4. Asthma and allergic Rhinitis are common health
problems that cause major illness and disability
world wide.
Both are common chronic diseases that affect the
quality of life of patients and have a significant
economic impact .
European Respiratory Disease 2006
5. The prevalence of asthma and rhinitis varies
all over the world with allergic Rhinitis being
two times more prevalent than asthma.
The worldwide incidence of allergic Rhinitis
and asthma has been on the rise .
European Respiratory Disease 2006
6. Australia
asthma 18%
rhinitis 25%
Canada
asthma 13%
rhinitis 25%
Sweden
asthma 8%
rhinitis 15%
China
asthma 5%
rhinitis 10%
Brasil
asthma 10%
rhinitis 22%
Kenya
asthma 8%
rhinitis 13%
ISAAC study, Lancet 1998
Worldwide prevalence
7. Using a conservative estimate, it is proposed
that allergic rhinitis occurs in around 500 million
people .
Studies suggest that there are more than 300
million persons worldwide who are affected by
asthma .
8.
9. Slide 9
Adapted from Bousquet J et al J Allergy Clin Immunol 2001;108(suppl 5):S147–S334;
Sibbald B, Rink E Thorax 1991;46:895–901; Leynaert B et al J Allergy Clin Immunol
1999;104:301–304; Brydon MJ Asthma J 1996:29–32.
Up to 80%
of all asthmatic patients have allergic rhinitis
All asthmatic patients
Epidemiological link
10. Allergic Rhinitis and Asthma
frequently occur together
40% of allergic rhinitis patients have asthma .
80% of asthma patients have concomitant
Rhinitis symptoms .
European Respiratory Disease 2006
12. Co-Existence of Asthma and
Allergic Rhinitis: A 23-Year follow-
Up Study of College Students
William A. Greinsner, Robert J. Settipane and Guy A. Settipane
Allergy and Asthma Proc 1998
13. 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.
Adapted from Settipane RJ et al Allergy Proc 1994;15:21-25.
12
10
8
6
4
2
0
Subjects with
asthma at 23-
year follow-
up (%)
10.5
Allergic rhinitis
at baseline
(n=162)
3.6
No allergic rhinitis
at baseline
(n=528)
p<0.002
14. Rhinitis as an independent risk factor for adult-
onset asthma (atopic and non-atopic)
(European Community Respiratory Health Survey)
Adapted from Leynaert B et al. J Allergy Clin Immunol 1999;
Asthma (%)
Atopic Non atopic
no rhinitis, N=5198
rhinitis, N=1412
OR=11
OR=17
0
5
10
15
20
25
15. The prevalence of asthma in patients with Rhinitis
varies from 10 to 40% depending on studies .
Patients with moderate/severe persistent Rhinitis may
be more likely to suffer from asthma than those with
an intermittent and/or a milder form of the disease .
16. - 591 patients
- 502 controls
- allergic to pollens, mite,
-epithelia
0
5
10
15
20
25
30
35
%subjects
contr mild severe mild severe
intermittent persistent
%pazienti
Prevalence of asthma (physician diagnosed) in Rhinitis
Bousquet, CEA 2005
17. BHR was found in 24% to 40%
of patients with active Rhinitis
(In the general population the BHR prevalence is 10-20%)
Di Lorenzo G. et al.
“ Non-specific airway responsiveness in mono-sensitive Sicilian patients
with allergic rhinitis: its relationship to total serum IgE levels
and blood eosinophils during and out of the pollen season”
Clin Exp Allergy 1997; 27: 1052-59
Ramsdale EH et al.
“ Asymptomatic bronchial hyperresponsiveness in rhinitis”
J Allergy Clin Immunol 1985; 75: 573-577
Annesi I. et al.
“ Relationship of upper airways disorders to FEV1 and bronchial
hyperresponsiveness in an epidemiological study”
Eur Respir J 1992; 5: 1104-1110
18. Braman SS et al.
“ Airway hyperresponsiveness in allergic rhinitis:
a risk factor for asthma”
Chest 1987; 91: 671-674
Laprise C. et al.
“ Asymptomatic airway hyperresponsiveness:
A three-year follow-up”
Am J Respir Crit Care Med 1997; 156: 403-9
Several studies suggested that patients
with allergic Rhinitis and BHR are at
higher risk of developing asthma
21. The Allergy March: CHDs
CHDs
Atopic
Dermatitis
GI
Distress
Recurrent
Otitis
Media
Allergic
Asthma
Allergic
Rhinitis
Food
Sensitivity
Inhalant
Sensitivity
Time (~years)
Genetic
Predispositio
n
22. Atopic Dermatitis
Food Allergy
Allergic Rhinitis
Allergic Childhood Asthma
Adult Asthma
Atopic or Allergy March
Natural sequence of allergic clinical conditions
appearing during a certain age period and
persisting over a number of years from childhood
to adulthood
Atopy is the inherited tendency to develop
harmful immune responses to harmless
substances
Allergy can affect different children in
different ways
23. “ The Allergy March ”
Food
Allergy
Atopic Eczema
Allergic Rhinitis
Asthma
‘ The Atopic March ’
24. 24
Asthma Predictive Index (API)
Wheezing during the first 3 years of life
PLUS
1 Major Criterion 2 Minor CriteriaOR
Parental history of
asthma
Physician-diagnosed
atopic dermatitis
Physician-diagnosed
allergic Rhinitis
Wheezing unrelated to
colds
Eosinophilia (4%)
Castro-Rodriguez et al. Am J Respir Crit Care Med. 2000;162:1403-1406.
25. Allergic rhinitis as a predictor for wheezing onset in
school-aged children.
Rochat et al, JACI 2010
Cohort of 1,314 children followed from birth to 13 yrs
26. Allergic rhinitis is one of the strongest risk factors
for asthma
Children who suffer from asthma and concomitant
allergic rhinitis tend to have :
1. a much worse quality of life
2. more difficult to control asthma
3. 2.5 times more asthma associated hospital
admissions
Thomas M,et al. Pediatrics 2005: 115: 129–34.
Sazonov Kocevar V,et al.Allergy 2005: 60: 338–42.
27. The Proceedings of the American Thoracic Society (2009)
• .
Allergic asthma and Rhinitis are manifestations of the
atopic syndrome and often coexist.
Genetic and environmental factors are recognized as
contributing factors to the development of the allergic
airway syndrome.
Immunological Link
28. The Proceedings of the American Thoracic Society (2009)
• .
The atopic syndrome is a hereditary disorder in subjects
who are particularly susceptible to the development of
IgE-mediated allergic reactions manifested by:
1. Infantile eczema
2. Nasal and conjunctival allergy
3. Allergic asthma
The atopic syndrome
29. Allergies affect people from the early stages of their life and
continue until their late adult ages
30. Th2
Th1
Th2
Balanced
Th1/Th2
at ~2yr
Neonatal & infant immune systems
The intrauterine environment is powerfully Th2 –
this imprints Th2 dominance upon the neonate
Serial infections
Age
Immune
response
31. Th1
Th2
Unbalanced
Th1/Th2
Th2 dominance
at ~2yr
Delayed maturation of Th1 capacity
Few serial infections – hygiene, small family size etc
Age
Immune
response
Longer period of time in which to make and establish
Th2 responses to environmental antigens (i.e.
allergens)
32. Immune System Development and the Hygiene Hypothesis
Older siblings:
Many infections
[TH1 stimuli]
TH1
No allergies
Still TH2
Allergies
Only child:
Few infections
Allergen
Exposure
Source: Busse WW, Lemanske RF. N Engl J Med 2001.
Birth:TH2
45. In many individuals, an asthma attack comprises immediate (mainly
bronchospasm) and delayed (inflammatory reaction) phases
0 2 4 6 8
Time (hours)
1.0
1.5
2.0
2.5
3.0
FEV1(lires)
Inhalation of
grass pollen
Early phase
(bronchospasm)
Late phase
(inflammation)
46.
47. • .
Allergic Rhinitis and asthma share
similar inflammatory processes
Common triggers
Similar inflammatory cascade on exposure to allergen
Similar pattern of early- and late-phase responses
Infiltration by the same inflammatory cells
(e.g.eosinophils)
Several potential connecting pathways including
systemic transmission of inflammatory mediators
48. Eosinophils in airway mucosa are regarded as the
hallmark of allergic Rhinitis and asthma .
Eosinophilic inflammation has been found in the
lower airways of allergic Rhinitis patients without
asthma and in the upper airways of asthmatic
patients without nasal complaints .
49. Bronchial biopsioes after
Specific provocation in
patients with rhinitis or
asthma
Crimi E et al, JAP 2001
ASTHMA
RHINITIS ALONE
Same inflammation
50. Nasal allergen challenge
Increases bronchial reactivity
Induces bronchial inflammation
Littell NT, Changes in airways resistance following nasal provocation. Am Rev Respir Dis 1990
Corren J Changes in bronchial responsiveness following nasal provocation with allergens. JACI 1992
Small P ET AL The effects of allergen-induced nasal provocation on pulmonary function in patients with
perennial allergic rhinitis. Am J Rhinol 1989
52. Togias A Allergy 1999;54(suppl 57):94..
Aspiration of
Inflammatory
Material
Oral breathing
Nasopharyngo-bronchial
reflex
Systemic
Propagation of
Nasal
Inflammation
Mechanisms of pathologic relationships
between upper and lower airways.
53. AllergicRhinitis and asthma are manifestations of one
syndrome, in 2 parts of the respiratory tract , the upper
and lower airways.
At the low end of the severity spectrum, Rhinitis may
occur alone , in the middle range of the spectrum,
Rhinitis and AHR may be present and, at the high end,
Rhinitis and asthma may both be present.
.
Togias A, J Allergy Clin Immunol Jun2003
56. The allergic Rhinitis and asthma frequently co-exist
leading to the concept that these seemingly separate
disorders are manifestations of the same disease
expressed to a greater or lesser extent in either
the upper or the lower airways.
Togias A, J Allergy Clin Immunol Jun2003
57. The nose-lung interaction in
allergic rhinitis and asthma:
united airways disease
G.Passalacqua,
G.Ciprandi & G.W.Canonica
2004
Asthma and Rhinitis as different
Aspects of a sinlge disorder
In some patients Rhinitis predominates and asthma is
undiagnosed or sub-clinical, in others it is reversed, while
in many both are clinically expressed .
64. Adams et al. J.A.C.I. 2002
Treatment of Rhinitis reduces
emergency visits for asthma
Crystal-Peters, JACI 2002
Fuhlbrigge, Curr Opin Allergy Immunol 2003
Baena-Cagnani et al, Int Arch Allergy Immunol 2003
Nelson HS, JACI 2003
65.
66. No. of GP visits
(Mean)
No. of SAß2A
prescriptions
% Hospitalizations
1.4
0.5
Children with
Asthma
(n=7.643)
Children with
Asthma + Allergic
Rhinitis
(n=1.879)
<0,0001
3.4
4.4
0
3
5
4
2
1
<0,001
1.8
2.3
<0,001
per patient / year
68. Those patients whose allergic rhinitis was severe or poorly
controlled had worse asthma control and tended to have
more persistent asthma than those with mild or well
controlled rhinitis.
In addition, bronchial hyperresponsiveness can be present
in patients with allergic rhinitis without clinical evidence of
asthma
ARIA 2008
69. Prompt and effective treatment of nasal disease can have a
marked effect on preventing the development of asthma,
and on existing asthma symptoms.
The World Allergy Organization IAACI, 2003
Treatment of rhinitis has the potential to reduce asthma
symptoms to such an extent that treatment with asthma
medications may be unnecessary in some patients.
Curr Opin Allergy Clin Immunol 2003
70. The recommended clinical approach is to manage the
two disorders discretely but simultaneously.
You should treat each disease separately; that even
though it's 1 disease, you can't just treat the nose and
take care of the asthma,or treat the asthma and take
care of the nose. Each one has to be treated
appropriately.
73. Asthma, irrespective of the severity, is
a chronic inflammatory disorder of the airways.
Airway inflammation is associated with:
● Airway hyperresponsiveness
● Airflow limitation
● Respiratory symptoms.
Definition of Asthma
74.
75. Controllers vs Relievers
Controllers =
medications taken
daily on a long-term
basis to keep asthma
under clinical control
due to
antiinflammatory
effects
Relievers =
medications used on
an as-needed basis
that act quickly to
reverse
bronchoconstriction
and relieve its
symptoms
77. 77
• Inhaled corticosteroids are the recommended
& most effective preventer drug for adults and
children with asthma , for achieving overall
treatment goals.
82. 82
1. Oropharyngeal candidiasis
2. Hoarseness
3. Coughing
To reduce the potential for adverse affects:
Use the lowest dose necessary to maintain control.
Administer with spacers/holding chambers.
Advise patients to (Rinse with water , gargle and
spit out) after inhalation.
Local side effects
84. Problems with inhaler technique are common in
clinical practice & can lead to poor asthma control
All patients should be trained in technique & trainers
should be competent with the inhalation technique
Assess inhaler technique
85. Invest the time to train each patient in proper inhaler
technique
Recheck inhaler technique on each revisit
Assess inhaler technique
86.
87.
88.
89. 89
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
90. 90
Fate of inhaled drugs – Good Technique
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
80%
20%
Schematic representation of potential dose distribution
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Adapted from Barnes et al. AJRCCM 1998;157:S1-S53
Swallowed
GI tract
Deposited in lung
Lungs
Metabolism or absorption
from the lung
Liver
Oral
bioavailability
Absorption
from gut
First-pass
metabolism
Systemic
Circulation
Mouth
pharynx
mucociliary
clearance
95%
5%
Schematic representation of potential dose distributionAdapted from Barnes et al. AJRCCM 1998;157:S1-S53
A Guide to Aerosol Delivery Devices for Respiratory Therapists. American Association for
Respiratory Care. 1st Edition. Page 1.
Webpage: http://www.aarc.org/education/aerosol_devices/
Fate of inhaled drugs – Poor Technique
91. Treatment Options for adult Patients
Not Controlled on Iow dose ICS
Patients not controlled on inhaled steroids (ICS)
Increase the
dose of inhaled
steroid
Add leukotriene
receptor
antagonists
Add long-acting
beta2-agonists
Add SR
theophylline
98. Allergic rhinitis (AR) is the most common chronic disease
in childhood is often ignored, misdiagnosed and/or
mistreated.
Undertreated AR impairs quality of life, exacerbates
asthma and is a major factor in asthma development.
99. Allergic rhinitis (AR) is an under-recognised inflammatory
condition of the nasal mucosa, caused by IgE-mediated
early-phase and late-phase hypersensitivity responses,
usually to inhalant allergens, similar to those in allergic
asthma.
Allergic rhinitis is caused by an IgE-mediated reaction to
specific seasonal , perennial or episodic aeroallergens.
100. ALLERGIC RHINITIS
• In relation to symptom frequency classified as :
Intermittent Vs. Persistent
• In relation to Severity classified as :
Mild Vs. Moderate/severe
• In relation to allergen exposure classified as:
Perineal Vs Seasonal Vs Episodic
101. Perennial AR is typically caused by sensitization to indoor allergens
such as dust mites, mold and animal dander (Symptoms are
present throughout the year)
Seasonal AR is most often due to sensitization to pollen allergens
(Symptoms appear in or around a particular season).
Episodic AR results from sporadic exposures to aeroallergens that
are not typically encountered, such as visiting a farm or home with
animal allergens that an individual would not typically encounter
102. Symptoms of Allergic rhinitis
(AR) is characterized by one
or more symptoms including
Nasal congestion,rhinorrhea,
sneezing and itching on
consecutive days .
•
106. Minimal persistent inflammation is also
Present in patients with seasonal allergic
rhinitis
V. Ricca, M.Landi, P.Ferrero, A.Bairo, C.Tazzer,G.W.Canonica
and G.Ciprandi
gw111199
J.A.C.I. 2001
109. Instead of considering allergic rhinitis as a disease of
acute symptoms, it needs to be understood as a chronic
inflammatory disease.
Even in the absence of symptoms, continuous exposure to
low levels of allergen results in an inflammatory infiltration
and ICAM-1 expression, which is known as "minimal
persistent inflammation" (MPI).
110. The concept of minimal persistent inflammation suggests
a different approach to therapy in which symptoms can be
considered the “tip of the iceberg” of the allergic reaction
with inflammation and hyper-responsiveness representing
the submerged iceberg
Therefore, any optimal therapeutic strategy for AR should
focus on minimizing inflammatory phenomena rather than
only on alleviating acute symptoms.
111. Therapeutic implications
The intranasal corticosteroids (INCSs) are the current
first-line therapy for moderate to severe cases of
seasonal and perennial AR
Regular persistent use of INCSs has been effective in
reducing all symptoms nasal congestion, rhinorrhoea,
sneezing, and nasal itching in both adults and children.
112. INCS are
the most effective drug
In A.R.
ICS are
the milestone
asthma treatment
• ICS+INCS in the same UAD patients???????
113. Simplified AR Treatment Algorithm
Small and Kim. AACI Nov 2011.
Treatments can be used individually or in any combination
Allergen avoidance
Allergen immunotherapy (SCIT/SLIT)
Oral or intranasal antihistamines
Leukotriene receptor antagonists
Intranasal corticosteroids
114.
115.
116.
117.
118.
119.
120.
121.
122.
123.
124.
125.
126.
127. Recognized as the most effective agent for symptom
control in allergic rhinitis, are currently recommended
as first-line therapy for patients with moderate-to-
severe symptoms or those with nasal congestion as
the dominant complaint.
The onset of action ranges from 3 to 36 hours after the
first dose, and continuous use is more effective than
intermittent use.
The intranasal corticosteroids
128. No single product is recommended over another, as
studies have shown comparable efficacy among
products.
In the control of nasal symptoms, intranasal steroids
have shown superior efficacy compared with oral
antihistamines; however, intranasal antihistamines
have a faster onset of action
The intranasal corticosteroids
129. Concerns over stunted growth in children precipitated
several clinical trials; reduced growth was seen with
budesonide and beclomethasone, but not with fluticasone
furoate, triamcinolone acetonide, mometasone furoate, or
fluticasone propionate.
Accordingly, for pediatric patients, guidelines recommend
using those agents not shown to reduce growth.
The intranasal corticosteroids
130. The intranasal corticosteroids
• The most common side effects of INS are a result of
local irritation and include dryness, burning, stinging,
blood tinged secretions, and epistaxis.
• The incidence of epistaxis with different preparations
ranges from 4% to 8% over short treatment periods
ranging from 2 to 12 weeks with no differences
between placebo and active therapy.
131. The intranasal corticosteroids
• Epistaxis can be minimized with proper INS positioning
and administration, generally pointed away from the
septum within each side of the nose.
• Septal perforations, although rare, have been reported.
• Biopsy specimens from the nasal mucosa of patients
with perennial rhinitis who have been treated with INS
continuously for 1 to 5 years showed no evidence of
atrophy
132. The intranasal corticosteroids
• Studies in adults and children evaluating the effects of
INS on the hypothalamic-pituitary axis using morning
cortisol concentrations, cosyntropin stimulation, and 24-
hour urinary free cortisol excretion show no adverse
effects
• Studies with INS given over several months have failed to
show development of posterior subcapsular cataracts,
significant increases in intraocular pressure, or
glaucoma.
141. Oral Leukotriene receptor Antagonists (LTRAs)
• Leukotriene Receptor Antagonists, are No longer
recommended as primary therapy in allergic rhinitis,
only are reserved for combination therapy
• LTRA (montelukast) was found to be either equally
effective or less effective than oral antihistamines, and
it was less efficacious than intranasal steroids.
• Because this agent treats both allergic rhinitis and
asthma, a patient with both conditions is the best
candidate .
142.
143. Immunotherapy
• Immunotherapy is the only proven treatment for AR that
has the potential to change the natural history of the
disease.
• It must be emphasized that demonstration of IgE-
mediated allergy based on history and confirmed by
specific allergy testing (skin or in vitro) is a prerequisite
for all forms of immunotherapy, both SLIT and SCIT.
• The typical duration of treatment for either form of
immunotherapy is several years, typically 3 to 5 years.
144. Immunotherapy
• With a clear patient history, diagnosis can be made without
further tests. However, if in doubt, looking for the likely IgE
molecules by skin prick or blood test can be helpful, although
this should be guided by history, rather than performed in a
random fashion.
• Positive tests do not always indicate clinical disease, a
positive test to an allergen with no pertinence to patient’s
history has no relevance for diagnosis and might result in
over-diagnosis .
• Testing should always be considered in the context of the
possible clinical benefit, which can be from allergen
avoidance, if the patient is able and willing tocomply, allergen
specific immunotherapy.
145. Immunotherapy
• Patients on SIT should be monitored on a regular basis
for effectiveness based on clinical parameters such
as symptoms and medication use;
• Typically, positive benefits of immunotherapy on AR
symptoms appear from several weeks to 1 year after
initiation of therapy.
146. Immunotherapy
• Due to the potential for serious reactions, current
practice guidelines indicate that SCIT should not be
used in patients with severe, uncontrolled asthma .
• SCIT should be administered in a physician’s office
where serious reactions can be promptly recognized,
and the patient should be observed for 30 minutes after
injection.
153. Scores
Total scores > 24
indicate good
disease control
Score of the upper
airway: controlled if
score is > 8
Score of the lower
airway : controlled if
score is > 16
155. “Allergic rhinitis and asthma are chronic inflammatory
disorders that have been linked epidemiologically,
immunologically , pathophysiologically, and
therapeutically as “one airway disease.”
Final Remarks
156. Final Remarks
1-Patients with persistent Rhinitis should be evaluated
for asthma
2-Patients with persistent asthma should be evaluated for
Rhinitis
3-A combined strategy should be used in the treatment
of upper and lower airways
