CBL - Asthma

Question 1

Define asthma [1]

Answer 1

A chronic inflammatory condition of the airways that is associated with widespread but variable bronchoconstriction and airflow limitation that is at least partly reversible, either spontaneously or with treatment

Question 2

What are the characteristic symptoms of asthma? [6]

Answer 2

• recurrent episodes of:
  
  1. wheezing,
  2. breathlessness,
  3. chest tightness and
  4. cough,
  5. particularly at night and/or early morning

Question 3

What are the main pathological features of asthma? [3]

Answer 3

1. increased airways hyper-responsiveness to a variety of stimuli resulting in episodic bronchoconstricton
2. inflammation of the bronchial walls
3. increased mucus secretion

Question 4

What are the clinical features of a moderate exacerbation of asthma? [3]

Answer 4

1. Increasing symptoms
2. PEF >50-75% best or predicted
3. No features of acute severe asthma

Question 5

What are the clinical features of an acute severe asthma attack? [4]

Answer 5

• Any one of:
  
  1. PEF 33-50% best or predicted
  2. Respiratory rate ≥25/min
  3. Heart Rate 110/min
  4. Inability to complete sentences in one breath

Question 6

What are the clinical features of a life-threatening asthma attack? [9]

Answer 6

• In a patient with severe asthma, any one of:
  
  1. PEF < 33% best or predicted
  2. SpO₂ < 92%
  3. PaO₂ < 8kPa
  4. Normal PaCO₂ (4.6-6 kPa)
  5. Silent chest
  6. Cyanosis
  7. Poor respiratory effort
  8. Arrhythmia
  9. Exhaustion, altered conscious level

Question 7

What are the clinical features of a near fatal asthma attack? [3]

Answer 7

Raised PaCO₂ and/or requiring mechanical ventilation with raised inflation pressures

Question 8

Describe the 2 types of asthma [6]

Answer 8

1. Atopic Asthma (Extrinsic asthma)
   
   • usually starts in childhood
   • atopic individuals have a raised total serum lgE and the presence of specific lgE against common aeroallergens
2. Non-atopic (Intrinsic asthma)
   
   • often starts in middle age
   • possible triggers include respiratory viruses, air pollutants

Question 9

List the potential causes/triggers of asthma [10]

Answer 9

1. Occupational Sensitisers
2. Viral infections
3. Atmospheric pollution
4. Drugs
5. Irritant dusts, vapours and fumes
6. Exercise
7. Cold air
8. Emotion
9. Genetic Factors

Question 10

Describe the pathophysiology of allergen-induced asthma under the following headings:

1. immediate asthma (early reaction) [6]
2. late-phase reactions [3]

Answer 10

1. Immediate Asthma (early reaction)
   
   • starts within minutes, maximal at 15-20minutes, subsides by 1 hour
   • bronchoconstriction triggered by:
     
     • direct stimulation of subepithelial vagal receptors,
     • increased mucus production,
     • vasodilatation and
     • increased vascular permeability
2. Late-phase Reactions
   
   • follows immediate reaction,
   • more sustained attack of airflow limitation that may respond less well to bronchodilators
   • inflammation with recruitment of eosinophils, neutrophils and lymphocytes

Question 11

Name the inflammatory cells involved in airway inflammation in asthma and describe the features of each [8]

Answer 11

1. activated T helper (TH2) lymphocytes
   
   • produce IL-3, IL-4, IL-5 and IL-13 which maintain the allergic phenotype
2. eosinophils
   
   • found in bronchial walls and secretions of asthmatics
   • attracted to airways by IL-3, IL-5, GMCSF and chemokines (eotaxin, RANTES),
   • releases mediators such as LTC₄ when activated
3. mast cells
   
   • increased in mucous glands, smooth muscle and epithelium
   • produces histamine, PGD₂, cysteinyl leukotrienes, tryptase
4. dendritic cells
   
   • present allergens to T lymphocytes

Question 12

What does IL-4 do? [1]

Answer 12

stimulates IgE production

Question 13

What does IL-5 do? [1]

Answer 13

activates eosinophils

Question 14

What does IL-13 do? [2]

Answer 14

1. stimulates mucus secretion
2. promotes IgE production

Question 15

List the mediators in the late acute asthma response and what they result in [5]

Answer 15

1. Leukotrienes: LT C₄, D₄, E₄
   
   • _​​bronchoconstriciton,
   • increase vascular permeability,
   • increase mucus secretion
2. Acetylcholine:
   
   • released from intrapulmonary nerves
   • directly stimulates muscarinic receptors on airway smooth muscle
3. Histamine:
   
   • bronchoconstrictor
4. Prostaglandin PGD₂
   
   • bronchoconstriction
   • vasodilation
5. Others:
   
   • Platelet-activating factor,
   • IL-1,
   • TNF,
   • IL-6,
   • chemokines,
   • neuropeptdides (eotaxin),
   • nitric oxide

Question 16

List the main pathological features in asthmatic airways [6]

Answer 16

1. Increased Airway Inflammatory cells
2. Plasma exudation
3. Oedema
4. Smooth Muscle hypertrophy
5. Mucus plugging
6. Shedding of epithelium

Question 17

What are the features of airway remodelling that occur in chronic asthma that leads to irreversible airflow obstruction? [5]

Answer 17

1. Overall thickening of the airway wall
2. Epithelium:
   
   • loss of ciliated columnar cells,
   • increased number and activity of mucus secreting goblet cells
3. Epithelial basement membrane:
   
   • sub-basement membrane fibrosis due to deposition of collagen and proteoglycans
4. Smooth muscle:
   
   • hypertrophy and/or hyperplasia of smooth muscle layer
5. In the inflammation of chronic asthma – Th1 cells also activated + TNF-α production

Question 18

Describe the treatment options for asthma [3]

Answer 18

1. Regular preventer:
   
   • SABA
   • Low dose inhaled corticosteroids (ICS)
2. Initial add-on therapy:
   
   • SABA
   • Low dose ICS
   • Inhaled LABA
3. Additional controller therapies:
   
   • SABA
   • Consider:
     
     • Increasing ICS to medium dose
     • Or adding leukotriene receptor antagonists (LTRA)