Syamsu 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.

COMPARISON OF ALLERGY WITH OTHER RESPONSES

Disease Allergy Immunity Autoimmu nity Toxicity

Mechanism Immunologic Immunologic Immunologic

Antigen Source Foreign Foreign Self

Result Disease Prophylaxis Disease

Toxic

Foreign

Disease

Disease
Allergic Asthma Atopic rhinitis
Atopic dermatitis Allergic bronchopulmonary aspergillosis Parasitic diseases Hyper-IgE syndrome Ataxia-telangiectasia

Possible explanation
Multiple atopic allergies Multiple atopic allergies
Multiple allergen and linkage to non MHC gene Unknown; varies with disease activity IgE associated with protective immunity Unknown T-supressor cell defect ?

Wiskott-Aldrich syndrome Thymic Alymphoplacia IgE meloma

Unknown Unknown Neoplasm of IgE producing plasma cells; Ig E is monoclonal

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)
Early phase Late phase
TNF- IL-

Very late phase

APC

Epithelium

Ag
FceRI

MBP, ECP, EDN, CLC etc

Mast cells
Th2 B cells

IL-4
Th0

Eos Histamin, PGD2, LTs etc

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
VCAM-1

RANTES MCP-4 Eotaxin

MBP, ECP, EDN, CLC etc

TNF- IL-4 IL-5 IL-8 GM-CSF MIP-1 MCP-3

Th2

RANTES Ectaxin IL-8 GM-CSF Endothelium PAF

ICAM-1 VCAM-1 E-selection

Baso Histamin, LTC4

RANTES Eotaxin IL-8 GM-CSF PAF

Endothelium
Eos Th2 Baso

Eos

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

CLASSIFYING ASTHMA SEVERITY AND INITIATING TREATMENT IN YOUTHS > 12 YEARS AND ADULTS EPR-3, p74, 344

Components of Severity

Classification of Asthma Severity

Intermittent Mild Persistent Moderate
Daily >1x/week not nightly <2 days/week none
Normal FEV1 between exacerbations FEV1 > 80% FEV1/FVC normal

Severe
Continuous

Symptoms

<2 days/week <2x/month

Impairment
Nighttime Awakenings Normal FEV1/FVC
SABA use for sx control
Interference with normal activity

>2 days/week not daily 3-4x/month

>2 days/week

Often nightly

Daily

Several times daily

not daily
Minor limitation FEV1 >80% FEV1/FVC normal > 2 /year Some limitation Extremely limited FEV1 >60% but < 80% FEV1/FVC reduced 5% FEV1 <60% FEV1/FVC reduced> 5%

8-19 yr 85%
20-39 yr 80% 40-59 yr 75% 60-80 yr 70%

Lung Function

Exacerbations

0-2/year

Risk

(consider frequency and severity)

Frequency and severity may vary over time for patients in any category Relative annual risk of excaerbations may be related to FEV

Step 1 Recommended Step for Initiating Treatment

Step 2

Consider short course of oral steroids

Step 3

Step 4 or 5

In 2 -6 weeks, evaluate asthma control that is achieved and adjust therapy 24 accordingly

ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN YOUTHS > 12 YEARS OF AGE AND ADULTS

EPR-3, p77, 345

Classification of Asthma Control Components of Control

Symptoms
Nighttime awakenings

Well Controlled
< 2 days/week
< 2/month none < 2 days/week > 80% predicted/ personal best 0/> 20 0- 1 per year

Not Well Controlled

> 2 days/week
1-3/week Some limitation > 2 days/week 60-80% predicted/ personal best 1-2/16-19 2 - 3 per year

Throughout the day

> 4/week Extremely limited Several times/day <60% predicted/ personal best 3-4/< 15 > 3 per year

IMPAIRMENT

Interference with normal activity SABA use FEV1or peak flow Validated questionnaires ATAQ/ACT Exacerbations Progressive loss of lung function Rx-related adverse effects

RISK

Evaluation requires long-term follow up care

Consider in overall assessment of risk
Maintain current step Step up 1 step Reevaluate in 2 - 6 weeks Consider oral steroids Step up 1-2 weeks and reevaluate in 2 25 weeks

Recommended Action For Treatment

Consider step down if well controlled at least 3 months

SEVERITY OF ASTHMA EXACERBATION

GINA 2006

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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

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Other drugs -Other anti inlammation : methotrexate, gold salt, cyclosporine, anti TNF -Anti leukotrine : zafirlukast, montelukast -Anti IgE : omalizumab

EPR-3, p333-343

STEPWISE APPROACH FOR MANAGING ASTHMA IN YOUTHS > 12 YEARS AND ADULTS
Intermittent Asthma Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 or higher care is required Consider consultation at step 3 Step up if needed (check adherence, Preferred: environmental Step 5 High-dose ICS control and Preferred: + LABA + oral High dose ICS Corticosteroid comorbidities) + LABA

Step 6

Step 4 Step 3 Step 2 Step 1

Preferred: SABA prn Preferred: Low-dose ICS Low-dose ICS+ Alternative: either LABA, LTRA LTRA, Cromolyn Theophylline Theophylline Or Zileutin Preferred: Medium-dose ICS OR Preferred: Medium-dose ICS+LABA Alternative: Medium-dose ICS+either LTRA, Theophlline Or Zileutin

AND AND Consider Olamizumab for patients with allergies Consider Olamizumab for patients with allergies

Assess Control

Step down if possible (asthma well controlled for 3 months)

Patient Education and Environmental Control at Each Step

EPR-3, p333-343
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