Pathophysiology and clinical aspects of obstructive airway disease

Question 1

What factors contribute to asthma?

Answer 1

1. Genetic factors (cause certain people to react to allergens in ways that others do not)
2. Environmental factors
3. Acute triggers (can be non-allergenic)

Question 2

How can asthma be classified?

Answer 2

Extrinsic (atopic) - result of inappropriate immune response to an inhaled antigen, associated with atopy (hayfever, eczema), typically starts in childhood with sensitisation and effector phases

Intrinsic (non-atopic) - no family history of asthma, onset tends to be middle-age often following a URTI

Question 3

What is the pathophysiology of asthma?

Answer 3

Triad of features:

1. Airway obstruction (reversible)
2. Airway hyper-responsiveness
3. Airway inflammation (increased leukocytes)

+ increased Goblet cells and hypertrophy of submucosal glands secreting mucus, thickened basement membrane and hypertrophy/hyperplasia of smooth muscle cells

Question 4

What are the sensitisation and effector phases of atopic asthma?

Answer 4

Sensitisation phase:

1. Allergens travel through epithelium of airways
2. Taken up by antigen-presenting cell
3. Presented to a Th2 lymphocyte
4. Primes other lymphocytes (e.g. B Cells) which secrete immunoglobulin-E

Effector phase:

1. Mast cells are major effectors
2. IgE bind to mast cells to secrete bronchoconstrictors (e.g. histamines and leukotrienes)

Question 5

What are the 3 phases of pathogenesis in asthma?

Answer 5

1. Immediate/ early (e.g. sensitisation and effector phases)
2. Late (lymphocyte infiltration resulting in inflammatory response and increased mucus secretion)
3. Re-modelling/ Chronic (smooth muscle hypertrophy and hyperplasia, epithelial damage, basement membrane thickening)

Question 6

What features would you expect to be present when taking a history from a patient with asthma?

Answer 6

Usually acute exacerbations of chronic inflammation (asthma attacks)

Cough, wheeziness, chest tightness, shortness of breath - symptoms often worse at night.

Usually associated with atopy and allergy

Question 7

What are the common signs of an exacerbation?

Answer 7

Difficulty completing sentences
Wheeze
Tachypnoea (increased RR) 
Tachycardia (increased HR) 
Use of accessory muscles 
Reduced breath sounds in severe cases

Question 8

How do you diagnose asthma?

Answer 8

There is no gold standard for treating asthma - instead a process of trialing treatment and assessing response (e.g. able to measure reversibility on spirometry by taking a result before and after treatment)

+ peak flow monitoring and FeNO

Question 9

How is the severity of acute asthma classified?

Answer 9

1. Moderate acute (e.g. Peak flow = 50-75%)
2. Acute severe (e.g. Peak flow = 33-50%, inability to complete sentence in one breath)
3. Life threatening (arrhythmia, cyanosis, hypotension, poor respiratory effort)
4. Near-fatal (generally requiring mechanical ventilation)

Question 10

What drugs are used to treat smooth muscle dysfunction in asthma?

Answer 10

Bronchoconstrictors:

Beta2 antagonists
Anticholinergics
Leukotriene antagonists

Question 11

What drugs are used to treat airway inflammation in asthma?

Answer 11

Glucocorticoids

Question 12

What is COPD?

Answer 12

Chronic, irreversible, obstructive airway changes

Umbrella term including chronic bronchitis and emphysema

Question 13

What are the key features of chronic bronchitis?

Answer 13

Larger airways (bronchus and bronchioles)
Mucous gland hypertrophy and hyperplasia
Hypersecretion of mucous

Question 14

What are the common causes of COPD?

Answer 14

Smoking - most common cause
Other pollutants
alpha1-antitrypsin deficiency

Question 15

What are the key features of emphysema?

Answer 15

Smaller airways (smaller bronchioles and alveoli) 
Air space enlargement 
Alveolar wall destruction

Question 16

What are the key features of extrinsic (atopic) asthma?

Answer 16

Result of an inappropriate adaptive immune response to an inhaled antigen
Typical onset in childhood
Associated with atopic factors (e.g. hayfever and eczema)
Sensitisation and effector phases

Question 17

What are the key features of intrinsic (non-atopic) asthma?

Answer 17

Generally no personal or family history of asthma or atopy
Usually onsets in middle age
Onset often follows an upper airway infection

Question 18

What are the key reversible causes of airflow obstruction in COPD?

Answer 18

1. Accumulation of inflammatory cells, mucus and plasma exudate in bronchi
2. Smooth muscle contraction in peripheral and central airways
3. Dynamic hyperinflation during exercise

Question 19

What are the key irreversible causes of airflow obstruction in COPD?

Answer 19

1. Fibrosis and narrowing of the airways
2. Loss of elastic recoil due to alveolar destruction
3. Destruction of alveolar support that maintains patency on small airways

Question 20

What are the clinical features of COPD?

Answer 20

Productive cough 
Wheeze
Breathlessness (dyspnoea) 
Frequent infective exacerbations with purulent sputum 
Signs of respiratory failure

Question 21

How is COPD diagnosed?

Answer 21

1. Spirometry (reduced FEV1 : FVC ratio)
2. Chest X-ray (may look normal or show hyperinflation)
3. Haemoglobin (may be raised in chronic hypoxia)

Question 22

How is COPD managed?

Answer 22

Smoking cessation
Bronchodilator therapy (e.g. Salbutamol, Ipratropium)
Combination therapy (e.g. long acting beta2-agonist + inhaled steroid, long acting anticholinergic)
Home oxygen
Pulmonary rehabilitation and multidisciplinary management (e.g. education, exercise, self-management strategies etc.)
Vaccinations (e.g. influenza)

Question 23

What does FeNO measure?

Answer 23

Fractional exhaled nitric oxide - measures eosinophilic inflammation in airways
Can be used to aid asthma diagnosis

Question 24

How is acute asthma managed?

Answer 24

Oxygen 
Salbutamol (nebuliser)
Hydrocortisone (IV) or Prednisolone (oral) 
Ipratropium Bromide (nebuliser)
Theophylline

Question 25

What causes alveolar wall destruction in emphysema?

Answer 25

1. Smoking/ air pollutants + genetic predisposition (more rare cause is congenital alpha1-antitrypsin deficiency)
2. Oxidative stress (reactive oxidate species - free radicals released by cigarette smoke, other inhaled particles or activated inflammatory cells) cause tissue damage and inflammation
3. Inflammatory mediators attract more inflammatory cells from the circulation amplifying process and induce structural changes (e.g. neutrophils, macrophages and cytotoxic T cells) - infection can exacerbate
4. Protease - anti-protease imbalance (deficiency of protective anti-proteases in emphysema allowing proteases to break down connective tissue)

Question 26

What might pulmonary rehabilitation and multidisciplinary management involve for patients with COPD?

Answer 26

Eduction
Exercise
Self-management strategies
Nutrition 
Dyspnoea management 
Social assessment 
Smoking cessation 
Management of anxiety/ depression 
Occupational therapy
Palliative care

Question 27

How would an acute exacerbation of COPD be managed?

Answer 27

Inhalers (+/- nebuliser)
Corticosteroids (7 days oral Prednisolone)
Antibiotics (if infection present)
Non-invasive ventilation

Question 28

How can peak flow be used to diagnose asthma?

Answer 28

Measures peak expiratory flow rate (L/min)

2 week diary can be used to assess symptoms - a 20% variability between highest and lowest score indicates asthma