S y a m s u

Division of Allergy and Immunology

Department of Internal Medicine
Medical Faculty Hasanuddin University
Makassar
Atopy is the propensity of an individual to produce IgE
in response to various environmental antigens and to
develop strong immediate hypersensitivity (allergic)

People who have allergies to environmental antigens
such as pollen or house dust, are said to be atopic.

Allergic rhinitis and allergic asthma are the most common
manifestation. Atopic dermatitis is less common, and
allergic gastroenteropathy is rare. These manifestation may
simultaneously coexist in the same patient or at different
time. Atopy can also be asymptomatic
The etiology of atopy is unknown.
There is substantial evidence for
complex of genes with variable degree
of expression encoding protein
factors, some of which are
pathogenic and others protective.
Disease Mechanism Antigen
Source
Result
Allergy Immunologic Foreign Disease
Immunity Immunologic Foreign Prophylaxis
Autoimmu
nity
Immunologic Self Disease
Toxicity Toxic Foreign Disease
COMPARISON OF ALLERGY WITH OTHER RESPONSES
Disease Possible explanation
Allergic Asthma Multiple atopic allergies
Atopic rhinitis Multiple atopic allergies
Atopic dermatitis Multiple allergen and linkage to
non MHC gene
Allergic bronchopulmonary
aspergillosis
Unknown; varies with disease
activity
Parasitic diseases IgE associated with protective
immunity
Hyper-IgE syndrome Unknown
Ataxia-telangiectasia T-supressor cell defect ?
Wiskott-Aldrich syndrome Unknown
Thymic Alymphoplacia Unknown
IgE meloma Neoplasm of IgE producing plasma
cells; Ig E is monoclonal
Graft versus host
reaction
Transient T-suppressor cell
defect ?
Definition
Chronic inflammatory disorder of the airways
leading to episodes that are associated to
airflow obstruction which is often reversible.
Increased bronchial hyperresponsiveness
Multiple cells and cellular components
involved
Reversibility may be incomplete
A. Extrinsic Asthma (allergic, atopic, or immunologic)
Generally develop early in life, usually in infancy or
childhood, often coexist with eczema or allergic rhinitis.
A family history of atopic disease is common.
Skin test show positive reaction to the causative allergen
Total serum IgE elevated , but sometimes normal

B. Intrinsic Asthma (nonallergic or idiopathic)
Appears first during adult life, usually after respiratory
infection, but sometimes develop during chidhood.
Skin test are negative to the usual allergens,
The serum IgE concentration is normal.
Blood and sputum eosinophilia is present.
Personal and family history for atopic disease usually
negative
Mechanisms of the late phase allergic reaction
0 1 6 8 24 48 (h)
RANTES
Ectaxin
IL-8
GM-CSF
PAF
TNF-
IL-4
IL-5
IL-8
GM-CSF
MIP-1
MCP-3
TNF-
IL-
IL-3
IL-4
IL-5
IL-8
GM-CSF
IL-3
IL-4
IL-5
IL-6
IL-13
RANTES
IL-4
IL-13
MIP-1
RANTES
Eotaxin
IL-8
GM-CSF
PAF
RANTES
MCP-4
Eotaxin
ICAM-1
VCAM-1
E-selection
Histamin, PGD
2
,
LTs etc
MBP, ECP,
EDN, CLC etc
MBP, ECP,
EDN, CLC etc
Early phase
Late phase
Very late phase
APC
IL-4
Endothelium
Epithelium
Endothelium
VCAM-1
Th2
B cells
Ag
Mast cells
FceRI
Th2
Th0
Eos Eos Baso
Baso
Eos
Th2
Histamin, LTC
4

Mediators and cytokines involved in chronic
allergic inflammation
Infection : Viral resp. infection
Physiological Factors : . Exercise, Hyperventilation, Deep
breathing, Psychologic factors
Atmospheric factors : SO2, NH2, Cold air, O2, dest.water
Ingestants, Propanolol, aspirin, NSAID, Sulfit
Experimental inhalants : hypertonic solution, citric acid,
histamine, metacholine, PGF2
Occupational inhalant : isocyanate, wool, cotton, coffee,
fragrance etc
A. Symptoms
Attack of wheezing, dyspnea, cough and tightness of chest
Fever is absent but fatigue, malaise, irritability, palpitations
and sweating are occasional systemic complaints
B. Sign
Tachypnea, audible wheezing, expiration >>inspiration.
Use of the accessory muscles of respiration.
Pulsus paradoxus indicate severe asthma
In severe attack with high grade obstruction breath sound
and wheezing may both absent
C. Laboratory Findings
- Increased total eosinophil count in peripheral blood
in nasal secretion, sputum, Charcot Leyden crystals and
Curschmans spiral
- CXR may be normal or show hyperinflation
- Total serum IgE is usually elevated in childhood allergic
asthma and normal in adult intrinsic asthma, but this test
lack specificity for diagnosis
- PFT : PFR and FEV1 are decreased
VC may be normal or decreased
Bronchodilatation test (+) if FEV1 > 15 %
Diagnosis made by history, physical examination and PFT
to show reversible bronchial obstruction.
Blood and sputum eosinophilia is confirmatory.
CXR is useful to exclude other cardipulmonary diseases
Metacholin challenge test for instances which history and
PFT is normal
Skin Prick test or RAST for trigger allergens
Classification of Asthma Severity
Persistent
Intermittent
Mild Moderate Severe
Components of
Severity
Impairment

Normal
FEV
1
/FVC
8-19 yr 85%
20-39 yr 80%
40-59 yr 75%
60-80 yr 70%
Risk
Recommended Step for
Initiating Treatment
Symptoms
Nighttime
Awakenings
SABA use for sx
control
Interference with
normal activity
Lung Function
Exacerbations
(consider
frequency and
severity)
In 2 -6 weeks, evaluate asthma control that is achieved and adjust therapy
accordingly
Step 1 Step 2 Step 3 Step 4 or 5
Relative annual risk of excaerbations may be related to FEV
0-2/year > 2 /year
Frequency and severity may vary over time for patients in any category
<2 days/week
>2 days/week
not daily
Daily Continuous
<2x/month
3-4x/month
>1x/week
not nightly
Often nightly
none Minor limitation Some limitation Extremely limited
<2 days/week
>2 days/week
not daily
Daily Several times daily
Consider short course of oral steroids
Normal FEV
1
between
exacerbations
FEV
1
> 80%
FEV
1
/FVC normal
FEV
1
>80%
FEV
1
/FVC
normal
FEV
1
>60%
but < 80%
FEV
1
/FVC reduced
5%
FEV
1
<60%
FEV
1
/FVC
reduced> 5%
CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN
YOUTHS > 12 YEARS AND ADULTS
EPR-3, p74, 344
24
Classification of Asthma Control
Components of Control
ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN
YOUTHS > 12 YEARS OF AGE AND ADULTS
IMPAIRMENT
RISK
Recommended Action
For Treatment
Well Controlled
Not Well
Controlled
Symptoms
Nighttime awakenings
Interference with
normal activity
SABA use
FEV
1
or peak flow
Validated questionnaires
ATAQ/ACT
Exacerbations
Progressive loss of lung
function
Rx-related adverse effects Consider in overall assessment of risk
Evaluation requires long-term follow up care
0- 1 per year 2 - 3 per year > 3 per year
none Some limitation Extremely limited
< 2 days/week > 2 days/week Throughout the day
< 2/month 1-3/week > 4/week
< 2 days/week > 2 days/week Several times/day
> 80% predicted/
personal best
60-80% predicted/
personal best
<60% predicted/
personal best
0/> 20 1-2/16-19 3-4/< 15
Maintain current step
Consider step down
if well controlled at
least 3 months
Step up 1 step
Reevaluate in 2 - 6
weeks
Consider oral
steroids
Step up 1-2 weeks
and reevaluate in 2
weeks
EPR-3, p77,
345
25
SEVERITY OF ASTHMA EXACERBATION
GINA 2006
26
27
Pharmacologic Treatment
Reliever
- Rapid acting inhaled 2 agonist
- Anticholinergic
- Theophylline
- Short- acting oral 2 -- agonist

Controller
- Inhaled glucocorticoid
- Oral antileucotrienes
- inhaled long-acting 2-agonist
- Cromones
- ( Theophylline )
- Oral long-acting 2-agonist
- Oral anti-Ig.E
- Systemic glucocorticoid
- Oral antiallergic
- Allergen specific immunotherapy
28
Other drugs
-Other anti inlammation : methotrexate,
gold salt, cyclosporine, anti TNF
-Anti leukotrine : zafirlukast, montelukast
-Anti IgE : omalizumab
Intermittent
Asthma
Persistent Asthma: Daily Medication
Consult with asthma specialist if step 4 or higher care is required
Consider consultation at step 3
Patient Education and Environmental Control at Each Step
Step 1
Preferred:
SABA prn

Step 2
Preferred:
Low-dose ICS
Alternative:
LTRA
Cromolyn
Theophylline



Step 3
Preferred:
Medium-dose
ICS OR
Low-dose ICS+
either LABA,
LTRA,
Theophylline
Or Zileutin


Step 4

Preferred:
Medium-dose
ICS+LABA

Alternative:
Medium-dose
ICS+either
LTRA,
Theophlline
Or Zileutin
Step 5
Preferred:
High dose ICS
+ LABA


AND

Consider
Olamizumab
for
patients with
allergies
Step 6

Preferred:
High-dose ICS
+ LABA + oral
Corticosteroid


AND

Consider
Olamizumab
for
patients with
allergies

Assess
Control
STEPWISE APPROACH FOR MANAGING ASTHMA
IN YOUTHS > 12 YEARS AND ADULTS
Step up if
needed (check
adherence,
environmental
control and
comorbidities)
Step down if
possible
(asthma well
controlled
for 3
months)
EPR-3, p333-343
EPR-3, p333-343
30