Asthma Flashcards
What are the three classic characteristics of asthma?
- Airflow limitation which is usually reversible spontaneously or with treatment
- Airway hyper-responsiveness to a wide range of stimuli
- Bronchial inflammation with T lymphocytes, mast cells, eosinophils with associated plasma exudation, oedema, smooth muscle hypertrophy, matrix deposition, mucus plugging and epithelial damage
What are the two main aetiological factors of asthma?
- Genetics
2. Environment
What are the genetic factors that predispose someone to develop asthma?
IL-4 and IL-13 strongly associated in asthma
and IL-5
What environmental factors can predispose someone to develop asthma?
There are different environmental influences on asthma:
- Early childhood exposure to allergens (hygiene hypothesis)
- Maternal smoking
- Intestinal bacteria
What factors can precipitate asthma?
- Occupational factors
- Cold air and exercise
- Atmospheric pollution and irritant dusts, vapours and fumes
- Diet - Increased intakes of fresh fruit and vegetables have been shown to be protective
- Emotion
- Drugs
What drives inflammation in asthma?
Th2-type T lymphocytes which facilitate IgE synthesis through the production of IL-4 and eosinophilic inflammation through IL-5
Late-stage asthma can be driven by Th1 response, triggering TNF-alpha
What cells are involved in the inflammatory response in asthma?
- Mast cells
- Eosinophils
- Dendritic cells and lymphocytes
Where in the airways can mast cells be found?
asthma
Increased in epithelium, smooth muscle and mucous glands
Where in the airways can eosinophils be found?
asthma
Found in large numbers in the bronchial wall
They are attracted to the airways by the eosinophilopoietic cytokines IL-3, IL-5 and GM-CSF
What do eosinophils do in asthma?
When activated, eosinophils release LTC4, and basic proteins such as major basic protein (MBP), eosinophil cationic protein (ECP) and eosinophils peroxidase (EPX) that are toxic to epithelial cells
Where in the airways can dendritic cells be found?
asthma
Mostly abundant in mucous membranes in the alveoli
What do dendritic cells do in asthma?
Dendritic cells have a role in the initial uptake and presentation of allergens to lymphocytes → T helper lymphocytes (CD4+) show evidence of activation and the release of their cytokines plays a key part in the migration and activation of mast cells (IL-3, IL-4, IL-9 and IL-13) and eosinophils
What are the remodeling changes that happen in asthma?
- Deposition of matrix proteins
- Swelling and cellular infiltration expand the submucosa beneath the epithelium so that for a given degree of smooth muscle shortening there is excess airway narrowing
- Swelling outside the smooth muscle layer spreads the retractile forces exerted by the surrounding alveoli over a greater surface area so that the airways close more easily
What are the principal symptoms of asthma?
- Wheezing attacks
2. Episodic shortness of breath
At what time of the day are asthma symptoms worst?
Symptoms are usually worst during the night, especially in uncontrolled disease
What investigations would you do for suspected asthma?
- Peak expiratory flow rate (shows variable airway limitation)
- Spirometry (FEV1/FVC <0.7)
How would you diagnose asthma?
Asthma can be diagnosed by demonstrating a greater than 15% improvement in FEV1 or PEFR following the inhalation of a bronchodilator
What is the spirometry pattern of asthma?
Obstructive lung disease
Reduced FEV1 (<80% of the predicted normal) Reduced FVC (but to a lesser extent than FEV1) FEV1/FVC ratio reduced (<0.7)
How would you assess reversibility in asthma?
To assess reversibility, administer 400 micrograms of salbutamol and repeat spirometry after 15 minutes:
What is the treatment pathway for adults with asthma?
- SABA
- SABA + low dose ICS
- SABA + low dose ICS + leukotriene receptor antagonist
- SABA + ICS + LABA (maybe LTRA)
- SABA + high dose ICS + LABA (+ LTRA)
Name two SABAs
Salbutamol, terbutaline
Name two LABA
Salmeterol, formoterol
Name three leukotriene modifiers
Montelukast, zafirlukast, zileuton
What dose salbutamol would you give in asthma?
4 mg 3-4 times per day
What is the mechanism of action for SABAs?
Bind to bronchial beta-2 receptors, causing smooth muscle relaxation and dilatation of the airways
How long does salbutamol last for?
Up to 4 hours
What dose salmeterol would you give?
50 micrograms twice daily
Name three inhaled ICS
beclometasone, budesonide, fluticasone
What dose beclometasone would you prescribe?
50-100 micrograms twice daily
What is the mechanism of action for ICS?
Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor. The activated glucocorticoid receptor-glucocorticoid complex up-regulates the expression of anti-inflammatory proteins in the nucleus and represses the expression of proinflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus
What dose montelukast would you prescribe in asthma?
10 mg daily, taken in the evening
What is the mechanism of action Montelukast?
It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle
How does a case of severe asthma often present?
Inability to complete sentence
RR > 25 breaths/min
Tachycardia > 110 bpm
PEFR <50%
What are features of a life-threatening asthma attack?
Silent chest Cyanosis Feeble respiratory effort Exhaustion, confusion, coma Bradycardia, hypotension PEFR <30%
PCO2 > 6kPa
PO2 < 8kPa
Low and falling arterial pH
How would you treat a severe exacerbation of asthma?
Oxygen 40-60% is given 5mg nebulised salbutamol Nebulised ipratropium bromide 0.5mg IV Hydrocortisone 200mg given 4-hourly for 24 hours Prednisolone 60mg for 2 weeks
If no improvement, IV salbutamol, terbutaline r magnesium sulphate
