1.
Asthma Rhinitis link

2.
By
Dr . Ashraf El-Adawy
Consultant Chest Physcian
TB TEAM Expert - WHO

3.
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

4.
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

5.
Australia
asthma 18%
rhinitis 25%
Canada
asthma 13%
rhinitis 25%
Sweden
asthma 8%
rhinitis 15%
China
asthma 5%
rhinitis 10%
Worldwide prevalence
Brasil
asthma 10%
rhinitis 22%
Kenya
asthma 8%
rhinitis 13%
ISAAC study, Lancet 1998

6.
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

7.
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

8.
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

9.
Most Patients with Asthma Have Allergic Rhinitis
• Approximately 80% of asthmatics have allergic rhinitis
Asthma
alone
Allergic rhinitis
alone
Allergic
rhinitis
+
asthma
Adapted from The Workshop Expert Panel. Management of Allergic Rhinitis and its Impact on Asthma (ARIA) Pocket Guide. A
Pocket Guide for Physicians and Nurses. 2001; Bousquet J and the ARIA Workshop Group J Allergy Clin Immunol 2001;108(5):S147-
S334; Sibbald B, Rink E Thorax 1991;46:895-901; Leynaert B et al Am J Respir Crit
Care Med 2000;162:1391-1396.

10.
IMPACT OF ASTHMA AND
ALLERGIC RHINITIS ON EACH
• Epidemiologic
• Anatomic
• Physiologic
• Immunopathologic
• Therapeutic

11.
Allergic Rhinitis is a risk factor for asthma
Allergic Rhinitis increased the risk of asthma ~3-fold
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
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.
Rhinitis as an independent risk factor for adult-onset
asthma (atopic and non-atopic)
(European Community Respiratory Health Survey)
Asthma (%)
Atopic Non atopic
25
20
15
10
5
Adapted from Leynaert B et al. J Allergy Clin Immunol 1999;
no rhinitis, N=5198
rhinitis, N=1412
OR=11
OR=17
0

13.
Prevalence of asthma (physician diagnosed) in Rhinitis
- 591 patients
- 502 controls
- allergic to pollens, mite,
-epithelia
Bousquet, CEA 2005
35
30
25
20
% subjects
15
10
5
0
contr mild severe mild severe
intermittent persistent
% pazienti

14.
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

15.
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

16.
Several studies suggested that patients
with allergic Rhinitis and BHR are at
higher risk of developing asthma
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

17.
The current concept is that AR precedes
Rhinitis
asthma
Disease severity
time
Togias, Allergy 1999
asthma in most patients

18.
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

19.
Links between Rhinitis and asthma
Epidemiologic evidence
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.

20.
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

21.
Allergic Rhinitis and Asthma Share
Common Triggers

22.
• .
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

23.
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

24.
Bronchial biopsioes after
Specific provocation in
patients with rhinitis or
asthma
ASTHMA
Crimi E et al, JAP 2001
RHINITIS ALONE
Same inflammation

25.
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

26.
Induces nasal inflammation
Bronchial endoscopic challenge
With allergen

27.
Mechanisms of pathologic relationships
between upper and lower airways.
Togias A Allergy 1999;54(suppl 57):94..
Aspiration of
Inflammatory
Material
Oral breathing
Nasopharyngo-bronchial
reflex
Systemic
Propagation of
Nasal
Inflammation

28.
Naso-bronchial reflex
Allergen
INFLAMMATION
nose
Cytokines bone marrow
bronchi
Bronchial hyperreactivity
physical filter function
adhesion molecules
viral infection

29.
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

30.
Chronic Allergic Inflammatory Airway
Syndrome
Allergic Rhinitis
Allergic rhinitis + Bronchial Hyperreactivity
Allergic Rhinitis + Asthma

31.
Allergic Rhinitis and Asthma:
Two Related Conditions Linked
by One Common Airway
The United Airways Disease

32.
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

33.
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

34.
Clinical links

35.
Influence of comorbid conditions on asthma
Boulet LP, ERJ 2009

36.
Risk factors of frequent exacerbation
in difficult-to-treat asthma
Ten Brinke A et al Eur Resp J 2005
51

37.
Clinical aspects of the link between
chronic sinonasal diseases and asthma.
Dursun et al. Allergy Asthma Proc 2006

38.
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

39.
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.

40.
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

41.
Cruz, Allergy 2008

42.
Untreated rhinitis increases the risk of asthma
attacks.
Asthma
Asthma + rhinitis
Bousquet, Clin Exp Allergy 2005

43.
Treatment of Rhinitis reduces
emergency visits for asthma
Baena-Cagnani et al, Int Arch Allergy Immunol 2003
Nelson HS, JACI 2003
Crystal-Peters, JACI 2002
Fuhlbrigge, Curr Opin Allergy Immunol 2003
Adams et al. J.A.C.I. 2002

44.
Treating allergic rhinitis cuts asthma costs
• 61% fewer hospitalisations in treated patients
0.9
2.3
p<0.01
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

45.
• therapeutic
Therapeutic aspects

46.
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

47.
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

48.
Among a population with co-existing asthma and
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

49.
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
management.

50.
Asthma Pathophysiology
Symptoms
The tip of the iceberg
Airflow
obstruction
Bronchial
hyperresponsiveness
Airway
inflammation

51.
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

52.
Concept of "minimal persistent inflammation"
Threshold level
for symptoms
100
10
1
0,1
0 2 4 6 8 10 12 Months
mite allergen (μg/g of dust)
Minimal persistent
inflammation
Symptoms
inflammation
Ciprandi et al, J Allergy Clin Immunol 1996

53.
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).

54.
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.

55.
Therapeutic implications of minimal persistent
inflammation
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.

56.
INCS are
the most effective drug
In A.R.
ICS are
the milestone
asthma treatment
• ICS+INCS in the same UAD patients???????

57.
Taramarcaz, Cochrane 2008

58.
Conclusions: Treatment of nasal conditions, particularly
with intranasal steroids, confers significant protection
against exac-erbations of asthma leading to ED visits for
asthma.
These results support the use of intranasal steroids by
individuals with asthma and upper airways conditions.
J Allergy Clin Immunol. 2002
Apr;109(4):636-42

59.
mild
intermittent
TREATMENT OF ALLERGIC RHINITIS
ARIA -Allergic Rhinitis and its Impact on Asthma
Mild
persistent
Moderate-severe
intermittent
Moderate-severe
persistent
Antileukotrienes (if asthma)
Nasal steroid
Cromones
2nd Generation antihistamine
Decongestant (<10 days)
Allergen avoidance
Im immunotherapy

60.
Treatment of comorbid Rhinitis & asthma

61.
"integrated" therapeutic approach in patients with rhinitis and asthma.

62.
Treatment of rhinitis and asthma using
a single approach
● Oral H1-antihistamines are not recommended, but
not contraindicated in the treatment of asthma.
● Intranasal glucocorticosteroids are at best
moderately effective in asthma.
● Intranasal glucocorticosteroids may be effective in
reducing asthma exacerbations and
hospitalizations.
● The role of intrabronchial glucocorticosteroids in
rhinitis is unknown.
ARIA 2008

63.
● Montelukast is effective in the treatment of allergic
rhinitis and asthma in patients over 6 years of age.
● Subcutaneous immunotherapy is recommended in
both rhinitis and asthma in adults, but it is burdened
by side effects, in particular in asthmatics.
● Anti-IgE monoclonal antibody is effective for both
rhinitis and asthma.
ARIA 2008

64.
combined simultaneous treatment of
co-existing asthma & rhinitis
Pulmonary
steroid
Twice daily
&
Pulmonary
bronchodilator
Rescue
medication
Oral
Anti-histamine
Once daily
Or
Oral
Anti-leukotriene
Once daily
+ + &
Nasal
steroid
Once daily
Or
Pulmonary
combination
:
ICS+LABA
Twice daily
+ +

65.
When to Consider Immunotherapy
Mild
Moderate ±
conjunctivitis
Allergen avoidance when possible
RHINITIS
Pharmacotherapy
Severe ±
conjunctivitis
Consider immunotherapy
Intermittent Mild persistent
Pharmacotherapy
Moderate
persistent
Consider immunotherapy
Severe
persistent

66.
Final Remarks
“Allergic rhinitis and asthma are chronic
inflammatory disorders that have been linked
epidemiologically, pathophysiologically, and
therapeutically as “one airway disease.”

67.
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

68.
Thank you for staying awake!