus Asthma

Allergic Rhini2s

Asthma, allergic rhinitis and rhinosinusitis The link between upper to lower airways disease

Central Sensitization and Nasopharyngo- Bronchial reflexes

Dripping and Aspiration of Inflammatory materail

Systemic Propagation of (para)nasal inflammation

Lower airways disease

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Percentage distribution of rhinitis severity according to the severity of coexistent asthma.

No association was found between severity of rhinitis and severity of coexisting asthma (P= NS)

Intermi9ent asthma

Mild Persistent asthma

Moderate Persistent asthma

Severe Persistent asthma

apallergy.org

Rhinitis in children less than 6 years old

http://dx.doi.org/10.5415/apallergy.2011.1.3.115 119

rhinitis. However, there were protective e!ects against rhinitis at low and high levels of endotoxins instead [18]. Another study of the association between exposure to components of dust and moulds suggested a possible protective factor, though it is only observed in one of the two groups of subjects [32].

Dietary patterns may have protective effects. Several studies have found extended period of breastfeeding to be protective [18, 33]. However, this protective e!ect was not consistently observed [18, 21, 23, 28]. Though the age of introduction of solid foods in general did not a!ect the risk of rhinitis [34], early introduction of fish into diet of infants were shown to be correlated to reduced risk of AR [23, 28, 33]. Interestingly a study was done to assess the correlation between maternal vitamin D intake during pregnancy and AR outcome at 5 years old where maternal vitamin D intake from food protected against rhinitis [35].

The role of viral infectionsRespiratory virus infections have been suggested to play a

significant role in the inception and exacerbation of asthma [36]. The biological link between respiratory virus infection with wheezing and asthma had been also been studied widely [37]. Birth cohort studies focused on studying asthma have shown that respiratory viruses are commonly detected in infants and young children with rhinorrhoea [38, 39]. Till date, there have not been 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 in"ammatory 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 the development of AR or NAR. An ongoing birth cohort study in 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-morbiditiesBesides its direct ef fect 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 lower airway disorders as one airway, one disease which includes a holistic approach towards the management of co-morbidities

such as asthma, sinusitis, otitis media and conjunctivitis [42]. Adenoidal hypertrophy may be associated with AR [43].

Conversely adenoidal hypertrophy may mimic the symptoms of AR and therefore should always be considered in young children diagnosed with a diagnosis of AR [7]. Otitis media with effusion is often a co-morbidity of AR and NAR and should be evaluated in all young children with rhinitis. Recent onset otitis media with e!usion in children [44] or occurring in the #rst 2 years of life [45] is associated with rhinitis at 6 years of age.

Management of rhinitisThe management of rhinitis and its co-morbidities in young

children may require a multidisciplinary approach involving the paediatrician or paediatric allergist and the otolaryngologist. Fig. 4 is a suggested management strategy for young children with rhinitis.

A signif icant unmet need lies in the pharmacological armamentarum that is approved for use in children less than 2 years of age. First generation antihistamines are not recommended due to its sedative e!ect [2, 7, 8]. A second generation antihistamine, fexofenadine, had been tested to be safe in children 2 years old or older for management of AR [46] and from 6 months for chronic urticaria . Cetirizine and desloratidine have approval of use for AR in children as young as 6 months of age.

Intranasal corticosteroids such as mometasone furoate and 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 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.

Fig. 3. Relationship of rhinitis and its co-morbidities.

Relationship of rhinitis and its co-morbidies

Asia Pacific Allergy 2011.

Allergic Rhini2s symptoms in Children and Adults

0 10 20 30 40 50 60 70 80 90

100

Itching Sneezing Rhinorrhea Obstruction Eye symptoms

Adult

Children

1. Bunnag C. APJAI 2000 2. Poachanukoon O, et al. APJAI 2008.

% o

f pat

ient

s

30% of patients had asthma

8 2 PE: swelling of turbinate, clear discharge PEFR-normal a. Asthma b. Rhinosinusitis c. Acute bronchitis d. Allergic rhinoconjuntivitis e. Nonallergic rhinitis

Case 4

admit ICS

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

Sinusitis and chronic cough in children

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.

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Symptoms between ARS and CRS

Poachanukoon et al. APJAI 2012

rhinorrhea, cough, congestion

periorbital pain, sleep apnea ARS

CRS

International Immunopharmacology 2011

0 10 20 30 40 50 60 70 80 90

100

Itching Sneezing Rhinorrhea ObstrucJon Eye symptoms

Adult

Children

1. Bunnag C. APJAI 2000 2. Poachanukoon O, et al. APJAI 2008.

Per

cent

12

Symptoms of Patients with AR

" " " / " // " "

5 6

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Classification of AR symptoms

Symptom Sneezers and runners Blockers Sneezing Rhinorrhea Nasal itching Nasal blocker Diurnal rhythm conjunctivitis

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

Scadding GK et al. Fast Facts: Rhinitis 2007

Blocker Type

Linkage between upper and lower airways

25-70 % Rhini2s

PNDS 86%

Asthma Cough

OSA

Obesity

GERD NERD

?

Upper Airway Obstruc2on

Sinusi2s/Polyps 30 million cases/year

Mild

Normal sleep; no Impairment of daily,

leisure, or sport activities; Normal work or school; no

troublesome symptoms

Moderate-severe One or more of the

Following: abnormal sleep; Impairment of daily,

Leisure, or sport activities; Abnormal work or school; Troublesome symptoms

Intermittent AR Persistent

AR

>4day/week and >4 weeks

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-

-

Intermittent Persistent

- - Antileukotrienes*

- - * - Antileukotrienes*

- - - Antileukotrienes*

2 - 4 2 - 4

* antileukotrienes

?

- -

3

- 2 - - - 1 ipratropium bromide

1

1

/

Mild intermittent: ATH, LTRA ( AS) Mod. to severe intermittent/mild persistent:

ATH, INS, LTRA ( AS) Mod. to severe persistent: INS, ATH, LTRA

() F/U at 2-4 weeks

Check asthma in severe or persistent AR

12 2 CPM

a. INS

b. 2 generation ATH + pseudoephidrine

c. ATH + LTRA

d. ATH + intraocular mast cell stabilizer

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

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Correlation of binding of glucocorticoid to human nasal tissue with RRA

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

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

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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

31 19 36

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

47 28 13 12

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

a. Add oral prednisolone (short course)

b. Double dose ATH

c. Add oral decongestant

d. Add LTRAs

12 2 CPM

add LTRA

a. Add systemic steroids

b. Add intranasal ephedrine

c. Add first generation ATH

d. immunotherapy

Stepwise algorithm for treatment of AR

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

Allergen avoidance

Oral antihistamines

Intranasal corticosteroids

Leukotriene receptor antigonists

Allergen immunotherapy

Allergen-specific immunotherapy: indication in respiratory allergy

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.

Saline irrigation in upper respiratory conditions

Am Fam Physician 2009: 1117-9.

Key clinical recommendation Evidence rating

Effective adjunctive treatment for CRS A

Effective adjunctive treatment for AR, irritant rhinitis, viral URI congestion, post-op FESS

B

Mild to moderate rhinitis of pregnancy, ARS C

Side effect, mild, self-limited B

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QoL, satisfaction and effectiveness at 2,4 weeks

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%)

Side effect, no 24 (96%) 22 (95.7%) 22 (88%) 20 (95.2%)

* 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.

Nasal Saline douches

Bubble mixed saline nasal irrigation Nasal Irriga2on on

TU Bubble Mixed Saline Nasal Irrigator h9p://www.youtube.com/watch?v=aBawLjyOSgE

http://youtu.be/rFHV912Ykuo

www.tuasthmaclub.com

acknowledge the fact that each of these factors may act inconcert to induce sinonasal inflammation. Like in AR, similarenvironmental and hormonal factors may aggravate sinonasalinflammation. In addition, immune deficiencies, mucociliarydysfunction and cystic fibrosis may underlie uncontrolledCRS (3). CRS is often found in asthma and COPD patients(24), with more recurrent disease after surgery in the asthmapatients than in nonasthma patients (25). Within the CRSgroup, patients with NP represent a group with a typical

inflammatory profile, with aspirin-intolerant patients present-ing with the most severe form of CRSwNP (3).

Diagnosis-related factors of uncontrolled upper airwaysymptoms

In uncontrolled upper airway disease, one needs to reconsiderthe diagnosis of AR and/or CRS at a certain stage (Fig. 2and 3), in an attempt to find out whether any other factors

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Figure 3 Treatment algorithm for CRS in relation to the recently

proposed terminology of disease control, with proposed treat-

ments adapted from the treatment algorithms of EPOS update

2012 (3).

2012 John Wiley & Sons A/S

Control in rhinitis and rhinosinusitis Hellings et al.Treatment of AR relation to control (adapted from ARIA) Allergy 2012.

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Thai guideline

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12 2 AR SPT positive to HDM INS ATH 3

. INS

. ATH

. ATH+INS 3-6

.

Strategies and Evidence for step up/down

Moderate to severe symptoms:

antihistamines + intranasal corticosteroids

(influence different pathogenic mechanism)

For resistant nasal symptoms: add LTRAs

After control of symptoms with combination therapy, discontinue add on medications

NEJM 2005; 353: 1934-44.

Continuous or on-demand therapy

Mild intermittent: on demand treatment

Mod. to severe intermittent: continuous to prevent development of persistent rhinitis

Persistent: continuous treatment

ATH and INCs are more effective if continuous

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

Symptoms

No symptoms

Inflammation

Minimal Persistent Inflammation

ALLERGENS

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

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

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.

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