This document contains questions related to asthma pathophysiology, treatment, and management. It covers topics such as the causes of asthma symptoms, lung anatomy, types of asthma medications and their mechanisms of action, factors that influence medication adherence, and the placebo effect. Non-adherence to asthma treatment is common, with typical rates around 30-50%. Improving communication between doctors and patients can help increase treatment adherence.

1. Amy’s Asthma
Scenario Briefing
1. What could be the causes of instantaneous breathlessness? 1
2. Why is it important to examine whether the chest expands symmetrically or
differentially on one side? 2
3. What does hyper-resonance on percussion of the chest indicate?3
4. What are the two main pathogenic causes of airway obstruction, and hence
wheezing and where would you hear it? 4
5. What would crackling sounds in the airways mean? 5
6. Which generations of airways correspond to (i) bronchi (ii) bronchioles, (ii)
respiratory bronchioles (vi) alveolar ducts and sacs6
7. What factors increase hemolytic tone?7
8. What factors decrease broncho-motor tone? 8
9. What are the physiological effects of asthma on the epithelium and respiratory
tract?9
10.What are the main signs of hypercapnia?10
1 Pulmonary embolism or pneumothorax
2 No movement on one side could indicate a tension pneumothorax or collapsed lung.
3 Either surgical removal of the lung or lung collapse
4Asthma and COPD, all over the lungs since these areas are not localised to particular airways (as cancer
or an inhaled object might). Wheezing would be most obviously heard on breathing out since this requires
more force, in severe disease this becomes ʻgas trappingʼ.
5Fluid in the small airways, if you have L ventricular failure blood wonʼt leaving the lungs adequately and so
fluid may build up and cause breathlessness.
6 Bronchi (2-12), bronchioles (12-16), respiratory (17-19), alveolar ducts and sacs (20-23)
7 Irritant receptors and inflammatory mediators, vagal nerve stimulation (parasympathetic)
8 Sympathetic stimulation through activation of B2 receptors by adrenaline
9Thickening of basement membrane, smooth muscle hypertrophy, vasodilation, mucus gland hyperplasia,
desquamation of epithelium, mucus plug in lumen, oedema of mucosa, white blood cells enter mucosa
10Hypercapnia is having too much CO2 in the blood. Signs are flushed skin (red), vasodilation,
hyperventilation

2. 11.What would the oxygen saturation level of blood need to be in order for
haemoglobin to lose the ability to retain oxygen?11
Hypersensitivity
1. What are IgE, IgM, IgG and IgA?12
2. What is type 1 hypersensitivity? 13
3. Which are the two most important types of hypersensitivity in asthma? 14
4. What is Der P?15
5. What is Atopy?16
6. What substance causes increased permeability of vessels to fluid and causes the
localised oedema or wheal seen after a skin prick allergy test?17
7. What is involved in a RAST test?18
8. What is type 2 hypersensitivity? 19
9. What are the main causes of type 3 hypersensitivity (antigen-complex mediated,
when there is little antibody and an excess of antigen)?20
11 Around 40% or 8kPa
12IgE = least abundant but plays major role in type 1 hypersensitivity, IgM = produced in the spleen by B
cells, binds to specific antigens, IgG = produced in plasma by B cells controls infection in intracellular fluid
and thus responsible for what enters tissues. IgA = main antibody for mucosal linings
13Immediate inflammatory/allergic response, mediated by IgE and mast cells releasing histamine, typically
onset in 1-5 minutes and ends after 15 minutes.
14 Types 1 and 4
15 The allergen produced by dust mite gut bacteria, the main allergen involved in asthma
16 Atopy is hypersensitivity to allergens (allergy)
17 Histamine
18 Take patient serum containing IgE, detect bound IgE via enzyme or anti synthetic IgE antigen.
19IgM antibodies to foreign cell membrane proteins, recruitment of inflammatory cells which leads to attack
by killer cells, release of c3a and c5a (chemoattractants which attract inflammatory cells), antibody
dependent cytotoxicity.
20Incompatible blood transfusions, hemolytic disease of the newborn (where maternal IgG antibodies which
have passed across the placenta, attack the fetal red blood cells), diabetes (antibodies to insulin/islet cells
produced), myasthenia gravis (antibodies attack acetylcholine receptors resulting in muscle weakness).

3. 10.What is the difference between type 2 (antibody) and type 3 (complex)
hypersensitivities?21
11.What is type 4 hypersensitivity? 22
12.What is the difference between atopic/extrinsic asthma and non-atopic/intrinsic
asthma? 23
13.Why should NSAIDS and aspirin not be given to asthmatics?24
14.Describe the type 1 and type 4 responses to an asthmatic response?25
Control of Breathing
1. What are the main factors which control automatic (involuntary) breathing?26
2. Which part of the brain has direct, higher central control which is able to bypass
ANS control of breathing? 27
3. What is the pneumotaxic centre?28
4. What kinds of receptors control the lungs and breathing?29
21Type 3 is a soluble complex (i.e. dissolved in blood plasma) whereas type 2 is antibodies on the skin
surface/epithelium. In type 3 large complexes activate an array of killer cells which often damage host cells
with ʻfriendly fireʼ.
22 Delayed response inflammation, antibody independent, T-cell mediated, antigen presenting cells find the
allergen and present it to T killer cells. This is the mechanism for delayed asthmatic response and TB.
23Atopic/extrinsic has a defined (allergic) cause and usually starts in childhood, non-atopic/intrinsic has an
undefined cause and is later onset.
24 Because they can provoke a serious asthma attack in 5% of asthmatics.
25Type 1 is the initial onset, lumen mucus increased, immune mediators released but recede again after 15
minutes and breathing recovered. Hours later, the type 4 onset begins, antigen goes to dendritic cells, then
presented to T-cell and eosinophil activation, further allergic response.
26Neural controls from brainstem and lung receptors, Chemical controls from response to PCO2, PO2 and
pH, as well as central chemoreceptors.
27The medulla (below the pons), so cutting the medulla would mean breathing was still ok whilst awake but
would result in sleep apnoea
28A network of neurons in the pons which regulates the amount of air a person can take into the body in
each breath. Ventilation needs to match metabolism.
29Mechanical stretch receptors (fire when stretched to prevent over-inflation of lungs), irritant receptors,
higher centres of temperature control, chemoreceptors (CO2, O2 and pH).

4. 5. What is the Henring Breuer Inflation Reflex? 30
6. What are irritant receptors responsible for?31
7. What does stimulation of the arterial baroreceptors do to breathing? 32
8. What change occurs to the chemical ventilation control mechanism in the case of
metabolic acidosis or alkalosis?33
9. What could be a likely source of a high level of HCO3-?34
10.Where would you find the chemoreceptors which affect breathing?35
11.Why would it be worse for a hypoxic patient to breathe 100% oxygen than it
would to breathe normal air? 36
12.What is the most likely cause of sleep apnea and why?37
Pharmacology of Asthma
1. What types of drug are used for the treatment of asthma? 38
2. How is airway smooth muscle contraction innervated/stimulated?39
30 The rule that inhalation innately inhibits exhalation and vice versa.
31The deep, augmented breaths you take every 5-20 minutes. Coughing and some reflex laryngeal/
bronchoconstriction
32 Inhibits breathing
33In acidosis it takes a lower CO2 level to cause ventilation to increase, so you are more likely to
hyperventilate. The reverse is true in alkalosis.
34 Vomiting, loss of acid means HCO3- not used up and builds up
35Chemoreceptors located mostly around the exit of cranial nerves IX and X which detect O2, CO2 and pH
based on HCO3- in the CSF.
36Because this would lead to absence of CO2 and loss of the hypoxic drive, which would actually deplete
oxygen levels
37Most likely if patient is overweight, larynx and soft tissues in the neck become loose and breathing space
reduced. Anyone who snores has a degree of obstructive sleep apnea.
38B2 agonists, anti-cholinergic, anti-inflammatory glucocorticoid, phosphodiesterase inhibitor, anti-
leukotriene, cromone or ʻmast cell stabilizerʼ.
39Parasympathetic vagal efferents, Excitatory non-adrenergic, non-cholinergic (an ANS transmitter which is
neither noradrenaline or acetylcholine) c-fibre efferents.

5. 3. How is airway smooth muscle relaxation innervated/stimulated?40
4. Where is airway smooth muscle located in the respiratory system? 41
5. Out of bronchodilators, prophylactics and anti-inflammatories, which are ‘relievers’
and which are ‘preventers’?42
6. Give 3 examples of ‘relievers’ and 3 of ‘preveters’43
7. What are the half lives of salbutamol and salmeterol? 44
8. What is the main mechanism of B2 receptor agonists? 45
9. Why are relievers such as Ipratropium Bromide not that useful for allergen
induced asthma? 46
10.What is the main mechanism of anti-cholinergics?47
11.When would you use xanthines to treat asthma?48
12.What is the main mechanism of xanthines like theophylline and aminophylline49
40Sympathetic stimulation by adrenaline B2 receptors (adrenal medulla), sympathetic efferents to
parasympathetic ganglia, Nitric oxide (a bronchodilator just like it is a vasodilator)
41 All the way from the trachea to the respiratory bronchioles, arranged in ring structure around the lumen.
42 Relievers are bronchodilators (for acute symptoms), preventers are prophylactics and anti-inflammatories
(for relief of chronic symptoms)
43Relievers - B2 selective agonist (e.g. Salbutamol for short acting, Salmeterol for long acting), Anti-
cholinergics, Xanthines (Theophylline, Aminophylline), Preventers - Glucocorticosteriods, Cromones, Anti-
leukotrienes, Xanthines
44Salbutamol is a short acting reliever with a 5-6 hour half life. Salmeterol is a long acting reliever with a 17
hour half life.
45Increase cyclic AMP levels in target cells to induce smooth muscle relaxation, mast cell stabilisation (anti-
histamine), mucus clearance by increasing cilia activity
46
47Its all in the name - block effects of acetylcholine released from cholinergic parasympathetic nerve fibres
and so block parasympathetic induced SM contraction. Also prevent mucus hyper-secretion.
48 Generally used if B2 agonists not effective, can be given in slow (for nocturnal asthma) or fast release
forms
49 Mostly as relievers as they have a short half life, mechanism is to inhibit phosphodiesterases (which
convert cyclicAMP into AMP), so xanthines potentiate cyclic AMP production and induce relaxation of SM.
Used if B2 agonists arenʼt effective. Xanthines also reduce eosinophil (WBC specifically responsible for
allergic reaction, present in blood from haematopoiesis) survival.

6. 13.What are beclamethosone and prednisolone?50
14.What is the mechanism of glucocorticosteriods?51
15.Why would you use cromones such as cromolyn sodium? 52
16. What are the main side effects of glucocorticosteriods? 53
17.What are the effects of cromones54
18.What are two drug classes of anti-leukotrienes? 55
19.Why might you use anti-leukotrienes as opposed to other preventers?56
20.What is the mechanism of anti-leukotrienes? 57
21.What are the side effects of B2 agonists? 58
22.What are the side effects of Xanthines? 59
23.What are the side effects of (oral) anti-leukotrienes?60
24.What is bronchial thermoplasty?61
50 Glucocorticosteriods (Preventers), take one hour before effects are seen
51Suppress inflammatory gene activation by penetrating the cell nucleus and blocking the effects of
inflammatory cytokines on transcription factors in the cell nucleus. Reduces inflammatory effects such as
mucosal oedema and improves airflow.
52Because they produce less side effects (glucocorticosteroids can cause cough, hoarseness and even
retarded growth, weight gain, eye problems and diabetes) so are often given to children in preference
53Inhaled: cough, hoarseness, Oral: retarded growth (so rarely given to children), diabetes, osteoporosis,
water retention, weight gain, eye problems, diabetes, psychosis, hypertension.
54Mechanism is uncertain but they block release of sensory neuropetides, stabilise mast cells and prevent
eosinophil (WBC specifically responsible for allergic reaction) activation
55 5 Lipoxygenase Inhibitors (Zileuton, USA only) and Leukotriene receptor antagonists (e.g. Montelukast)
56 In aspirin induced asthma (few unwanted side effects)
575 -lipoxygenase inhibitors inhibit the enzyme converting arachidonic acid into leukotrienes and leukotriene
receptor antagonists stop the leukotrienes taking effect
58 Skeletal muscle tremor, sometimes tachycardia (fast heart rate)
59(Have a very narrow therapeutic range). Headaches, nausea, cardiac arrhythmia, diuresis, behavioural
changes. (Constant therapeutic monitoring required).
60 Headaches and GI disturbances
61 Radiofrequency ablation of parts of the airway wall to reduce ASM contractibility

7. Adherence and Placebo
1. How many people (%) in the UK have a chronic illness or disability?62
2. What is ‘compliance’? 63
3. What is ‘adherence’? 64
4. What is ‘concordance’?65
5. What is the typical rate of non-adherence?66
6. What methods could be used to measure adherence? 67
7. What are the four main determinants of non-adherence (cost-benefit)?68
8. What 3 factors lead to increased compliance in Ley’s model? 69
9. How might you improve adherence?70
10.What factors could affect the effectiveness of a placebo?71
62 15% of the total population
63 The extent to which the patientʼs behaviour matches the prescriberʼs reccomendations
64 The extent to which the patientʼs behaviour matches the agreed recommendations from the prescriber. I.e.
like compliance but where there has been a collective decision involved
65A consultation process where the doctor and patient agree on therapeutic decisions that incorporate their
respective views
66 30-50%
67Self-report questionnaire, self monitoring, pill counts or prescription refills, marked sign technique (inactive
drug markers), biochemical indicators (e.g. urine sample), clinical outcomes
68 Cost: Time, side effects, Benefit: Progression, symptoms
69 Understanding, satisfaction and memory
70 Removing barriers (cost, repeat prescription), Identifying maladaptive illness and modifying treatment
prescriptions (e.g. symptoms, drug concerns). Improving communication (knowledge) & doctor patient
relationship, memory cues (take with food), simple well organised information.
71Size, shape, colour, administration or medication. Setting: home or hospital. Patient characteristics
(beliefs, anxiety, adherence), Practitioner characteristics: status, empathy, Patient-practitioner relationship