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
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
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
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
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
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
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
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
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
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