Bronchial Asthma Asthma 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 inflammatory disorder of bronchi Chronic inflammatory disorder of bronchi Episodic - Reversible bronchospasm Episodic - Reversible bronchospasm Affects 10% of children & 5% adults Affects 10% of children & 5% adults Half of cases appear in patients younger than 10 years Half of cases appear in patients younger than 10 years Initial attack of the disease can occur at any age Initial attack of the disease can occur at any age

Asthma was classically divided into Extrinsic (allergic) Intrinsic (idiosyncratic) depending on inciting factors.

Asthma Extrinsic (allergic)Triggers Allergic asthma Pollens Animal hair or fur House dust (with mite) Allergic Bronchopulmonary Aspergillosis Occupational asthma Cedar wood Platinum salts Cotton dust Anhydrides (epoxy hardeners) Isocyanates Epoxy resins Lab animals Vinyl chloride (in meat packing) Flour processing Crab processing Oil mists Formaldehyde 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 Type I hypersensitivity reaction induced by exposure to an extrinsic antigen. Type I hypersensitivity reaction induced by 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 of Allergic Asthma

Asthma Primary Mediators (1) Histamine (2) Eosinophilic and neutrophilic chemotactic factors (e.g., leukotriene B4) Secondary Mediators (1) Leukotrienes: (C4, D4, E4) (2) Prostaglandin D2 (PGD2) (3) Platelet-activating factor (PAF) (4) cytokines (IL-1, TNF, IL-6)

Asthma Mast cells in Asthma Pathogenesis

Asthma Eosinophils in Asthma Pathogenesis

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 Occupational asthma Industrial asthma is a serious problem: Industrial asthma is a serious problem: cedar wood cedar wood platinum salt platinum salt cotton dust cotton dust anhydrides (epoxy hardeners) anhydrides (epoxy hardeners) isocyanates isocyanates epoxy resins epoxy resins lab animals lab animals vinyl chloride (in meat packing) vinyl chloride (in meat packing) flour processing flour processing crab processing crab processing oil mists oil mists formaldehyde and toluene (path labs) formaldehyde 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 FACTORS in Asthma bronchiale AIR POLLUTION and EMOTIONAL FACTORS in Asthma bronchiale Air pollution Air pollution SO2 SO2 Oxides of nitrogen Oxides of nitrogen Ozone Ozone Odors Odors Foul smelling gases Foul smelling gases Perfume Perfume Temperature inversions Temperature inversions Psychological stress Psychological stress Vagal efferent stimulation Vagal efferent stimulation

AsthmaPathology From autopsies on patients who have died in status asthmaticus

Asthma Gross Pathology The lungs are overdistended because of overinflation The lungs are overdistended because of overinflation Small areas of atelectasis Small areas of atelectasis Occlusion of bronchi and bronchioles by thick, tenacious and adherent mucous plugs Occlusion of bronchi and bronchioles by thick, tenacious and adherent mucous plugs

Asthma Bronchial inflammation Bronchial inflammation Edema, Mucousplugging Edema, Mucousplugging Bronchospasm Bronchospasm Obstruction Obstruction Over inflation/Atelectasis Over inflation/Atelectasis COPD COPD

AsthmaHyperinflation

Mucous plugs

Asthma Mucous plug

Asthma Microscopy Mucous plugs ( Mucous plugs (strips of epithelium and many eosinophils) Curschmann spirals ( Curschmann spirals (mucoid exudate casts - may be expelled with coughing) Charcot Layden crystals ( Charcot Layden crystals (phospholipids of the eosinophil cell membrane) Creola bodies Creola bodies (compact clusters of epithelial cells in the sputum) Patchy necrosis of epithelium Patchy necrosis of epithelium Submucosal glandular hyperplasia Submucosal glandular hyperplasia Goblet cell hyperplasia Goblet cell hyperplasia Hypertrophy of bronchial smooth muscle Hypertrophy of bronchial smooth muscle Mixed inflammatory infiltrate: Eosinophils (5-50%) + Lympho (T H 2, CD 4 ) Mixed inflammatory infiltrate: Eosinophils (5-50%) + Lympho (T H 2, CD 4 ) Mast cells Mast cells

Asthma Obstructed Inflammed Bronchi

Asthma Bronchial morphology Inflammation Inflammation Eosinophils Eosinophils Gland hyperplasia Gland hyperplasia Mucous plug in lumen Mucous plug in lumen Hypertrophy of muscle layer Hypertrophy of muscle layer

Asthma Bronchial morphology Inflammation Inflammation Mucous Plug Mucous Plug Eosinophils Eosinophils

AsthmaEosinophils

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

Asthma The Reality  Asthma is not yet curable * Asthma is not yet curable * Underdiagnosis & Undermanagement Underdiagnosis & Undermanagement Therapy is still evolving Therapy is still evolving Hope Hope Better understanding of Pathology Better understanding of Pathology New line of Promissing Drugs New line of Promissing Drugs Proper management  Normal life Proper management  Normal life

Asthma Asthma Pathology - Modern view Allergen Mucus hypersecretion Hyperplasia Vasodilatation New vessels Edema Bronchoconstriction Hypertrophy/hyperplasia Cholinergic reflex Subepithelial fibrosis Sensory nerve activation Eosinophil Mast cell Th2 cell Neutrophil Macrophage/ dendritic cell Mucus plug Epithelial shedding Nerve activation Leukotrienes C4, D4 & E4

Asthma An important clinical finding: Wheezing An important clinical finding: Wheezing Asthma bronchiale Asthma bronchiale Foreign body or tumor in the upper airway Foreign body or tumor in the upper airway Pulmonary edema (especially left-sided congestive heart failure) Pulmonary edema (especially left-sided congestive heart failure) Pulmonary embolus Pulmonary embolus Chronic bronchitis Chronic bronchitis Carcinoid syndrome Carcinoid syndrome