Bronchial asthmaBronchial asthma

Dr. amira kamal El-Hawary

Dr. AZZa Abdel-AZiZ A. Ali

IntroductionIntroduction::

Humoral ImmunityHumoral Immunity B lymphocytes - AntibodyB lymphocytes - Antibody

Cell mediated ImmunityCell mediated Immunity T lymphocytes – T lymphocytes – MacrophagesMacrophages

Non-Specific immunityNon-Specific immunity Neutrophils, MacrophagesNeutrophils, Macrophages

IntroductionIntroduction::

Immunity is not Immunity is not inheritedinherited..

Primary response – slow, Primary response – slow, weak.weak. Learning period, memory cells.Learning period, memory cells.

Secondary response – Secondary response – rapid, strongrapid, strong

Immune DisordersImmune Disorders:: Immunodeficiency disordersImmunodeficiency disorders

AIDS, antibody deficiencyAIDS, antibody deficiency Hypersensitivity Disorders (allergy) Hypersensitivity Disorders (allergy)

excessive or altered reaction to an antigen excessive or altered reaction to an antigen producing adverse effects on the body. it is producing adverse effects on the body. it is classified into 4 typesclassified into 4 types Type-I (IgE),Type-I (IgE), Type II-IgG, Type II-IgG, Type III-Immune complex, Type III-Immune complex, Type IV-Cell mediated.Type IV-Cell mediated.

Autoimmune disordersAutoimmune disorders SLE, Rheumatoid, Rheumatic fever.SLE, Rheumatoid, Rheumatic fever.

Type I hypersensitivity reactionType I hypersensitivity reaction(Atopy)(Atopy)

- -Pathogenesis:-Pathogenesis:- - First exposure- First exposure to an antigen to an antigen stimulation of B-lymphocytes to stimulation of B-lymphocytes to transform to IgE secreting plasma transform to IgE secreting plasma cells cells ( helped by CD4+ T-lymphocytes) ( helped by CD4+ T-lymphocytes) IgE binds to the surface of mast IgE binds to the surface of mast cells and basophilscells and basophils

First exposure

Type I hypersensitivity reactionType I hypersensitivity reaction

- -Second exposureSecond exposure to the same antigen to the same antigen results in cross-linking of Ig E on the results in cross-linking of Ig E on the surface of mast cells surface of mast cells Degranulation of the cells with Degranulation of the cells with release of chemical mediatorsrelease of chemical mediators

SECOND EXPOSURE FIRST EXPOSURE

Chronic obstructive pulmonary Chronic obstructive pulmonary disease (COPD)disease (COPD)

COPD is a disease state COPD is a disease state characterized by airflow limitation characterized by airflow limitation that is not fully reversible. The that is not fully reversible. The airflow limitation is usually both airflow limitation is usually both progressive and associated with an progressive and associated with an abnormal inflammatory response of abnormal inflammatory response of the lungs to particles or gases.the lungs to particles or gases.

Obstructive Pulmonary DiseasesObstructive Pulmonary Diseases Classical COPDsClassical COPDs

EmphysemaEmphysema Chronic BronchitisChronic Bronchitis

Bronchial AsthmaBronchial Asthma

Bronchial asthmaBronchial asthma

Increased responsiveness of the Increased responsiveness of the bronchial tree to various stimuli that bronchial tree to various stimuli that results in results in paroxysms of paroxysms of BronchospasmBronchospasm

reversible bronchospasmreversible bronchospasm later later chronic bronchial inflammation chronic bronchial inflammation develop develop and airflow is limited by and airflow is limited by bronchoconstriction, mucus plugs, and bronchoconstriction, mucus plugs, and increased inflammation increased inflammation and obstructive and obstructive lung disease developlung disease develop

It is episodic, reversible It is episodic, reversible bronchospasm resulting from an bronchospasm resulting from an exaggerated bronchoconstricton exaggerated bronchoconstricton response to various stimuliresponse to various stimuli..

Incidence of asthmaIncidence of asthma

It is a common disease affecting It is a common disease affecting 5% of adults and 7-10% of 5% of adults and 7-10% of childrenchildren . .

There has been a significant There has been a significant increase in the incidence of increase in the incidence of asthma in the Western world in asthma in the Western world in the past three decadesthe past three decades

- --Clinically , it is manifested by Clinically , it is manifested by recurrent episodes of wheezing, recurrent episodes of wheezing, breathlessness, and coughbreathlessness, and cough. . These These symptoms are usually associated symptoms are usually associated with bronchoconstriction and with bronchoconstriction and airflow limitation that is at least airflow limitation that is at least partly reversible, either partly reversible, either spontaneously or with treatmentspontaneously or with treatment. . Between the attacks, patients may Between the attacks, patients may be virtually asymptomatic be virtually asymptomatic

- Rarely, a state of unremitting Rarely, a state of unremitting attacks, called status asthmaticus, attacks, called status asthmaticus, proves fatal; usually, such patients proves fatal; usually, such patients have had a long history of asthmahave had a long history of asthma. .

- --

Why does constriction occur Why does constriction occur periodically? periodically?

Constriction occurs because bronchi Constriction occurs because bronchi are hyper reactive to a variety of are hyper reactive to a variety of stimuli to which the patient is stimuli to which the patient is exposed intermittentlyexposed intermittently. .

What are the Triggering FactorsWhat are the Triggering Factors??

Domestic dust Domestic dust mitesmites

Air pollutionAir pollution Tobacco smokeTobacco smoke Occupational Occupational

irritantsirritants Cockroach Cockroach Animal with furAnimal with fur PollenPollen

Triggering Factors ( cont.)Triggering Factors ( cont.)

Respiratory (viral) Respiratory (viral) infectionsinfections

Chemical irritantsChemical irritants Strong emotional Strong emotional

expressionsexpressions Drugs ( aspirin, Drugs ( aspirin,

beta blockers)beta blockers)

INFLAMMATIONINFLAMMATIONAirflow Limitation

SYMPTOMSCough Wheeze

Dyspnoea

TRIGGERS Allergens, Exercise,

Cold Air, SO2 Particulates

PathogenesisPathogenesisAirway hypersensitivity

INDUCERSAllergens, Air pollutants,

Virus infections

PathogenesisPathogenesis What initiates the inflammatory process in What initiates the inflammatory process in

the first place and makes some persons the first place and makes some persons susceptible to its effects is an area of susceptible to its effects is an area of active investigationactive investigation. .

There is not yet a definitive answer to this There is not yet a definitive answer to this question question . . The expression of asthma is a The expression of asthma is a complex, interactive process that depends complex, interactive process that depends on the interplay between two major on the interplay between two major factors—host factors factors—host factors ((particularly particularly geneticsgenetics) ) and environmental exposures and environmental exposures that occur at a crucial time in the that occur at a crucial time in the development of the immune systemdevelopment of the immune system early early in lifein life

Pathogenetic TypesPathogenetic Types ExtrinsicExtrinsic and and IntrinsicIntrinsic asthma asthma

The concept that there are two The concept that there are two types of asthma, extrinsic (due to types of asthma, extrinsic (due to allergy) allergy) and intrinsic ( due to constitutional and intrinsic ( due to constitutional factors) is not so sharp and there factors) is not so sharp and there is much overlap between asthma is much overlap between asthma with different triggers.with different triggers.

ExtrinsicExtrinsic

--Type-I (IgE-mediated) Type-I (IgE-mediated) hyper-sensitivity or hyper-sensitivity or allergic reactionallergic reaction

--Triggered by Triggered by environmental environmental antigens (dust, antigens (dust, pollens, food, ..)pollens, food, ..)

--Family history of Family history of AtopyAtopy

- -Begins in childhoodBegins in childhood . .

IntrinsicIntrinsic

--Not allergicNot allergic

--Triggered by Triggered by respiratory tract respiratory tract infections &drugs infections &drugs (aspirin)(aspirin)..

--No family historyNo family history

Bronchial Asthma

SECOND EXPOSURE FIRST EXPOSURE

Bronchial Asthma - PathophysiologyBronchial Asthma - Pathophysiology

- -Pathogenesis of extrinsic (atopic) Pathogenesis of extrinsic (atopic)

asthmaasthma 11 - -Meeting the specific allergen causes Meeting the specific allergen causes

sensitization of CD4+ (T н2) cells resulting in sensitization of CD4+ (T н2) cells resulting in release of cytokines (IL-4,5, and 13).release of cytokines (IL-4,5, and 13).

2- IL-4,5 and 13 cause 2- IL-4,5 and 13 cause a. Stimulation of IgE production a. Stimulation of IgE production b. Growth of mast cells. b. Growth of mast cells. c. Growth and activation of eosinophils. c. Growth and activation of eosinophils.

3- Meeting the specific allergen for the second 3- Meeting the specific allergen for the second time results in an immune reaction which time results in an immune reaction which passes into two phasespasses into two phasesi- An early phase starting 30-60 min.after i- An early phase starting 30-60 min.after inhalation of the antigen then inhalation of the antigen then ii- A late phase develops after 4-8 hoursii- A late phase develops after 4-8 hours..

Pathogenesis of extrinsic (atopic) Pathogenesis of extrinsic (atopic) asthmaasthma

44 - -During the During the early phaseearly phase, , primary mediators are primary mediators are released. They includereleased. They include- Leucotriens which are - Leucotriens which are sythesized from sythesized from phospholipid by phospholipid by phospholipase enzymephospholipase enzyme- Histamine - Histamine - Platelet –Activating Factor- Platelet –Activating Factor

- -These mediators produce ….. These mediators produce ….. bronchoconstriction, bronchoconstriction, vasodilatation, increased vasodilatation, increased vascular permeability and vascular permeability and increased mucin secretionincreased mucin secretion..

Pathogenesis of extrinsic (atopic) Pathogenesis of extrinsic (atopic) asthmaasthma

55 - -During the During the late phaselate phase secondary secondary mediators are released mediators are released includingincluding- Eosinophil and neutrophil - Eosinophil and neutrophil chemotactic factors chemotactic factors - IL-4 &5- IL-4 &5- Platelet Activating factor - Platelet Activating factor - TNF- TNF- These mediators - These mediators produce…..eosinophil and produce…..eosinophil and neutrophil infiltration to the neutrophil infiltration to the site of the lesion these cells site of the lesion these cells produceproducea- More mediators that activate a- More mediators that activate mast cells and intensify the mast cells and intensify the initial response.initial response.b. Epithelial cell damageb. Epithelial cell damage . .

Pathogenesis of intrinsic Pathogenesis of intrinsic asthmaasthma

Not fully understood, but a considerable Not fully understood, but a considerable overlap with extrinsic asthma is overlap with extrinsic asthma is present and present and eosinophilseosinophils seem to play seem to play an important role in both types. It may an important role in both types. It may bebe : :

Virus-induced inflammation of respiratory mucosa Virus-induced inflammation of respiratory mucosa lowers threshold of vagal receptors to irritantslowers threshold of vagal receptors to irritants

Aspirin-sensitive asthmaAspirin-sensitive asthma Occupational asthmaOccupational asthma

Bronchial AsthmaBronchial AsthmaPathogenesisPathogenesis

Atopic AsthmaAtopic Asthma Exposure of Exposure of

presensitised IgE-coated presensitised IgE-coated mast cells to antigen mast cells to antigen causes acute immediate causes acute immediate responseresponse

Chemical mediators Chemical mediators (histamine, PAF, (histamine, PAF, leukotrienes)leukotrienes)

Late-phase reactionLate-phase reaction

Nonatopic AsthmaNonatopic Asthma Virus-induced Virus-induced

inflammation of inflammation of respiratory mucosa respiratory mucosa lowers threshold of lowers threshold of vagal receptors to vagal receptors to irritantsirritants

Aspirin-sensitive Aspirin-sensitive asthmaasthma

Occupational asthmaOccupational asthma

Pathogenesis - Atopic AsthmaPathogenesis - Atopic Asthma::

What is the What is the PathophysiologyPathophysiology??

Trigger FactorTrigger Factor Mast cellMast cell Mediators: Mediators:

histamine,prostaglandin,leukotrienes,as well as histamine,prostaglandin,leukotrienes,as well as cytokines.cytokines.

Inflammatory cellsInflammatory cells Contraction of airway smooth muscles Contraction of airway smooth muscles

(Bronchoconstriction)(Bronchoconstriction) Airway wall swelling (mucosal edema)Airway wall swelling (mucosal edema) Chronic changesChronic changes Hypertrophy of the smooth muscles, Airway Hypertrophy of the smooth muscles, Airway

obstructionobstruction

Lung Morphology in AsthmaLung Morphology in Asthma

Mucous pluggingMucous plugging BronchospasmBronchospasm Over inflationOver inflation

Lung Hyperinflation in AsthmaLung Hyperinflation in Asthma

Thick bronchi with Mucous Thick bronchi with Mucous plugsplugs

Epidemiology/pathology

AsthmaNormal

Barnes PJ

Asthma - Asthma - Microscopic PathologyMicroscopic Pathology

Patchy Patchy necrosisnecrosis of epithelium of epithelium Sub-mucosal Sub-mucosal glandularglandular hyperplasiahyperplasia Hypertrophy of bronchial Hypertrophy of bronchial smoothsmooth musclemuscle EosinophilsEosinophils, , mastmast cellscells; ; lympholympho (TH2, CD4) (TH2, CD4) Mucous Mucous plugsplugs, Whorled mucous plugs , Whorled mucous plugs

((Curschmann’s spiralsCurschmann’s spirals) ) Debris of eosinophils (Debris of eosinophils (Charcot-Leyden Charcot-Leyden

crystalscrystals

Microscopic PathologyMicroscopic Pathology

Asthma Microscopic PathologyAsthma Microscopic Pathology

ObstructedInflammedBronchi

Asthma - Bronchial morphologyAsthma - Bronchial morphology

inflammationinflammation Gland hyperplasiaGland hyperplasia Mucous plug in Mucous plug in

lumenlumen

Asthma - Bronchial morphologyAsthma - Bronchial morphology

InflammationInflammation Mucous PlugMucous Plug EosinophilsEosinophils

Inflammation epithelial damage

Eosinophils in AsthmaEosinophils in Asthma::

Curschmann's spiralsCurschmann's spirals::

Bronchial AsthmaBronchial Asthma

Therapy - PathologyTherapy - Pathology::

Barnes PJ

What is AsthmaWhat is Asthma?? Hypersensitivity – Allergy , Type IHypersensitivity – Allergy , Type I

of airways of lungs - Bronchiof airways of lungs - Bronchi Allergens – in the air, mast cell - IgE ab.Allergens – in the air, mast cell - IgE ab. Inflammation of airways -Bronchitis.Inflammation of airways -Bronchitis. Genetic, Environmental, Age.Genetic, Environmental, Age. High in industrial cities 4-19%, High in industrial cities 4-19%,

Increasing incidence …!Increasing incidence …!