Asthma Flashcards
Define Asthma
A chronic inflammatory airway disease characterised by intermittent airway obstruction and hyper-reactivity
What are the 5 defining characteristics of asthma?
- Chronic inflammatory process
- Susceptibility
- Variable airflow obstruction
- Airway hyper-responsiveness
- Reversibility
Explain the basic pathophysiology of asthma
Chronic inflammatory response driven by TH2 cells
- Macrophages present antigens to T lymphocytes which activates T cells, preferentially activating TH2
- TH2 cells release cytokines which attract inflammatory cells → mast cells and eosinophils
- TH2 cells activate B cells to produce IgE
Asthma is initially a type 1 hypersensitivity reaction, explain what this is
- On 1st exposure to the allergen T cells are activated and TH2 cells proliferate, activating B cells to produce IgE
- IgE antibodies cause mast cell degranulation to release inflammatory mediators (histamine, tryptase, prostaglanding D2 and leukotriene)
- Inflammatory mediators cause bronchial smooth muscle contraction → bronchoconstriction
What happens in the late phase response of asthma?
- Type IV hypersensitivity reaction
- Inflammatory cells: eosinophils, mast cells, lymphocytes and neutrophils release mediators that cause airway inflammation
How does airway inflammation reduce airway calibre?
- Mucosal swelling (oedema) due to vascular leak
- Thickening of bronchial walls due to infiltration by inflammatory cells
- Mucus over production
- Smooth muscle contraction
- Epithelium is shed and incorporated into thick mucus
What history would you expect to see in a patient with asthma?
- Cough - dry, worse at night
- Wheeze
- Breathlessness
- Chest tightness
- Atopy - umbrella of allergic conditions (asthma, hayfever, eczema)
What precipitating factors can make symptoms of asthma worse?
- allergens - pollen, pets
- Dust
- Cigarette smoke
- Cold Weather
- Exercise
- Infection
- Aerosols
How does asthma present on examination?
Typically hear a wheeze in both lungs
How do you diagnose asthma?
- Peak Flow meter readings
- Scalloping on flow, time loops
- Improvement seen after bronchodilators
What is the primary prevention method of asthma management?
Avoidance of potential triggers during pregnancy and childhood
(Evidence is lacking)
What is secondary prevention in asthma management?
Remove Triggers
- Pets
- Dust
- Smoke
- Occupation
- Vaccination
Pharmacological
What are the 2 main classes of drugs used in asthma treatment?
- Bronchodilators
- Steroids
What are the bronchodilators used in asthma?
- B2 agonists (Long and Short Acting)
- Antimuscarinics (Ipatropium Bromide)
Effect of both is to open airways and stop bronchospasm
How to inhaled corticosteroids help in asthma?
Stop inflammation of the lining of the airways
Explain the mechanism of action of Salbutamol
- Salbutamol is a B2 adrenoreceptor agonist
- Binds to B2 GPCR causing GDP exchange for GTP causing the alpha s subunit to dissociate from the beta and gamma
- Galpha s subunit activates andenylyl cyclase to convert ATP→ cAMP
- cAMP secondary messenger activates PKA to cause bronchial smooth muscle relaxation
Which inhalers and ‘relievers’ and which are ‘preventers’
Reliever = salbutamol (blue)
Preventer = inhaled corticosteroid (brown)
