bronchial asthma

Bronchial asthmaBronchial asthmaBy Dr:Ahmad ElmadanaBy Dr:Ahmad Elmadana

DefinitionDefinition

It is a chronic recurrent obstructive disorder of bronchi, characterized by attacks of shortness of breath (muscle spasm, mucosa edema, hypersecretion) and based on genetically determined bronchi hyperreactivity.

EpidemiologyEpidemiology

Asthma is a problem worldwide, with an estimated 300 million affected individuals.

10 million lost school days each year and costing more than $12 billion per year

About 10% school-age children are affected in urban areas

Most frequent respiratory pathology (≈30%)

Morbidity is growing every year

EpidemiologyEpidemiology

African-American children have been affected more frequently than Caucasian children (2:1).

Hospitalization rates also were markedly higher for African-American children (4:1).

Predisposing factorsPredisposing factors

HOST FACTORSGenetic, e.g.,• Genes pre-disposing to atopy• Genes pre-disposing to airway

hyperresponsivenessObesitySex

Predisposing factorsPredisposing factors

ENVIRONMENTAL FACTORSAllergens• Indoor: Domestic mites, furred animals

(dogs, cats, mice), cockroach allergen, fungi, molds, yeasts

• Outdoor: Pollens, fungi, molds, yeasts

Predisposing factorsPredisposing factors

ENVIRONMENTAL FACTORS

Infections (predominantly viral) Occupational sensitizersTobacco smoke• Passive smoking• Active smokingOutdoor/Indoor Air PollutionDiet

Genetic predispositionGenetic predisposition

On chromosomes 5q23–31, 11q and 12q. Classical positional cloning approaches have led to identification of new genes of potential importance on chromosome 14q24 and chromosome 20p13 (ADAM33).

Genetic predispositionGenetic predisposition

Multiple gene predisposition instead of one-gene coding

ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS

Allergic sensitisation to Dermatophagoides pteronyssinus

Passive smokingAir pollutionCow milk feedingFood allergens during 1st year of life

ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS

Mycoplasma pneumoniaeChlamydia species Respiratory syncytial virus

Treatment with antibiotics appropriate for these organisms improves the clinical signs and symptoms of asthma.

Periods of developmentPeriods of development

1st - inherited predisposition2nd – allergic sensitization3rd – allergic reactions

Examples of Agents Causing Asthma inSelected Occupations

Occupation/occupational field Agent

Animal and Plant Proteins

Bakers Flour, amylase

Fish food manufacturing Midges, parasites

Food processing Coffee bean dust, meat tenderizer, tea, shellfish,amylase, egg proteins, pancreatic enzymes,papain

Organic chemicals

Hospital workers Disinfectants (sulfathiazole, chloramines,formaldehyde, glutaraldehyde), latex

Manufacturing Antibiotics, piperazine, methyldopa, salbutamol,cimetidine

Automobile painting Ethanolamine, dissocyanates

MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA

Mast cells:

activated mucosal mast cells release bronchoconstrictor mediators (histamine,

cysteinyl leukotrienes, prostaglandin D2). These cells are activated by allergens through high-affinity IgE receptors, as well as by osmotic stimuli (accounting for exercise-induced bronchoconstriction). Increased

mast cell numbers in airway smooth muscle may be linked to airway hyperresponsiveness.

MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA

Eosinophils

present in increased numbers in the airways, release basic proteins that may damage airway epithelial cells.They may also have a role in the release of growth factors and airway remodeling.

MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA

T-lymphocytes

present in increased numbers in the airways,release specific cytokines, including IL-4, IL-5,

IL-9, and IL-13, that orchestrate eosinophilic inflammation and IgE production by B lymphocytes. An increase in Th2 cell activity may be due in part to a reduction in regulatory T cells that normally inhibit Th2 cells. There may also be an increase in inKT cells, which release large amounts of T helper 1 (Th1) and Th2 cytokines.

MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA

Dendritic cells

sample allergens from the airway surface and migrate to regional lymph nodes, where they interact with regulatory T cells and ultimately stimulate production of Th2

cells from naive T cells.

MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA

Macrophages

increase in number in the airways and may be activated by allergens through low-affinity IgE receptors to release inflammatory mediators and cytokines that amplify the inflammatory response.

MECHANISMS OF ASTHMAMECHANISMS OF ASTHMA

Neutrophil numbers

are increased in the airways and sputum of

patients with severe asthma and in smoking asthmatics, but the pathophysiological role of these cells is uncertain and their increase may even be due to glucocorticosteroid therapy.

Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma

Airway epithelial cells sense their mechanical environment,

express multiple inflammatory proteins in asthma, and release

cytokines, chemokines, and lipid mediators. Viruses and air

pollutants interact with epithelial cells.

Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma

Airway smooth muscle cells express similar inflammatory

proteins to epithelial cells101.

Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma

Endothelial cells of the bronchial circulation play a role in

recruiting inflammatory cells from the circulation into the airway.

Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma

Fibroblasts and myofibroblasts produce connective tissue

components, such as collagens and proteoglycans, that are

involved in airway remodeling.

Airway Structural Cells Involved in Airway Structural Cells Involved in thethe Pathogenesis of AsthmaPathogenesis of Asthma

Airway nerves are also involved. Cholinergic nerves may be activated by reflex triggers in the airways and cause

bronchoconstriction and mucus secretion. Sensory nerves, which may be sensitized by inflammatory stimuli including

neurotrophins, cause reflex changes and symptoms such as cough and chest tightness, and may release inflammatory

neuropeptides.

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Sun Ying и соавт., 2006

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

3. Allergic reactions3. Allergic reactions

3 phases: ImmunologicPathochemicalPathophysiological

ImmunologicImmunologic

Antibody + Antigen formationComplement involvementAuto-Ab and auto-Ags

PathochemicalPathochemical

Active substances release in “shock” organs (mucous and muscles of bronchi and bronchioli)

PathophysiologicalPathophysiological

Muscle spasmMucous edemaHypersecretion (thick exudate)

Pathogenesis – Pathogenesis – acute asthmaacute asthma

Bronchial smooth muscle contractionMucous gland hypersecretionSubmucosal, peribronchial, and interstitial

edemaCellular infiltrative changes involving

plasma cells, lymphocytes, macrophages, and leukocytes.

Pathogenesis – Pathogenesis – cchronic asthma hronic asthma

Smooth muscle hyperplasiaPostinflammatory thickening of the

bronchial basement membranesMucous gland hypertrophy

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Symptoms Symptoms of bronchial asthmaof bronchial asthma

Breathlessness Anxiety Cough Chest tightness Diaphoresis Exacerbation with exercise

Signs of bronchial asthmaSigns of bronchial asthma

Barrel chest Global or focal wheezes Pallor Pulsus paradoxus Use of accessory muscles Exercise limitation

BronchodilatorsBronchodilators

Beta-adrenergicMethylxanthineAnticholinergic medications

BBetaeta-2-2-adrenergic-adrenergic

Short-acting:SalbutamolTerbutalinBerotek Long-acting:SelmeterolFormoterol

Nonselective adrenergicNonselective adrenergic

Beta-nonselective:AstmopentAlupentIsadrin NovodrinAlfa-,beta-adrenergic:Adrenalin

MMethylxanthineethylxanthine

EuphillinTeophilllin

AAnticholinergic medicationsnticholinergic medications

AtroventOxyvent

AntiallergicAntiallergic

Cromoglycates and nedocromils:IntalZaditenKetotifen

Other drugsOther drugs

Antibiotics Expectorants

Newer choisesNewer choises

Leukotrien inhibitors:Montelucast, zafirlucast – very low

efficacy Were tested for aspirin-dependent

asthma, asthma of physical stress

Survived? Survived? Any questions? Any questions?