1. Rhinitis:
Symptomatic disorder of the nose
characterized by itching, nasal
discharge, sneezing and nasal airway
obstruction
cterized by itching, nasal discharge,
sneezing and nasal airway obstruction
3. The nose is that part of the lung
which is accessible to the finger
4. Relationship between rhinitis and
asthma – implications for treatment
• Is there a relationship between
rhinitis and asthma ?
• Is the relationship causal ?
• Does treating rhinitis
improve asthma?
5. Allergic rhinitis is a risk factor for asthma
Allergic rhinitis increased the risk of asthma ~3-fold
23-year follow-up of college freshmen undergoing allergy testing; data based on 738 individuals (69%
male) with average age of 40 years.
12
10
8
6
4
2
0
%ofpatientswhodevelopedasthma
10.5
Allergic rhinitis
at baseline
(n=162)
3.6
No allergic rhinitis
at baseline
(n=528)
p<0.002
Settipane RJ et al Allergy Proc 1994;15:21-25.
8. Does treating hayfever help
patients with asthma?
Antihistamines
Leukotriene antagonists
Nasal corticosteroids
Allergen immunotherapy
9. Effect of cetirizine in patients with seasonal rhinitis
and concomitant asthma
placebo
cetirizine
1 2 3 4 5 6
1 2 3 4 5 6
2
4
6
8
0
2
4
6
8
0
10
Study week
Study week
Meantotal
rhinitisscore
Meantotal
asthmascore
Grant et al. J Allergy Clin Immmunol 1995; 97: 923–732
10. Intranasal and inhaled fluticasone propionate for
pollen-induced rhinitis and asthma
Dahl R. Allergy 2005: 60: 875–881
Geometric mean PD20 methacholine measured at baseline () and after 4 weeks treatment () (*** p < 0.001 IHFP
± INFP vs INFP or placebo). INFP, fluticasone proprionate nasal spray; IHFP, inhaled fluticasone propionate.
11. • Is there a relationship between
rhinitis and asthma ? Yes
• Is the relationship causal ? Yes
• Does treating rhinitis Maybe
improve asthma?
Relationship between rhinitis and
asthma – implications for treatment
12. Patients with rhinitis should be evaluated
for asthma
Patients with asthma should be evaluated
for rhinitis
A strategy should combine the treatment
of upper and lower airways in terms of
efficacy and safety
Recommendations
13. 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
14. Allergic Rhinitis
• Inflammation to the mucosal lining of the
nose caused by inappropriate hypersensitivity
reaction to an aeroallergen.
• IgE mediated immune response, with mast
cell activation and release of cytokines
20. Intermittent
Symptoms
• < 4 days / week
• or < 4 weeks
Persistent
Symptoms
• > 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
22. 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
23. rhinitis
odds ratio
for the
association
with asthma
1
3
6
9
Guerra S et al. J Allergy Clin Immunol 2002;109:419
Test for trend, p < 0.001 Test for trend, p < 0.001
Association of rhinitis with incident asthma
in an adult cohort
(173 incident cases and 2,177 controls; approx. 10-yr follow-up)
24. 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
26. Screening Tests
• Negative result usually requires no additional
testing
• Positive result requires further testing of other
antigens in the group or family. There may be
some cross-reactivity, especially with molds.
• Contain 12 to 14 antigens, (pollen, mold,
weeds, dust mite, animal dander)
28. Skin prick
• Droplet of antigen is introduced about 1 mm deep
into the skin.
• Correlates with RAST, and set endpoint dilutional
testing (81-89%). Gungor et al Grade A
• Disadvantages
– Patient discomfort
– Intertester variability
– Non-standardized allergen extracts, and different
interpretation scales
29. Intradermal dilutional testing
• Intradermal testing utilizing serial dilutions to
quantify degree of sensitivity to specific
antigen.
• Labor intensive
• Patient discomfort due to multiple sticks
• SET – skin endpoint titration
31. 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
33. Environmental control
• House dust mites
• Pets
• Cockroaches
• Molds
• Pollen
1. Allergens
2. Pollutants and Irritants
34. Environmental intervention in urban US
children with asthma
• Tailored to
• Skin test profile
• Environmental exposure
• Caretaker’s report
• House dust mite
• Passive smoking
Adapted from Morgan WJ et al. New Engl J Med 2004;351:1068-80
• Cockroaches
• Pets
• Rodents
• Mold
35. 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)
39. Efficacy of an antihistamine over 6 months in
persistent allergic rhinitis
Sneezing Rhinorrhea Pruritus Nose Pruritus Eyes Congestion
*
*
*
*
*
*
*
*
*
*
*
*
*
1.0
0.8
0.6
0.4
0.2
0
1 wk
4 wk
6 mo 1 wk
4 wk
6 mo 1 wk
4 wk
6 mo 1 wk
4 wk
6 mo 1 wk
4 wk
6 mo
mean
Individual
symptom
score
improvement
* P<0.05
fexofenadine120 mg, N = 276
Placebo, N = 271
Baseline total symptom score: 8.95
40. Placebo
N =201
Fexofenadine 120 mg
N =211
Fexofenadine 180 mg
N =202
Cetirizine 10 mg
N =207
*
* *
Change from
baseline in
total symptom
score
(AM, instantaneous,
trough)
0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
Newer antihistamines are equally effective
in the treatment of allergic rhinitis
Baseline symptoms
Study duration
43. 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%)
45. 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
49. Sublingual immunotherapy
• Subcutaneous immunotherapy (SCIT)currently
represents the standard immunotherapy
modality,with well ascertained clinical efficacy.
• The first SLIT randomized DBPC-RCT was
published in 1986. The rationale proposed for
SLIT was to improve the safety and to make
the treatment more convenient.
50. • In SLIT, the allergen extract (prepared as drops
or tablets) is kept under the tongue for 1 to 2
minutes and then swallowed; thus, this route
is also called sublingual-swallow. In some
studies a different method was adopted, the
allergen was kept under the tongue and then
spat out (sublingual-spit).24 Presently, only
the sublingual-swallow route is used,
therefore the acronym SLIT refers to the
sublingual-swallow modality.
51. Mode of action
• Oral mucosa is a natural site of immune tolerance (Langerhans cells,
FcR1, IL-10, IDO [indoleamine
• 2,3-dioxygenase]).
• Sublingual immunotherapy in optimal doses is effective and may
induce remission after discontinuation and prevent new
sensitizations, features consistentwith induction of tolerance.
• Sublingual immunotherapy is associated with:
- Retention of allergen in sublingual mucosa for several hours.
- Marked early increases in antigen-specific IgE,blunting of seasonal
IgE.
- Modest increases in antigen-specific IgG4 and IgEblocking activity.
- Inhibition of eosinophils, reduction of adhesion molecules in target
organ.
- Some evidence of increase in peripheral T cell IL-10
52. Selection of patient
• To be eligible for SLIT, patients should have:
- A clinical history of allergy.
- Documented ALLERGEN SPECIFIC IgE positive test.
- The allergen used for immunotherapy must be clinically
relevant to their clinical history.
- Patients uncontrolled with optimal pharmacotherapy
(SCUAD).
- Patients in whom pharmacotherapy induces undesirable side
effects.
- Patients refusing injections.
- Patients who do not want to be on constant or longterm
pharmacotherapy
53. Important!
• Age does not seem to be a limitation.
• Monosensitized patients are ideal candidates for SLIT, and
recently single allergen SLIT has been demonstrated to be
effective in polysensitized patients.
• SLIT may be considered as initial treatment. Failure of
pharmacological treatment is not an essential prerequisite for
the use of SLIT.
• SLIT may be proposed as an early treatment in respiratory
allergy therapeutic strategy
54. Paediatric essentials…
• SLIT is effective in allergic rhinitis in children>= 5
years of age.
• SLIT may be safe in allergic rhinitis in children>= 3
years of age.
• SLIT can be used for allergic rhinitis in children
with asthma.
• SLIT should not be suggested as monotherapy for
treating asthma.
55. • The most important concern that still remains
is to determine the optimal dose of allergen
for SLIT, because the treatment has been
shown effective over a very large range of
doses (from5–300 times the dose used for
SCIT). However, it is clear that the effective
doses of allergens for SLIT must be higher than
for SCIT
57. 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
58. NARES
NARES, non-allergic rhinitis with
eosinophilia syndrome, is characterized on
the basis of 20-25% or greater eosinophils in
nasal smears of pt with rhinitis.
There is lack of allergy by skin test, or IgE
antibodies.
Prevalence ranges from 13-33% of non-
allergic rhinitis.
60. Idiopathic Rhinitis
Exclusion criteria for IR
Positive allergy test
Smoking
Nasal polyps
Pregnancy
Medications affecting nasal function
Beneficial effects of nasal corticosteroid spray (NARES)
61. Treatment
Immunologic therapy has no benefit to
non-allergic rhinitis and therefore it is
important to distinguish the disease before
considering starting immunotherapy.
Nasal saline lavage has minor decongestant
benefits and improves mucociliary function
in both allergic and non-allergic rhinitis.
62. Topical nasal steroids are widely used for
treatment of NAR.
They work on the nasal mucosa by
decreasing neutrophils and eosinophil
chemotaxis, reduced mast cell release and
thus decrease edema and inflammation.
