Immunologic diseases in Respiratory system

Assoc.Prof.Chulapan Engchanil,MD.
Pediatrics(Infectious Disease), Clinical Pathology.

chulapan.engchanil@gmail.com

Outline
1.Asthma -Definition -Diagnosis -Clinical Sign and Symtomps -Pathogenesis and Pathology -Treatment 2. Goodpasture's syndrome: overview 3. Wegener's granulomatosis: overview

Definition of asthma
Airway inflammation Airway hyperresponsiveness (~ Stimuli) Reversible airway obstruction

Sensitization phase

Cross bridge

Effector phase: re-exposure

Mediators of Mast Cells and Allergy

H, PGD2, LTs, PAF Kinin

Blood Vessels

Urticaria, Angioedema Laryngeal edema, Shock

Bronchospasm Abd. pain, Vomiting Diarrhea, Rhinorhea Bronchial secretion

Smooth Muscles
H, PGD2, LTs, PAF

H
Mast Cell Basophil

Mucus Glands

LTB4 PAF IL3, IL5 Chemokines Leukocytes

Sensory Nerves

Itching

Inflammation - LPAR

Pathogenesis of Allergic Disease

Adjuvant factors:
Tobacco smoke Air pollutants

Genetic Susceptibility

Lack of protective factors:

Infection ? Immunization ? Nutrition ?

Allergic Sensitzation Allergen Exposure

Upper/lower airway or Skin hyperresponsiveness

Pollutants Infection Excercise

Allergic Diseases

Vary in spectrum and severity

 Cough Wheeze Dyspnea

Reversible airway obstruction

Diagnostic criteria
Airway obstruction Reversible/partial reversible airway obstruction Exclude other causes of airway obstruction

Diagnosis

History and patterns of symptoms Physical examination Measurements of lung function

Spirometry
FEV1/ FVC <70%

Peak Flow meter ( )

PEF (peak expiratory flow)

Bronchodilator Test
Peak Flow 15 FEV1 15 % PEFR 20%
Salbutamol inhaler 2 puff 15

PEFR
390-300 300

PEFR =300 L/min

PEFR =390 L/min

= 30%

Clinical sign and symptoms

1. History : cough, wheeze, dyspnea -recurrent -following respiratory tract infection, exercise, chemical or allergen exposion -response to bronchodilator -clinical of other allergic diseases.

2 .Physical examination -Cough, wheeze, dyspnea (forced inspiratory /expiratory wheeze) -Increased A-P diameter of chest -Clinical signs of other allergic diseases

Hyperinflation

Barrel chest

Pathology of asthma
Smooth muscle hypertrophy

Mucosal disruption Mucus plug Cells infiltration

Airway remodelling
1. Persistent airway obstruction
2. Persistent airway hyperresponsiveness

Normal

Asthma

Concept of asthmatic treatment

Short-acting b2-agonists
Bronchospasm

Inh-corticosteroid Combination

Inflammation

Airway Hyperresponsiveness

Remodelling

Lab investigation
1. Pulmonary function test 2. Chest X-ray

3. FEV1 PEF (peak expiratory flow) 15 4. Peak flow variability = PEFmax - PEFmin x100% 1/2(PEFmax + PEFmin) > 20%

Allergen skin testing

1. Skin prick test

2. Specific IgE

Prick test

Johnson grass

Bermuda grass

Principle of Treatment for Allergic disease

1. Allergen avoidance 2. Mediator antagonist 3. Mast cell stabilizer

4. Steroid 5. Immunotherapy

Factors Affecting Clinical Outcomes

of Allergic Diseases

Enivronmental
Allergens
Irritants Westernization

Treatment
Anti-allergic Relievers

Genetic
Degree of atopy

Anti-inflammatory

Compliance
Infection
Viral
Bacterial

Avoidance

Medication uses

Allergen Immunotherapy

Allergic Diseases
Remission Mild

Future Therapy ?

Moderate

Severe

Treatment
Severity assessment Treatment - inhaled b2-agonist - systemic corticosteroids - theophylline, anticholinergic drug - oxygen exacerbations

Relievers Inhaled fast-acting b2-agonists

Controllers

Inhaled corticosteroids Inhaled long-acting b2-agonists Oral anti-leukotrienes Oral theophyllines

Inhaled corticosteroids
Fluticasone Budesonide
Beclomethasone

Allergen Immunotherapy

COPD
Definition COPD airflow limitation

not fully reversible.

progressive abnormal inflammatory response to noxious particles or gases.

Wegener's granulomatosis
Autoimmune disease: Vasculitis Pathology: Inflammation with granuloma formation Clinical: extremely variable Rapid progressive glomerulonephritis ( 75% Renal failure) Pulmonary nodule, hemmorrhage Arthritis Lab: Immunofluorescence pattern: c-ANCA Treatment: Steroid, Cyclofosfamind,Plasmapheresis

Goodpasture's syndrome
anti-glomerular basement antibody disease Autoimmune disease Type II Hypersensitivity Clinical : Glomerulonephritis with Pulmonary hemorrhage Kidney biopsy : linear IgG deposits along basement membrane Treatment: Steroid ,Immunosuppressant, Transplantation.