Bronchial Bronchial AsthmaAsthmaAsthma bronchialeAsthma bronchiale

Asthma is characterized by episodic air-flow obstruction in response to a number of stimuli.

Patients typically have paroxysms of wheezing, dyspnea and cough.

Acute episodes of asthma may alternate with asymptomatic periods or be superimposed on a background of chronic airway obstruction.

Severe acute asthma unresponsive to therapy is termed status asthmaticus.

Most asthmatic patients, even when apparently well, have some persistent air-flow obstruction and morphologic lesions.

Asthma

Chronic Chronic iinflammatorynflammatory disorder of disorder of bronchi bronchi

EEpisodicpisodic - - RReversibleeversible bronchospasmbronchospasm Affects 10% of children & 5% adultsAffects 10% of children & 5% adults

Half of cases appear in patients younger Half of cases appear in patients younger than 10 yearsthan 10 years

Initial attack of the disease can occur at Initial attack of the disease can occur at any ageany age

Asthma was classically divided into Extrinsic (allergic) Intrinsic (idiosyncratic)

depending on inciting factors.

Asthma

Extrinsic (allergic) Triggers

Allergic asthma PollensAnimal hair or furHouse dust (with mite)Allergic Bronchopulmonary Aspergillosis

Occupational asthma Cedar woodPlatinum saltsCotton dustAnhydrides (epoxy hardeners)IsocyanatesEpoxy resinsLab animalsVinyl chloride (in meat packing)Flour processingCrab processingOil mistsFormaldehyde and Toluene (path labs)

Intrinsic (idiosyncratic)

Aspirin (and some NSAIDs)Tartrazine yellow Respiratory tract infection viruses (e.g., rhinovirus, parainfluenza virus)

Asthma

ALLERGIC ASTHMA Most common form of asthma and is usually seen

in children TType I hypersensitivityype I hypersensitivity reaction reaction induced by induced by

exposure to an extrinsic antigen.exposure to an extrinsic antigen. One third to one half of all patients with asthma

have known or suspected reactions to such allergens as pollens, animal hair or fur, and house dust contaminated with mites

Allergic asthma is strongly correlated with skin-test reactivity

Half of all children with asthma have a substantial or complete remission of symptoms by age 20 but in many, asthma may recur after age 30

Asthma

Pathogenesis Pathogenesis of of AAllergicllergic Asthma Asthma

Asthma

Primary MediatorsPrimary Mediators

(1) (1) HHistamineistamine

(2) (2) EEosinophilic and neutrophilic osinophilic and neutrophilic chemotactic factorschemotactic factors (e.g., leukotriene (e.g., leukotriene B4)B4)

Secondary MediatorsSecondary Mediators

(1) L(1) Leukotrieneseukotrienes:: ((C4, D4, E4C4, D4, E4))

(2) (2) PProstaglandin D2rostaglandin D2 (PGD2)(PGD2)

(3) (3) PPlatelet-activating factorlatelet-activating factor (PAF)(PAF)

(4) cytokines(4) cytokines ((IL-1, TNF, IL-6IL-1, TNF, IL-6))

Asthma

Mast cells in Asthma PathogenesisMast cells in Asthma Pathogenesis

Asthma

Eosinophils in Asthma Eosinophils in Asthma PathogenesisPathogenesis

Asthma

INFECTIOUS ASTHMA

A common precipitating factor in childhood asthma is a viral respiratory tract infection rather than an allergic stimulus.

In children under 2 years, Human respiratory syncytial virus (RSV) is the usual agent; in older children, rhinovirus, influenza, and parainfluenza are common inciting organisms.

The inflammatory response to viral infection in a susceptible person is believed to trigger the episode of bronchoconstriction.

Asthma

EXERCISE-INDUCED ASTHMA

Exercise can precipitate some bronchospasm in more than half of all asthmatics. In some patients, exercise is the only inciting factor.

Exercise-induced asthma is related to the magnitude of heat or water loss from the airway epithelium. The more rapid the ventilation (severity of exercise)

and the colder and drier the air breathed, the more likely is an attack of asthma.

The mechanisms underlying exercise-induced asthma are unclear.

Asthma

OCCUPATIONAL ASTHMA More than 100 different occupational exposures

have been linked to the development of asthma. In some instances, these substances provoke

allergic asthma via IgE-related hypersensitivity. Examples of those so affected are animal

handlers, bakers, and workers exposed to wood and vegetable dusts, metal salts, pharmaceutical agents, and industrial chemicals.

In other cases, occupational asthma seems to result from direct release of mediators of smooth muscle contraction after contact with an offending agent.

Some occupational exposures affect the autonomic nervous system directly.

Asthma

OOccupational asthmaccupational asthma Industrial asthma is a serious problemIndustrial asthma is a serious problem::

cedar woodcedar wood platinum saltplatinum salt cotton dustcotton dust anhydrides (epoxy hardenersanhydrides (epoxy hardeners)) isocyanatesisocyanates epoxy resins epoxy resins lab animalslab animals vinyl chloride vinyl chloride ((in meat packingin meat packing)) fflourlour processingprocessing crab processing crab processing oil mistsoil mists fformaldehydeormaldehyde and toluene (path labs) and toluene (path labs)

Asthma

DRUG-INDUCED ASTHMA

Drug-induced bronchospasm occurs mostly in patients with known asthma.

The best-known offender is aspirin but other nonsteroidal anti-inflammatory agents also have been implicated.

Aspirin induce arachidonic acid metabolism and elaboration of the bronchoconstrictor leukotrienes.

It is estimated that up to 10% of adult asthmatics are sensitive to aspirin.

Asthma

Immediate hypersensitivity does not seem to be involved, and these patients can be desensitized by daily administrations of small doses of aspirin.

Serum IgE levels are normal. Skin test results are usually negative. Rhinitis and nasal polyps are also frequent

findings in aspirin-sensitive individuals. -Adrenergic antagonists consistently

induce bronchoconstriction in asthmatics and are contraindicated in such patients.

Asthma

AIR POLLUTION and EMOTIONAL AIR POLLUTION and EMOTIONAL FACTORS in Asthma bronchialeFACTORS in Asthma bronchiale

Air pollutionAir pollution SO2 SO2 Oxides of nitrogen Oxides of nitrogen Ozone Ozone

OdorsOdors Foul smelling gasesFoul smelling gases PerfumePerfume

Temperature inversionsTemperature inversions Psychological stress Psychological stress

Vagal efferent stimulationVagal efferent stimulation

Asthma

PathologyPathology

From autopsies on patients who have died in status asthmaticus

Asthma

Gross PathologyGross Pathology The lungs are overdistended because of The lungs are overdistended because of

overinflationoverinflation Small areas of atelectasis Small areas of atelectasis Occlusion of bronchi and bronchioles by Occlusion of bronchi and bronchioles by

thick, tenacious thick, tenacious and adherent and adherent mucous plugsmucous plugs

Asthma

Bronchial Bronchial inflammationinflammation

Edema, Edema, MucouspluggingMucousplugging

BronchospasmBronchospasm ObstructionObstruction Over Over

inflation/Atelectasisinflation/Atelectasis COPDCOPD

Asthma

HyperinflationHyperinflation

Asthma

Mucous plugsMucous plugs

Asthma

Mucous plugMucous plug

Asthma

MicroMicroscopyscopy

Mucous Mucous plugsplugs ((strips of epithelium and many eosinophils) Curschmann spiralsCurschmann spirals ((mucoid exudate casts - may be expelled

with coughing) Charcot Layden crystalsCharcot Layden crystals ((phospholipids of the eosinophil cell

membrane) Creola bodiesCreola bodies (compact clusters of epithelial cells in the

sputum) Patchy Patchy necrosisnecrosis of epithelium of epithelium Submucosal Submucosal glandularglandular hyperplasiahyperplasia Goblet cellGoblet cell hyperplasia hyperplasia Hypertrophy of bronchial Hypertrophy of bronchial smoothsmooth musclemuscle Mixed inflammatory infiltrate: Mixed inflammatory infiltrate: EosinophilsEosinophils (5-50%) + L (5-50%) + Lymphoympho

(T(THH2, CD2, CD44) ) MMastast cellscells

Asthma

Obstructed Inflammed Bronchi

Asthma

Bronchial morphologyBronchial morphology

IInflammation nflammation EosinophilsEosinophils Gland Gland

hyperplasiahyperplasia Mucous plug in Mucous plug in

lumenlumen Hypertrophy of Hypertrophy of

muscle layermuscle layer

Asthma

Bronchial morphologyBronchial morphology

InflammatioInflammationn

Mucous Mucous PlugPlug

EosinophilsEosinophils

Asthma

EosinophilsEosinophils

Asthma

Curschmann's spiralsCurschmann's spirals ((mucoid exudate - may be expelled with coughing)

Asthma

The Reality The Reality Asthma is not yet curable *Asthma is not yet curable * Underdiagnosis & Underdiagnosis &

UndermanagementUndermanagement Therapy is still evolvingTherapy is still evolving

Hope Hope Better understanding of Better understanding of PathologyPathology

New line of Promissing DrugsNew line of Promissing Drugs Proper management Proper management NNormal lifeormal life

Asthma

Asthma Pathology - Modern Asthma Pathology - Modern viewview

Allergen

MucushypersecretionHyperplasia

VasodilatationNew vessels

Edema

BronchoconstrictionHypertrophy/hyperplasia

Cholinergic reflex

Subepithelialfibrosis

Sensory nerve activation

Eosinophil

Mast cell

Th2 cell Neutrophil

Macrophage/dendritic cell

Mucus plugEpithelial shedding

Nerve activation

LeukotrienesC4, D4 & E4

Asthma

An important clinical finding: An important clinical finding: WheezingWheezing Asthma bronchialeAsthma bronchiale Foreign body or tumor in the upper airway Foreign body or tumor in the upper airway Pulmonary edemaPulmonary edema (especially left-sided (especially left-sided

congestive heart failure) congestive heart failure) Pulmonary embolus Pulmonary embolus Chronic bronchitis Chronic bronchitis Carcinoid syndrome Carcinoid syndrome