investigating and managing upper airway disorders-kalayci · 2015. 10. 2. · – routinely query...
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RHINITIS
Ömer KALAYCI, MDProfessor of Pediatrics, Allergy, AsthmaHacettepe University School of Medicine
Ankara, Turkey
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• 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.
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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
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Non-allergic rhinitis
• Has a multifactorial etiology.
• Is a risk factor for the development of asthma.
• If eosinophilic, usually responds to treatment with corticosteroids.
• May be a presenting complaint for systemic disorders such as Wegener’s granulomatosis, Churg–Strauss and sarcoidoisis.
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Infectious rhinitis
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• 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 (skier’s nose)
• Atrophic (rhinitis of the elderly)
Rhinitis Phenotypes
less common forms
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• Cystic fibrosis
• Mucociliary defects
• Cerebrospinal rhinorrhoea
• Anatomic abnormalities
• Foreign bodies
• Tumors
• Granulomas: Sarcoid, Wegener’s, Midline Granuloma
Conditions that Mimic Rhinitis
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Non-Allergic, Non-Infectious Rhinitis(a poorly-defined phenotype)
Pathophysiologic hypotheses
• Non-inflammatory (vasomotor)– Sensorineural hyperresponsiveness
– Hyperesthesia– Dysautonomia
• Local allergic reaction
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Cameron et al J Immunol 2003;171:3816
In situ hybridization for Iε mRNA - tissue obtained from subjects with alleric rhinitis
Iε RNA+ cells(germline transcript)
Not exposed toragweed
Exposed toragweed
IgE can be produced in the nasal mucosa
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Local Allergic Reaction(nasal challenges with allergen in non-allergic rhinitics)
Carney et al. Clin Exp Allergy 2002;32:1436
Resistance(most obstructed
nostril)
Individual dataIndividual data
N=21N=21
00
prepre --challengechallenge
postpost --challengechallenge
1010
88
66
44
22
All these subjects hadno response to a control challenge with diluent
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Allergic Rhinitis: Impact
• High prevalence
• Impaired quality of life
• Work and school absence
• Impaired learning
• Impaired sleeping
• Associated asthma, sinusitis, otitis
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Adapted from Meltzer EO et al. J Allergy Clin Immunol. 1997;99:S815
Short Form Health Survey (SF-36) Profiles of Patients with Allergic Rhinitis
*
*
*
*
**
50
55
60
65
70
75
80
85
90
PhysicalFunctioning
Role–Physical
Bodily Pain
GeneralHealth
Vitality Social
Functioning
Role–Emotional
MentalHealth
Change inHealth
allergic rhinitis (n=312)
controls (n=139)
†
Declininghealthstatus
Domains
scale: 0 to 100
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Allergic Rhinitis Co-Morbidities
• Conjunctivitis
• Sinusitis
• Otitis Media
• Cough
• Asthma
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Berrettini et al., Allergy. 1999;54:242-8.
Presence of Sinus Disease Based on CT Findings in Patients with Allergic Rhinitis and Controls
67.5%
33.4%
0
5
10
15
20
25
30
35
40
Number of subjects
Allergic rhinitis Controls
Total With positive sinus CT
p=0.017
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Allergic Rhinitis as a Risk Factor for Chronic Sinu sitis
Ear Nose Throat-related flight disqualifying events that developed over a 5-year period in Naval Flight Personnel with only allergic
rhinitis (N=465) versus controls (N=12,628)
Walker C. et al. Aviat Space Environ Med. 1998; 69:952
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)
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Allergic rhinitis: The basis of co-morbidity with o titis media with effusion
Allergic inflammation and edema obstruct the eustachian tube
Allergic nasopharyngeal obstruction and secretions facilitate microbial middle ear inflammation
Middle ear functions as an allergic target organ
Adapted from Sobotta, Atlas der Anatomie des Menschen. Bd. 1, 21; 2000.
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ALLERGIC RHINITIS AND ITS IMPACT ON ASTHMAARIA
JACI 2001:56: 813-824
Allergy 2008: 63 (Suppl. 86): 8–160
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Perennial Rhinitis: an Independent Risk Factor for Asthma
(European Community Respiratory Health Survey)
adapted from Leynaert B et al. J Allergy Clin Immunol 1999; 104:301
asthma (%)
Atopic Non atopic
no rhinitis, N=5198
rhinitis, N=1412
OR=11
OR=17
0
5
10
15
20
25
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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
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IntermittentSymptoms
• < 4 days / week• or < 4 weeks
PersistentSymptoms
• > 4 days / week• or > 4 weeks
Mild• Sleep: normal• Daily activities (incl. sports): normal• Work-school activities: normal• Severe symptoms: no
Moderate- severe• Sleep: disturbed• Daily activities: Restricted• Work and school activities: disrupted• Severe symptoms: yes
Allergic Rhinitis Classification
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Seasonal Allergic Rhinitis ≠ IntermittentPerennial Allergic Rhinitis ≠ Persistent
Intermittent Persistent
SeasonalAllergic
Rhinitis (n=193)133 60
PerennialAllergic
Rhinitis (n=208)151 57
Bauchau, V. & Durham, S. R. Allergy 2005; 60 (3), 350-353.
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Globally Important Sources of Allergens
• House dust mites• Grass, tree and
weed pollen• Pets• Cockroaches• Molds
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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
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Allergy Skin Prick Testing
• Skin prick test / positive result
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Primary Ab
Secondary Ab
Enzyme
Sample to be measured
Substrate
Concept of In Vitro IgE Assays
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In Vitro Specific IgE Assay (standard curve)
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
0 200 400 600 800 1000 1200
IgE IU/ml
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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
Immunoassay vs Skin Test for Diagnosis of Allergy
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Other Diagnostic Tests
• Nasal secretion / scraping cytology• Nasal allergen challenge• Nasal endoscopy • CT scan
– anatomic abnormalities – concomitant presence of sinusitis
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Peak nasal inspiratory flow
• Determines nasal airway patency using a nasal inspiratoryflow meter.
•• The results are reproducible and correlate with rhinoscopic
evidence of rhinitis but not with symptom scores
• Most useful for comparing changes in airway patency within the same subject
Allergy 2005; 60:795–800
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Acoustic rhinometry.
• Measures changes in mucosal congestion using reflectedsound.
• Sound in the nasal cavity is reflected by changes in acoustic impedance caused by changes in cavity dimensions.
• The change in acoustic impedance between the incident wave and reflected sound waves is proportional to the cross-sectional area.
• The method requires standardization and considerable experience to interpret and obtain reproducible results.
Rhinology 2000; 16 (Suppl.):3–17.
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Rhinomanometry
• Estimation of nasal resistance from pressure–flow relationships.
• Considered as an accurate measure of nasal airway patency.
• Anterior RM: Pressure sensor is placed at the tip of each nostril and resistance is
• measured in each nostril separately.
• Posterior RM: Pressure sensor is placed in the back of the nasal cavity and total nasal airway resistance is determined.
• Expensive equipment
• Requires considerable experience in interpretation
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Endothelialcell activation
Leukocyteinfiltration and activation(lymphocytes, eosinophils,
basophils)
IMMEDIATE (early)RESPONSE
LATE-PHASERESPONSES
preformed &newly formed
mediators/cytokines
mast cell
SneezingPruritusRhinorrheaNasal obstructionOcular symptoms
Nasal obstructionRhinorrhea
Nasal hyperresponsiveness
To allergens(priming)
To irritants and toatmospheric
changes
IgE
allergen
dendritic cell
T-lymphocyte
cytokineschemokines
allergen
B-lymphocyte
IgE
IL-4IL-13
The Nasal Allergic Response
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brain
SNEEZING
PRURITUS
RHINORRHEA
OBSTRUCTION
sensorynerves
epithelium
glands (mucous)blood vessels
histamine
sulfidopeptide leukotrienes
The Immediate (early phase) Allergic Reaction in the Nose
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0
1
2
3
4
5
6
7
Sneezesinduced byhistamine*
Perennial AllergicRhinitis
Healthy
N = 25
N = 18
p<0.0001
Sanico et al. Int Arch Allergy Immunol 1999;118:154
* same dose in both groups
Nasal Hyperresponsiveness in Allergic Rhinitis
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MANAGEMENT OF
ALLERGIC RHINITIS
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mildintermittent
mildpersistentmoderate
severeintermittent
moderatesevere
persistent
avoidance of allergens, irritant and pollutants
immunotherapy
intranasal decongestant (<10 days) or oral deconges tant
intranasal steroid
oral or local nonsedative H1-blocker
Management of Allergic Rhinitis: ARIA Guidelines
Modified from Bousquet J et al. J Allergy Clin Immunol. 2001;108:S147.
leukotriene receptor antagonists
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Stepwise Management of Allergic RhinitisEnvironmental control
Intermittent symptoms Persistent symptoms
Mild
• Oral H1-blocker or• Intranasal H1
blocker• and/or decongestant• or LTRA
Moderate MildSevere
• Oral H1 blocker or• Intranasal H1 blocker• and/or decongestant or• Intranasal CS• or anti-leukotriene
Re-evaluate patient with persistent symptoms in 2-4 weeks
Modified from ARIA workshop, 2001
ModerateSevere
• Intranasal CS ±• H1 blocker or • anti-leukotriene
Re-evaluate in 2-4 weeks
Responsive:Step downContinue treatmentfor > 1 month
Unresponsive:Re-evaluatecompliancediagnosisinfections
Add or increase CS
Rhinorrhea:add ipratropium
Congestion:add decongestant± short course oforal CS
Unresponsive:Immunotherapy
Consider surgical approaches (?)
Responsive:Continue treatmentfor 1 month
Unresponsive:Step-up
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Environmental Control
• House dust mites• Pets• Cockroaches• Molds• Pollen
1. Allergens
2. Pollutants and Irritants
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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
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House dust mite allergen avoidance
– Provide adequate ventilation to decrease humidity
– Wash bedding regularly at 60°C
– 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
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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)
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PHARMACOTHERAPY OF
ALLERGIC RHINITIS
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Modified from van Cauwenberge P Allergy 2000;55:116-134
Agents and Actions
Oral antihistami
nes
Nasal antihistam
ines
Cys-LT1 receptor
antagonists
Nasal steroids
Nasal decongest
ants
Oral decongest
ants
Nasal ipratropium
Nasal cromones
Rhinorrhea + + ++ ++ +++ 0 0 +++ +
Congestion + + + +++ ++++ ++ 0 +
Sneezing ++ ++ ++ +++ 0 0 0 +
Pruritus ++ ++ + +++ 0 0 0 +
Ocular symptoms ++ 0 ++ ++ 0 0 0 0
Onset of action 1 hr 15 min 48 hr 12 hr 5-15 min 1 hr15-30 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
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Oral Antihistamines
• First generation agents
Chlorpheniramine
Brompheniramine
Diphenydramine
Promethazine
Tripolidine
Hydroxyzine
Azatadine
• Newer agents
Acrivastine
Azelastine
Cetirizine
Desloratadine
Fexofenadine
Levocetirizine
Loratadine
Mizolastine
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Nasal Antihistamines
Azelastine
Levocabastine
Olopatadine
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Simons, F. E. R. N Engl J Med 2004;351:2203
Simplified Two-State Model of the Histamine H1-Rece ptor
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Sneezing Rhinorrhea Pruritus Nose Pruritus Eyes Congestion
*
*
*
*
*
*
*
*
*
*
*
*
*
1.0
0.8
0.6
0.4
0.2
01 wk
4 wk6 mo 1 wk
4 wk6 mo 1 wk
4 wk6 mo 1 wk
4 wk6 mo 1 wk
4 wk6 mo
Bachert C et al. J Allergy Clin Immunol 2004:114:838
meanIndividualsymptom
scoreimprovement
Levocetirizine, 5 mg, N = 276Placebo, N = 271
Efficacy of an Antihistamine over 6 Months inPersistent Allergic Rhinitis
Baseline total symptom score: 8.95
* P<0.05
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PlaceboN =201
Fexofenadine 120 mgN =211
Fexofenadine 180 mgN =202
Cetirizine 10 mgN =207
** *
Change frombaseline in
total symptomscore
(AM, instantaneous,trough)
0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
Newer Antihistamines are Equally Effectivein the Treatment of Allergic Rhinitis
Howarth P et al. J Allergy Clin Immunol 1999;104:927
*: <0.05 compared to placebo
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Newer Generation Oral AntihistaminesSomnolence/Drowsiness
Active Placebo Data Source
Cetirizine
10 mg qd13.7% 6.3% www.PDR.net
Desloratadine
5 mg qd2.1% 1.8% www.PDR.net
Fexofenadine60 mg bid
1.3% 0.9% www.PDR.net
Levocetirizine5 mg qd
6.8% 1.8%Bachert et al
JACI 2004;114:838
Loratadine
10 mg qd8% 6% www.PDR.net
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• 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
Newer Generation Oral Antihistamines
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Decongestants: Alpha-2 Adrenergic Agonists
• Oral
Pseudoephedrine
• Nasal
Phenylephrine
Oxymetazoline
Xylometazoline
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0.0
1.0
0.8
0.6
0.4
0.2
Day 4 Endpoint Overall(15 days)
Pseudoephedrine 120 mg twice daily, N=211Placebo, N=212
Mean reductionin “nasal stuffiness” score
from baseline
*
*
*
Adapted from Bronsky E. et al. J Allergy Clin Immunol 1995;96:139
Efficacy of Pseudoephedrine inSeasonal Allergic Rhinitis
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0.5
0.9
1.3
1.7
2.1
0 2 4 6 8 10 12 14 16 18 20 21
Day
Nasal obstructionseverity score
(scale: 0-3)
Cetirizine 5mg twice daily, N=70
Pseudoephedrine 120 mg twice daily , N=70
Combination, N=70
Bertrand et al. Rhinology 1996;34:91
Nasal Obstruction: Antihistamine vs Decongestant vs Combination in Allergic Rhinitis with Perennial Sym ptoms
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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
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Mechanism of Action of Ipratropium Bromide
brain
RHINORRHEA
sensorynerves
epithelium
submucosal glands
vidian nerve
Acetylcholineon
muscarinic receptors
X
X
direct effect of mediators: not cholinergic
indirect effect: cholinergic
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Adapted from Meltzer E at al. J Allergy Clin Immunol 1992;90:242
Efficacy of Ipratropium Bromide AgainstRhinorrhea in Allergic Rhinitis with Perennial Symp toms
6.0 3.0
5.0
4.0
3.0
2.0
1.0
0
2.5
2.0
1.5
1.0
0.5
0
**
**
* **
Ipratropium, 42 µg/nostril three times daily, N=42Ipratropium, 21 µg/nostril three times daily, N=39Placebo, N=42
Mean SeverityScore
(scale: 0-5)
Mean Duration(hours/day)
Baseline Wk 4Wk 1 Wk 2 Wk 3 Baseline Wk 4Wk 1 Wk 2 Wk 3
* p<0.05 against Placebo
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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
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Anti-Leukotriene Agents
CysLT1 Receptor
Antagonists
Montelukast *
Pranlukast *
Zafirlukast
5-Lipoxygenase
Inhibitors
Zileuton
* Approved for allergic rhinitis
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nucleus
cytosolicphospholipase A2
arachidonicacid
5-lipoxygenaseactivating
protein
leukotriene A4
5-lipoxygenase leukotriene C4synthase
leukotriene C4
leukotriene C4
leukotriene D4
leukotriene E4
CysLT1receptor
mast cellsbasophilseosinophilsmacrophages
+
Cysteinyl-Leukotriene Production and the CysLT1 Receptor
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Daytime Nasal Symptoms Score (0-3 point scale)
-0.6
-0.4
-0.2
0
Adapted from Nayak, et al. Ann Allergy Asthma Immunol. 2002;88: 592
Change frombaseline
(mean, 95% CI)
mean baseline=2.0
* *placebo, N=149
montelukast, N=155
loratadine, N=301*p<0.01 vs placebo
Efficacy of a CysLT1 Receptor Antagonistin Allergic Rhinitis with Seasonal Symptoms
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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%)
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Nasal Corticosteroids
Beclomethasone dipropionate
Budesonide
Ciclesonide*
Flunisolide
Fluticasone propionate
Mometasone furoate
Triamcinolone acetonide
* Currently only approved for asthma
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Nasal Corticosteroids
reduction ofsymptoms and exacerbations
reduction ofmucosal inflammation
reduction oflate phase reactions
primingnasal hyperresponsiveness
1
reduction ofmucosal mast cells
reduction ofacute allergic reactions
2
• suppression ofglandular activityand vascular leakage• induction ofvasoconstriction
3
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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.
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Mandl M. et al. Ann Allergy Asthma Immunol 1997;79:370
Comparative Efficacy of Nasal Corticosteroids
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Adapted from Di Lorenzo et al. Clin Exp Allergy 2004;934:259
0.5 0.8 1.1 1.4
fluticasone, N=20
fluticasone + cetirizine, N=20
fluticasone + montelukast, N=20
placebo, N=20
cetirizine + montelukast, N=20
Average congestion score over 6 weeks[95% CI]
*
Various Treatment Combinations in Seasonal Allergic Rhinitis
Nasal congestion score, Scale: 0-3
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Adapted from Di Lorenzo et al. Clin Exp Allergy 2004;934:259
Average total symptom score over 6 weeks[95% CI]
fluticasone, N=20
fluticasone + cetirizine, N=20
fluticasone + montelukast, N=20
cetirizine + montelukast, N=20
placebo, N=20
0 1 2 3 4 5
*
*
Various Treatment Combinations in Seasonal Allergic Rhinitis
total symptom scoreScale: 0-12
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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
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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)
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Allergen Immunotherapy (Vaccines)
Subcutaneous
Sublingual
Nasal
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DCTh0-lymphocyte
Treg-lymphocyte
Possible Mechanisms of Immune Response Regulation by Allergen Immunotherapy
Th1
Th2
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Possible Mechanism: Allergen Immunotherapy Induces Regulatory T-Lymphocytes
TH2lymphocyte
Treglymphocyte
Blymphocyte
interleukin 10TGFβ
interleukin 10TGFβ
IgG4
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Subcutaneous Immunotherapy: Effect on Serum Specific IgE
10
20
30
40
50
60
70
Anti - ragweedIgE
(ng/ml)
Initiation ofimmunotherapy
August
November
baseline year 1 year 2 year 6 year 7 year 8
Adapted from: Peng et al. J Allergy Clin Immunol 1992;89:519
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Long-Term Efficacy of Subcutaneous Immunotherapy
Placebo Immunotherapy
80
60
40
20
May June July Aug.
Symptom score
1989
Durham et al. N Eng J Med 1999;341:468
80 80
Immunotherapy continued
80
60
40
20
May June July Aug.
1993
60
40
20
May June July Aug.
Symptom score
1994
60
40
20
May June July Aug.
1995
Immunotherapy discontinued
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Dahl R et al., J Allergy Clin Immunol. 2006;118:434.
Sublingual Immunotherapy in Grass Pollen-Induced Allergic Rhinitis
Treatment: grass allergentablets
SLIT, N=316Placebo, N=318
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Omalizumab
IgE
Humanized MonoclonalAnti-IgE Antibody: Omalizumab
Cε3region
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Efficacy of Omalizumab in Seasonal Allergic Rhiniti s(ragweed pollen season)
Averageweekly
symptomscore
Placebo, N=136
Omalizumab50mg, N=137 150mg, N=134 300mg. N=129
4 13 20 27 3Aug
10 17 24 1Sep Oct
8 15 22 29
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
Casale T, et al. JAMA 2001;286:2956
• SQ treatments every 3-4 weeks x 3-4• First dose prior to the pollen season
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Omalizumab and Subcutaneous Immunotherapy in Children: Study design
Week 0 Week 12 Week 36
SIT titration SIT maintenance + study drug
Prescreening
SIT (grass) + omalizumab
SIT (birch) + omalizumab
SIT (birch) + placebo
SIT (grass) + placebo
n = 55
n = 54
n = 59
n = 53
Randomization
Kuehr J et al. J Allergy Clin Immunol 2002;109:274
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0
1.0
OmalizumabPlacebo
+ birch SIT
OmalizumabPlacebo
+ grass SIT
0.8
0.6
0.4
0.2
n=55n=54 n=59n=53
p<0.001
Omalizumab and Subcutaneous Immunotherapy in Children: Symptom Load
(rescue medications + symptom severity scores)grass pollen season
0.26
0.61
0.89
0.49
p=0.03
p=0.001
Symptomloadscore
(median)
Kuehr J et al. J Allergy Clin Immunol 2002;109:274
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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
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