Asthma

• Chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness and cough, particularly at night or early morning
• Characterised by paroxysmal reversible bronchospasm of the tracheobronchila airways due to smooth muscle hyper-reactivity
• There has been a significance increase in the incidence of asthma in the west over the part three decades

 

Pathology

• Two major types are recognised;
  • Atopic
    • Begins in childhood and is triggered by environmental antigens such as dust, pollen and animal dander
    • A family history of atopy is common
    • T cell differentiation seems to be skewed towards Th2 and subsequent IgE and eosinophil mediated immune responses
    • Sensitisation results in a Th2 response characterised by high levels of IL4 and IL5 which promote IgE production by B cells and growth and activation of mast cells and eosinophils
    • Subsequent  IgE mediated reaction to inhaled allergens elicits an acute response and a late phase response
    • In the acute response, antigen binding to IgE coated mast cells causes leukotriene, cytokine and neuropeptide release resulting in;
      • Bronchospasm
      • Oedema
      • Mucus secretion
      • Leukocyte recruitment
    • Late phase response is mediated by the recruited leukocytes e.g. eosinophils, lyphocytes, monocytes, basophils and neutrophils
      • Starts 4-8 hours after acute response and may last 12-24 hours
      • It is characterised by persistent bronchospasm, oedema, leukocyte infiltration and epithelial damage and loss
    • Skin testing for the specific antigen results in a wheal and flare reaction
  • Non atopic asthma
    • Often triggered by respiratory infections (particularly viruses), chemical irritants or drugs
    • There is generally no family history of atophy and no apparent IgE involvement
    • The cause of the increased airway reactivity is not known however it is thought thayt virus induced inflammation of the respiratory mucosa lowers the threshold of the subepithelial vagal receptors to irritants

 

Morphology

• Grossly the lungs are hyperinflated and there may be small areas of atelectasis
• The bronchi and bronchioles are occluded by thick mucus plugs
• Histologically the mucus plugs contain whorls of shed epithelium giving rise to CURSCHMANN SPIRALS
• There are lots of eosinophils and CHARCOT-LEYDEN CRYSTALS which are composed of crystalloid eosinophil granule debris
• Asthma is also characterised by structural changes called ‘airway remodelling’. Histologically these changes include;
• Thickening of the bronchial epithelial basement membrane
• Oedema and inflammatory infiltrate with a predominance of mast cells and eosinophils
• Increase in the size of the submucosal glands

Hypertrophy of the bronchial wall smooth muscle