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Interactions between rhinitis & asthma
Interactions between
rhinitis & asthma
By
Dr . Ashraf El-Adawy
Consultant Chest Physcian
TB TEAM Expert - WHO
Mansoura - Egypt
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
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
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
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
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
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
Slide 10
Epidemiologic Links between Allergic Rhinitis and Asthma
Many Patients with Asthma Have
Allergic Rhinitis
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
• Epidemiologic
• Anatomic
• Physiologic
• Immunopathologic
• Therapeutic
IMPACT OF ASTHMA AND
ALLERGIC RHINITIS ON EACH
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
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
- 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
The prevalence of asthma in subjects without Rhinitis
is usually less than 2%.
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
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
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
Rhinitis
asthma
Diseaseseverity
time
Togias, Allergy 1999
The current concept is that AR precedes
asthma in most patients
The Allergy March: A Progression of Seemingly Unrelated Diseases CHDs
CHDs
Atopic
Dermatitis
GI
Distress
Recurrent
Otitis
Media
Allergic
Asthma
Allergic
Rhinitis
Food
Sensitivity
Inhalant
Sensitivity
Time (~years)
Genetic
Predispositi
on
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
Rhinitis is a significant risk factor for adult-
onset asthma in both atopic and non-atopic
subjects increased the risk by about 3 times.
76% asthmatic patients reported presence
of Rhinitis before onset asthma.
Links between Rhinitis and asthma
Epidemiologic evidence
Patients with moderate/severe persistent Rhinitis
may be more likely to suffer from asthma than
those with an intermittent and/or mild Rhinitis
Asthma prevalence is increased in allergic and
non-allergic Rhinitis
Non-specific bronchial hyperreactivity is
increased in persistent Rhinitis
Links between Rhinitis and asthma
Epidemiologic evidence
Allergic Rhinitis and Asthma Share
Common Triggers
• .
Allergic Rhinitis and asthma share
similar inflammatory processes
Common triggers
Similar inflammatory cascade on exposure to an
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
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
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)
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
The Hygiene Hypothesis
Allergy: A Dysregulation of the Immune System
APC
Th0
Th1Th2
B lymphocyte
Mast cell
Eosinophil
Allergic Symptoms
IFN 
IL 4
IL 10
IL 5
IFN IL 4
IL 13
IL 9
IL 12
IL 18
IL 12
IL 18
IL 4
Allergens
IgE
Sensitization Phase
Allergy: A Dysregulation of the Immune System
Mast cell
Basophil
Eosinophil
Inflammatory Mediators Release
Allergens
Histamine - Prostaglandins – Leucotriens – Tryptase - ECP
Allergic Symptoms
Activation Phase
Shared Immunological Mechanisms in
Interactions between rhinitis & asthma
Interactions between rhinitis & asthma
Interactions between rhinitis & asthma
Allergic asthma and allergic Rhinitis are
characterized by a similar inflammatory process
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
Bronchial biopsioes after
Specific provocation in
patients with rhinitis or
asthma
Crimi E et al, JAP 2001
ASTHMA
RHINITIS ALONE
Same inflammation
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
Bronchial endoscopic challenge
With allergen
Induces nasal inflammation
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.
The relationships between Rhinitis and asthma can be
viewed under the concept that the 2 conditions are
manifestations of one syndrome, in 2 parts of the
respiratory tract , the upper and lower airways,
respectively
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, with the
severity of each condition tracking in parallel.
.
Togias A, J Allergy Clin Immunol Jun2003
Chronic Allergic Inflammatory Airway
Syndrome
Allergic Rhinitis
Allergic rhinitis + Bronchial Hyperreactivity
Allergic Rhinitis + Asthma
Allergic Rhinitis and Asthma:
Two Related Conditions Linked
by One Common Airway
The United Airways Disease
Interactions between rhinitis & asthma
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.
In some patients Rhinitis predominates and asthma is
undiagnosed or sub-clinical, in others it is reversed,
while in many both are clinically expressed.
Togias A, J Allergy Clin Immunol Jun2003
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
Clinical links
Influence of comorbid conditions on asthma
Boulet LP, ERJ 2009
Ten Brinke A et al Eur Resp J 2005
51
Risk factors of frequent exacerbation
in difficult-to-treat asthma
Clinical aspects of the link between chronic
sinonasal diseases and asthma.
Dursun et al. Allergy Asthma Proc 2006
The coexistence of sinusitis and asthma, especially in
children, is known, and infection of the paranasal
sinuses is frequently implicated in the development
of disease of the lower respiratory tract in allergic
patients.
Sinusitis and/or adenoiditis have been shown by
endoscopic assessment to occur in more than 50%
of children with asthma.
ARIA 2008
Infected sinuses are a reservoir of proliferating
bacteria and are frequently associated with
worsening of asthma.
Endotoxins from the cell walls of gram-negative
bacteria have potent pro-inflammatory properties,
and inhalation of endotoxin has been shown to
induce airway narrowing and hyperresponsiveness
in patients with asthma.
Good correlation among abnormal sinus x-rays,
blood eosinophilia and asthma symptoms
Steroid-dependent asthmatics usually have abnormal
sinus computed tomography
The sinonasal inflammation is a risk for asthma
exacerbation
Treatment of sinusitis improves asthma
Cruz, Allergy 2008
Untreated rhinitis increases the risk of asthma
attacks.
Asthma
Asthma + rhinitis
Bousquet, Clin Exp Allergy 2005
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
0.9
2.3
p<0.01
Treating allergic rhinitis cuts asthma costs
• 61% fewer hospitalisations in treated patients
Patients
hospitalised
over 1-year
period (%)
Patients untreated
for AR
(n=1357)
Patients treated
for AR
(n=3587)
2.5
2.0
1.5
1.0
0.5
0.0
• therapeutic
Therapeutic aspects
The severity of allergic rhinitis was shown to be directly
correlated with asthma severity.
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
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
prophylactic anti-asthma drugs may be unnecessary in
some patients with a diagnosis of mild asthma.
Curr Opin Allergy Clin Immunol 2003
Among a population with co-existing asthma & allergic
rhinitis, treatment for allergic rhinitis was associated with
a decrease in the risk of subsequent asthma-related
events by one-third to one-half compared with persons
who did not receive treatment for this disorder.
Fuhlbrigge A, Curr Opin Allergy Clin Immunol 2003
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.
Asthma Management: An Expert Interview With Harold Nelson, MD 4/1/2005
Harold Nelson, MD, Professor of Medicine at National Jewish Medical and
Research Center, discusses data presented at AAAAI 2005 in asthma
Airway
inflammation
Airflow
obstruction
Bronchial
hyperresponsiveness
Symptoms
Asthma Pathophysiology
The tip of the iceberg
Interactions between rhinitis & asthma
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
Asthma therapy
Controllers
 Inhaled corticosteroids
 Inhaled long-acting b2-
agonists
 Oral anti-leukotrienes
 Oral theophyllines
Relievers
 Inhaled fast-acting b2-
agonists
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
Concept of "minimal persistent inflammation"
Threshold level
for symptoms
0,1
1
10
100
0 2 4 6 8 10 12 Months
miteallergen(µg/gofdust)
Minimal persistent
inflammation
Symptoms
inflammation
Ciprandi et al, J Allergy Clin Immunol 1996
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&ICAM-1 expression, which is known as
"minimal persistent inflammation" (MPI).
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.
Interactions between rhinitis & asthma
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 antihistamines
Leukotriene receptor antagonists
Intranasal corticosteroids
Interactions between rhinitis & asthma
Interactions between rhinitis & asthma
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. They also suppress multiple mediators and
several stages of the inflammatory process.
Interactions between rhinitis & asthma
• ICS+INCS in the same UAD patients???????
INCS are
the most effective drug
In A.R.
ICS are
the milestone
asthma treatment
mild
intermittent
Mild
persistent
Moderate-
severe
intermittent
Moderate-
severe
persistent
Allergen avoidance
Decongestant (<10 days)
Nasal steroid
2nd Generation antihistamine
Im immunotherapy
TREATMENT OF ALLERGIC RHINITIS
ARIA -Allergic Rhinitis and its Impact on Asthma
Cromones
Antileukotrienes (if asthma)
Treatment of comorbid Rhinitis & asthma
"integrated" therapeutic approach in patients with rhinitis and asthma.
Interactions between rhinitis & asthma
● Montelukast is effective in the treatment of allergic
rhinitis and asthma .
● Subcutaneous immunotherapy is recommended in
both rhinitis and asthma in adults.
● Anti-IgE monoclonal antibody is effective for both
rhinitis and asthma.
ARIA 2008
Interactions between rhinitis & asthma
Dymista : New Spray for Allergic Rhinitis
Drug Approval
In 2012, the FDA approved a new nasal spray to treat
seasonal allergic rhinitis in patients ages 12 and older.
Dymista is a combination of the antihistamine
azelastine (Astelin, Astepro) and
corticosteroid fluticasone (Flonase, generic).
.
Interactions between rhinitis & asthma
Interactions between rhinitis & asthma
“Allergic rhinitis and asthma are chronic
inflammatory disorders that have been linked
epidemiologically, pathophysiologically, and
therapeutically as “one airway disease.”
Final Remarks
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
Thank you for staying awake!

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Interactions between rhinitis & asthma

  • 3. By Dr . Ashraf El-Adawy Consultant Chest Physcian TB TEAM Expert - WHO Mansoura - Egypt
  • 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. 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
  • 9. 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
  • 10. Slide 10 Epidemiologic Links between Allergic Rhinitis and Asthma Many Patients with Asthma Have Allergic Rhinitis 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
  • 11. • Epidemiologic • Anatomic • Physiologic • Immunopathologic • Therapeutic IMPACT OF ASTHMA AND ALLERGIC RHINITIS ON EACH
  • 12. 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
  • 13. 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
  • 14. - 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
  • 15. The prevalence of asthma in subjects without Rhinitis is usually less than 2%. 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. 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
  • 17. 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
  • 18. Rhinitis asthma Diseaseseverity time Togias, Allergy 1999 The current concept is that AR precedes asthma in most patients
  • 19. The Allergy March: A Progression of Seemingly Unrelated Diseases CHDs CHDs Atopic Dermatitis GI Distress Recurrent Otitis Media Allergic Asthma Allergic Rhinitis Food Sensitivity Inhalant Sensitivity Time (~years) Genetic Predispositi on
  • 20. 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
  • 21. Rhinitis is a significant risk factor for adult- onset asthma in both atopic and non-atopic subjects increased the risk by about 3 times. 76% asthmatic patients reported presence of Rhinitis before onset asthma. Links between Rhinitis and asthma Epidemiologic evidence
  • 22. Patients with moderate/severe persistent Rhinitis may be more likely to suffer from asthma than those with an intermittent and/or mild Rhinitis Asthma prevalence is increased in allergic and non-allergic Rhinitis Non-specific bronchial hyperreactivity is increased in persistent Rhinitis Links between Rhinitis and asthma Epidemiologic evidence
  • 23. Allergic Rhinitis and Asthma Share Common Triggers
  • 24. • . Allergic Rhinitis and asthma share similar inflammatory processes Common triggers Similar inflammatory cascade on exposure to an 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
  • 25. 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
  • 26. 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)
  • 27. 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
  • 29. Allergy: A Dysregulation of the Immune System APC Th0 Th1Th2 B lymphocyte Mast cell Eosinophil Allergic Symptoms IFN  IL 4 IL 10 IL 5 IFN IL 4 IL 13 IL 9 IL 12 IL 18 IL 12 IL 18 IL 4 Allergens IgE Sensitization Phase
  • 30. Allergy: A Dysregulation of the Immune System Mast cell Basophil Eosinophil Inflammatory Mediators Release Allergens Histamine - Prostaglandins – Leucotriens – Tryptase - ECP Allergic Symptoms Activation Phase
  • 35. Allergic asthma and allergic Rhinitis are characterized by a similar inflammatory process 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
  • 36. Bronchial biopsioes after Specific provocation in patients with rhinitis or asthma Crimi E et al, JAP 2001 ASTHMA RHINITIS ALONE Same inflammation
  • 37. 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
  • 38. Bronchial endoscopic challenge With allergen Induces nasal inflammation
  • 39. 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.
  • 40. The relationships between Rhinitis and asthma can be viewed under the concept that the 2 conditions are manifestations of one syndrome, in 2 parts of the respiratory tract , the upper and lower airways, respectively 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, with the severity of each condition tracking in parallel. . Togias A, J Allergy Clin Immunol Jun2003
  • 41. Chronic Allergic Inflammatory Airway Syndrome Allergic Rhinitis Allergic rhinitis + Bronchial Hyperreactivity Allergic Rhinitis + Asthma
  • 42. Allergic Rhinitis and Asthma: Two Related Conditions Linked by One Common Airway The United Airways Disease
  • 44. 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. In some patients Rhinitis predominates and asthma is undiagnosed or sub-clinical, in others it is reversed, while in many both are clinically expressed. Togias A, J Allergy Clin Immunol Jun2003
  • 45. 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
  • 47. Influence of comorbid conditions on asthma Boulet LP, ERJ 2009
  • 48. Ten Brinke A et al Eur Resp J 2005 51 Risk factors of frequent exacerbation in difficult-to-treat asthma
  • 49. Clinical aspects of the link between chronic sinonasal diseases and asthma. Dursun et al. Allergy Asthma Proc 2006
  • 50. The coexistence of sinusitis and asthma, especially in children, is known, and infection of the paranasal sinuses is frequently implicated in the development of disease of the lower respiratory tract in allergic patients. Sinusitis and/or adenoiditis have been shown by endoscopic assessment to occur in more than 50% of children with asthma. ARIA 2008
  • 51. Infected sinuses are a reservoir of proliferating bacteria and are frequently associated with worsening of asthma. Endotoxins from the cell walls of gram-negative bacteria have potent pro-inflammatory properties, and inhalation of endotoxin has been shown to induce airway narrowing and hyperresponsiveness in patients with asthma.
  • 52. Good correlation among abnormal sinus x-rays, blood eosinophilia and asthma symptoms Steroid-dependent asthmatics usually have abnormal sinus computed tomography The sinonasal inflammation is a risk for asthma exacerbation Treatment of sinusitis improves asthma
  • 54. Untreated rhinitis increases the risk of asthma attacks. Asthma Asthma + rhinitis Bousquet, Clin Exp Allergy 2005
  • 55. 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
  • 56. 0.9 2.3 p<0.01 Treating allergic rhinitis cuts asthma costs • 61% fewer hospitalisations in treated patients Patients hospitalised over 1-year period (%) Patients untreated for AR (n=1357) Patients treated for AR (n=3587) 2.5 2.0 1.5 1.0 0.5 0.0
  • 58. The severity of allergic rhinitis was shown to be directly correlated with asthma severity. 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
  • 59. 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 prophylactic anti-asthma drugs may be unnecessary in some patients with a diagnosis of mild asthma. Curr Opin Allergy Clin Immunol 2003
  • 60. Among a population with co-existing asthma & allergic rhinitis, treatment for allergic rhinitis was associated with a decrease in the risk of subsequent asthma-related events by one-third to one-half compared with persons who did not receive treatment for this disorder. Fuhlbrigge A, Curr Opin Allergy Clin Immunol 2003
  • 61. 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. Asthma Management: An Expert Interview With Harold Nelson, MD 4/1/2005 Harold Nelson, MD, Professor of Medicine at National Jewish Medical and Research Center, discusses data presented at AAAAI 2005 in asthma
  • 64. 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
  • 65. Asthma therapy Controllers  Inhaled corticosteroids  Inhaled long-acting b2- agonists  Oral anti-leukotrienes  Oral theophyllines Relievers  Inhaled fast-acting b2- agonists
  • 66. 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
  • 67. Concept of "minimal persistent inflammation" Threshold level for symptoms 0,1 1 10 100 0 2 4 6 8 10 12 Months miteallergen(µg/gofdust) Minimal persistent inflammation Symptoms inflammation Ciprandi et al, J Allergy Clin Immunol 1996
  • 68. 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&ICAM-1 expression, which is known as "minimal persistent inflammation" (MPI).
  • 69. 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.
  • 71. 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 antihistamines Leukotriene receptor antagonists Intranasal corticosteroids
  • 74. 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. They also suppress multiple mediators and several stages of the inflammatory process.
  • 76. • ICS+INCS in the same UAD patients??????? INCS are the most effective drug In A.R. ICS are the milestone asthma treatment
  • 77. mild intermittent Mild persistent Moderate- severe intermittent Moderate- severe persistent Allergen avoidance Decongestant (<10 days) Nasal steroid 2nd Generation antihistamine Im immunotherapy TREATMENT OF ALLERGIC RHINITIS ARIA -Allergic Rhinitis and its Impact on Asthma Cromones Antileukotrienes (if asthma)
  • 78. Treatment of comorbid Rhinitis & asthma
  • 79. "integrated" therapeutic approach in patients with rhinitis and asthma.
  • 81. ● Montelukast is effective in the treatment of allergic rhinitis and asthma . ● Subcutaneous immunotherapy is recommended in both rhinitis and asthma in adults. ● Anti-IgE monoclonal antibody is effective for both rhinitis and asthma. ARIA 2008
  • 83. Dymista : New Spray for Allergic Rhinitis Drug Approval In 2012, the FDA approved a new nasal spray to treat seasonal allergic rhinitis in patients ages 12 and older. Dymista is a combination of the antihistamine azelastine (Astelin, Astepro) and corticosteroid fluticasone (Flonase, generic). .
  • 86. “Allergic rhinitis and asthma are chronic inflammatory disorders that have been linked epidemiologically, pathophysiologically, and therapeutically as “one airway disease.” Final Remarks
  • 87. 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
  • 88. Thank you for staying awake!