PATHOGENESIS OF ASTHMA
* Based on the stimuli initiating Bronchial asthma, two broad etiologic types are traditionally described:
* Extrinsic(allergic,atropic) Asthma
* Intrinsic(idiosyncratic, non-atropic) Asthma
* A third type is a mixed pattern in which the features do not fit clearly into either of the two main types.
EXTRINSIC (ATROPIC, ALLERGIC) ASTHMA
* This is the most common type of asthma.
* It usually begins in childhood or in early adult life.
* Most patients of this type of asthma have personal and or family history of preceeding allergic diseases such as rhinitis, urticaria.
* Hypersensitivity to various extrinsic antigenic substances or allergens is usually present in these cases.
* Most of these allergens cause ill effects by inhalation.
* EXAMPLE: house dust, pollens, animal danders, moulds.
* Occupational asthma stimulated by fumes, gases and organic and chemical dusts is a variant of extrinsic asthma.
* There is increased level of IgE in the serum and positive skin test with the specific offending inhaled antigen representing an IgE mediated type hypersensitivity reaction, which includes an acute immediate response or a late phase reaction.
* Acute immediate response is initiated by IgE sesitised mast cells on the mucosal surface.
* Mast cells on degranulation release mediators like histamine, leukotrienes, prostaglandins, platelet activating factors and chemotactic factors for eosinophil and neutrophils.
* The net effects of these mediators are bronchoconstriction, edema, mucus hypersecretion and accumulation of eosinophils and neutrophils.
* Acute immediate response is initiated by IgE sesitised mast cells on the mucosal surface.
* Mast cells on degranulation release mediators like histamine, leukotrienes, prostaglandins, platelet activating factors and chemotactic factors for eosinophil and neutrophils.
* The net effects of these mediators are bronchoconstriction, edema, mucus hypersecretion and accumulation of eosinophils and neutrophils.
* Late phase reaction follows the acute immediate response and is responsible for the prolonged manifestation of asthma.
*It is caused by excessive mobilisation of blood leukocytes that include basophils besides eosinophils and neutrophils.
* These result in further release of mediators which accentuate the above mentioned effects.
* In addition inflammatory injury is caused by neutrophils and by major basic protein(MBP) of eosinophils.
* Intrinsic(Idiosyncratic , non-atropic) asthma:
* This type of asthma develops later in adult life with negative personal or family history of allergy, negative skin test and normal serum levels of IgE.
* Most of these patients develop typical symptom complex after an upper respiratory tract infection by viruses.
* Associated nasal polyps and chronic bronchitis are commonly present.
* It is hypothesised that upper and lower airways both show similar airways hyperresponsiveness and manifestation of the same underlying allergicinflammatory process.
* Thus allergic rhinitis is frequently associated with bronchial asthma.
* There are no recognisable allergens but about 10 percent of patients become hypersensitive to drugs, most notably to small doses of asthma.
Mixed type:
* Many patients do not clearly fit into either of the above two categories and have mixed features of both.
* Those patients who develop asthma in early life have strong allergic components, while those who develop the disease late tend to be non-allergic.
* Either type of asthma can be precipitated by cold, exercise and emotional stress.
