optimizing management of ar-tpac2013.pdf
TRANSCRIPT
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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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