BRONCHIAL ASTHMA

Dr. Gangadhar
MAHSA University ,
Desired Learning Outcome
• On completion of this topic, you should be able to:
• define asthma.
a) describe the differences between bronchial asthma and cardiac asthma.
b) classify bronchial asthma based on the etiological factors
• explain the pathogenesis of bronchial asthma
• discuss the role of different types of hypersensitivity reactions in asthma.
• discuss the role of a) different types of hypersensitivity reactions
b) beta receptors insensitive to catecholamines
c) gene ADAM33 and platelet activating factor in the pathogenesis of asthma.
• describe the pathological features –both macroscopic and microscopic changes
• describe the clinicopathological correlation of asthma

Contents
• Definition of asthma
• Classification of asthma – Atopic, Non-atopic, Aspirin-induced, Occupational, Allergic
bronchopulmonary aspergillosis
• Pathological changes in the bronchi: inflammation, mucus gland hypertrophy, bronchial
wall smooth muscle hypertrophy and thickening of bronchial basement membrane.
• Pathogenesis of asthma - Type I and Type III hypersensitivity reactions, the role of
bronchial β-receptors insensitive to catecholamine, role of nonspecific factors etc
• The role of gene ADAM33 and the platelet activating factor
• Differences between the various types of asthma.
EPIDEMIOLOGICAL SIGNIFICANCE

Growing global prevalence

300 million cases worldwide
250,000 deaths per year
History of exposure to an antigen.
Intermittently asymptomatic small airway disease
Supervened by chronic bronchitis and cor pulmonale.
•AIR
POLLUTANTS
BRONCHIAL ASTHMA: Introduction

Disease characterized by increased responsiveness of

the tracheo- bronchial tree to various stimuli,
potentiating paroxysmal constriction of the bronchial
airways. (Broncho-spasm)

Distressing disease :
Associated with severe dyspnoea and wheezing
triggered by bronchospasm.
ETIOLOGICAL AGENTS
House dust mite (Faeces)
Pets
Moulds
Food stuffs (peanuts)
Drugs: (Aspirin and Beta-Blockers)
Active and passive smoking
Preservatives and coloring materials
(Tartrazine)
Carpets
Cold and allergic rhinitis
Cockroaches
ETIOLOGY:
ADAM33 Gene (chromosome 20p13)
(A Disintegrin And Metalloprotease)

Expressed by:
i. Lung fibroblasts
ii. Bronchial smooth muscle
iii. NOT by bronchial epithelial cells
Role:ADAM33 GENE

i. Fibroblast proliferation-myofibroblast-smooth
muscle.
ii. Sub-epithelial fibrosis
iii. Increased matrix deposition
iv. Smooth muscle hyperplasia
v. Bronchial Hyper-Responsiveness.
vi. Airway modeling
TYPICAL ASTHMATIC ATTACK

1. Characterized by the sudden development of

broncho-constriction.

2. Difficulty with both inspiration and expiration,

more so with expiration since the airways widen
and lengthen during inspiration.

3.The constricted airways cause wheezing, principally

during expiration
4 Accompanied by dyspnea.
5. Hyperinflation of the lung : Air trapped distal to
mucus plug obstructions.

6. Duration: One to several hours and subside

spontaneously or with therapy

7. Course: Asthma is rarely fatal.

STATUS ASTHMATICUS: Failure of broncho-

constriction to reverse for days or weeks.

Death: Acute respiratory failure or superimposed

infection.
PATHOLOGIC CHANGES:

Due to immuno-phenotype of the inflammatory cells

in the asthmatic airway.

1. Mast Cells
2. Basophils
3. Eosinophils
4. Macrophages
5. Lymphocytes
6. Neutrophils
PATHOPHYSIOLOGY

Type I Hypersensitive Response

IgE produced by plasma cell.

Binds to Fc receptors: mast cells and basophils
Sensitized Mast Cells and Basophils:
Cross links IgE on re-exposure to allergen:
Mast cell degranulation
i Histamine
ii. Leukotrienes
iii. Prostaglandins
BRONCHIAL ASTHMA
PHASES:
a. Early phase response. Releases:
1. Preformed (primary) mediators (leukotrienes)
2. Secondary mediators (cytokines) via
mast cells and basophils.
b. Late phase response. Increased leucocyte
infiltration E/L/N/M causing:
i. Inflammation and edema.
ii. Persistent broncho-spasm.
iii. Loss of damaged epithelial cells
STRUCTURAL CHANGES
Caused by early and late phase response:

i. Epithelial cell disruption and desquamation.

ii. Goblet cell hyperplasia.
iii. Increased mucus production (mucus plugs).
iv. Eosinophils in bronchial walls, blood and
sputum.
v. Increased bronchial vasculature due to
inflammation.
FUNDAMENTAL INMMUNOLOGIC
COMPONENTS OF ALLERGY

1. Mast cells cause:

i. Hyperplasia of inflamed mucosal epithelium and
smooth muscle
ii. Initiate eosinophil mediated inflammatory responses.

2. Ig E : binds to mast cell and basophil cell membrane

receptors on reexposure (antigen+IgE):-->
Degranulation.
CYTOKINES ORCHESTRATING ASTHMA

Interleukins:
IL-I, TNF, IL-6, in COPD

T Helper 2 cells ie: T(H)2 cells:

(CD 4 T lymphocytes)

T(H)2 cytokines:
IL-4, IL-5, IL-9 and IL-13 play important role
in patho-physiology of allergic diseases:
ASTHMA
Role of T cell derived T(H)2 cytokines:

NK T cells:
Secrete cytokines.

NK T cells with T(H)2 cells:

Bronchial hyper - reactivity. (BHR)
CLASSIFICATION

Asthma can be classified based on these stimuli or more

traditionally, into two types:

EXTRINSIC (immunologic or allergic or atopic)

INTRINSIC (non-immunologic or idiosyncratic).

EXTRINSIC ASTHMA (REAGINIC)

Extrinsic asthma: In children and young adults.

History of atopy ( reagin mediated )
Family history of multiple allergies.

Type I hypersensitivity
Elevated serum Ig E levels
Peripheral blood eosinophilia.
Typically, this type of asthma abates in adulthood.
ALLERGY TO ?
FEATURES

1. Airway resistance
2. FEV1 decreased
3. FEV1/FVC ratio = < 0.7 (reduced)
4. Residual volume (expiration) – increased
5. Total lung capacity – increased
6. “Barrel chest” due to hyperinflation.

BRONCHIAL ASTHMA: Reversible

INTRINSIC ASTHMA (NON-REAGINIC)

Intrinsic asthma : In adulthood

Initiated by non-immune mechanisms
(aspirin ingestion; pulmonary infections, especially
viral; cold; inhaled irritants; stress -pregnancy; and
exercise)

Ig E levels and eosinophil counts are

normal.

Patients may have primary or underlying chronic

bronchitis upon which airway hyper-reactivity
develops. (OVERLAP)
MICROSCOPIC:

i. HYPERPLASIA: Epithelial basal cells/Sq. metaplasia

ii. HYPERPLASIA: Goblet cells.
iii. HYPERTROPHY of airway glands
iv. HYPERPLASIA: Mucous cells
v. HYPERPLASIA of airway smooth muscle

Thickening of the epithelial "basement membrane”

Normal:7.5um
Asthma:17.5 um
Edema and inflammation of airway walls
MUCOUS PLUGS IN ASTHMA

Mucus plugs:
i. Creola Bodies
Rich in eosinophils and contain whorls of sloughed
bronchial or bronchiolar epithelium.

ii. Curshmann Spirals:

Coiled basophilic mucus plugs containing
desquamated epithelium.
iii. Charcot-Leyden crystals:
Collections of crystals derived from eosinophils.
CURSHMANN’S SPIRAL
CHARCOT LEYDEN
CRYSTALS
CREOLA BODY
 Oedema
Cartilage

Lumen
Smooth muscle
hypertyrophy
Eosinophils
Submucosa
DIAGNOSTIC TESTS

No single satisfactory test

1. Lung function tests
2. Peak flow charts (Spirometry)
3. Exercise test
4. Histamine or methacholine provocation test
5. Corticosteroid trial test
DIAGNOSTIC TESTS

6.Allergen provocation test

7. Blood and sputum test
(Eosinophils increased)
8. Chest X-ray.
9 Skin test (Patch Tests)
CONTROL MEASURES

House dust mite

Pets
Moulds
Food stuffs (peanuts)
Drugs: (Aspirin and Beta-Blockers)
Active and passive smoking
Preservatives and coloring materials (Tartrazine)
Carpets
Cold and allergic rhinitis
OBSTRUCTIVE AIRWAY DISEASE
i. FEV1-Reduced (< 80%)
ii. FEV1/FVC ratio: Lower than normal.
or FEV1/FVC ratio: <0.7
However: FVC is normal or near normal

RESTRICTIVE LUNG DISEASE

i. FVC is less
- Physical deformity
- Fibrosis
ii. FEV1: reduced
iii. FEV1/FVC: Normal
Disease Predominant Pathology Etiology Symptoms
Anatomic Site

Chronic bronchitis Bronchus Mucous gland Tobacco smoke; air Cough, sputum
hyperplasia; pollutants production
hypersecretion

Chronic bronchitis--small Bronchiole Inflammatory Tobacco smoke; air Cough, dyspnea

airway disease scarring/obliteration pollutants;
(bronchiolitis) miscellaneous

Bronchiectasis Bronchus Airway dilation and Persistent or severe Cough, purulent

scarring infections sputum, fever

Asthma Bronchus Smooth muscle Immunologic or Episodic wheezing,

hyperplasia; excess undefined causes cough dyspnea
mucus; inflammation

Emphysema Acinus Airspace enlargement; Tobacco smoke Dyspnea

wall destruction