SBA SCE style Questions

Question 1

A 22 year old with no prior medical history arrives in ED with a low GCS. His friends state that he was complaining of headaches, nausea and dizziness prior to the drowsiness. They deny any alcohol or illicit drug use. They state that a new boiler was installed in the patient’s flat last week, and he was concerned that the workman did not seem competent. The landlord had declined to come and check the work. Observations: T 37.3, P 95, BP 110/70, Sats 98% on air, GCS 11 (E3 V3 M5)

What is the single most appropriate initial management plan?
A. Call the intensive care department to request intubation
B. Controlled oxygen with target sats 94-98%
C. High-flow oxygen 15L through a reservoir mask
D. Initiate non-invasive ventilation
E. Venturi mask 40% flow

Answer 1

C. High flow oxygen 15L through a reservoir bag

A normal/high oximetry reading should be disregarded in suspected CO poisining as saturation monitors cannot differentiate between COHb & HbO2, owing to their similar absorbances. This is a rare example of when a reservoir mask at 15 L/min should be used. COHb levels should be checked. These can be slightly high in smokers, but a significantly raised level would be expected in cases of CO poisoning (>3% in non-smokers, >10% in smokers). Levels correlate poorly with clinical severity. Oxygen hastens the dissociation of CO from COHb, turning it back into Hb. Hyperbaric oxygen is also a useful treatment where available. NIV & intubation are not usually required. Prevention of CO poisoning can be simply achieved by the maintenance of boilers, generators & stoves, & the use of CO detectors. In England landlords only have to fit a CO alarm in a room with a solid fuel burning appliance.

Question 2

A 42 year old woman wants to stop smoking. She has tried on two previous occasions, using nicotine replacement therapy in the form of patches. She has recently had a health scare, and is very keen to successfully quit this time around. She asks you for advice about the most effective ways to stop smoking.

What is the single most accurate statement about smoking cessation interventions?

A. A combination of psychological support and pharmacological treatment is no more successful than pharmacological treatment alone
B. E-cigarettes have the same efficacy in achieving abstinence from tobacco smoking as other smoking cessation interventions
C. Patients with COPD are as likely to quit as smokers without COPD following smoking cessation interventions
D. Smoking cessation interventions lead to a quit rate of 50% at 1 year
E. Varenicline is more likely to be effective than psychological support alone

Answer 2

E. Varenicline is more likely to be effective than psychological support alone.

In a double blind placebo controlled RCT in patients with COPD from abstinence at 9-12wks was 42% with varenicline, compared to 8.8% in the placebo arm (https://t.co/TUPBDz982q).

A meta-analysis from 2006 in concluded varenicline > bupropin > nicotine replacement in supporting smokers to quit at 3 months. Indirect comparisons were used (https://t.co/kRMeNTsS0P).

In a pragmatic RCT people were randomised to nicotine e-cigarettes, placebo e-cigarettes or nicotine patches. E-cigarettes had similar rates of abstinence to patches, but quit rates were low in this study (https://t.co/clnEnVBa1D).

In a 2019 UK study e-cigarettes were significantly more effective than NRT. 1yr quit rates were 18% for e-cigarettes, 9.9% for NRT. They were also shown to be cost-effective (https://t.co/lZApHsvsSf).

Question 3

A 42 year old woman is awaiting a cholecystectomy, and has spirometry as part of a pre-op assessment.
Spirometry shows:
FEV1 0.95L (36% predicted – SR –2.11)
FVC 2.15 (70% predicted – SR –1.76)
Ratio 44%

What is the single best description of these results?
A. Consistent with obesity
B. Mild restrictive defect
C. Poor effort, therefore un-interpretable
D. Severe obstructive defect
E. Within normal limits

Answer 3

D. Severe obstructive defect

In this example FEV1 is very low, whereas the FVC is almost within normal range. The ratio is 0.44 which shows severe obstruction, as per GOLD guidelines.

GOLD 1 mild, FEV1 >80% predicted
GOLD 2 moderate, 50% < FEV1 >80% predicted
GOLD 3 severe, 30% <FEV1>50% predicted
GOLD 4 very severe, <30% predicted</FEV1>

SR (standard residuals) are very useful. For a conventional 90% lower confidence limit, an SR value more negative than -1.645 means the index is abnormal.

A restrictive defect, as would be expected in obesity, would have a FEV1/FVC of >0.7.

We can’t fully interpret these results - we’d want to see a flow volume loop, a TLCO & a slow VC. There could well be a mixed defect. But from the info given the best answer is severe obstruction

Question 4

A patient with COPD wishes to fly to see relatives in Tokyo, Japan. A direct flight is 11hr 50min. They ask whether it is safe for them to fly and whether they will need to arrange in-flight oxygen. Their COPD symptoms are currently stable. They take a combination LABA/LAMA inhaler and carbocisteine. They have never been admitted to ICU but had ward based NIV for hypercapnic respiratory failure 6 months ago due to influenza A leading to a severe exacerbation. On outpatient testing pCO2 had normalised by 6 weeks.

Which one of these suggests the patient is at risk of in-flight hypoxia, and therefore needs to undergo a hypoxic challenge test?
A. Exacerbation within the last 3 months
B. Hospital admission within the last 6 months
C. MRC breathlessness score of 2
D. Resting Spo2 <98%
E. Six minute walk test desaturation to <84%

Answer 4

E. Six minute walk test desaturation to <85%

Patients with COPD who should undergo hypoxic challenge testing include: resting SpO2 ≤95%; MRC score 3 or greater; and desaturation to <84% on 6MWT or SWT in whom there are concerns about hypercapnia.

BTS guidelines on air travel: https://t.co/jH4GCrchFk

European & N American regulations limit max cabin altitude to 2438m (8000 ft) under normal operating conditions. This is based on the oxyhaemoglobin dissociation curve - up to this level SaO2 remain >90% in the average healthy individual. In a study of 1260 healthy volunteers, no significant changes occurred in (SpO2) during a simulated 8-hour flight at cabin altitudes up to 2438m (8000 ft). However, if cabin altitude exceeds 3048m (10000 ft) SaO2 falls to∼89% (https://t.co/X8d6oLx5nf).

The hypoxic challenge test uses an inspired gas mixture containing 15% oxygen, which gives similar PO2 to breathing air at the max allowable cabin pressure altitude. The patient breathes the hypoxic gas mixture for 20min, or until SpO2 reaches 85%.

When interpreting the hypoxic challenge test
PaO2 ≥6.6kPa (≥50mm Hg) or SpO2 ≥85%: in-flight oxygen NOT required.
PaO2 <6.6kPa (<50mm Hg) or SpO2 <85%: in-flight oxygen recommended

Question 5

A 21 year old patient with Cystic Fibrosis is being assessed for eligibility for CTFR modulators. They have one copy of the F508del mutation and another previously undescribed residual function mutation.

Which ONE of the following CFTR modulators is the single best treatment option?
A. Kaftrio
B. Kalydeco
C. Lumacaftor
D. Orkambi
E. Symkevi

Answer 5

E. Kaftrio

There are now several CFTR modulators available, in three main classes: potentiators, correctors and premature stop codon suppressors. Kaftrio is triple combination therapy, ivacaftor, tezacaftor and elexacaftor (Trikafta in the USA). It’s available for patients with two copies of the F508del mutation or one copy of F508del and any other mutation.

There are 6 classes of CFTR mutation. Class I & II CFTR mutations are characterised by a reduction in the quantity of expressed CFTR protein. This ERS review is a great read: https://t.co/K3Eisej6qh.

Class I mutations can result from nonsense & frame-shift mutations, as well as mRNA splicing defects. E.g. G542X is a nonsense or stop mutation. Introduction of a premature stop codon leads to production of truncated CFTR protein. Class II mutations, including F508del, have folding or maturation defects, which can result in premature CFTR degradation.

Question 6

You are in the regional respiratory failure unit for a placement. You spend time with the specialist respiratory physiotherapist and comment on the fact that there are a significant number of young adults treated by the service. You discuss causes of respiratory failure in young people.

Which ONE of the following is at highest risk of respiratory decompensation by adolescence?
A. Duchenne muscular dystrophy
B. Limb girdle muscular dystrophy
C. McArdle disease
D. MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes)
E. Pompe disease

Answer 6

A. Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is one of the most frequent genetic conditions affecting approx 1/ 3500 male births worldwide (it is X-linked). It leads to progressive weakness & respiratory failure by adolescence.

Pompe disease and McArdle disease are glycogen storage disorders, and limb girdle muscular dystrophy is a sarcoglycanopathy, all of which are highly variable. MELAS (Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes) may also progress to respiratory failure, but this is typically in adulthood.

Question 7

You are teaching final year medical students about normal thoracic physiology and how it is relevant to respiratory disease. During a discussion on pneumothorax and chest drains, a students asks you to explain intrapleural pressure changes.

Which ONE of the following is the most accurate estimation of intrapleural pressure at end expiration?

A. -8kPa
B. -4kPa
C. 0kPa
D. 4kPa
E. 8kPa

Answer 7

B -4kPa

Intrapleural pressure depends on the ventilation phase, atmospheric pressure, and the volume of the intrapleural cavity. At end expiration there is a negative intrapleural pressure of -4kPa below atmospheric pressure. This is due to the recoil of the chest and lungs away from each other.

Question 8

You are asked by your consultant to do a presentation at your weekly departmental educational meeting. Your heart sinks when they tell you that the theme is ‘tumours of the mediastinum’.

Which ONE of the following is the single most common anterior mediastinal tumour ?
A. Lymphangioma
B. Parathyroid adenoma
C. Seminoma
D. Teratoma
E. Thymoma

Answer 8

D. Thymoma

The mediastinum is an anatomical space between the lungs that houses: thymus, heart, large blood vessels, lymph nodes, nerves, & parts of the oesophagus & trachea. Mediastinal boundaries are anteriorly: sternum; posteriorly: thoracic vertebrae; superiorly: thoracic inlet; inferiorly: diaphragm; laterally: pericardial & mediastinal pleurae. It has anterior, middle, & posterior compartments.

Mediastinal masses range from benign to malignant. 50% of mediastinal masses are in the anterior compartment, the most common of which are: thymoma, teratoma, thyroid goitre & lymphoma.

Thymomas represent approximately 20% of anterior mediastinal tumours. Teratomas and seminomas are both germ cell tumours and together account for approximately 15% of tumours. Lymphangiomas and parathyroid adenomas are rare.

Thymomas typically occur in adults >40yrs, & affect males & females equally. 30% - 50% of patients with a thymoma have myasthenia gravis, whereas 10–15% of patients with myasthenia gravis have a thymoma

Question 9

A 55 year old presented with uveitis and fatigue. A CT chest showed bilateral hilar lymphadenopathy. EBUS-TBNA showed non-caseating granulomas. His pulmonary function tests were normal. Topical steroids were given for his uveitis. At follow-up he complains of episodes of palpitations. He has had one episode where he briefly lost consciousness but he did not seek medical attention. He feels well today.

Which ONE of the following is the most appropriate action?
A. Cardiac MRI
B. Coronary angiogram
C. Reassure and continue 6 monthly review
D. Refer for cardiac biopsy
E. Start prednisolone 60mg OD

Answer 9

A. Cardiac MRI

Cardiac sarcoidosis can lead to arrhythmias including complete heart block and cardiac failure. An ECG and echocardiogram would be useful initial tests, along with a Holter monitor but would not be diagnostic. Biopsy would provide a definitive diagnosis but is invasive and has significant risks. It would not be justified prior to non-invasive options. Diagnosis is often achieved by cardiac MRI so this is the next step.

The incidence of cardiac #sarcoidosis has been increasingly recognised, with a large 25-year Finnish cohort study reporting an exponential increase from 1988 to 2012, with a prevalence of 2.2 per 100,000 adults (https://t.co/VdBS1woHte).

Among patients with systemic #sarcoidosis ~5% will have clinically manifest cardiac sarcoidosis, but 25% may have evidence of cardiac involvement on autopsy or imaging studies.

Question 10

A 58 year old woman is seen in clinic with breathlessness. She is a non-smoker but had significant second hand smoke exposure from age 18-40. She has had 2 pneumothoraces and required VATS pleurodesis with apical bullectomy 2 years ago. Her daughter recently had a pneumothorax and the patient is concerned that her lung condition is heritable. Her CT scan shows panlobular emphysema with basal predominance.

Which ONE of the following is the most useful investigation?
A. Alpha-1-antitrypsin phenotype (AAT)
B. Beryllium Lymphocyte Proliferation Test (BeLPT)
C. Human Leukocyte Antigen B27 (HLA-B27)
D. Serum Angiotensin Converting Enzyme (sACE)
E. Serum Vascular Endothelial Growth Factor- D (VEGF-D)

Answer 10

A. Alpha-1-antitrypsin phenotype (AAT)

Alpha-1-antitrypsin (AAT) deficiency is a genetic disorder that produces inactive/defective AAT due to mutations in the SERPINA1 gene. The disease is associated with decreased activity of AAT in the lungs and deposition of excessive defective AAT protein in the liver. Approx 1–5% of patients with diagnosed COPD are estimated to have AAT deficiency.

AAT deficiency can present with liver dysfunction from childhood & with COPD from 30 years. People with AAT deficiency are also at increased risk for panniculitis (migratory, inflammatory, tender skin nodules which may ulcerate).

Phenotypic expression varies within & between families with AAT deficiency. In adults, smoking is the major factor in accelerating the development of COPD; non-smokers may have a normal life span, but can also develop lung &/or liver disease.

Diagnosis of AAT deficiency is through demonstration of low serum concentration of AAT & protease inhibitor (PI) typing. The most common (normal) allele is PIM, the most common pathogenic allele is PIZ.

Most patients with AAT deficiency have panlobular emphysema, typically with basal predominance. However patients with a less severe PI allele combination (i.e. PISZ) have more apical involvement than those with the most severe (PIZZ)

Question 11

A patient states that since moving from Norfolk to London their asthma has been much worse. They have more daily symptoms and exacerbations, and it does not seem to be seasonal. They are concerned that the higher exposure to air pollution is to blame and ask for your advice on what to do to reduce exposure.

Which ONE of the following is the most accurate statement?
A. Cloth face masks remove >20% particulate matter
B. Driving to work with the windows closed will reduce your exposure compared to walking or cycling
C. Segregated and on-road bike lanes have the same level of pollution
D. The protective effects of exercise outweigh risks from exposure
E. Using an Ecodesign woodburning stove to heat your home will avoid indoor pollution

Answer 11

D. The protective effects of exercise outweigh risks from exposure

Air Pollution is particles & gases harmful to human health. We particularly worry about PM2.5 NO2 & ground level O3. Air Pollution affects every organ & all ages. It affects everyone, but not equally, causing health inequalities. Air Pollution from burning Fossil Fuels like coal & diesel is responsible for about 1 in 5 deaths worldwide.

Clinicians must be able to advise patients on how to reduce their exposure and contribution to air pollution. Although patients with Respiratory disease should be advised to avoid strenuous exercise at high risk times of high pollution days, overall exercise has so many health benefits that these outweigh the risks even for those living in high pollution areas.

Question 12

A 51 year old man is referred to the sleep clinic. He has recently started a new relationship and his partner has noticed loud snoring, and witnessed apnoeas. He is also sleepy during the day. His STOP BANG score is 5. His Epworth Sleepiness Scale is 16/24. His BMI is 34kg/m^2. An overnight oximetry is arranged. The oximetry trace shows a saw tooth pattern of desaturations with associated rises in pulse rate.

Which ONE of the following is the most appropriate next step in management?
A. Advice to lose weight
B. Mandibular advancement device
C. Refer for uvulopalatoplasty
D. Trial of CPAP
E. Trial of NIV

Answer 12

D. Trial of CPAP

CPAP is the first-line treatment option for patients with moderate to severe OSAS. Weight loss, in some cases, can reduce the need for CPAP but will take time. This patient is symptomatic and the severity of OSAS warrants CPAP as first-line treatment. Snoring or mild OSA could be treated by mandibular advancement splint, but not severe OSA with significant sleepiness as in this case. There is no evidence of a need for NIV, but it would be useful to see an ABG and TCO2 trace.

Question 13

A 48 year old who had a bilateral lung transplant 6 years ago for emphysema associated with inhaled drug use in his youth, has progressive breathlessness. He has no chest pain, minimal sputum production, no fevers and weight has remained stable. Serial spirometry over the last 4 months has shown a decline, falling more rapidly in the last 2 weeks. FEV1 has fallen from 3.6L to 2.3L. FVC has fallen from 4.4L to 4.0L.

What is the single most likely cause of lung function decline?
A. Acute rejection
B. Chronic Lung Allograft Dysfunction (CLAD)
C. Cytomegalovirus reactivation
D. Post-transplant Lymphoproliferative Disease (PTLD)
E. Restrictive allograft syndrome (RAS)

Answer 13

B. Chronic Lung Allograft Dysfunction (CLAD)

These terms may be unfamiliar but you can arrive at the correct answer by a process of elimination. The timeline is not right for acute rejection or CMV reactivation. Symptoms other than progressive breathlessness would also be expected. PTLD is the most common cancer in the first year post-transplant but remains a risk later. Late PTLD is more commonly extra-thoracic, and even if thoracic would be unlikely to present with breathlessness. This leaves CLAD or RAS.
The lung function results show an obstructive pattern. RAS is a subtype of CLAD but would have a restrictive pattern on spirometry.

Rejection can happen at any time after lung transplantation. Around 1/3 of patients will develop ‘acute rejection’ in the 1st year.
This is often an immune reaction to the donor tissue, & may be T-cell mediated &/or
antibody-mediated. Lung transplant recipients with acute rejection may be asymptomatic or may have non-specific symptoms eg dyspnea, cough, sputum production, & low-grade fever. Severity is graded pathologically. It’s essential to detect acute cellular rejection in lung transplant recipients as it is a major risk for chronic rejection. Acute cellular rejection grades A2 or higher require treatment, generally with pulsed IVMP.

Question 14

You attend a chronic breathlessness specialist service and discuss the complex nature of the sensation, including physiological, psychosocial, social and environmental factors. Your supervisor asks about your knowledge of neural pathways implicated in breathlessness.

Which one of the following areas of the brain is most associated with the sensation of breathlessness?
A. Cerebellar vermis
B. Hippocampus
C. Insular cortex
D. Pineal gland
E. Prefrontal Cortex

Answer 14

C. Insular cortex

Breathlessness is a complex symptom with many contributors. These include: chest wall mechanoreceptors, chemoreceptors, sensory afferents in the airways & parenchyma, (RARs & SARs), vagal C fibres & central nervous system pathways

Research using functional neuroimaging (fMRI) has identified a consistent set of brain areas that are associated with breathlessness, in both patients and in experimentally induced air hunger. These areas include the insular cortex, cingulate and sensory cortices, the amygdala and the periaqueductal gray matter. Breathlessness, just like pain, is not a purely somatic (physical) phenomenon, but arises from inferences made by the brain’s integration of expectations, emotions and
sensory inputs.

Question 15

A new biomarker blood test, LYCA1, has been developed to identify Idiopathic Pulmonary Fibrosis (IPF) in the hope of predicting who will respond to anti-fibrotic medications nintadenib & pirfenidone. In a study of 100 patients with probable UIP pattern or indeterminate for UIP pattern on CT scan 65 patients had positive LYCA1 tests, and 50 of those had IPF on biopsy. There were also 20 patients who had IPF on biopsy but who had negative LYCA1 blood tests.

Which one of the following is most accurate in relation to the LYCA1 test?
A. The false positive rate was 30%
B. The true negative rate was 20%
C. The prevalence of IPF in this study population was 65%
D. The sensitivity was 71%
E. The specificity was 56%

Answer 15

D. The sensitivity was 71%

The best way to approach this sort of question is to construct a 2x2 table. You can then answer questions on true and false positive/negative rates, sensitivity, specificity, positive predictive value and negative predictive value.

The study had 100 participants, and 70 (50+20) of them had IPF according to the gold standard test of lung biopsy. The prevalence was therefore 70%.

65 patients had a positive LYCA1 test & 50 of those had IPF on biopsy, so 15 had a false positive test. Sensitivity is the % of people who test positive, among those who have the disease: 50/(50+20) = 71%. A sensitive test helps rule out a disease when the test is negative - if LYCA1 is negative we can be quite confident they don’t have IPF. The specificity of a test is the % of people who test negative among all those who do not have that disease: 15/(15+15) =50%. A specific test helps rule a disease in when positive - if LYCA1 is positive we can’t be very confident they have IPF. The positive predictive value of the LYCA1 test is the probability that following a positive test result, that individual will truly have IPF: 50/(50+15)=77%. The negative predictive value of the LYCA1 test is the probability that following a negative test result, that individual will truly not have IPF: 15/(15+20)=43%.

The PPV & NPV of a test are affected by prevalence. As prevalence increases, PPV also increases but NPV decreases. Similarly, as prevalence decreases PPV decreases while NPV increases.

Question 16

A 24 year old has recurrent community acquired pneumonia. He also has a history of otitis media and immune thrombocytopenia. There is no relevant family history. A CT scan reveals mild lower lobe bronchiectasis. Blood tests show Hb 130g/dL, WCC 8.3x10^9/L, MCV 98fL, Plt 75x10^9/L, IgG 340 (600-1600mg/dL), IgA 75 (80-300mg/dL), IgM 40 (40-250mg/dL). HIV, Hepatitis B and C are negative. Tetanus antibody titre 0.005 (0.01-0.15 IU/mL), HiB antibody titre 0.2 (>1.0mg/L).

Which of the following is the single most likely diagnosis?
A. Common Variable Immunodeficiency
B. Pearson Syndrome
C. Severe Combined Immunodeficiency
D. Selective IgA deficiency
E. X-linked agammaglobulinaemia

Answer 16

A. Common Variable Immunodeficiency

This patient has typical features of CVID, with recurrent bacterial infections including pneumonia and otitis media, chronic lung disease in the form of bronchiectasis, and an autoimmune condition (present in 25% cases), in this case immune thrombocytopenia. Blood tests show low levels of immunoglobulin G (IgG) and IgA, as well as IgM in some patients. IgG levels are generally <400, with more severe phenotypes <100mg/dL. There is also a lack of antibody response to vaccinations. The other answers are all other immunodeficiency syndromes, which may have recurrent infections, but not these blood results, except Pearson syndrome, a rare mitochondrial disorder leading to bone marrow failure.

CVID is a primary immune deficiency disease caused by a variety of different genetic abnormalities that result in disorders of B-cell differentiation & maturation with dysfunctional antibody production. CVID affects 1/25,000 - 50,000 varying across populations/regions. Most people present in their 20-30s but it can affect any age. Late diagnosis is common. Most cases arise randomly, but 5% - 25% cases are inherited (AR or AD). Interestingly the gut #microbiome has been suggested as a contributor to CVID as a mechanism through which epigenetic factors influence the interplay of genes, environmental factors, & dysregulation of immune cells. Clinical features of CVID are recurrent bacterial infections (less so viruses), particularly chest, sinonasal, ears. GI infection/ inflammation is also common. 20% have an autoimmune cndition eg ITP, AIHA. Splenomegaly & lymphadenopathy occur. Some people with CVID are more prone to developing some cancers eg lymphoma, skin cancer & gastric cancer (almost 50x risk in patients with CVID). Lung involvement in CVID is recognised, including bronchiectasis, OP & ILD. A number of ILDs have been described including LIP & GLILD.

Question 17

A 61 year old is referred to the Lung Cancer pathway after a CT incidentally shows a 6mm left perifissural lung nodule. The patient has a cough which has been unchanged for 2 years. They have no other symptoms. They have COPD, OSA and hypertension. They are tobacco dependant, smoking 15 cigarettes a day at present. There is no family history of cancer.

Which ONE of the following is the most appropiate management plan?
A. No follow up
B. CT 8 weeks
C. CT 3 months
D. CT 12 months
E. FDG-PET scan

Answer 17

C. CT 3 months

When managing pulmonary nodules, guidelines seek to balance avoiding overinvestigatoin of likely benign lesions, and not missing early lung cancers at a point where they can be radically treated. Solid nodules which are 5-6mm or <80mm^3 if volumetry is available, are low risk and should be scanned until 12 months. Any solid nodule equal to or more than 6mm and a Brock score should be calculated to determine if a 3 month interval CT or a PET is recommended as the next step. In this case Brock <10% means 3 month CT is recommended. Download the BTS /Cancer Research app to support your revision and daily practice.

Question 18

A 31 year old previously well man is admitted with fevers, weakness, chest and neck pain. Observations are T 38.3 SpO2 95% on air, RR 20, HR 96, BP 110/70.Blood tests show: CRP 460, Creat 380, Ur 14, WCC 6.8, Neut 6.8, Plt 80, HIV negative, EBV/hepatitis screen –ve. Blood film shows left shifted and toxic neutrophila with thrombocytopenia. He has a CT chest and neck. A right internal jugular thrombus is seen. Multiple cavitatory lung lesions are seen on CT.

Which ONE of the following is the most likely organism isolated from blood cultures?
A. Acinobacter baumannii
B. Fusobacterium necrophorum
C. Klebsiella pneumoniae
D. Mycobacterium Tuberculosis
E. Streptococcus anginosus

Answer 18

B. Fusobacterium necrophorum

This is classsic Lemierre’s syndrome; a combination of bacteremia, internal jugular vein thrombophlebitis, and metastatic septic emboli secondary to acute pharyngeal infections (pharygitis or tonsillitis). It often occurs in otherwise healthy young people. The most common causative organism is Fusobacterium necrophorum, followed by Fusobacterium nucleatum and anaerobic bacteria such as streptococci, staphylococci, and Klebsiella pneumoniae. The symptoms may be misdiagnosed as a viral infection. It’s essential to recognise as the patient needs prolonged iv antibiotics. Anticoagulation is rarely required.

Lemierre’s syndrome is a rare disease with most recent estimates of incidence of approx 1per million/persons/year. Rates increased alongside decreased use of antibiotics for sore throats. It is easily misdiagnosed. Neck (not just throat) pain/tenderness should ring alarm bells, as should arthralgia & chest symptoms incl pain, breathlessness & haemoptysis. nvestigations help. Very high CRP is common. Subclinical hyperbilirubinemia occurs in up to 50% & mild DIC with thrombocytopenia in up to 23%.

F. necrophorum is usually susceptible to penicillin, cephalosporins, metro, clinda, tetracyclines &chloramphenicol. β-lactamase-producing strains are rare. Metro has good tissue penetration & should be used with penicillin.

Question 19

A 35 year old tobacco dependant woman with no past medical history presents with severe fatigue. On assessment in the ambulatory care unit she is found to be hyponatraemic with a sodium of 116mmol/L. She is euvolemic. She has serum osmolality 251, urine osmolality 902, urinary sodium 158mmol/L. She requires admission for hypertonic saline and then tolvaptan before sodium levels are in a safe range. A CT Chest shows a lung mass, and she goes on to have an FDG CT-PET scan. This shows an avid left sided mass as well as uptake in multiple lymph nodes (incl cervical & axillary) & bones (rib & vertebral body). It is noted in the MDT that she had a normal X-ray of the chest 6 months ago.

What is the single most likely diagnosis?
A. Ewing sarcoma
B. Large cell neuroendocrine tumour
C. Small cell lung cancer
D. Squamous cell lung cancer
E. Transitional cell carcinoma of the bladder

Answer 19

C. Small cell lung cancer

The blood and urine tests show that this patient has SIADH. Several cancers can cause SIADH, including small cell lung cancer, transitional cell carcinoma of the bladder, mesothelioma, endometrial cancer, prostate cancer, lymphoma, thymoma, Ewing sarcoma, brain tumours and cancers of the GI tract. The rapid progression and the pattern of uptake on PET in this young patient point to small cell lung cancer. Squamous cell carcinoma can cause hypercalcaemia as a paraneoplastic phenomenon. and neuroendocrine cancers of the lung may cause Cushings or carcinoid syndrome.

Small Cell Lung Cancer (SCLC) is the most common subtype to be associated with paraneoplastic syndromes. SIADH in SCLC is due to ectopic production of ADH. SCLC can also cause Cushing’s syndrome due to ectopic ACTH release. Approx 10-45% of patients with SCLC having SIADH & SCLC accounts for most cases of paraneoplastic SIADH. Other tumours include bladder, endometrial, prostate, GI, thymoma, mesothelioma, lymphoma, Ewing sarcoma & brain tumours

Question 20

A 68-year-old woman with lifelong severe asthma is in clinic. She has fixed airflow obstruction, but a confirmed eosinophilic asthma diagnosis, with excellent adherence to high dose ICS/LABA and peak blood eosinophils of 0.4 in the last year with a FeNO of 48. She is not sensitized to any perennial aeroallergens, has no pets and is a never smoker. In the last 12 months she has had 4 exacerbations requiring oral steroids, one of which necessitated hospital admission.

Which of the following biologics would be available for her, according to NICE guidelines?

A. Mepolizumab, Reslizumab & Benralizumab​
B. Mepolizumab, Reslizumab, Benralizumab & Dupilumab​
C. Mepolizumab, Reslizumab, Benralizumab, Dupilumab & Tezepelumab​
D. Omalizumab, Mepolizumab, Benralizumab & Dupilumab​
E. Omalizumab, Mepolizumab, Benralizumab, Reslizumab & Dupilumab​

Answer 20

A . Mepolizumab, Reslizumab & Benralizumab

This patient has a confirmed diagnosis of eosinophilia asthma, with good adherence to appropriate inhaled therapies. Her asthma is poorly controlled despite this, so biologics should be considered. There are a growing number of drugs available, with slightly different indications and licences. Mepo, Resli and Benra are all NICE approved for refractory severe eosinophilic asthma. Dupilumab would be available if the patient was not suitable or had failed the others, but would not be available to her now. Tezepelumab is not yet NICE approved. Omaluzimab is for severe allergic IgE-mediated asthma.

Omaluzimab (Xolair) was the first licenced biologic for asthma, in 2005. It binds to free circulating IgE, inhibiting attachment to its receptor, reducing downstream inflammatory responses. Omaluzimab is available in the UK to people with severe allergic asthma, which means a positive skin prick test or in vitro reactivity to a perennial aeroallergen, & ≥4 severe exacerbations in the last year (or the need for continuous oral corticosteroids).

In 2015 Mepoluzimab was licenced for severe eosinophilic asthma. It’s an anti IL-5 MAb. IL-5 is crucial for development, migration & survival of eosinophils. Mepo reduces blood & sputum eos numbers. Mepoluzimab is available in the UK to people with severe eosinophilic asthma, as well as those with EGPA or Chronic Rhinosinusitis with Nasal Polyps. In #asthma, patients need eos ≥300 & 4 severe exacerbations, or eos ≥400 & 3 severe exacerbations in 12 months.

Reslizumab is a recombinant humanised IgG4 mAb that, like mepolizumab, binds IL-5. It is intravenous, not subcut like the others, & was licenced in 2017. Reslizumab is available to people with severe eosinophilic #asthma ie eos ≥400 & 3 severe exacerbations in 12 months.

Benraluzimab ligates the α subunit of the IL-5 receptor, expressed on eosinophils & basophils inducing antibody-dependent cell mediated cytotoxicity & apoptosis. Benraluzimab is available to people with severe eosinophilic #asthma ie eos ≥400 & 3 severe exacerbations in 12 months. Benraluzimab induces almost total eosinopenia - eos rapidly fall within 4hr of the first dose & are usually undetectable after.

Dupilumab is a mAb targeted against the α subunit of the IL-4 receptor, a ligand for both IL-4 and IL-13. It was initially rejected by
NICE but licenced in 2021 for asthma patients with type 2 inflammation. Dupilumab is available in the UK for severe asthma with eos ≥400 & FeNO ≥25ppb & 4 exacerbations in 12 months. Importantly patients have to have failed or not be eligible for mepo/resli/benra to get Dupi according to
NICE guidelines.

Tezepelumab is a mAb targeting the alarmin TSLP, which is released by epithelial cells in response to pro-inflammatory stimuli. It sits higher up the inflammatory cascade than IL-5, IL-4 & IL-13 so blocking it may have broader effects. The Phase 3 trial of Tezepelumab was published in NEJM in 2021 but it is not
NICE approved & therefore not available on the NHS in the UK (as of Feb 2023).

Question 21

A 31-year-old woman with recurrent pneumothoraces is diagnosed with LAM (Lymphangioleiomyomatosis) on the basis of a characteristic pattern of multiple thin walled cysts on CT, in addition to a renal angiomyolipoma. She also has a raised serum VEGF-D level. She has evidence of declining lung function and is referred to the National LAM centre, where she is offered drug treatment with sirolimus as part of a clinical trial.

Which ONE of the following is the single best description of the mechanism of action of sirolimus?
A. Calcineurin inhibitor​
B. EGFR inhibitor
C. Interleukin 6 inhibitor
D. mTOR inhibitor
E. ​Purine synthesis inhibitor

Answer 21

D. mTOR inhibitor

Sirolimus (also known as rapamycin) is an mTOR inhibitor, used in the treatment of LAM and as an immunosuppressive agent in some post-transplant regimes. Calcineurin inhibitors include tacrolimus and ciclosporin, used as immunosuppression post-transplant and in autoimmune disease such as SLE, myositis, and some forms of ILD. EGFR inhibitors can be tyrosine kinase inhibitors (erlotinib, gefitinib used to treat NSCLC) or monoclonal antibodies (cetuximab used to treat head and neck cancers). IL6 inhibitors include Tociluzimab, used to treat rheumatological conditions and, more recently, severe COVID19 pneumonia. Purine synthesis inhibitors include azathioprine and mycophenolate mofetil, used to treat some ILDs.

LAM ia a rare, multisystem disease predominantly affecting young & middle-aged women. It presents with breathlessness, pneumothorax, chylothorax, or with characteristic imaging findings (cysts). LAM occurs sporadically (S-LAM) or in combination with tuberous sclerosis complex (TSC-LAM), an inherited condition. In both cases, abnormal LAM cells circulate in blood & lymphatic vessels & deposit in the lungs, causing cysts & lung damage. LAM cells have inactivating mutations in TSC proteins that result in mammalian target of rapamycin complex 1 (mTORC1) pathway-driven cellular proliferation, migration, & survival contributing to the uncontrolled proliferation of LAM cells.

Sirolimus, a macrolide produced by Streptomyces hygroscopicus also known as rapamycin, binds to FK-binding protein-12 (FKBP-12) to form a complex (SRL/FKBP12) that binds to & inhibits the activation of mTORC1. The landmark MILES study showed that Sirolimus stabilized lung function, reduced serum VEGF-D levels, & was associated with a reduction in symptoms & improvement in quality of life in LAM.

Question 22

You are checking results following a pleural clinic. One of the patients you saw does not yet have a diagnosis, presenting with symptoms of fatigue, weight loss and night sweats. Imaging showed a unilateral effusion with pleural enhancement on CT. Pleural fluid results reveal an exudative effusion with a protein of 40g/dL, pH 7.4, glucose 4.1mmol/L, LDH 550 IU/L, adenosine deaminase 35 U/L. Cytology reveals a lymphocytic effusion. No malignant cells or organisms are seen.

What is the single most likely diagnosis
A. Complicated parapneumonic effusion
B. Lymphoma
C. Mesothelioma
D. Rheumatoid arthritis
E. Tuberculosis

Answer 22

E. Tuberculosis
There are several differentials for a lymphocytic predominant, exudative effusion. In this case the glucose is low, LDH is high but not very high, and protein is very high. Alongside the clinical features of fatigue, weight loss and most importantly sweats, this makes TB most likely. The ADA in this case is a little high. In TB you would usually expect it to be >40U/L but it can be low in older patients and those who are critically ill. Some demographics would of course be helpful along with a travel history. If you thought it was mesothelioma this is a reasonable answer and arguably also correct, but sweats are uncommon and LDH would typically be higher.

Question 23

You are on your ICU rotation and ask for advice about a patient who you are struggling to adequately oxygenate despite altering ventilator settings. You discuss factors affecting ventilation and perfusion with a Consultant which leads to a discussion on alveolar dead space.

Which one of the following would increase alveolar dead-space ?
A. Increasing PEEP
B. Pneumothorax
C. Putting patient head down 45 degrees
D. Reducing tidal volume
E. Severe mitral stenosis

Answer 23

A. Increasing PEEP

Dead space is the volume of a breath that does not participate in gas exchange: ventilation without perfusion. Alveolar dead space is the volume of gas within unperfused alveoli, usually negligible in a healthy awake person. When a person is ventilated with positive pressure blood vessels can become completely collapsed by alveolar pressure and blood does not flow through these regions (alveolar dead space). Reducing tidal volume could increase alveolar dead space but this is dependant on other factors such as respiratory rate. Mitral stenosis increases venous pressure, reducing the tendency to develop dead space. Changing position from upright to supine and pneumothorax would decrease the likelihood of deadspace. Head down positioning has only a negligible effect.

Question 24

A 41 year old in her 23rd week of pregnancy is seen in the acute medical unit with a 2 day history of increased breathlessness. She has no past medical history. On examination chest is clear to auscultation although breath sounds are reduced at the bases. Both ankles are swollen but the right calf is also swollen and warm. Her chest x-ray is normal.
Observations: P 128/min BP 100/70 RR 26 SpO2 94% on air T 36.7.

What is the single most appropriate next investigation?
A. Arterial blood gas
B. Compression ultrasonography of the legs
C. CT pulmonary angiogram
D. D-dimer
E. Ventilation / perfusion scintigraphy

Answer 24

B. Compression Ultrasonography of the legs

The suspected diagnosis is PE and DVT given the examination findings. An ABG will not help to confirm or refute the diagnosis and with SpO2 in the target range will add little. CTPA and VQ scan would both be reasonable but would expose the mother and foetus to ionising radiation. We can avoid this by first performing compression ultrasonography of the legs. If a DVT is confirmed then anticoagulation can be initiated without the need to confirm PE on imaging.

D-dimer would not help in this case as we have a high clinical suspicion of PE so even if low we will need to perform other tests. If D-dimer is high, this will also not help, it is often raised in pregnancy.

Question 25

A 46 year old is seen in clinic due to progressive breathlessness over months. He has a past history of alcohol dependance and cirrhosis Child Pugh B. He has been abstinent from alcohol for 2 weeks. He is tobacco dependant, smoking 10 cigarettes a day. He reports limited exercise tolerance and a blue discoloration of his fingers which is improved, along with his breathlessness, if he lies down.

On examination he has central cyanosis and clubbing of the fingers and toes. He has multiple spider naevi over the upper chest and back. Heart sounds are normal. There is a mild end expiratory wheeze. There is minimal ascites.

Observations in clinic: P 81/min, BP 115/75, RR 22, SpO2 87% on air

Spirometry: FEV1 2.7L (72%, Z score -2.2) FVC 4.1L (89%, Z score -1.07) Ratio 0.65 (Z score -2.16)

What is the single most likely diagnosis?
A. Alpha-1-antitrypsin deficiency
B. Chronic thromboembolic disease
C. Hepatopulmonary syndrome
D. Portopulmonary hypertension
E. Systemic sclerosis

Answer 25

C. Hepatopulmonary syndrome

This patient is breathless in the context of chronic liver disease. The history is suggestive of platypnoea and orthodeoxia which are signs of hepatopulmonary syndrome. On examination there are no signs of systemic sclerosis. The clubbing of fingers and toes also strongly suggests hepatopulmonary syndrome. You would not expect clubbing in alpha-1-antitrypsin deficiency. None of the information provided would allow you to confidently diagnose chronic thromboembolic disease and it would not explain the examination findings.

Portopulmonary syndrome is characterised by pulmonary hypertension which there is no evidence of in this case. The spirometry is obstructive so the patient also has COPD due to tobacco dependance but it is not the primary issue.

Question 26

A 54 year old woman presents with arm twitching, headaches and episodic word finding difficulties. She is diagnosed with metastatic small call lung cancer T2a N3 M1c. PDL1 is 3%. On CT head there are multiple brain metastases in all lobes. A total of 12 brain metastases are identified, the largest 31mm diameter. There is significant surrounding oedema. The patient has a good response to high dose dexamethasone with resolution of most symptoms.

What is the single best treatment for the brain metastases?
A. Gefitinib
B. Neurosurgical resection
C. Pembroluzimab
D. Stereotactic radiosurgery
E. Whole brain radiotherapy

Answer 26

E. Whole Brain Radiotherapy

This question focuses on the treatment of symptomatic small cell lung cancer brain metastases. The patient should be offered whole brain irradiation, unless they have a poor performance status or mental impairment. Gefitinib and Pembroluzimab are more commonly used to treat non-small cell lung cancers. Gefitinib has been used to treat small cell lung cancer but has poor blood brain barrier penetration. In small cell lung cancer Pembroluzimab is only approved if there is disease progression after platinum-based chemotherapy and at least 1 other prior line of therapy.

Neurosurgical resection is unlikely to be offered given the number of widespread brain metastases. Similarly stereotactic radiotherapy is usually reserved for <12 brain metastases, although all cases should go through a neuro-oncology MDM as there may be options.

Question 27

A 24 year old attends the emergency department with a severe asthma attack. He is given nebulisers and iv hydrocortisone but remains hypoxaemic and is intubated. He spends 3 days on ICU and is then stepped down to a ward. He is seen by a specialist Respiratory nurse who makes a comprehensive assessment and presents his case at the weekly integrated care MDM due to concern about ongoing risk.

Which one of the following is a recognised risk factor for fatal asthma attack in the future?
A. Anxiety treated with sertraline and cognitive behavioural therapy
B. Eosinophil count >0.3 at diagnosis
C. Personalised asthma action plan issued over 12 months ago
D. Seafood allergy
E. Sensitisation to house dust mite

Answer 27

D. Seafood allergy

The National Review of Asthma Deaths report in 2015 and data since has identified a number of factors which predict poor outcomes, and specifically mortality, in asthma. The most important is over-reliance on short acting beta agonists and inadequate use of inhaled corticosteroids. Other risk factors include: poor inhaler technique; previous hospital admission (especially to ICU); lack of a personalised asthma action plan; exposure to cigarette smoke; psychosocial factors (treated anxiety is common and not a significant psychosocial factor); and food allergy. Eosinophil levels >0.4 have been associated with higher risk of admission and asthma mortality. House dust mite sensitisation confers a higher risk of having asthma in children, but is not associated with asthma mortality.

Question 28

A 29-year-old from Lesotho, now living in London, has had loose stools, low grade fevers, and weight loss over the last 8 weeks. He left Lesotho and stayed for a period of time in South Africa where he received treatment for smear-positive pulmonary TB with RHZE. He started to gain weight, but only completed 1 months treatment before he left South Africa. When seen in hospital in London he has has been off treatment for 10 weeks. On examination he is cachectic with BMI 18. In ED he has a temperature of 37.6. Chest xray is abnormal and he goes on to have a CT scan. A HIV test is negative. Sputum smear and PCR have been requested
but results are not yet available. CT shows multiple cavitating nodules in all lobes.

Which one of the following is the most appropriate plan?
A. Await results of molecular susceptibility testing
B. Complete 2RHZE/4HR
C. Extend treatment to 2HRZE/10HR
D. Initiate 2HRZES/1HRZE/5HRE
E. Treat with 8Km-Bdp-Lzd-Mfx/12Bdp-Lzd-Mfx

Answer 28

A. Await results of molecular susceptibility testing

This patient has Mycobacterium Tuberculosis and has defaulted on treatment, completing only 1 month of a standard regime. The concern is therefore that the TB could now have developed resistance, as previous incomplete treatment is a strong risk factor. Using rapid molecular tests MDR can be confirmed or excluded within 1–2 days. Therefore waiting for these results and planning a treatment regime according to drug susceptibilities is recommended. The patient is sick but not so sick that treatment can’t wait a few days. If rapid drug susceptibility tests are not available, or treatment cannot wait, then empirical treatment should be started based on the likelihood of MDR-TB.

Question 29

A 34 year old man complains of sleepiness worsening over 4 years. He goes to bed at 10pm and has no problems falling asleep at night but often wakes suddenly as he is falling asleep, with a feeling that he is falling from a great height. He also sometimes wakes during the night following nightmares in which he is tied down and can’t escape. In the morning he wakes with an alarm at 7am and does not feel refreshed. He thinks he is a mild snorer, although sleeps alone. He works as a graphic designer and has fallen asleep at work, including in an important meeting, despite consuming 6 cups of coffee during the day. On examination chest is clear and heart sounds are normal. He has a BMI of 29kgm^3, neck circumference is 40cm, Mallampati score 1.

Pulse 77bpm, BP 125/77, RR 12 SpO2 98% on air.

Which one of the following is the most likely investigation result?
A. Actigraphy showing sleep efficiency of 84%
B. Limited polysomnography showing transition to REM within 10mins
C. Multiple sleep latency test with sleep latency average 9 mins
D. Overnight oximetry showing ODI 4
E. CSF hypocretin concentration 400pg/mL

Answer 29

B. Limited polysomnography showing transition to REM within 10mins

The history is suggestive of narcolepsy, specifically a young person with sleepiness with no difficulty falling asleep, hypnogognic phenomena, sleep paralysis and uncontrollable napping even in situations of high stress, with no effect of high caffeine intake. There is no suggestion of cataplexy but not all people with narcolepsy experience cataplexy.

OSA would be the main differential, especilally in a snorer, but BMI, neck circumference and Mallampati are not suggestive. All the investigations listed have normal results other than the polysomnography showing rapid transition to REM.

Question 30

A 58 year old patient with COPD brings a newspaper cutting to clinic which describes the life changing impact of bronchoscopic valves for a patient in the US. They ask whether this treatment would be available for them. The patient is mMRC score 3 and leaves the house once a week to visit friends. They have had 3 hospital admissions in 12 months with exacerbations. They are frustrated with their declining quality of life, particularly as they perceive little benefit from stopping smoking crack cocaine 10 years ago, and tobacco 9 months ago. Past medical history includes benign prostatic hypertrophy and anxiety.
Medications include: Trelegy Ellipta T OD, carbocisteine 750mg BD, Azithromycin 500mg Mon/Wed/Fri. They use ambulatory oxygen 2L/min). A recent echocardiogram showed mildly dilated RV but RVSP in normal range.

CT scan shows emphysema in a predominantly paraseptal pattern. Lung function tests 3 months ago showed: FEV1 0.8L (23%), FVC 3.2L (73%), ratio 0.25, no significant reversibility, TLCO 54%, KCO 60%, TLC 170%, RV/TLC 65%. A recent blood gas on air showed: pO2 7.8kpa, pCO2 5.7kPa, pH 7.39 SpO2 88%, COHb 1.3%.

Which one of the following is the most appropriate recommendation?
A. Bronchoscopic valves
B. Bullectomy
C. Lung transplantation
D. Lung volume reduction surgery
E. Pulmonary rehabilitation

Answer 30

E. Pulmonary rehabilitation

This patient has very severe COPD with significant airflow obstruction, low TLCO, hyperinflation, a significant symptom burden and a high exacerbation rate. They have stopped smoking, and are on triple inhaled therapy and ambulatory oxygen. They do not meet criteria for LTOT on the basis of the information required. In terms of high impact interventions for COPD we would want to ensure they were offered vaccination against flu, COVID19 and pneumonia. We would recommend Pulmonary Rehabilitation if not done in the last year.
We would consider additional interventions such as LVRS, bronchoscopic valves or transplant, but PR would be essential before asssessment for any of these interventions.

Question 31

A 56 year old is seen in the Respiratory outpatient clinic following investigation for fatigue and chronic cough. They are not breathless except on strenuous activity, and have had no documented fevers. They have lost 8kg in weight over 6 months.

Serial CT scans have shown progressive nodular change and consolidation. A representative slice from the recent CT scan is shown below. 2 sputum samples, a month apart, were AFB negative but have cultured M avium complex, with a further sample negative at 8 weeks. Following a shared decision making discussion the patient wishes to proceed with treatment.

Which one of the following is the single best recommended regime?
A. Clarithromycin, clofazimine, linezolid, moxifloxacin and nebulised amikacin for minimum 12 months
B. Rifampicin, ethambutol, azithromycin and Moxifloxacin for minimum 18 months
C. Rifampicin, ethambutol and azithromycin for minimum 24 months
D. Rifampicin, ethambutol and clarithromycin for minimum 12 months after culture conversion
E. Rifampicin, ethambutol, isoniazid and nebulised amikacin for minimum 12 months after culture conversion

Answer 31

D. Rifampicin, ethambutol and clarithromycin for minimum 12 months after culture conversion

This patient has MAC-PD without any features of severe disease such as cavitation, or any suggestion of resistance. D is therefore the most appropriate treatment regime but the others are plausible. Answer A would be recommended for maintenance phase of M abscessus PD (clari sensitive) but the duration would be 12 months after culture conversion. Answer B would be appropriate treatment for non severe M xenopi-PD but again duration would be 12 months after culture conversion. Answer E would be an appropriate treatment regime for clarithromycin resistant MAC-PD.

Question 32

You see a new patient in the general Respiratory Clinic, a 28 year old man who has chronic sputum production and recurrent infections. He was preterm and had chest infections as a child. He has had 3 courses of antibiotics in the last 6 months, and a history of several chest and sinus infections a year for the last few years. He is also under assessment for subfertility. Spirometry shows a mixed obstructive-restrictive pattern. His liver function tests and ultrasound are normal. HbAlC is normal.

Which one of the following is the single most likely investigation to confirm the diagnosis?
A. CT Chest
B. Immunoglobulin levels
C. Nasal nitric oxide
D. Sweat chloride level
E. Total IgE level

Answer 32

C. Nasal nitric oxide

This question requires you to work out the diagnosis, and then select the test which is most likely to confirm the diagnosis. The recurrent chest and sinus infections, chronic sputum production, and subfertility should make you think of PCD (Primary Ciliary Dyskinesia). Cystic fibrosis is also possible but the age of onset and lack of diabetes or liver involvement makes this less likely. Of the options, nasal NO is the most useful test. If positive then the patient would need further specialist testing eg video microscopy analysis and transmission electron microscopy of cilia, as well as genetic testing. CT would show bronchiectasis but this is non-specific. It may show situs inversus but the lack of this would not help diagnostically. Immunoglobulins and total IgE levels would be normal.

Question 33

A 58 year old non-smoker who is a school biology teacher is diagnosed with adenocarcinoma. They read a news article which states that although cigarette smoking is the biggest risk factor for lung cancer, outdoor air pollution causes around 1 in 10 cases of lung cancer in the UK. They ask you to explain how air pollution causes lung cancer.

Which one of the following best describes the mechanism through which particulate matter (PM2.5) causes non small cell lung cancer?

A. Acceleration of angiogenesis via VEGF epigenetic alterations
B. DNA methylation
C. Inhibition of tumour suppression gene p53
D. Interleukin-1β inflammation promoting EGFR mutant cells
E. KRAS activating mutation enhancing the mTOR pathway

Answer 33

D. Interleukin-1β inflammation promoting EGFR mutant cells

Air polllution has been associated with higher lung cancer rates in epidemiological studies for a while, but the mechanism remained elusive. Recently the team at UCL and The Crick Institute published a series of findings which show that the increase in lung cancer is associated with PM2.5 air pollution specifically, and that the mechanism is not related to DNA damage, but instead inflammation mediated by interluekin 1β. This leads to actication of cancer causing cells, particularly those with EGFR mutations.

Question 34

A 66 year old is seen in the outpatient Respiratory clinic following an admission to hospital with an influenza A related acute exacerbation of COPD. You focus on high value interventions and ensure that they are aware of the benefits of vaccination, and access support to stop smoking. You also recommend participation in a pulmonary rehabilitation (PR) programme. The patient asks whether pulmonary rehabilitation has any specific benefits?

Which one of the following is true in relation to PR?
A. Cost per QALY for PR is lower than flu vaccination in COPD
B. Hospital admission rates are lower in those who complete PR
C. PR is not an evidence based treatment in interstitial lung disease
D. There is no difference in PR completion rates according to index of multiple deprivation
E. There is a mortality benefit from attendance at a PR programme

Answer 34

B. Hospital admission rates are lower in those who complete PR

Pulmonary rehabilitation is a high value effective intervention in people with a range of lung diseases. The most evidence is in COPD, but there is evidence of benefit in ILD, lung cancer and bronchiectasis. Pulmonary rehabilitation improves health-related quality of life, reduces anxiety and reduces hospital admission rates in COPD and other chronic lung diseases.

Pulmonary rehabilitation is a high value intervention but is more resource intense than vaccination and therefore has a higher cost/QALY. Both uptake and completion rates are lower in those in lower quintiles of index of multiple deprivation, adding to health inequalities. Some studies have demonstrated a mortality benefit for PRicompletion in COPD but this has not been consistently replicated.

Question 35

A 71 year old with COPD GOLD stage E, severe airflow obstruction (FEV1 33%) and chronic breathlessness (mMRC 3) is reviewed in clinic. He has completed pulmonary rehabilitation and stopped smoking 2 years ago. His eosinophil count is 0.25. He struggles with daily sputum production and recurrent exacerbations. His medications include Trelegy Ellipta and carbocisteine. He was trialled on azithromycin but this was stopped due to prolonged QTc. Roflumilast is suggested as add on therapy.

Which one of the following best describes the mechanism of action of Roflumilast?
A. Analogue of eicosanoid prostacyclin PGI2
B. M3 muscarinic receptor antagonist
C. Monoclonal antibody against human immunoglobulin E
D. Partial agonist of the α4β2 nicotinic acetylcholine receptor
E. Phosphodiesterase-4 inhibitor

Answer 35

E. Phosphodiesterase-4 inhibitor

This is a straightforward knowledge question, but you should know some respiratory pharmacology for the SCE and day to day practice. Roflumilast is NICE approved in COPD with FEV1 <50% and frequent exacerbations despite optimised inhaled therapy. Use is limited due to frequent side effects, particularly diarrhoea and headaches.

The other answers are also respiratory drugs. Epoprostonol is an analogue of eicosanoid prostacyclin PGI2 and is used to treat pulmonary hypertension. Tiotropium is an example of an M3 muscarinic receptor antagonist, used to treat COPD and other conditions. Omaluzimab is a monoclonal antibody against human immunoglobulin E, used to treat severe asthma. Varenicline is a partial agonist of the α4β2 nicotinic acetylcholine receptor and is an effective treatment for tobacco dependance.

Question 36

A 62 year old has been stepped down the the ward after an admission to the Respiratory High Dependancy Unit for acute NIV to treat a virally induced exacerbation of COPD. They have had a medication review and inhaler technique check, and have been referred for pulmonary rehabilitation. They are an ex-smoker with a history of ischaemic heart disease and psoriasis. The day before discharge, when they have been off NIV for 4 days, they have an ABG which shows: pH 7.36 pO2 8.6 pCO2 5.9 HCO3 31 SpO2 91%.

Which one of the following is the most appropriate management plan?
A. Discharge with routine follow up in the COPD clinic
B. Keep as inpatient to set up domiciliary NIV
C. Organise home oxygen
D. Remain as inpatient for further 24hours and repeat ABG
E. Send home and arrange ABG in outpatients in 2 weeks

Answer 36

E. Send home and arrange ABG in outpatients in 2 weeks

This patient has had an episode of acute type 2 Respiratory failure treated effectively with NIV. Before discharge, their blood gas showed that they were no longer acidotic (pH 7.36) or hypercapnic (pCO2 5.9). They were also not hypoxaemic with a pO2 of 8.6 which is acceptable. The patient needs follow up in the COPD clinic, but this is not enough in this case; they also need to have a repeat ABG at 2 weeks to ensure that they are not drifting back into hypercapnia. This is based on the HOT-HMV trial.

The patient would not meet criteria for home oxygen, and there is no justification for inpatient home NIV setup. Keeping the patient in for a further 24hrs and performing another ABG would provide no additional information and would not be best for the patient, or in terms of resource use.

Question 37

A 32 year old woman has just moved to the UK and is seen by her GP. She has no medical records available but says that she has a lung condition diagnosed in childhood. She says she was always ill as a child, with respiratory distress as a newborn, and then chest infections & ear infections as she grew up. She wears a hearing aid. There is no family history of similar problems & her younger sister is well. She has no history of GI problems. She is keen to pursue fertility assessments after being unable to conceive for a year. On examination there are coarse crackles at the bases. Heart sounds are normal. Pulse 65bpm, BP 120/75, RR 14, SpO2 98% on air. There are abnormal areas on her CT scan in the middle and lower lobes with dilated airways and mucus plugging. Initial blood tests including FBC, U&E, CRP, immunoglobulins, HbA1C and vaccine titres are normal.
Which ONE of the following is the single most likely cause of this patient’s condition?
A. Autosomal dominant inheritance of mutation of protein CFAP57
B. Complement deficiency
C. Failure of pre-B cells to differentiate into mature B lymphocytes
D. Missense mutation of CFTR
E. Mutation of protein encoding cilia outer dynein arm

Answer 37

E. Mutation of protein encoding cilia outer dynein arm
This patient has a history of childhood respiratory infection and ear infections leading to hearing loss. There is no evidence of other organ involvement and we are specifically told there is no diabetes or GI history. There is a suggestion of sub fertility in the history. The CT scan shows bronchiectasis. The history and investigations are consistent with primary ciliary dyskinesia which result from a mutation in the cilia. A plausible alternative diagnosis would be cystic fibrosis (answer D) but the lack of other organ involvement, and the hearing loss make this less likely.

Question 38

A 57 year old is referred to clinic due to breathlessness. It has come on slowly over the last 3 years but he now feels out of breath with a tight chest after climbing the two flights of stairs in his house. When he rushes up the stairs he feels weird, like he might faint, and has to sit down. He is generally well but had a splenectomy after abdominal trauma 30 years ago. He takes Pen V, and also sertraline for anxiety. He is an ex-smoker 15 years ago. 2 years ago he had a back injury and spent 2 weeks in bed. He developed a DVT and PE. This was treated with anticoagulation for 3 months and he then opted to stop the medication in consultation with a haematologist. In clinic observations show: HR 93 BP 130/65 RR 14 SpO2 91% on air. Spirometry: FEV1 2.3L (64%) FVC 3.0L (66%) ratio 0.76. CTPA: Eccentric filling defect in a right upper lobe segmental pulmonary artery with a suggestion of webbing and mosaic attenuation in the right upper lobe. Pulmonary artery is dilated and RV:LV diameter >1. There is bowing of the intraventricular septum.
Echocardiogram: normal LV, dilated RV, flattened interventricular septum. TV Vmax 4.2m/s.

Which ONE of the following is most likely to be found on right heart catheterisation?
A. mPAP 10mmHg PAWP 6mmHg PVR 1WU
B. mPAP 15mmHg PAWP 8mmHg 2WU PVR
C. mPAP 28mmHg PAWP 18mmHg PVR 2WU
D. mPAP 38mmHg PAWP 20mmHg PVR 6WU
E. mPAP 42mmHg PAWP 12mmHg PVR 4WU

Answer 38

E. mPAP 42mmHg PAWP 12mmHg PVR 4WU

The patient has a history of venous thromboembolism and has developed breathlessness over years which is now limiting. They have low oxygen saturations at rest. Symptoms in the history suggest this is exacerbated on exercise, accompanied by inadequate cardiac output leading to presyncope. The spirometry is restrictive. The CT scan shows evidence of chronic thrumbus and features of pulmonary hypertension (PH). The echocardiogram further supports the finding of PH. The unifying diagnosis is CTEPH (chronic thromboembolic pulmonary hypertension). For a diagnosis of PH mPAP >20mmHg. CTEPH is a precapillary form of PH. Therefore we would expect PAWP ≤15mmHg and PVR ≥3WU.

Question 39

A 54-year-old patient with newly diagnosed smear positive cavitating pulmonary tuberculosis (TB) is initiated on a standard four-drug anti-TB regimen, including rifampin, isoniazid, pyrazinamide, and ethambutol (RHZE). After three weeks of treatment, the patient develops jaundice, fatigue, and right upper quadrant pain and is admitted to hospital.
Laboratory tests show:
ALT 225 IU/L (7-56 IU/L)
Bilirubin 4.5 mg/dL (0.3-1.0 mg/dL)

Which ONE is the single most appropriate next step in management?
A. Continue Ethambutol, add moxifloxacin, but stop other drugs until ALT< twice upper limit of normal then reintroduce sequentially
B. Continue TB treatment but halve the doses of all drugs and increase frequency of LFT monitoring
C. Stop all drugs until ALT and bilirubin are within normal range then reintroduce sequentially
D. Stop all drugs for 21 days then reintroduce sequentially, starting with pyrazinamide
E. Stop all drugs and organise a liver ultrasound before attempting to restart treatment

Answer 39

A. Continue Ethambutol, add moxifloxacin, but stop other drugs until ALT< twice upper limit of normal then reintroduce sequentially.

This patient has a drug induced liver injury (DILI), the most common complication of anti-TB treatment leading to treatment interription. There is a lack of evidence on the most clinically & cost effective way to reintroduce treatment after DILI & variation in practice. NICE recommends wait until AST or ALT levels fall <2x upper limit of normal, bilirubin is normal range & symptoms have resolved then sequentially reintroduce drugs at full dose over no more than 10 days, starting with ethambutol plus isoniazid (with pyridoxine) or rifampicin. In severe/highly infectious disease NICE recommends a combination of at least 2 anti‑TB drugs of low hepatotoxicity such as ethambutol +/- streptomycin +/- a fluoroquinolone.

Question 40

A 26 year old presents to the emergency department with a 1 week history of worsening fatigue, nausea, breathlessness and cough. The cough is minimally productive of clear phlegm but has been streaked with blood in the last 2 days. He has no past medical history and there is no relevant family history. He is generally well, but has recently recovered from a mild upper respiratory tract infection. He works as a computer programmer. He occasionally smokes tobacco and marijuana, and uses cocaine at social events.
On examination he is warm and well perfused but tachycardic and tachypnoeic. Heart sounds are normal. There are crackles bilaterally in the mid and lower zones, more on the right. Abdominal/neurological examination are normal.
Obs: T 37.3, P 115bpm, BP 120/65, RR 20, SpO2 94% on 28% oxygen via venturi mask.
ECG: sinus tachycardia
Bloods: Hb 110 g/L, MCV 80, HCT 0.32, Plt 440x10^9/L, WCC 11x10^9/L, neut 5.7 x10^9/L, lymph 6.0 x10^9/L, mono 1.1x10^9/L, eos 0.31x10^9/L, Na K Urea 15.9mmol/L, Creat 164μmol/L, Bili 12μmol/L, ALP IU/L, ALT 31IU/L, CRP 14
Urine dip: pH 7.2, specific gravity 1.124mOsm/kg, nit -ve, ket -ve, protein ++, blood +, glu -ve.
Chest xray shows bilateral perihilar infiltrates.

Which ONE of the following blood tests would confirm the most likely diagnosis?
A. Anti-CCP
B. Anti-dsDNA
C. Anti-GBM
D. Anti-Jo1
E. Anti-MPO

Answer 40

C. Anti-GBM
This patient has pulmonary renal syndrome. There is a short history of non-specific symptoms, with haemoptysis at presentation. There are bilateral crackles and the xray shows perihilar infiltrates. He is tachycardic and hypoxaemic. Blood tests show low haemoglobin and haematocrit from diffuse alveolar damage, raised white cells, predominantly lymphocytic and acute kidney injury. Urine dip shows evidence of nephritis (blood & protein).
There are several possible diagnoses, including ANCA-positive vasculitides (anti-MPO), but the eosinophils are not raised so EGPA is unlikely. SLE (anti-dsDNA) is possible but this would be an unusual presentation with a lack of classic features. The presentation is not consisent with rheumatoid arthritis (anti-CCP) or polymyositis (anti-Jo1) . Goodpasture’s syndrome (anti-GBM) explains all the features, and can be precipitated by smoking and cocaine use.

Question 41

A 58 year old is referred on the two week wait pathway due to recurrent infections and fatigue. The GP referral says that the patient has a history of mild COPD but prior to the last 3 months had not had problems with infections. They are tobacco dependant, attempting to cut down, currently smoking 10 roll ups a day.

They have a CT scan which is reported as:
There is a 43mm mass in the right lower lobe which abuts the diaphragm. There is a further small nodule at the right costophrenic recess which is 24mm in maximum diameter. There is a band of atelectasis at the right base and scattered ground glass opacities in the lower lobes. There is bulky lymphadenopathy at the right hilum and subcarinal lymph nodes. There is an indeterminate lesion in the liver which may be a haemangioma. Further characterisation with ultrasound is recommended. There is what appears to be a bone island in the right femur. No other bony lesions are seen.

Assuming this is a non-small cell lung cancer, based on the CT report which ONE of the following is the most accurate staging?
A. T2b N2b M0
B. T2b N3 M1c
C. T3 N2 M0
D. T3 N2 M1c
E. T4 N3 M1c

Answer 41

C. T3 N2 M0

A 43mm mass would be T2b, but this is upstaged by the satellite nodule in the same lobe to T3. There are no features described which would upstage to T4 (eg invasion of diaphragm, mediastinum, trachea, spine or nodule in separate ipsilateral lobe). In terms of the nodal staging, the bulky right hilar nodes are N1, with the subcarinal node making it N2. When considering the M stage careful reading of the report is important. Benign lesions in the liver are common, and in this case there are features consistent with a haemangioma, so the patient should be given the benefit of the doubt, and further imaging arranged if necessary. Similarly, the report notes a bone island in the femur but no other bone lesions. If this was a metastasis it would be M1b (single extrathoracic met), but a bone island is a common benign finding (sclerotic lesions previously known as enostoses). This is a stage IIIB tumour.

Question 42

A 48 year old who recently stopped smoking after support from a tobacco dependence specialist has a persistent productive cough and exercise limitation. They have a CT scan which shows mild centrilobular emphysema and minimal bronchial wall thickening. Post-bronchodilator spirometry shows FEV1 2.2L (76%) FVC 3.1L (87% within LLN), ratio 0.71. They are told that they do not have COPD, but have pre-COPD, also known as PRISm (preserved ratio impaired spirometry).

Which ONE of the following is true of patients with PRISm?
A. Early treatment with LABA/ICS reduces risk of progression
B. Male gender is a risk factor for progression to COPD
C. Over 60% of patients develop COPD within 10 years
D. Prevalence is 10% in cohorts of ex-smokers
E. Vaping is an established risk factor

Answer 42

D. Prevalence is 10% in cohorts of ex-smokers

COPD is defined as the presence of non fully reversible airflow obstruction (FEV1/FVC <0.7 post-bronchodilation) in the appropriate context (ie given exposure to cigarette or other smoke). However, some people may have structural or physiological abnormalities which do not meet these criteria. The term PRISm (Preserved Ratio Impaired Spirometry) is used to describe the presence of a normal ratio (FEV1/FVC >0.8 post-bronchodilation) but abnormal spirometry (FEV1 <80%). PRISm is associated with female sex, obesity and multimorbidity. Prevalence is 7-11% in population based studies, and 10.4-11.3% in smokers/ex-smokers in the COPDgene cohort. PRISm may progress to COPD but may not. 20-30% progress in cohort studies, with a higher risk is those with lower baseline FEV1, higher age and ongoing smoking. There is no evidence that early treatment with LABA/ICS alters risk of progression. There is insufficient data on any association between vaping and PRISm.