Asthma Flashcards

1
Q

What are the three classic characteristics of asthma?

A
  1. Airflow limitation which is usually reversible spontaneously or with treatment
  2. Airway hyper-responsiveness to a wide range of stimuli
  3. Bronchial inflammation with T lymphocytes, mast cells, eosinophils with associated plasma exudation, oedema, smooth muscle hypertrophy, matrix deposition, mucus plugging and epithelial damage
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2
Q

What are the two main aetiological factors of asthma?

A
  1. Genetics

2. Environment

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3
Q

What are the genetic factors that predispose someone to develop asthma?

A

IL-4 and IL-13 strongly associated in asthma

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4
Q

What environmental factors can predispose someone to develop asthma?

A

There are different environmental influences on asthma:

  1. Early childhood exposure to allergens (hygiene hypothesis)
  2. Maternal smoking
  3. Intestinal bacteria
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5
Q

What factors can precipitate asthma?

A
  1. Occupational factors
  2. Cold air and exercise
  3. Atmospheric pollution and irritant dusts, vapours and fumes
  4. Diet - Increased intakes of fresh fruit and vegetables have been shown to be protective
  5. Emotion
  6. Drugs
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6
Q

What drives inflammation in asthma?

A

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

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7
Q

What cells are involved in the inflammatory response in asthma?

A
  1. Mast cells
  2. Eosinophils
  3. Dendritic cells and lymphocytes
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8
Q

Where in the airways can mast cells be found?

asthma

A

Increased in epithelium, smooth muscle and mucous glands

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9
Q

Where in the airways can eosinophils be found?

asthma

A

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

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10
Q

What do eosinophils do in asthma?

A

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

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11
Q

Where in the airways can dendritic cells be found?

asthma

A

Mostly abundant in mucous membranes in the alveoli

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12
Q

What do dendritic cells do in asthma?

A

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

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13
Q

What are the remodeling changes that happen in asthma?

A
  1. Deposition of matrix proteins
  2. 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
  3. 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
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14
Q

What are the principal symptoms of asthma?

A
  1. Wheezing attacks

2. Episodic shortness of breath

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15
Q

At what time of the day are asthma symptoms worst?

A

Symptoms are usually worst during the night, especially in uncontrolled disease

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16
Q

What investigations would you do for suspected asthma?

A
  1. Peak expiratory flow rate (shows variable airway limitation)
  2. Spirometry (FEV1/FVC <0.7)
17
Q

How would you diagnose asthma?

A

Asthma can be diagnosed by demonstrating a greater than 15% improvement in FEV1 or PEFR following the inhalation of a bronchodilator

18
Q

What is the spirometry pattern of asthma?

A

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)
19
Q

How would you assess reversibility in asthma?

A

To assess reversibility, administer 400 micrograms of salbutamol and repeat spirometry after 15 minutes:

20
Q

What is the treatment pathway for adults with asthma?

A
  1. SABA
  2. SABA + low dose ICS
  3. SABA + low dose ICS + leukotriene receptor antagonist
  4. SABA + ICS + LABA (maybe LTRA)
  5. SABA + high dose ICS + LABA (+ LTRA)
21
Q

Name two SABAs

A

Salbutamol, terbutaline

22
Q

Name two LABA

A

Salmeterol, formoterol

23
Q

Name three leukotriene modifiers

A

Montelukast, zafirlukast, zileuton

24
Q

What dose salbutamol would you give in asthma?

A

4 mg 3-4 times per day

25
Q

What is the mechanism of action for SABAs?

A

Bind to bronchial beta-2 receptors, causing smooth muscle relaxation and dilatation of the airways

26
Q

How long does salbutamol last for?

A

Up to 4 hours

27
Q

What dose salmeterol would you give?

A

50 micrograms twice daily

28
Q

Name three inhaled ICS

A

beclometasone, budesonide, fluticasone

29
Q

What dose beclometasone would you prescribe?

A

50-100 micrograms twice daily

30
Q

What is the mechanism of action for ICS?

A

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

31
Q

What dose montelukast would you prescribe in asthma?

A

10 mg daily, taken in the evening

32
Q

What is the mechanism of action Montelukast?

A

It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle

33
Q

How does a case of severe asthma often present?

A

Inability to complete sentence
RR > 25 breaths/min
Tachycardia > 110 bpm
PEFR <50%

34
Q

What are features of a life-threatening asthma attack?

A
Silent chest
Cyanosis
Feeble respiratory effort
Exhaustion, confusion, coma
Bradycardia, hypotension
PEFR <30%

PCO2 > 6kPa
PO2 < 8kPa
Low and falling arterial pH

35
Q

How would you treat a severe exacerbation of asthma?

A
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