Page 378 - Concise Pathology for Exam Preparation ( PDFDrive )

13 The Lung 363

morning. It is associated with variable degree of bronchoconstriction, inflammation of the
bronchial walls and increased mucous secretion.
Pathogenesis
• Genetic predisposition to Type I hypersensitivity (atopy) and exposure to certain
environmental triggers (inhaled allergens like house dust, mites, pets, etc., viruses
like rhinovirus and respiratory syncytial virus; air pollutants, smoking and drugs like
beta adrenergic blockers and aspirin) induce bronchial hyper-responsiveness leading to
acute and chronic airway inflammation.
• T H 2 cells induce bronchial inflammation and secrete cytokines like interleukin-4
(which stimulates B cells to produce IgE); interleukin-5 (which activates eosinophils)
and interleukin-13 (which stimulates mucous secretion from bronchial submucous
glands)
• T H 1 cells normally secrete cytokines that inhibit T H 2 cells and vice versa. Imbal-
ance in this reciprocal arrangement can lead to the development of asthma. T H 1 cells
produce g interferon, which suppresses inflammation in airways. A transcription factor,
called T-bet, required for T H 1 cell differentiation, is found to be absent from lung lym-
phocytes in asthmatic patients. In the absence of the restraining influence of interferon
g, T H 2 cells provoke airway inflammation.
• Microenvironment in the bronchial wall may be altered due to ADAM 33 polymor-
phisms (ADAM 33 is expressed by lung fibroblasts and bronchial smooth muscle cells
and belongs to a subfamily of matrix metalloproteinases; Flowchart 13.5)

ADAM polymorphisms
Unknown mechanism
Accelerated proliferation of bronchial smooth muscle cells and fibroblasts
• Recruitment of mast cells
• Release of vasoactive mediators, cytokines and growth factors
Structural changes in bronchial wall (airway remodelling)
FLOWCHART 13.5. Airway remodelling due to ADAM polymorphisms.

Types
1. Based on frequency and severity of symptoms
(a) Mild intermittent
(b) Mild
(c) Moderate
(d) Severe persistent
2. Based on response to steroids
(a) Steroid dependent
(b) Steroid resistant
3. Based on initiating factors
(a) Extrinsic: Induced by an extrinsic antigen and initiated by a Type 1 hypersensitivity
reaction
(b) Intrinsic: Initiated by diverse nonimmune mechanisms, eg, aspirin ingestion, cold,
stress, exercise, precipitated by several factors unique to the patient
4. Based on aetiology
(a) Atopic asthma (Type 1 IgE-mediated response triggered by environmental allergens
like food, dust, pollen, animal dander; most common type of asthma; begins in
childhood; positive family history and skin reaction)
(b) Nonatopic asthma (No identifiable causative external agents; no family history or
positive skin test)

mebooksfree.com