Respiratory

Question 1

COPD severity criteria and category

Answer 1

GOLD - by FEV1 %
- 1 >80
- 2 50-79
- 3 30-49
- 4 <30

A for asymptomatic
B for symptomatic
E for exacerbations - 2 or more, or 1 leading to hospital

Question 2

A 70yo man with severe COPD is admitted to hospital with an exacerbation of COPD requiring 24hrs of non-invasive ventilation, oxygen therapy, oral steroids and oral antibiotics. After four days, he is discharged home with outpatient follow-up. What is his approximate 12-month mortality risk after this episode?

• 5% * 10% * 25% * 50% * 70%

Answer 2

25% - mortality

65% - readmission

Question 3

A 73yo male with moderate COPD presents to clinic for review. He has symptoms on exertion but no history of exacerbations. He is on no inhaled therapy currently. He has no history suggestive of asthma and his peripheral eosinophil count is 0.1. Which of the following inhalers would be expected to have the greatest effect on AECOPD, hospitalization and symptoms.

• LAMA monotherapy
• ICS/LABA
• ICS monotherapy
• LABA/LAMA
• LABA monotherapy

Answer 3

• LABA/LAMA

Question 4

Factors favouring use of ICS in COPD (3)

Answer 4

Hospitalisation for exacerbation
2 or more exacerbations
Eosinophils >300 (or >0.3)
History of asthma

mortality benefit demonstrated with triple therapy

Question 5

Which of the following therapies are not associated with a reduction in mortality in people with COPD?

• Smoking cessation
• Long-term oxygen therapy
• Pulmonary rehabilitation
• Non-invasive ventilation
• LABA+LAMA+ICS
• Long-term macrolide antibiotic

Answer 5

• Long-term macrolide antibiotic

lung volume reduction also has mortality benefit

Question 6

A 50yo man attends your clinic and you discuss his current smoking habit and strategies to quit. You outline options for smoking cessation pharmacotherapy for him. Which of the following comorbidities would preclude the use of combination nicotine replacement therapy?
* Unstable ischaemic heart disease
* Bipolar disorder
* Schizophrenia
* Suicidal ideation
* Stable ischaemic heart disease

Answer 6

• Unstable ischaemic heart disease

Question 7

Evidence based smoking cessation strategies

Answer 7

Brief counselling RR 1.86 v usual care

Combination NRT (short + long) + behaviour intervention is the best

Combo NRT = Varenicline > bupropion (antidepressant with weak norepinephrine and dopamine uptake inhibition)

Question 8

Acute NIV can be used to treat respiratory failure. Which of the following scenarios should NIV be considered “off-label” therapy?
* Post-extubation respiratory failure
* Hypercapnic respiratory failure due to AECOPD * Acute severe asthma
* Acute cardiogenic pulmonary oedema
* None of the above

Answer 8

• Acute severe asthma

Question 9

What is the most likely diagnosis?
A 67yo woman presents to clinic with cough and some exertional dyspnoea. She is an ex-smoker with 30 pack year history. She has been started on LAMA therapy by her GP for presumed COPD
Spirometry is performed (flow-volume loop normal, both pre and post salbutamol)

• COPD
• Interstitial lung disease
• Asthma
• Malingering
• Uninterpretable spirometry due to lack of effor

Answer 9

• Asthma

COPD/ ILD are out because of normal loop
It is interpretable
Asthma is very common

Question 10

Z-score cut-off for “normal” in spirometry

Answer 10

-1.645

Question 11

Which of the following statements regarding asthma and/or cough are most correct?

• negative mannitol bronchoprovication test excludes asthma
• A low FeNO (<10ppb) excludes asthma
• Cough that is caused by ACE inhibitor occurs within 4 weeks of commencing therapy
• A low PEFR confirms asthma as the most likely diagnosis
• negative methacholine bronchoprovocation test excludes asthma

Answer 11

Negative methacholine bronchoprovocation test excludes asthma
- positive test would mean >20% fall in FEV1

Manitol or hypertonic saline
- positive would mean >15% fall in FEV1
- better positive predictive value (i.e. diagnose rather than exclude)

PEFR - peak expiratory flow rate, usually monitored over a few weeks, if variable then identifies Asthma, good to identify triggers

FeNO - correlates with increased Eosinophilic inflammation > predicts steroid responsiveness; diagnostic value not demonstrated

Question 12

Bronchodilator reversibility

Answer 12

> 12% AND >200mL increase in FEV1

Question 13

Asthma categories (4)

Answer 13

INTERMITTENT ASTHMA
– normal FEV1, symptoms/SABA <2/week, no limitations

PERSISTENT ASTHMA
MILD – normal FEV1, symptoms/SABA >2/week, minor limitation
MODERATE – mildly abnormal FEV1 (60-80%), daily symptoms, some limitation
SEVERE – abnormal FEV1 <60%, daily symptoms + nocturnal, limited function

Question 14

Asthma treatment

Answer 14

PRN ICS/ LABA for mild
- better than SABA alone
- non-inferior to regular to ICS with 17% of steroid exposure
Then regular with increasing dose
Then add on LAMA
Then advanced therapies

Question 15

Biological therapy targeng which of the following molecular targets would be unlikely to improve asthma control?

• IgE
• IL-5
• Eosinophilic aromatase
• IL-5 receptor
• thymic stromal lymphopoien (TSLP)
• IL-4 and IL-13

Answer 15

*Eosinophilic aromatase

Omalizumab - IgE
Mepolizumab - IL-5
Benralizumab - IL-5 receptor
Tezepelumab - TSLP (may be effective in those without eosinophilic inflammation)
Dupilimab - IL-4 and IL-13

Question 16

Severe asthma definition

Answer 16

Either maximal therapy or symptoms on maximal therapy

Main issue is adherence 15-54%
- 25% increase would lead to 10% reduction in exacerbations

Inhaler technique is optimal in only 31%

Question 17

Omalizumab

Answer 17

Binds IgE - prevents binding to mast cells, basophils, eosinophils, T cells

25% less exacerbations
Less SABA
Less oral and inhaled steroids
Less symptoms
Better QoL

Question 18

Mepolizumab and Benralizumab

Answer 18

IL-5 and IL-5R - blocks eosinophil growth, differentiation, recruitment and activation

Eosinophil count >150 but ideal >300/uL

Reduced hospital presentation
50% reduction in oral corticosteroids
Better QoL

Question 19

Dupilimab

Answer 19

IL-4 + IL-13
- original use in atopic dermatitis
- elevated IgE or eosinophils

Reduced severe asthma exacerbations
Improvement in FEV1
Some benefit in those with lower eosinophils

Question 20

Tezepelumab

Answer 20

Thymic stromal lymphopoietin (TSLP) is upstream of IL-4, IL-5, IL-13, and IgE

Less exacerbation
Better FEV1
Better symptoms + QoL
Similar effect regardless of eosinophils

Question 21

A 68yo ex-smoker presents with gradually increasing dyspnea over the past 12 months. He has crackles on examinaon and is clubbed. He has no history of occupaonal exposures or clinical features of connecve ssue disease. He is referred for HRCT which is reviewed in a muldisciplinary meeng and a diagnosis of idiopathic pulmonary fibrosis is reached. Which of the following features on HRCT is least likely to be present?

• Honeycombing
• Subpleural reticular opacity
• Traction bronchiectasis
• Basal reticular opacity
• Widespread ground glass opacity

Answer 21

• Widespread ground glass opacity

Usual interstitial pneumonitis pattern = all four of
1. Honeycombing
2. Traction bronchiectasis
3. Reticular opacities - lower and peripheral
4. No atypical features

Question 22

When to consider biopsy for interstitial lung disease (3)

Answer 22

carries 1-2% mortality

age <50yo
atypical HRCT
rapidly progressive

transbronchial only helpful for centrilobular pathology

Question 23

A 60 year old non-smoker has been recently diagnosed with idiopathic pulmonary Bbrosis. You conduct a literature search to determine treatment opons for him. Which of the following would not be appropriate?

• Pirfenidone
• Referral to lung transplant team
• Nintendanib
• Prednisolone
• Oxygen therapy

Answer 23

Prednisolone
- increases mortality and hospitalisation with no benefit

Nintedanib (multiple TK inhibitor) and pirfinedone (TGF-b inhibitor) = anti-fibrotic
- mild/ moderate IPF
- slow rate of decline in FVC (no clear survival benefit)
- SE = diarrhoea, nausea

Question 24

alternative indication for nintendanib

Answer 24

non-ipf pattern progressive fibrosis
- known or unknown etiology ILD with fibrosis on HRCT and 2/3 of:
1. Worsening symptoms
2. Worsening PFTs
3. Worsening HRCT

Question 25

non-specific interstitial pneumonitis pattern (4)

Answer 25

1. Ground glass opacity 2. Traction bronchiectasis 3. Apical to basal gradient 4. Subpleural sparing NSIP pattern tends to indicate a potential for response to immunosuppression (but also a better prognosis than UIP pattern)

Question 26

What is NSIP associated with? (4)

Answer 26

1. CTD ( 88% in one study had laboratory or clinical features of undifferentiated CTD - lung disease may precede clinical CTD features) 2. HIV 3. Drugs: amiodarone, methotrexate, flecanide, nitrofurantoin 4. Hypersensitivity pneumonitis

Question 27

Treatment for NSIP (3 line agents)

Answer 27

1. First line agent: Glucocoricoids (long taper over 6-9 months assuming clinical response) 2. Second line agents: Mycophenolate or Azathioprine (implemented initially with more severe disease; those that fail to respond to first line agents; and those that worsen as steroids reduce 3. Third line agents: IV Cyclophosmamide monthly, Rituximab, lung transplant

Question 28

A 60yo pigeon breeder presents for a roune health assessment. He is an ex-smoker of 30 pack years. He is asymptomac with good exercise tolerance. His lungs are clear, oxygen sats are normal on room air and his PFTs demonstrate mild fixed airflow obstruction with a normal DLCO. His HRCT is reported as normal. Serum precipins are posive for IgG to pigeons. The most likely diagnosis is: A) Hypersensitivity pneumonitis (pigeon fanciers lung) B) Asthma C) COPD D) Sarcoidosis E) Idiopathic Pulmonary fibrosis

Answer 28

C - PFTs are suggestive of COPD, precipitins are common in bird handlers even without disease

Question 29

Risk factors/Clinical history clues for Hypersensitivity Pneumonitis

Answer 29

# Agricultural dusts * Recurrent ‘atypical’ pneumonia * Symptoms after moving to a new job or home * Exposure to pets (birds especially) * Water damage to home/office–moulds * Hot tub/sauna/swimming pool exposure * Other people with similar symptoms * Improvement when on holiday or over weekends Common aetiology: # Bioaerosols # Microorganisms # Reactive chemical species

Question 30

Diagnosis of hypersensitivity pneumonitis

Answer 30

THERE IS NO DIAGNOSTIC TEST The principle pathophysiological aetiology is around precipitins (specific IgG) Precipitans can be avian, fungal, or thermophilic actinomyces - Precipitins don’t rule in (30-40% asymptomatic farmers have + precipitins to common causes of HP) - Precipitins don’t rule out (tests can be nonreactive even if the causative antigen is included) 1) HRCT 2) Bronchoscopy, surgical lung biopsy 3) BAL - lymphocytic pattern suggestive (~30% lymphocytes) 4) TBBx can demonstrate non-caseating granulomas 5) Surgical lung biopsy or cryobiopsy where imaging, exposure, or BAL are inconclusive (after balancing risks vs benefits)

Question 31

HRCT features of hypersensitivity pneumonitis (3)

Answer 31

Typical features: 1) Centrilobular nodules and/or ground glass opacities 2) Mosaic attenuation (inspiratory), three density pattern, gas trapping (expiratory) 3) Fibrosis – linear opacities, coarse reticulation and lung distortion, traction bronchiectasis, honeycombing (relative sparing of lower zones, random involvement both axially and craniocaudally) Some HP will have a radiological pattern that is consistent with UIP => reinforces that the diagnosis of idiopathic pulmonary fibrosis is generally only reached if there are no features that suggest an alternative Dx

Question 32

Sarcoidosis - age

Answer 32

Multisystem granulomatous disorder – with 90% lung involvement - Peak incidence 20-39yrs - T cell mediated with granuloma formation and fibrosis due to Th2

Question 33

HRCT findings of sarcoidosis

Answer 33

HRCT findings are variable - Bilateral hilar and mediastinal LAD - Nodular (upper zone) + hilar and mediastinal LAD * Parenchymal = at least stage II disease **SARCOIDOSIS IS A DIAGNOSIS OF EXCLUSION** Non-caseating granulomas DDx – TB (demographics), lymphoma, other ILD, cancer

Question 34

A 50yo woman is referred to you with asymptomatic HRCT abnormalities including some bilateral upper zone nodular interstitial changes and bilateral hilar and mediastinal lymphadenopathy. After obtaining a history, examination and basic investigations you suspect sarcoidosis. Which of the following tests test is most likely to confirm your clinical diagnosis? A) Serum ACE level B) Spirometry and TLCO C) Bronchoscopy with broncho-alveolar lavage for elevated CD4:CD8 rao D) Bronchoscopy with transbronchial and endobronchial biopsy E) Endobronchial ultrasound guided transbronchial needle aspiraon of hilar lymph nodes

Answer 34

E Tissue diagnosis: * BAL–elevated CD4:CD8 is supportive(>3.5:1) * Endobronchial biopsy–positive in 40-70% * Transbronchial biopsy 50-75% * EBUS–80-90% Combined approach may have the highest yield (>90%) ** Mediastinoscopy or lung biopsy uncommonly required **

Question 35

Extrapulmonary complications/involvement of Sarcoidosis (4)

Answer 35

1) Ocular: requires ophthalmology review 2) Calcium: urinary calcium excretion rate, serum Ca2+, vit D (1,25) 3) Cardiac: ECG, ECHO -> MRI or PET 4) Brain: no routine investigation required, but can do MRI + LP

Question 36

When do you treat sarcoidosis? (7)

Answer 36

*** 70% of those with sarcoidosis require NO TREATMENT *** However, the condition is more aggressive in non-Caucasian populations) Indications for treatment: 1) Progressive symptomatic pulmonary disease 2) Asymptomatic pulmonary disease with persistent infiltrates or progressive loss of lung function 3) Cardiac disease 4) Neurological disease 5) Eye disease not responding to topical therapy 6) Symptomatic hypercalcaemia 7) Other symptomatic/progressive extrapulmonary disease * Sometimes measuring functional tests (6MWD, CPET) helps with treatment decision (and objectively measuring response)

Question 37

Treatment of Sarcoidosis

Answer 37

1) Inhaled corticosteroids – possibly helpful for cough, useful if co-morbid asthma 2) Oral corticosteroids – first line therapy for sarcoidosis: long taper over 12 months Other agents (primarily as steroid sparing agents): Methotrexate Hydroxychloroquine Azathioprine Mycophenolate Others rarely used: Infliximab, Adalimumab, Rituximab

Question 38

A 38 yo man presents with 18 months of cough and mild dyspnoea. His GP has arranged chest imaging that has been reported as demonstrating egg-shell calcification. What occupational exposure should be specifically sought? A) Asbestos B) Flour C) Beryllium D) Silica E) Birds

Answer 38

D

Question 39

What is silicosis

Answer 39

* Disease progression can occur even after exposure ceases * Accelerated silicosis assumed if lung function deteriorates at >10x expected age related decline * Uncertain how much exposure is required to develop disease * Grinding, cutting or polishing of artificial stone surfaces are the key risk area identified – generates fine respirable dust particles * No known treatments or disease modifiers * Screening with spiro/TLCO and imaging * Avoidance of exposure is the only strategy * Monitoring and referral for transplant for severely affected

Question 40

Ventilation strategies in ARDS (3)

Answer 40

1. Ventilate with low tidal volumes and inspiratory pressures 2. Prone positioning for severe 3. Higher PEEP can be tried (reduces atelectrauma)

Question 41

Predictors of NIV failure (4)

Answer 41

1. Acidosis <7.25 2. Marked acute hypoxemia PaO2/FiO2 <200 3. RR >25 4. Non-pulmonary organ failure

Question 42

NIV indications for neuromuscular disease (4)

Answer 42

1. Paradox or othopnea 2. Vital capacity <50% 3. SNIP <30cm H2O 4. pCO2 >56 mmHg

Question 43

OSA diagnosis - via sleep study, and severity

Answer 43

AHI >5 + symptoms OR AHI >15 5-15 is mild and >30 is severe

Question 44

OSA pathophysiology (4)

Answer 44

1. Narrow + collapsible upper airway 2. Low arousal threshold 3. Ineffective dilator muscles 4. Oversensitive ventilatory system

Question 45

Obesity hypoventilation syndrome triad and pathophysiology

Answer 45

1. Awake hypercapnia >45 2. BMI >30 3. Sleep disordered breathing Leptin resistance + increased load = blunted ventilatory response

Question 46

CPAP v NIV in OHS and OSA

Answer 46

OHS - mortality benefit of both, choose modality based on whether the phenotype is more OSA vs respiratory failure OSA - no cardiac mortality benefit, but improves everything else

Question 47

Narcolepsy type 1 and 2 and treatment

Answer 47

Type 1 - 3 months of sleepiness - cataplexy and MSLT <8mins or low CSF hypocretin Type 2 - 3 months sleepiness - NO cataplexy and MSLT or normal hypocretin Treatment = dexamphetamine, armodafinil, for cataplexy SSRI

Question 48

Bronchiectasis treatments (5)

Answer 48

1. Airway clearance - improves QOL - refer to physio 2. Inhaled hypertonic saline - reduces exacerbations 3. Infections for at least 10 days 4. Airway obstructions - no/low evidence - salbutamol and possible trial of ICS 5. Chronic inflammation - macrolides - erythromycin reduce exacerbation in frequent

Question 49

MAC treatment

Answer 49

Ethambutol, Rifampicin and Clarithromycin

Question 50

CF diagnosis

Answer 50

CFTR (1/25 carrier frequency) heel prick for trypsinogen chloride sweat test >60

Question 51

CF therapies (5)

Answer 51

1. CFTR modulators 2. Inhaled DNAse - increases FEV1 3. Macrolide - azithromycin 4. Hypertonic saline - increases FEV1 5. Lung transplantation

Question 52

CFTR modulators

Answer 52

Ivacaftor is a potentiator that opens channel Tezacaftor and Elexacaftor are correctors that move the protein to the cell surface Homozygous DF508 mut = ivacaftor/ tezacaftor Heterozygous = elexacaftor/ ivacaftor/ tezacaftor

Question 53

Major organ complications with CF (5)

Answer 53

1. Pancreatic insufficiency (85-90%) 2. GI: obstruction, reflux, prolapse, intussusception 3. Bone disease 4. Infertility 5. Psychiatric due to disease

Question 54

Demographics impacting lung cancer outcomes (3)

Answer 54

1. Remoteness 2. low SES 3. Indigenous status

Question 55

Benefit of CT scan screening for lung cancer

Answer 55

1-2 yearly - 50-80yo - 20+ pack years - current or quit within 15 years 20-33% reduction in mortality

Question 56

Early stage lunch cancer treatment

Answer 56

1. Surgical resection up to IIIA - VATS leads to less complications and shorter stay than thoracotomy OR radiotherapy 2. Adjuvant platinum chemo II-IIIA

Question 57

Locally advanced lung cancer treatment

Answer 57

1. Concurrent chemoradiotherapy 2. Follow with immunotherapy - first line if identified EGFR, ALK, ROS1

Question 58

Lung cancer targeted therapy

Answer 58

EGFR (10-30%) = gefitinib, erlotinib, afatinib, or osimertinib - Asian ALK (5%) = crizotinib, certinib, alecetinib, brigatinib, loratinib ROS1 (1-2%) = cirzotinib, entrectinib

Question 59

Lung cancer immunotherapy - 3 PD1 and 2 PDL1

Answer 59

PD1 Pembrolizumab - initial treatment single or combined with chemo Nivolumab - after progression on platinum Nivolumab + ipilimumab - first line stage 4 PDL1 Atezolizumab - initial with platinum and bevacizumab Durvalumab - stage III after platinum

Question 60

SCLC

Answer 60

- paraneoplastic: SIADH, Cushing, LEMS, encephalomyelitis, dermatomyositis - no benefit of screening CT - higher stage with poorer outcome - 50% brain mets >> prophylactic cranial irradiation - very responsive to cytotoxic - transient however

Question 61

Poor prognosis in mesothelioma (3)

Answer 61

1. Age 2. Male 3. Sarcomatoid subtype Mean survival 9-12 months (so generally poor anyways) No benefit of screening or following-up plaques

Question 62

Mesothelioma treatment

Answer 62

platinum based - 3 month improvement nivolumab + ipilimumab - additional 4 months

Question 63

PE treatment duration (4)

Answer 63

Provoked - 3 months unless permanent risk factors then consider indefinite Unprovoked 3-6 months Sub-massive 6-12 months Massive indefinite

Question 64

CTEPH after PE - when, who, what

Answer 64

6 months after massive PE OR if still symptomatic do a CTPA or V/Q and an echo

Question 65

PAH workup - main echo finding and decision making

Answer 65

TR 2.9-3.4 m/s - above is likely, below is unlikely - other echo features, risk factors, and associated conditions can make you consider repeating echo if below or further investigations if intermediate Follow with right heart Cath

Question 66

Group 1 PAH treatment pathways (3) and choice of therapy

Answer 66

1. Endothelin - receptor antagonists - ambriesantan, bosentan, macitentan 2. NO - PDE 5 inhibitors preventing breakdown of cGMP - sildenafil, tadalafil, riociguat 3. Prostacyclin derivatives - epoprostenol, iloprost, selexipag Initial therapy = combination oral therapy 1+2 Severe - add in 3

Question 67

Group 2 and 3 PAH - what happens if we use vasodilator therapy

Answer 67

Group 2 - vasodilation of pre capillary whilst there is already a high back pressure >> pulmonary edema Group 3 - tight V/Q match is disrupted leading to shunting and hypoxemia

Question 68

Slow vital capacity on spirometry

Answer 68

Eliminates dynamic airway collapse (cartilage weakness or membrane bowing) and would be higher than FVC if this is the case

Question 69

Fixed vs variable intrathoracic vs variable extra thoracic obstruction - PFT loop pattern - in other words which phase

Answer 69

Fixed - affects both Intrathoracic - affects exhalation Extrathoracic - affects inhalation

Question 70

Compensation in respiratory acidosis, respiratory alkalosis, metabolic alkalosis, and metabolic acidosis

Answer 70

Resp Acidosis - Acute response: HCO3 increase 1mmol/L for every 10mmHg rise in PaCO2 - Chronic: 4 for 10 Resp Alkalosis - Acute: decrease 2 for 10 - Chronic: 5 for 10 Metabolic Alkalosis - CO2 increases by 0.7 for 1 of HCO3 Metabolic Acidosis - CO2 decreases by 1.2 for 1

Question 71

ABG formulas - Aa - Anion gap

Answer 71

Aa = (FiO2x713 - 1.25xCO2) - a normal Aa = Age/4 + 4 Anion gap = Na + K - Cl - HCO3 = 11

Question 72

Risk factors for IPF (5)

Answer 72

1. Older age 2. Male 3. Smoking history 4. GORD 5. Family history

Question 73

A 32 year old lifelong non-smoking woman, with a history of 2 previous pneumothoraces, presents with progressive dyspnoea over 2 months and infrequent haemoptysis. Family history is remarkable for tuberous sclerosis. A CT chest (shown below) demonstrates multiple cystic changes throughout both lung fields. What is the most likely diagnosis? A. Cystic fibrosis B. Bronchiectasis C. Lymphangioleiomyomatosis D. Pulmonary Langerhan’s cell histiocytosis

Answer 73

Answer = C Lymphangioleiomyomatosis (LAM) - women of childbearing age - risk with oestrogen - strong association with tuberous sclerosis - Other features include renal angiomyolipoma, thoracic or abdominal chylous effusion, lymphangioleiomyoma or lymph-node - Treat with puffers + rehab + sirolomus - stabilises FEV1 Pulmonary Langerhan’s cell histiocytosis is a rare disorder that affects young adults who smoke with CT findings of nodules and small irregular shaped cysts. CF and bronchiectasis will have bronchiectatic changes.