Respiratory and Sleep

Question 1

Which phase of sleep is associated with the lowest muscle tone and therefore the highest rates of OSA?

Answer 1

REM

Question 2

What phase of sleep is shown in this PSG?

Answer 2

1. 30s per page = sleep staging (not breathing question)
   
   2. Eye movements not present (L oc and R oc) = not REM or awake
   3. EMG looks ‘fat’ = muscle tone is present, not REM
   4. K complexes and sleep spindles found on EEG

This is N2 sleep (light sleep)

Question 3

Which sleep phase is shown in this PSG?

Answer 3

• EEG shows large triangular ‘delta’ waves (but also some K complexes)
• No eye movements

This is N3 sleep (deep sleep)

Question 4

What sleep phase is shown in this PSG?

Answer 4

• Eye movements present - one electrode on the left and one on the right. So if you look to the left the LOC electrode goes up and the ROC electrode goes down (review above)
• In the other examples above, all of the waves are in the same direction - this indicates they are picking up brain waves (given they are located at the temples)
• EMG looks flat - hypotonia

This is REM - dream sleep

Question 5

What are the potential risks of long term melatonin use in children with chronic sleep issues?

Answer 5

There are melatonin receptors on testis and ovaries
There are concerns that long term melatonin use could potentially delay sexual maturation

Question 6

An adolescent presents with chronic fatigue.
Their actigraphy is shown below.
What is the diagnosis and treatment?

Answer 6

Diagnosis: Delayed sleep phase
• Sleep hygiene
○ Dim light before bed
○ No computer/TV in room
○ No stereo or texting
• Bright light when should be awake
• Advance bedtime by 15 minutes each 3 nights
Melatonin as adjuvant

Question 7

In what phase of sleep do night terrors occur?

Answer 7

N3 - deep sleep

Question 8

You see a 4 year old patient who’s parents report that they regularly wake from sleep and scream.
Their eyes are open, but they do not respond to their parents. They have noticed that they look sweaty and have dilated pupils.

Is the diagnosis

a. ADNFLE
b. night terror
c. nightmare

Answer 8

Answer is B, night terror

• 39% of children 
• Frequent in 3% of children 
• Trying to wake child will prolonged event 
• Clonazepam or zopiclone if extreme 
• Timing: 60-90 minutes into sleep  Child unable to be comforted, goes straight back to sleep, cannot recall event

Question 9

A child lets out a scream at 4 am.
When their parents go to comfort them they respond to questions by stating that they were being chased.

Is the diagnosis

a. ADNFLE
b. night terror
c. nightmare

Answer 9

C = nightmare

Occurs during REM sleep
Child can be woken/comforted
Will recall the event unlike in night terror

Question 10

A child shouts in sleep and makes abnormal pelvic thrusting and ‘bicycling’ movements
One of their parents reports that they used to do a similar thing

Is the diagnosis

a. ADNFLE
b. night terror
c. nightmare

Answer 10

A = autosomal dominant nocturnal frontal lobe epilepsy

Stereotyped movements - pelvic thrusts, bicycling
May vocalise
May walk
May have aura
rare

Question 11

What are the features of Klein-Levin syndrome?

Answer 11

Every 6 weeks, patient will get 2 weeks of hyperphagia, hypersomnolence and increased libido

Question 12

A patient undergoes MSLT (multiple sleep latency testing)
Their time is consistently <8 minutes
They have multiple episodes of SOREM (= sleep onset REM)
What is the diagnosis?

Answer 12

• Constant sleepiness
○ Narcolepsy (with and without cataplexy)
§ MSLT: short latency plus >= 2 REM onsets
○ Primary idiopathic hypersomnia with long or normal sleep time
§ MSLT: short latency but <2 REM onsets

Question 13

What is the first line treatment for narcolepsy?

Answer 13

Methylphenidate or dexamphetamine
If fails this can trial modafanil (not funded for 1st line)

Question 14

What is the frequency of CF carrier status amongst Caucasian populations?

Answer 14

1/25
Generally overall incidence of homozygosity this group is 1/2500 - 3000

Question 15

What class of mutation is F508 and what does this mean/

Answer 15

Class 2
Misfolded protein is arrested by endoplasmic reticulum quality control and is not trafficked to the cell membrane

Question 16

What is the second most common CF causing mutation in Australia and what class is it?

Answer 16

G551D
Class 3
Some protein reaches surface, but no function

Question 17

What class of mutation is G542X and how does this mutation cause disease?

Answer 17

Class 1
No functional protein produced

Question 18

Describe the pathophysiology of a class 4 cystic fibrosis causing mutation

Answer 18

protein reaches plasma membrane, has some function, which is impaired (decreased conductance)
Example would be R117H(5T)

Question 19

Describe type 5 CF causing mutations

Answer 19

Type 5: reduced total CFTR protein at cell surface
A455E, 2789+5G-A

Question 20

Describe type 6 CF causing mutations

Answer 20

Type 6: CFTR less stable (increased turnover)
120del23, N287Y, 432delTC

Question 21

Which electrolytes pass outwards through the CFTR?

Answer 21

Chloride and bicarbonate

Question 22

Which of the following is not a potential cause of a false positive sweat chloride test?

a. Klinefelters
b. Primary ciliary dyskinesia
c. congenital adrenal hyperplasia
d. eczema
e. hypothyroidism

Answer 22

Answer: B, PCD not a cause

Conditions causing false positives: eczema, malnutrition, anorexia, CAH, adrenal insufficiency, glucose-6-phosphatase deficiency, hypothyroidism, hypoparathyroidism, glycogen storage disorders, MPS, diabetes insipidus, klinefelters
False negative: malnutrition, skin oedema, mineralcorticoid use

Question 23

Which of the following 2 answers represent a sweat test result that is suggestive of cystic fibrosis?

Answer 23

A and B
>60mmol/L considered diagnostic, some centres use higher cut-offs. A borderline test result is more likely in a patient with retained pancreatic function.
30 - 60 may be considered positive in children <6 months of age
Sweat weight needs to be >75-100 mg

Question 24

What is the organism most commonly isolated in young patients with cystic fibrosis?

Answer 24

Staphylococcus aureus
Haemophilus influenzae also common, but not as much

Question 25

Which of the following is not an appropriate agent for use in the treatment of pseudomonas aeruginosa disease in cystic fibrosis? a. colistin b. ceftazadime c. tobramycin d. doxycycline e. aztreonam

Answer 25

Correct answer is D, p.aeruginosa would be resistant

Question 26

In which CF causing mutation would monoagent ivacaftor be appropriate?

Answer 26

G551D Class 3 - some protein on membrane surface, but does not function Ivacaftor is a 'potentiator' 'Iva opened up'

Question 27

What type of CFTR modulator is lumacaftor?

Answer 27

This is a 'corrector' which counteracts protein misfolding and trafficking (ie: active in class II mutations) Lumacaftor - 'loom' (protein sowing/folding) Tezacaftor - 'tears a lumacaftor a new one' - 2nd generation corrector

Question 28

Which 2 CFTR modulators make up Orkambi?

Answer 28

Lumacaftor/ivacaftor 3-4% improvement in FEV1 Symdeko is similar but is tezacaftor/ivacaftor Approved in F508 · Respiratory adverse effects: chest tightness, dyspnoea, bronchospasm, increased cough, pneumothorax Non-respiratory adverse effects: GI upset, myalgia with increase in CPK, fatigue, headache

Question 29

What 3 drugs make up trikafta?

Answer 29

Correctors: tezacaftor, elaxacaftor Potentiator: ivacaftor · In the first trial also showed improvements in sweat chloride, pulmonary exacerbations and BMI · Adverse effects o Common: headaches, URTI, abdominal pain, diarrhoea, rashes, increased liver enzymes (ALT, AST), nasal congestion, increased creatine kinase Associated with cataracts (hence opthal screening prior) FDA approved in 12 year old patients with at least 1 F508del

Question 30

Using a pulse oximeter, an oxygen saturation of 90%, under normal metabolic conditions, corresponds to a PaO2 of approximately

Answer 30

Pulse oximetry is accurate above 90% oxyhaemoglobin saturation, but much less so below 70%, and inaccurate below 50%. Pulse oximeters estimate arterial haemoglobin oxygen saturation (SaO2) and not arterial oxygen tension (PaO2). Because of the shape of the oxygen-dissociation curve, large changes in PaO2 may occur at the extremes of the curve with minimal change in SaO2. They have a response time of 10–30 seconds, depending on the signal averaging time, circulation time and the site of the probe. A simple way to remember the sats and the corresponding PaO2 is: 40-50-60 70-80-90… which basically means that… PaO2 is 40mmHg at SpO2 70% PaO2 is 50mmHg at SpO2 80% PaO2 is 60mmHg at SpO2 90%

Question 31

What is the current definition of chronic neonatal lung disease?

Answer 31

Currently defined as dependence on supplemental oxygen at 36 weeks corrected gestational age Previously described as oxygen dependency at 28 days of age (in the TSANZ position statement this definition is used for the term 'bronchopulmonary dysplasia')

Question 32

What target saturations are currently recommended for ex premature infants, and what is the evidence base underlying this?

Answer 32

93-95% BOOST 1 trial - no difference between 91 - 94 and 95-98% BOOST 2 - higher mortality with 85-89% target

Question 33

What is the fraction of inspired oxygen in most commercial airline cabins?

Answer 33

These cabins are pressurised to an equivalent of 1500 - 2400 m This corresponds to an oxygen tension of 15-17% Need fitness to fly test - show not going to have SpO2 <85%

Question 34

What is the significance of exhaled nitric oxide?

Answer 34

Eosinophilic inflammation Suggests asthma as diagnosis

Question 35

You see an asthmatic child in clinic who is using a mask with a spacer At what age should they transition to using a spacer without a mask?

Answer 35

2-4 possible to transition 5 - should transition

Question 36

Long acting B-agonists are potentially associated with increased risk of severe exacerbations in children. What mechanism underlies this?

Answer 36

Reduction in the density of B-2 receptors https://www.nps.org.au/australian-prescriber/articles/long-acting-beta2-agonists-for-childhood-asthma#:~:text=Safety%20of%20long%2Dacting%20beta2%20agonists%20in%20children&text=These%20observations%20are%20consistent%20with,used%20with%20concomitant%20inhaled%20corticosteroids.

Question 37

What is the mechanism of action of omalizumab?

Answer 37

Binds free IgE and prevents it from binding to eosinophils Reduces mediator release and allergic inflammation

Question 38

What is the mechanisms of action of mepoluzimab in asthma?

Answer 38

Anti IL-5

Question 39

You are reviewing a 13 year old patient with mild intermittent asthma and note they are currently only prescribed reliever therapy with salbutamol (ventolin) You would like to commence SMART therapy Which combination therapy would be appropriate? a. fluticasone/salmeterol b. budesonide/formoterol c. fluticasone and vilanterol

Answer 39

a. fluticasone/salmeterol - Seretide - INCORRECT b. budesonide/formoterol - Symbicort - CORRECT c. fluticasone and vilanterol - Breo Ellipta Only budesonide/formoterol products are approved because formoterol has a quick enough onset to be used as a reliever

Question 40

In the context of SMART therapy, what are the advantages of using a turbuhaler?

Answer 40

Symbicort tubuhaler is a DPI. Children can attempt a DPI at around age 5-6, most should be able to use by 8 It is more portable and has a lower carbon footprint The disadvantage is the slightly more difficult technique Note that the turbuhaler is 200/6 and rapihaler (ie MDI0 100/3) so starting preventer dose is 1 puff BD for former, 2 puffs BD for latter

Question 41

Describe the sequence of the tracheobronchial tree in the correct order IE: trachea...

Answer 41

Trachea --> right and left main bronchus --> secondary or lobar bronchus --> segmental or tertiary bronchi --> bronchioles (conducting --> terminal --> respiratory)

Question 42

At what point in the tracheobronchial tree does the conducting zone cease and the gas exchange zone begin?

Answer 42

Transition between the terminal bronchioles and the respiratory bronchioles Terminal - this is why they are called the terminal bronchioles Respiratory - have alveoli in their walls

Question 42

At what point in the tracheobronchial tree does the conducting zone cease and the gas exchange zone begin?

Answer 42

Transition between the terminal bronchioles and the respiratory bronchioles Terminal - this is why they are called the terminal bronchioles Respiratory - have alveoli in their walls

Question 43

Which bronchopulmonary segments tends to have fluid entrapment in a chronically bed-ridden individual?

Answer 43

Superior segment of the inferior lobe The tertiary bronchus that supplies this tends to be oriented quite posteriorly and is thus a dependant area if the patient is recumbent

Question 44

Describe the layers of the alveolar-capillary membrane

Answer 44

Squamous cell of the type 1 pneumocyte Shared basement membrane Squamous cell of the capillary 0.5 microns thick

Question 45

Name the stages of lung development?

Answer 45

Embryological Pseudo glandular Cannicular Saccular Alveolar

Question 46

What is the A-a gradient

Answer 46

The alveolar to arterial (A-a) oxygen gradient is a common measure of oxygenation ("A" denotes alveolar and "a" denotes arterial oxygenation) It is the difference between the amount of the oxygen in the alveoli (ie, the alveolar oxygen tension [PAO2]) and the amount of oxygen dissolved in the plasma (PaO2)

Question 47

In a healthy adult lung, what is the typical gross ration of ventilation to perfusion

Answer 47

0.8 4L/minute of ventilation 5L/minute of perfusion

Question 48

In what lobe of the lung is VQ mismatch highest?

Answer 48

Upper lobes

Question 49

True or false: carbon monoxide shifts the oxygen-haemoglobin saturation curve to the LEFT

Answer 49

This is true Carbon monoxide binds Hb and allosterically causes change in shape resulting in impaired oxygen offloading at tissues

Question 50

Which part of the airways does FEF25-75% represent?

Answer 50

Smaller conducting airways

Question 51

You review a patient in clinic with severe cystic fibrosis. Their FEV1 is 28%, FEV1/FVC ratio is reduced You note a low FVC Does this reflect? a. restrictive lung disease b. mixed obstructive and restrictive lung disease c. severe obstructive lung disease

Answer 51

Answer is C This is most likely severe obstructive lung disease with pseudo-restriction

Question 52

What disease process is shown in this flow volume loop?

Answer 52

Restrictive Can be shown as this also (see attached)

Question 53

What type of pathology is shown in this image?

Answer 53

Fixed upper airway obstruction

Question 54

What type of pathology is shown in this image?

Answer 54

Variable extra-thoracic airway obstruction

Question 55

What type of pathology is shown in this image?

Answer 55

Variable intrathoracic airway obstruction

Question 56

what type of pathology is shown in this image?

Answer 56

Thoracic inlet obstruction

Question 57

which congenital surfactant deficiency is known for causing fatal lung disease during infancy?

Answer 57

Surfactant protein B deficiency B = bad

Question 58

which congenital surfactant deficiency is known for causing interstitial lung disease during childhood?

Answer 58

Surfactant protein C deficiency C = childhood

Question 59

what electrolyte abnormalities would you expect in a CF patient on a hot day?

Answer 59

People with cystic fibrosis are more vulnerable to electrolyte disturbance from dehydration due to pseudo-Bartter’s syndrome (hyponatremic, hypokalemic, hypochloremic metabolic alkalosis). This occurs because sweat production is different in children with cystic fibrosis. Sweat is usually isotonic. However, in cystic fibrosis, sweat is hypertonic due to increased sodium and chloride loss in the sweat due to CFTR dysfunction. Under usual conditions, this increased tonicity is easily corrected. However, on hot days, there is an increased volume of sweat production which leads to hyponatremia. Hyponatremia triggers secondary hyperaldosteronism causing excessive renal potassium losses. Metabolic alkalosis occurs because there is intravascular volume depletion causing an increased extracellular concentration of bicarbonate.

Question 60

Management of new pseudomonas infection in a child with cystic fibrosis

Answer 60

See card 2 x anti-pseudomonal agents from different classes

Question 61

a 4 year old patient present with hypocalcaemic seizure and is found to have raised phosphate levels and normal vitmain D and parathyroid hormone They also have short stature, short 4th and 5th metacarpals and a round face what genetic locus is likely to be involved? a. GNAS b. AIRE c. SHOX d. NEMO

Answer 61

GNAS - codes the alpha subunit of the G protein coupled receptor signal If somatic mutations in some tissues causes McCune Alright syndrome Albright's hereditary osteodystrophy - brachydactyly, round face, intellectual disability, subcutaneous ossification Some aspects of GNAS are bi-allelically expressed, however, some of the hormone signalling pathways are normally paternally silenced and maternally expressed So if you inherit the mutation from your Mother you would have PTH (+/- TSH and GH) resistance, if inherited from Father would not https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417430/

Question 62

baby is being worked up for congenital hypothyroidism high TSH and low T4 99-pertechnetate scan shows good uptake, slightly larger gland what disorder is suggested?

Answer 62

Dyshormonogenesis/enzymatic defect

Question 63

baby is being worked up for congenital hypothyroidism high TSH and low T4 iodine-123 scan shows decreased uptake, normally located gland what are the differentials?

Answer 63

TSH receptor blocking antibody Inactivating TSH receptor mutation Sodium/iodine symporter mutation

Question 64

what is pendred syndrome?

Answer 64

Pendred syndrome – congenital hypothyroidism associated with sensorineural hearing defects; would expect low T4 and elevated TSH

Question 65

Boy with short stature, jittery, difficulties at school T$ and T3 elevated TSH 4 (normal <4)

Answer 65

Key points Mutation in TSH receptor gene – usually THRB gene Incidence 1/40,000 M=F Autosomal dominant (Note: Nelson’s autosomal recessive) Pathophysiology Resistance of pituitary thyrotrophs to thyroid hormone 🡪 ↑ TSH 🡪 ↑ T4 and T3 production from the thyroid gland The elevated levels of T3 and T4 do not downregulate TSH production as the pituitary gland is resistant Outcome = ↑ T3 and T4 and normal or ↑ TSH TSH secreted by these patients is rich in sialic acid and has increased bioactivity cf. normal TSH – results in high T4 and T3 and goitre even though TSH concentrations are normal or slightly high Effect on metabolism = Increased thyroid hormone secretion compensates for resistance – most patients are clinically euthyroid Clinical manifestations HIGHLY HETEROGENOUS Hallmark = paucity of symptoms and signs of thyroid dysfunction despite high T4 and T3 Most common clinical findings Goitre Hyperactivity Tachycardia Hearing loss – may be due to recurrent ear infections (more common in RTH) Sensorineural deafness is common among individuals with TR-beta gene deletion May have some signs of hypo or hyperthyroidism – variable and when present often inconstant If hypothyroidism present Growth retardation

Question 66

what is the primary mediator of short stature in chronic kidney disease?

Answer 66

low IGF-1 Growth hormone will be relatively high/normal

Question 67

what findings on chest drain fluid suggest chylothorax

Answer 67

High trigs >80% lymphocytes