Asthma

Question 1

Asthma triad

Answer 1

Airway inflammation (eosinophilic)
Airway hyper-responsiveness (airway inflammation causes twitchy ASM)
Reversible airflow obstruction

Question 2

Development of asthma

Answer 2

1. Allergen is phagocytosed by APC
2. Allergen presented to CD4+ T cell
3. Activated CD4+ T cell activates TH0 cell
4. TH0 cell differentiates into TH1 and TH2(favoured) cells
5. TH2 cells activate B cells (through IL-4 release)
6. B cells differentiate to plasma cells which secrete IgE

Question 3

Inflammatory cascade

Answer 3

1. Genetic predisposition and triggers
2. Eosinophilic airway inflammation
3. TH2 cytokines (IL-4, IL-5, IL-13) released from lymphocytes
   - IL-4 and IL-13 activate mast cells
   - IL-5 activates eosinophils
4. Twitchy ASM

Question 4

Asthma stages

Answer 4

Broncho-constriction
Chronic airway inflammation - lays down collagen
Airway remodelling - irreversible airway obstruction, collagen deposited, basement membrane thickens, smooth muscle hypertrophy

Question 5

Asthma attack phases (immediate, delayed)

Answer 5

Immediate - type 1 hypersensitivity reaction, reversible early phase, bronchospasm, early acute inflammatory response

Delayed - type IV hypersensitivity reaction, inflammatory reaction phase, delayed inflammation

Question 6

Symptoms

Answer 6

Episodic attacks of bronchoconstriction
Diurinal variability
Allergic triggers
Expiratory wheeze - due to turbulent air flow 
Difficulty breathing out
SOB 
Non-productive cough
Tight chest

Question 7

Signs

Answer 7

Wheeze on auscultation
Tachypnoea
Decreased air entry
Eosinophilic inflammation

Question 8

FEV1/FVC

Answer 8

FEV1 = low
FVC = normal
FEV1/FVC = low (<70%)
ie: obstructive airway disease

Question 9

Management (chronic)

Answer 9

1. Reliever - SABA. (PRN)
   * If taken more than once daily then move to step 2*
2. Preventer (first line) - ICS.
   * Increase dosage to max level until pt feels better, if this doesn’t work then move onto step 3*
3. Controller (second line) - LABA (can also be LAMA). Usually get a combination inhaler of (LABA+ICS)
   * If symptoms persist, move to step 4*
4. Add a controller with anti-inflammatory properties (e.g: LTRA, methylxanthine, cromone)
   * If symptoms continue to persist, move to step 5*
5. Add an oral steroid (prednisolone) and seek expert advice.

Question 10

Management (acute attack)

Answer 10

Oxygen - high flow to get target sats (94%-98%)
Salbutamol - nebulised, high dose
Hydrocortisone - IV (or prenisolone oral)
Ipratropium bromide - nebulised
Magnesium Sulphate - IV (single dose)
Theophyline - oral (or aminophyline IV)
Advice

Question 11

Relievers (and examples)

Answer 11

relax bronchial smooth muscle 
SABA (salbutamol, terbutaline)
LABA (salmeterol, formoterol) 
CysLTRA (montelukast) 
Methylxanthines (theophyline, aminophyline)

Question 12

Preventers/Controllers (and examples)

Answer 12

Anti-inflammatory properties that reduce airway inflammation
ICS (beclomethasone, budesonide, flucitasone)
Oral steroids (prednisolone)
Cromones (sodium chromoglycate)
Monoclonal antibodies (omalizumab)
Methylxanthines (theophylline, aminophyline)

Question 13

SABA

Answer 13

eg: salbutamol, terbutaline
Reliever - taken as needed (PRN) 
Act with in minutes
Administered by inhalational route - lowers systemic effects. 
Relaxes bronchial smooth muscle 
Increased mucous clearance 
Decreases mediator release from mast cells etc. 
Side effects: fine tremor, tachycardia.

Question 14

LABA

Answer 14

eg: salmeterol (slow onset) formoterol (fast onset)
Not recommended for acute relief of bronchospasm
Long duration of action
Helps nocturnal symptoms
Not used as mono-therapy

Question 15

Leukotriene Receptor Antagonists (LTRA)

Answer 15

eg: montelukast
Cys LT's (eg: LTC4, LTD4, LTE4) are released from mast cells and cause SM contraction, increased mucous secretion, oedema. 
LTRA block these effects: 
- relax bronchial SM 
- anti-inflammatory. 
Administered orally once daily

Question 16

Corticosteroids

Answer 16

ICS for maintenance eg: beclomethasone, budesomide, flucitasone)
Oral for acute exacerbations eg: Prednisolone
Anti inflammatory
Melt away eosinophils in the bronchial mucosa
Released from adrenal cortex (glucocorticoids and mineralocorticoids)
We don’t want mineralocorticoids in inflammatory conditions such as asthma.
Side effects of ICS: hoarse voice, oral thrush

Question 17

Methylxanthines

Answer 17

eg: theophyline (oral), aminophyline (IV)
Both bronchodilator and anti-inflammatory properties
Inhibit PDE’s which causes a build up of cAMP and thus leads to more muscle relaxation.
Inhibit mediator release from mast cells.
Narrow therapeutic window
Numerous drug interactions

Question 18

Cromones

Answer 18

eg: sodium cromoglycate 
Not used much
Effective in children 
Mast cell stabilisers (decrease histamine release from mast cells) 
Administered through inhalation

Question 19

Mild asthma attack
Severe asthma attack
Life threatening asthma attack

Answer 19

Mild -
Severe - Unable to complete sentences, pulse >110bpm, RR>25/min, PEF 33-50%
Life threatening - Silent chest, confusion, cyanosis, bradycardia, PEF<33%

Question 20

Chronic asthma investigations

Answer 20

PEF monitoring
Spirometry
CXR: hyperinflation

Question 21

Acute asthma investigations

Answer 21

O2 sats 
Peak flow
Sputum culture (for eosinophils)
ABG analysis
Blood cultures
CXR - to rule out infection