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Dr. Binu Krishnan.

MD, DTCD, FCCP


Consultant Pulmonologist
PRS Hospital, Trivandrum.

26-4-09
80
70
60

Cases 50 N=3355
per
1000 40
Children
30

20

10

0
Hay Fever Asthma Other Skin Digestive Cardiac Other
Respiratory Allergies Allergies Conditions Nonallergic
Allergies Conditions
*Patient assessment.
Adapted from Newacheck et al. J Pediatr. 1994;124:40.
Why do we have a nose?
Colds Asthma

Allergic
Rhinitis Sinus
Ear Infections
Infections
Nasal
Polyps
URI=upper respiratory infections.
Spector SL. J Allergy Clin Immunol. 1997;99:S773-S780. OME=otitis media with effusion.
Does Allergy Cause
Sinusitis?

Annual US incidence of sinusitis = 35 + million


In adult patients, CT demonstrated association
between extensive sinus disease and:
Allergy in 78% of patients
What About Ear Infections
in Children?
School
Children Nasal Allergy
(N=104)* Children (N=605)

7.9% 21%

OME = Otitis media with effusion.


*Control group.
Adapted from Tomonaga et al. Acta Otolaryngol (Stockh). 1988;458(suppl):41.
Have Allergy? How is your
brain working today?
Composite Learning Score

60
58
56
54 *
52
50
48
46
44
42 (N=21) (Placebo Treated)
* P<0.007 (N=52)
40
N orm al Children A llergic R hinitis
Vuurman et al. Ann Allergy 1993,71:121
Questions
What is the relationship between allergic rhinitis
and asthma?

Is there any interaction between upper and


lower airways?

What are the mechanisms that may play a role


in nasobronchial cross-talk?
Questions
What is the relationship between allergic
rhinitis and asthma?

Is there any interaction between upper and


lower airways?

What are the mechanisms that may play a role


in nasobronchial cross-talk?
ARIA
Objectives:
Update knowledge of AR
Recognise AR as global
health problem
Asthma and AR commonly
occur together
Evidence-based approach
to diagnosis and treatment
Management of allergic
airways disease

Bousquet et al, J Allergy Clin Immunol 2001


Pathogenesis allergic airway
disease
Environmental
Mucosal inflammation
factors

Atopic
sensitization

Phenotype

Genetic factors
Structural changes
Epidemiology
80-95% of asthmatic patients have rhinitis.

76% asthmatic patients reported presence


of rhinitis before onset asthma.

Asthma presence associated with duration


and severity of rhinitis.

Leynaert, J Allergy Clin Immunol 2004


Disease severity
rhinitis

asthma

time
Togias, Allergy 1999
Bronchial asthma.
Symptom less state can be achieved for
most patients [Asthma bronchiale.
Beschwerdefreiheit fur Mehrzahl der
Patienten erreichbar.] Fortschr Med
1999 Mar 20;117(8):24-6, 28, 30
passim    (ISSN: 0015-8178) Schmidt M
Medizinische Universitatsklinik Wurzburg.
Nasal inflammation and BHR
20
Nasal eosinophil number

10

0 PD20
22 3 11 12 methacholine

absent low moderate high

Ciprandi G. et al, Int Arch Allergy Immunol 2004


Lower airway involvement in
atopic patients
Eosinophils µm RBM
cell/mm2
10
60
** ** 9
* *
8
40
* 7
20
6

0 5
HC NANR RNA A+R HC NANR RNA A+R
n=16 n=8 n=18 n=19 n=16 n=8 n=18 n=19

* = p < 0.05 vs controls


Braunstahl GJ. et al, Clin Exp Allergy 2003
type I collagen type III collagen fibronectin
basement membrane thickness (µm)

25 25 25

20 20 20

15 15 15

10 10 10

5 5 5

0 0 0
controls rhinitis asthma controls rhinitis asthma controls rhinitis asthma

Chakir et al, Lab Invest 1996


Summary
Mucosal inflammation is present in
the entire airway of patients with
allergic rhinitis and/or asthma.

Upper airway inflammation is


associated with bronchial
Inflammation hyperresponsiveness

Lower airway remodeling is present


in asthmatic, but also in allergic
rhinitis patients.
Questions
What is the relationship between allergic rhinitis
and asthma?

Is there any interaction between upper and


lower airways?

What are the mechanisms that may play a role


in nasobronchial cross-talk?
Allergic inflammation

Baseline VCAM-1 Eosinophils

nose

lung
Nasal inflammation after SBP
MBP

Before bronchial After


100 x challenge
Summary

The interaction between nose and lung in allergic


airways disease is a bi-directional process
Questions
What is the relationship between allergic
rhinitis and asthma?

Is there any interaction between upper and


lower airways?

What are the mechanisms that may play a role


in nasobronchial cross-talk?
Nasal vs. oral ventilation
effect of cold air inhalation
5
NR cm H2O/L/sec NHV 4 NHV 4 OHV

FEV1

FEV1
B = baseline
R = frigid air

0 0 0
B R B R B R
P value 0.01 0.27 <0.001

McLane, J. Appl. Physiol. 2000


Pulmonary aspiration?
Radio-active markers
99m
Tc
1 hr 6 hr 24 hr

Maxillary sinus Oesophagus Rest of GI tract


nasopharynx stomach

Bardin et al, JACI, 1990


Systemic interaction?
effect of NP on IL-5 plasma
80

60
IL-5 (pg/mL)

40

*
20

0
pre post pre post
Allergen Placebo
* p < 0.001
Beeh et al, Clin Exp Allergy, 2003
pg/mL cell x 106
50
IL-5 400
eosinophils

40
* 300
*
30
200
20

100
10

0 0
before after before after
control
Braunstahl GJ et al, AJRCCM, 2001 allergic
Summary
Allergen
Nose breathing

Ingestion

Aspiration
Neural reflex
Mouth
breathing
Lymph nodes

Circulation
GINA Guideline clearly states that THERE
IS NO CURE FOR ASTHMA, But
appropriate management most often
leading to CONTROL of asthma
Best cure for any illness is to
forget about it and enjoy
your present moment.
In collaboration with the World Health Organization
Needs for guidelines in the
management of allergic rhinitis
• Although it is not usually a severe disease,
rhinitis alters social life and affects school
performance and work productivity.

• Implementation of guidelines improve the


condition of patients with allergic rhinitis.
allergen
allergen
avoidance
avoidance
indicated
indicated
when
whenpossible
possible

pharmacotherapy
pharmacotherapy immunotherapy
immunotherapy
safety
safety
effectiveness
effectiveness
AR
AR
effectiveness
effectiveness
specialist
specialistprescription
prescription
easy may
mayalter
alterthe
thenatural
natural
easyto
tobe
beadministered
administered course
courseofofthe
thedisease
disease

patient's
patient's
education
education
always
alwaysindicated
indicated
Treatment of allergic rhinitis (ARIA)
Allergic Rhinitis and its Impact on Asthma

moderate
severe
mild persistent
moderate persistent
severe
mild intermittent
intermittent intra-nasal steroid
local cromone
oral or local non-sedative H1-blocker
intra-nasal decongestant (<10 days) or oral decongestant
allergen and irritant avoidance
immunotherapy
Can Immunotherapy Treat
Asthma as Well as
Allergies?

 Altersdisease process
 Prevents allergic reactions
from occurring
 Changes immune system
response and development
Birth:TH2

Older siblings: Allergen Only child:


Many infections Exposure Few infections
[TH1 stimuli]

Still TH2
TH1 Allergies
No allergies

Source: Busse WW, Lemanske RF. N Engl J Med 2001.


Shift from TH2 to TH1-
like Response After
Immunotherapy
70

60

50

40

30

20

10

0
Before SIT After 3 Months After 12 Months

TH2 TH1

Source: Ebner et al. Clin Exp Allergy 1997


For Which Patients?
 Patients diagnosed with
allergic asthma
 Patients diagnosed with
allergies such as hay fever
 Patients diagnosed with
sinusitis that predisposes
them to asthma
 Patients diagnosed with
insect sting allergy
What’s the Evidence?
30
24
24
25 Meta-analysis of clinical studies
962 asthmatics with documented allergy
20 Immunotherapy clinically effective in 71% of studies
15
10
10 7
sei dut s f o r e b mu N

0
Total Studies Effective
No. of studies with children with children

Source: Ross RN, Nelson HS, Finegold I. Clin Ther 2000


Meta-Analysis
Results

Study Effective Ineffective Equivocal Total

Adults only 9 1 2 12

Children only 7 3 0 10

All Ages 1 0 1 2

TOTAL 17 4 3 24
Effectiveness of
Immunotherapy
3
2.87
2.76
2.5
2.00
1.81
2

1.5
improvement
Odds ratio of

1
Any odds ratio greater than
0.5
1.0 shows a positive effect
0
Reduced Reduced Reduced Improved
Asthma Bronchial Medication Pulmonary
Symptoms Challenge Use Function
When to Consider Immunotherapy

Moderate ± Severe ±
Mild conjunctivitis conjunctivitis

Allergen avoidance when possible


Pharmacotherapy
SI TI NI HR

Consider
Considerimmunotherapy
immunotherapy

Moderate Severe
Intermittent Mild persistent persistent persistent

Pharmacotherapy
Consider immunotherapy
TSA
Take home messages
Allergic rhinitis often precedes asthma.
Allergic rhinitis and asthma characterized by
global airway inflammation.
There is a bi-directional influence between
upper and lower airways.
The systemic pathway plays an important role
in the interaction between nose and lung
Thank you.

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