Respiratory

Question 1

Flow loop - Pattern and differentials (3)

Answer 1

Fixed obstruction

• Tracheal carcinoma
• Tracheal stenosis
• Goitre

Question 2

Flow loop

Pattern and differentials (4)

Answer 2

Variable extrathoracic
Differentials
-Vocal cord/fold paralysis
-extra-thoracic tracheomalacia
-Poly-chondritis
-Mobile tumours

Question 3

Pattern and differentials (2)

Answer 3

Variable intrathoracic obstruction
Differenitals
-Tracheomalacia
-Malignant tumours

Question 4

7 indicators of success for NIV

Answer 4

Question 5

3 diagnostic criteria for insomnia

Answer 5

Question 6

Absolute contraindications to lung transplantation (10)

Answer 6

Question 7

AC (Assist Control) ventilation aka continuous mandatory ventilation (CMV)

Answer 7

Patient triggers ventilation
Ventilator delivers specific volume to the patient (500ml - 600ml)
-Aim 8ml/kg (ideal body weight)
Back up mode (Rate) - sets a baseline rate of ventilation if patient does not breathe. Patient cannot breathe less than this rate
Pressure and volume and volume have an inverse relationship
Compliance = Change in Volume/Change in Pressure
Therefore you can set a volume but depending on lung compliance - pressure achieved will vary
-low compliance = high pressure

-high compliance = low pressure

Question 8

Advanced therapies in PH
-CCB

Answer 8

Vasoreactivity test - do before starting Rx ?respond

• Vasoreactivity testing is recommended in patients with IPAH, HPAH and PAH associated with drugs use to detect patients who can be treated with high doses of calcium channel blocker
• A positive response to vasoreactivity testing is defined as a reduction of mean PAP >10mmHg to reach an absolute value of mean PAP <40mmHg with an increased or unchanged cardiac output
• POSITIVE TEST = trial CCB, NEGATIVE = Rx with alternatives

CCB - prolong survival, functional and haemodynamic improvement

• nifedipine OR diltiazem
• Less than 10% of patients will respond to, or tolerate CCB long term

Question 9

Advanced therapies in PH
-Endothelin antagonists

Answer 9

Mech - endothelin 1 promotes vasoconstriction, cell proliferation, vascular remodelling. This blocks that = vasodilation + improved exercise capacity

ADR - anaemia, flushing, peripheral oedema, headache, nasal issues, abdo pain, hepatic dysfunction

Examples = ambrisentan, Bosentan, Macitentan

Question 10

Advanced therapies in PH
-Phosphodiesterase 5 inhibitors

Answer 10

• Mech - inhibit PDE5 = relaxation of smooth muscle in pulm vasc bed = vasodilation and reduction in pulm vascular resistance
• increase exercise capacity in pulmonary hypertension
• Examples - sildenafil, tadalafil

Question 11

Advanced therapies in PH
-Prostacyclins

Answer 11

• Mech - inhibit platelet aggregation. Cause direct vasodilation of pulm arterial bed = improved haemodynamics and exercise capacity
• ADR - increased bleeding, vasodilation, hypotension, dizziness, headache, jaw pain, nausea, vom, diarhoea
• Examples - epoprostenol, Iloprost, Treprostinil
• Do not stop drug suddenly = rapid deterioration

Question 12

Advanced therapies in PH - indications

Answer 12

Group 1 PAH (b/c nil primary therapies)
Symptoms
Group 4 if not operative candidate or bridge to surgery
Avoid:
Groups 2,3 - may be harmful in group 2, and no benefit proven with group 3
Unclear - group 5

Question 13

Airway Hyperresponsiveness

Answer 13

Direct - methacholine, histamine
Indirect - mannitol, hypertonic saline

Question 14

Alpha 1 anti-trypsin deficiency

• What does AAT do?
• How does it cause lung damage?
• How dose it cause liver damage? Which genotype is at highest risk?
• Inheritance?
• General principles of therapy?

Answer 14

• AAT is a serine protease inhibitor encoded by SERPINA1 (aka PI) on chromosome 14
• Classic presentation in COPD: panlobar (panacinar) basal emphysema in a young <45years patient
• null/null OR Z/null OR Z/Z - very high risk of COPD with
• ZZ also having high risk of liver disease
• SZ = increased risk of COPD + ?increase in lung disease
• M/null, M/Z - possible increase risk in COPD

Question 15

Anti-muscarinic drugs in COPD

Answer 15

• Block bronchoconstrictor effects of acetylcholine on M3 muscarinic receptors expressed in airway smooth muscle
• SAMAs (ipratropium and oxitropium) also block the inhibitory neuronal receptor M2, which potentially can cause vagally induced bronchoconstriction
• LAMAs eg tiotropium, have prolonged binding to M3 muscarinic recptors, with faster dissociation from M2 muscarinic receptors = prolonged bronchodilation
• LAMAs improve symptoms, health status, effectiveness of pulmonary rehab, reduce exacs and related hospitalisations
• Nil impact on lung function decline
• ADRs - inhaled LAMAs/SAMAs are poorly absorbed = less symptomatic anticholingeric effects
• SE - dry mouth, bitter/metallic taste
• ?small increase in cardiovascular events with ipratropium

Question 16

Antibiotics in STABLE COPD

Answer 16

Long term azithromycin and erythromycin Rx reduces exac over 1 year BUT
Azithromycin is associated with increased bacterial resistance and hearing impairments

Question 17

Benefits of CPAP in OSA

Answer 17

Improves

• MVA
• Daytime sleepiness
• Depression
• Cognitive dysfunction
• Quality of life
• Systolic and Diastolic BP

NO improvement

• Cardiovascular mortality (no RCT data)
• Cardiovascular event rates (SAVE and RICADDSA 2016 studies)
• SAVE - maybe less stroke with CPAP

Question 18

Benefits of NIV in COPD

Answer 18

(When commenced early)

• decreased mortality
• decreased intubation intiation and duration
• decreased ventilator associated pneumonia
• decreased ICU and hospital length of stay
• decreased treatment failure
• decreased symptoms of respiratory distress

Question 19

Benefits of pulmonary rehab

Answer 19

Improves:

1. Severity of dyspnoea
2. Exercise capacity
3. Health related QoL

Question 20

Beta2agonists in COPD

Answer 20

• Relax airway smooth muscle by stimulating beta2-adrenergic receptors = increased cAMP = functional antagonism to bronchoconstriction = bronchodilation
• Have no effect on mortality or rate of decline of lung function
• Improve FEV1 and symptoms
• SABAs wear off after 4 - 6 hours
• LABAs work for >12 hours
• ADRs -sinus tachycardia, cardiac arrhythmias, tremor

Question 21

Bronchiectasis

Answer 21

Question 22

Causes of High and Low DLCO

Answer 22

Question 23

Causes of hypoxia

Answer 23

Summary of causes

1. Ventilation-perfusion mismatch is nearly always the cause of clinically significant hypoxia (increased A-a gradient; good response to increased FiO2)
2. Hypoventilation -increased PaCO2, normal A-a gradient <15mmHg
3. Right-to-left shunt - increased A-a gradient, poor response to increased FiO2
4. Impaired diffusion - very rare
5. Low inspired environmental O2 eg. high altitude

Note: destaturation of mixed venous blood (eg. shock) can worsen hypoxemia drom other causes

Question 24

Causes of hypoxia with elevated A-a gradient

Answer 24

1. Diffusion defect
2. V/Q mismatch
3. Right to left shunt
4. Conditions of increased O2 extraction

Question 25

Causes of hypoxia with normal A-a gradient

Answer 25

1. Alveolar hypoventilation - But these patients have high PaCO2
2. Low PiO2 - When FiO2 <0.21 or barometric pressure <760mmHg

Question 26

Causes of pulmonary fibrosis

• Upper lobe: SCATO
• Lower lobe: RASHO

Answer 26

Question 27

Cystic Fibrosis epidemiology in Australia

Answer 27

• 1 in 2800 live births
• 1 in 25 people are asymptomatic carriers of a CF gene mutation
• 50% of the CF population were hospitalised at least once in 2003
• Life expectancy is improving

Question 28

CFTR modulator therapies

Answer 28

Ivacaftor - potentiator

• facilitates opening of Cl- channel and improves CFTR activity
• increases time open

Lumacaftor - corrector

• Improves CTFR production/processing
• puts more in

Tezacaftor combined with Ivacaftor

*

Question 29

Cheyne-Stokes breathing in PSG

Answer 29

• 3 consecutive central respiratory events, separated by the characteristic crescendo-decrescendo respiratory pattern.
• on average >5/hour of sleep characteristic apneas or hypopneas must occur
• length of each crescendo-decrescendo cycle must be at least 40 seconds
• Longer cycle lengths are associated with more severe cardiac disturbance.
• Associated in CCF, neurologic diseases or use of sedative medications

Question 30

Classification of Lung Ca

Answer 30

• NSCLC - 85%
• SCLC - 15%
• Remember EGFR and ALK - as have targetted agents

Question 31

Classification of pulmonary HTN

Answer 31

• Group 1 - Pulmonary arterial HTN (PAH)
  
  • causes: idiopathic, inherited, drugs, CTD (scleroderma, RA, SLE), HIV, portal HTN, CongHD, schistosomiasis
  • worst survival of all the groups
• Group 2 - PH due to left heart disease (also have elevated LA pressure > 14mmHg)
  
  • causes LV systolic/diastolic dysfunction, Mitral/aortic valve disease
• Group 3 - PH due to chronic lung disease and/or hypoxaemia
• Group 4 - PH due to chronic thromboembolic disease
• Group 5 - PH due to unclear multifactorial mechanisms

Question 32

Classification of severity of COPD

Answer 32

Question 33

Classification of Spontaneous Pneumothorax

Answer 33

Primary spontaneous vs Secondary Spontaneous

• Primary spontaneous: occurs in the absence of a precipitating event, in a person without known lung disease
• Secondary spontaneous: all other spontaneous pneumothoracies

Question 34

Clinical severity scale for obstructive ventilatory defects

Answer 34

• Mild - FEV1% predicted >70%
• Moderate - FEV1% predicted 60 - 69%
• Moderately Severe - FEV1%predicted 50 - 59%
• Severe - FEV1% predicted 35 - 49%
• Very severe - FEV1% predicted <35%
• A similar scale can be applied for restrictive defects with FVC substituted

Question 35

Combination Therapies in COPD

Answer 35

• Combinations of SABA + SAMA are more effective compared to either medication alone in improving FEV1 and Sx
• LAMAs>LABAs at reducing exacerbaions and decreasing hospitalisation
• LABA + LAMA increases FEV1, reduces Sx and exacs compared to monotherapy
• In summary combination therapies are more effective than the individual therapies

Question 36

Complications of OSA

Answer 36

• Poor daytime functioning - sleepiness and fatigue = increased risk of accidents
• Psychiatric disorders
• Cardiovascular morbidity - increased risk of systemic HTN, pulm HTN, CAD, arrhythmias, CCF, stroke
• Metabolic syndrome and T2DM
• NAFLD
• Increased perioperative complications
• Mortality - all cause if severe and untreated

Question 37

Conditions known to respond to NIV

Answer 37

• Exacerbations of crhonic obstructive pulmonary disease (COPD) that are complicated eby hypercapnic acidosis (PaCO2> 45mmHg or pH < 7.30)
• Cardiogenic pulmonary oedema
• Acute hypoxic respiratory failure

Question 38

Connective tissue disorders related to interstitial lung disease

Answer 38

Of note:

1. SLE - is LESS likely to cause ILD. More Pleural or serositis with diffuse alveolar damage (DAH) ie pulmonary haemorrhage
2. RA - UIP pattern is common
3. Scleroderma - NSIP pattern is common

Question 39

Contraindications to NIV (8)

-AKA the need for emergent intubation is required

Answer 39

1. cardiac or respiratory arrest
2. Inability to cooperate, protect the airway, or clear secretions
3. Severly impaired consciousness
4. Nonrespiratory organ failure that is acutely life threatening
5. Facial surgery, trauma or deformity
6. High aspiration risk
7. prolonged duration of mchanical ventilation anticipated
8. Recent oesophageal anastomosis

Question 40

CPAP (term used in NIV) = PEEP (term used in invasive vent)
Positive End Expiratory Pressure

Answer 40

• Continuous pressure - regardless of whether patient is inspiring or expiring
• Generally 5 to 20cmH2O (mmHg if PEEP)

Question 41

Criteria for Anti-fibrotic drugs for interstitial lung disease

Answer 41

• HRCT consistent with IPF in ast 12 months
• FEV1/FVC >0.7 - not obstructed
• FVC > 50%
• DLCO > 30%
• MULTIDISCIPLINARY DIAGNOSIS
• Patient must not have ILD due to other known causes including domestinc and occupational environmental exposures, CTD or drug toxicity
• Must by treated by specialist respiratory physician

Question 42

• *Chronic Thromboembolic Pulmonary Hypertension**
• epidemiology, 1 major RF
• cardinal symptom
• first test
• 3 steps of management - what is the definitive therapy?

Answer 42

Type 4 PAH

Question 43

Current recommendations for treatment of IPF

Answer 43

*pretty much only antifibronlytics

Question 44

CXR findings in PH

Answer 44

Enlargement of central pulmonary arteries with attenuation of peripheral vesels = oligemic lung fields
Also RV enlargement (diministed retrosternal space), RA dilation (prominent RH border)
+/- underlying cause = interstitial lung disease

Question 45

Define: Apnoea, hyponpnoea and Respiratory effort-related arousals in PSG

Answer 45

• Apnoea - >90% decrease in airflow compared with preceding signals for >10 seconds
• Obstructive = continued respiratory effort throughout event
• Central = NO respiratory effort throughout the event
• Mixed = NO respiratory effort at the start, followed by respiratory effort at a later part of the apnoea
• Hypnoea - reduction of airflow to a degree that is insufficient to be called an apnoea
  
  • Airflow decreases >30% but (<90%) c/f baseline
  • The diminished airflow lasts >10 seconds
  • Associated with either a 3% O2 desat from baseline or an EEG arousal
• RERA (respiratory effort related arousal) - change in ariflow that is insufficient to be called apnoea or hyponoea
  
  • event >10sec with flattening of the nasal pressure waveform and/or evidence of increased respiratory effort terminating in arousal

Question 46

Definition of Reversibility in Spirometry

Answer 46

• A >12% AND >200mL increase in FEV1 or FVC is a significant reversible response to bronchodilators
• If reversibility is substantial: >400ml then treat for asthma

Question 47

Diagnosis of Cystic fibrosis

Answer 47

• Newborn screening program
  
  • heel prick blood test 48 - 72 hours
  • measures immunoreactive trypsin (high sens, low spec)
• If elevated samples are tested for mutations in CFTR gene (but >2000 mutations)
• homozygous or compound heterozygous mutations = assumed CF
• Sweat test for confirmation (sweat chloride > 60mmol/L)
• NB: compound heterozygote = 2 different mutant alleles at a particular gene locus
• Clinical presentation at birth with meconium ileus

Question 48

Direct vs Indirect Bronchoprovocation Tests

• What does each detect, which is better for asthma
• What agents are for direct (2), indirect (3)
• What marks a positive test in each
• Which is more sensitive
• Which is more specific

Answer 48

Question 49

Drugs shown to slow disease progression in idiopathic pulmonary fibrosis (IPF)

Answer 49

• Pirfenidone - pleotrophic novel antifibrotic
  
  • ADR: GIT (nausea, diarrhoea, dyspepsia, and vomiting), photosensitive rash, derranged LFTs
• Nintendanib - intracellular TK inhibitor
  
  • ADR: Diarrhoea also nausea, vomiting and decreased appeptite, derranged LFTs. Possible cardiovasculat risk and bleeding risk for those anticoagulated
  • contraindicated if significant IHD
• As per FVC monitoring (ASCEND, IMPULSIS)
  
  • trials included only patients with mild-mod disease

Question 50

Easy formula for Aa gradient at sea level at room temp

Answer 50

PaCO2/0.8 = adding a quarter to it

Question 51

ECG features of PE

Answer 51

Sinus tachycardia +

1. peaked P waves
2. right axis deviation (S waves in lead I)
3. Tall R waves in lead Vi
4. Right bundle branch block
5. Inverted T waves in lead Vi (normal) spreading across to lead V2 or V3
6. A shift to transition point ot the left, so that the R wave equals ths S wave in lead V5 or V6 rather than in lead V3 or V4 (clockwise rotation). A deep S wave will persist in lead V6
7. Q wave in lead III resembling an inferior infarction

Question 52

ECG findings of pulmonary HTN

Answer 52

Signs of RVH or strain

• Right axis deviation,
• R wave: S wave ratio > 1 in lead V1,
• complete or incomplete right BBB
• p pulmonale (peaked p wave in II)

Question 53

Extrapulmonary manifestations of CF (10)

Answer 53

1. Sinus disease - common
2. Pancreatic disease
   
   • pancreatic insufficiency = 2/3 at birth 25% more during childhood.
   • 15% remain sufficient = risk of pancreatitis
   • CF related diabetes = 25% by 20 years, 50% of adults
3. Meconium ileus - up to 20% of newborns
4. Rectal prolapse - rare (more likely if pancreatic enzyme therapy not done)
5. Hepatobiliary disease - common but rarely progressive
6. Infertility - >95% of men most commonly due to absent vas deferens (Rx microsurgical epididymal sperm aspiration). CF women also less fertile than other women
7. MSK
   
   • reduced bone mineral content = increased risk of fractures and kyphoscoliosis
   • CF associated arthropathy - 2 to 9%
   • hypertrophic osteoarthropathy (uncommon) 5%
   • aquagenic wrinkling (wrinkling and nodules after immersion in water) - up to 80%
8. Recurrent VTE - ?related to long term CVC
9. Anaemia - 10% of children, more common with advancing age and declining lung function (Fe deficiency, chronic inflam)
10. Nephrolithiasis and neprocalcinosis - common (27 - 92%)

Question 54

Factors associated with accelerated decline in lung function in asthma

Answer 54

Question 55

Factors associated with increased risk of flare ups in asthma

Answer 55

Question 56

Factors associated with increased risk of life-threatening asthma

Answer 56

Question 57

Factors associated with treatment-related adverse events in asthma

Answer 57

Question 58

Features of life-threatening asthma (7)

Answer 58

1. Reduced consciousness or collapse
2. Exhaustion
3. Cyanosis
4. O2 saturation <90%
5. Poor respiratory effort,
6. Soft/absent breath sounds
7. Can’t speak

Question 59

Features that increase risk of recurrence of primary spontaneous pneumothorax

Answer 59

• Female gender
• Tall stature in men
• Low body weight
• Failure to stop smoking

Question 60

Fleischner guidelines for follow up of solid pulmonary nodule
-What 6 features makes someone high risk?

Answer 60

Probabiity of malignancy

• Low <5%
  
  • young, less smoking, no prior cancer, small nodule size, regular margins and non-upper lobe
• Intermediate (5-65%)
  
  • mixture of low and high probability features
• High (>65%)
  
  • older, heavy smoking, prior cancer, larger size, irregular margin, upper lobe location

Question 61

Flying post pneumothorax
-When can patient’s fly

Answer 61

1 week post full resolution

Question 62

Genetic Mutation of Cystic Fibrosis

Answer 62

Autosomal recessive mutation of cystic fibrosis transmembrane conductance regulator (CFTR) protein on Chromosome 7

• CFTR regulates Cl + Na channels - mutations lead to thickened secretions
• Most common mutation F508del AKA Delta F508 found in 70% Caucasian CF patients

There are categories of CFTR gene mutation

• Class I - defective protein production = 2 - 5% of cases worldwide
• Class II - defective protein procssing (inc Delta F508) = 70% in USA
• Class III - defective regulation
• Class IV - defective conduction
• Class V - Reduced amounts of functional CFTR

Question 63

Human airways - anatomy

Answer 63

• Terminal bronchioles are the smallest airways without alveoli
• The conducting zone = anatomical dead space (nil gas exchange), vol 150ml
• Respiratory zone = where gas exchange occurs, vol 2 - 3L

Question 64

Hypercapnic and Hypocapnic Central sleep apnoea

• Hypercapnic CSA = causes, phenotype
• Hypocapnic CSA = causes, phenotype

Answer 64

Question 65

Indications for home O2

Answer 65

PaO2 <55mmHg OR <60mmHg if end organ disease

Question 66

Indications for long-term O2 therapy in COPD

Answer 66

Question 67

Indications for lung biopsy in interstitial lung disease (ILD)

Answer 67

PEARL - definite UIP does NOT need a biopsy

Question 68

Indications for lung transplantation in IPF (7)

Answer 68

Lung Tx is the only definitive cure for IPF - refer all appropriate patients regardless of severity
Indications

1. Desaturation to <88% or distance <250m on 6 min walk test
2. >50m decline in 6 min walk test distance in 6 months
3. Fall in FVC >10% or DLCO >15% during 6 month follow up
4. Pulmonary HTN
5. Hospitalisation for acute exacerbation
6. Respiratory decline
7. Pneumothorax

Question 69

Indications for NIV (Non invasive ventilation) in COPD

Answer 69

Question 70

Inhaled corticosteroids in COPD

Answer 70

• ICS + LABA is more effective than either as monotherapy at improving lung function, health status and reducing exacerbations
• However regular ICS therapy increases risk of pneumonia especially if severe disease
• Triple Rx - ICS + LABA + LAMA improves lung function, Sx and health status, reduces exacs compared to to monotherapy
• In summary triple therapy is great but prolonged use of ICS increases risk of pneumonia
• Long term PO glucocorticoids have numerous SE an no benefits in stable COPD
  
  • Have a role in acute exac only
• ICS alone do not modify long-term decline of FEV1 nor mortality in COPD
• ADRs of ICS
  
  • PO candidiasis, hoarse voice, skin bruising, pneumonia

Question 71

Initial treatment options in asthma

Answer 71

Question 72

Intervention most likely to reduce exacerbations in COPD

Answer 72

Pulmonary Rehab

(no mortality benefit)

Question 73

Ivacaftor - drug profile

Answer 73

• Indication: CF with G551D or other gating (Class III) mutation or an R117H mutation of the CFTR gene
• Mechanism of action: Improve Cl transport by potentiating CFTR
• Benefits G551D pts: Reduces number of pulmonary exacerbations, improves FEV1 and weight
• ?Benefits in R117H pts: improved lung function and QoL
• Cautions
  
  • nil longterm safety data
  • may cause cataracts in long term use
  • drug interactions and hepatic metabolism

Question 74

Light’s Criteria for Pleural Effusion

Answer 74

If clinical suspicion of transudate
-Serum:pleural protein gradient if >31g/L likely transudate
=Serum Protein - Pleural Protein

• *If <31** can do albumin gradient if >12 most likely transudate
• *Ratio <0.6 is the most senstive for transudate**

Question 75

Lung Volume Reduction Surgery

Answer 75

Lung volume reduction surgery (LVRS) - reduction pneumoplasty is a surgical technique that involves reducing the lung volume by multiple wedge excision in areas where emphysematous changes are most marked. Typically the amount of tissue resected is 20 to 35 percent of the volume of each lung.

LVRS modestly improves spirometry, lung volumes, exercise capcity, dyspnoea and quality of life and may improve long-term survival among highly selected patients. Certain clinical features appear to influence the degree of risk and benefit.

Potential complications of LVRS include persistent air leak, intraoperative myocardial infarction, reintubation, prolonged mechanical ventilation, pneumonia, wound infection, arrythmias, DVT, PE and death.

Recommend NOT performing LVRS in high-risk patients (FEV1 20% of predicted or less and either a DLCO of 20% predicted or less or homogenous emphysema on CT)

Question 76

Management of Pleural Infection

Answer 76

Question 77

Management of Spontaneous Pneumothorax

Answer 77

Question 78

Mask choice in NIV

Answer 78

• Face mask - greatest physiological improvement, poorly tolerated and difficult to monitor for aspiration
• Nasal mask - best tolerated, but risk of airleak through mouth
• Oronasal mask is preferred for initial use - if no benefit trial full face mask

Question 79

Medication options in chemical pleurodesis
Tetracyclines vs Talc

Answer 79

Tetracycline (doxycycline or minocycline)

• SE: allergic reaction to ABx –> respiratory failure

Talc

• causes severe CP +/- chronic pain, ARDS

UTD prefers tetracyclines due to similar efficacy and no association with ARDS

Question 80

Mepolizumab

• mechanism
• indication + factor which indicates likely response
• 3 benefits
• 1 Caution

Answer 80

Question 81

Methylxanthines in COPD

Answer 81

Controversy re mechanism of action
-likely non-selective phosphodiesterase inhibitors
eg. Theophylline is metabolised by CYP450 mixed function oxidases
Clearance of drug declines with age, many other variables also alter drug metabolism
Improves FEV1 and Sx of breathlessness
ADRs - toxicity is dose related (bad because therapeutic levels are very close to toxic levels)
Fatal cardiac arrhythmias, grand mal convulsions (irrespective of prior epilepsy Hx), headaches, insomnia, nausea, heartburn (last 4 can occur in therapeutic range)
LOTS of drug interactions

Question 82

Most common aetiologies for secondary pneumothorax

Answer 82

• COPD - most common, worse COPD = worse risk
• CF
• Primary or metastatic lung malignancy
• Necrotising pneumonia
• Lots of others less common

Question 83

Nintedanib

Answer 83

Intracellular inhibitor that targets multiple TKs

• Effects
  
  • Significant reduction in FVC decline (approx 109ml) aka slows progression
  • NO change in time to first exacerbation or QOL
• ADR
  
  • GI upset - 60% diarrhoea, nausea
  • Similar efficiacy to Pirfenidone
  • Possible cardiovascular risk
  • Possible small increase in bleeding risk -avoid in those on anticoagulants

Question 84

Non-specific interstitial pneumonia (NSIP) pattern

Answer 84

• More ground glass opacities
• Less honeycombing
• Better prognosis
• no subpleura involvement

Question 85

Obesity Hypoventilation Syndrome

• define
• main RF
• main co-existing condition
• 2 pillars of therapy
• which Rx to avoid
• main cause of death

Answer 85

Question 86

Omalizumab in Asthma

Answer 86

• *Mech -** recombinant humanised mAb directed against IgE = reduces immune system response to allergen exposure
• *Indication -** maintence of mod-severe allergic asthma in pts Rx with ICS and with raised serum IgE levels
• *ADR -** thrombocytopenia, bleeding, MSK pain, ?Churg Strauss, anaphylaxis
• *AKA - Xolair**

Question 87

Only factors which improve survival in COPD

Answer 87

1. Smoking Cessation - also slows decline in FEV1
2. Oxygen Supplementation

Question 88

Pathogens of CF

Answer 88

• Initial - Staph. aureus, Haem. influenzae
• During adolescence and adulthood - pseudomonas aeruginosa
  
  • early pseudomonas is quite sensitive
  • later mucoid phenotype develops = biofilm => resistance to ABx
• Other
  
  • Burkholderia cepacia
  • Stenotrophomonas maltophilia
  • Achromobacter xylosoxidans
  • nTB and fungi

Question 89

Pathologic stages of ARDS

Answer 89

1. Exudate stage - diffuse alveolar damage, then after 7 - 10 days
2. Proliferative stage - resolution of pulmonary oedema, proliferation of type II alveolar cells, squamous metaplasia, interstitial infiltration by myofibroblasts, and early deposition of collagen
3. Some progress to Fibrotic stage - obliteration of normal lung architecture, diffuse fibrosis and cyst formation

Question 90

Pathological Findings in Asthma

Answer 90

• Airways are infilitrared by
  
  • eosinophils
  • Activated T lymphocytes
  • Activated mucosal mast cells
• There is also
  
  • thickening of the basement membrane due to collagen deposition in subepithelium
  • Hypertrophy of airway smooth muscle
• In fatal asthma
  
  • ​multiple airways occluded by mucous plugs
  • Airway oedema

Question 91

Pathophysiology of ARDS

Answer 91

1. Alveolar injury leads to
2. Release of inflammatory cytokines (TNF, IL1, IL6, IL8) these
3. Recruit neutrophils to the lungs where they become activated and
4. Release toxic mediators which
5. Damage capillary endothelium and alveolar epithelium which
6. Allows protein to escape vascular space which
7. Changes the oncotic gradient which normally favours resorption of fluid so
8. Fluid poors into interstitium, overwhelming lymphatics so
9. Airspaces fill with blood, proteinaceous oedema fluid and debris (and functional surfactant is lost
10. End result = alveolar collapse = impaired gas exchange, decreased complaince and increased pulm artery pressure

Question 92

PFT algorithm

Answer 92

Question 93

Pharmacological Management of IPF

Answer 93

Question 94

Phosphodiesterase-4 (PDE4) inhibitors in COPD ?not yet available in Australia

Answer 94

• Mechanism - reduce inflammation by inhibiting the breakdown of intracellular cAMP
• E.g. Roflumilast - reduces moderate and severe exac
• ADRs
  
  • GIT: Diarrhoea, nausea, reduced appetite –> LOW, abdo ppain
  • Other- sleep disturbance, headache, ?depression

Question 95

Pirfenidone

Answer 95

• Exact mechanism of action unknown - antifibrotic, antiinflammatory, antioxidant
  
  • Regulates TGF B1 and TNF alpha in vitro
  • Inhibits fibroblast proliferation and collagen synthesis
  • Reduces cellular and histological markers of fibrosis (animal models)
• Effects
  
  • 1. Reduction in decline in FVC and 6MWT
  • 2. Improved progression free survival
  • NO reduction in dyspnoea scores or death
• ADRs
  
  • 1. Photosensitivity - must wear sun protective clothing!!
  • 2. Nausea, diarrhoea
  • 3. Rash

Question 96

Poor prognostic factors in pulmonary HTN (12)

Answer 96

1. Age > 50 years
2. Male gender
3. WHO functional class III or IV
4. Failure to improve WHO functional class during Rx
5. RV dysfunction
6. Reduced pulmonary arterial capacitance (SV/pa pulse pressure)
7. Hypocapnia
8. Comorbidities (COPD, DM)
9. PAH associated with CTD
10. SSRI use
11. Low vWF levels
12. Bone morphogenetic protein receptor type 2 BMPR2 mutations

Question 97

Possible biomarker algorithm for pleural effusions

Answer 97

Question 98

Pressure Control (PC) Ventilation

Answer 98

• Patient or time can trigger ventilation
• Can independently determine pressure delivered to lungs
  
  • If low compliance of lungs = low lung volumes
  • If high compliance of lungs = high lung volumes

Question 99

Pressure Support Ventilation (PS)

Answer 99

• Patient initiates breaths
• Patient gets a specific pressure only on inhalation

Question 100

Primary therapies in pulmonary HTN

Answer 100

• Group 1 (idiopathic/inherited) = no primary therapies
• Group 2 (2nd to LH disease) = Rx underlying heart disease
• Group 3 (2nd to lung disease causing hypoxaemia) = Rx undering hypoxia cause and supplemental O2 (mortality benefit)
• Group 4 (2nd of chronic TE of prox/distal pulmonary vasculature) = anticoagulation, surgical thromboendartectomy
• Group 5 (2nd to multifactorial) = Rx underlying

Question 101

Principles of Pulmonary HTN treatment

Answer 101

1. Assess severity (WHO functional classification + echo +/-RHC)

• Class I - no limitations of physical activity
• Class II - slight limitation of physical activity, comfortable at rest
• Class III - marked limitation of physical activity, comfortable at rest
• Class IV - inability to complete physical activity without Sx. Sx at rest

1. Primary therapy - address underlying cause
2. Advanced therapy - directed at PH

Question 102

Prognostic markers in pleural infection
RAPID

Answer 102

Question 103

Progression of Pulmonary Disease in Cystic Fibrosis

Answer 103

• Start - recurrent cough which becomes persistent
• recurrent respiratory tract infection due to inability to clear secretions
• chronic infection/inflammation –> progressive tissue damage in airways
• lysosomal enzymes released from infiltrating neutrophils contribute to progressive airway destruction
• airway becomes floppy + collapsible under conditions of high flow = air trapping +airway hyperreactivity

Question 104

Pulmonary Function Testing in CF

Answer 104

Normal in newborns
Signs of deterioration by 6months
Overtime - develop obstructive pattern
Lung volumes (TLC and RV) will increase due to hyperinflation
FEV1 correlates with survival in CF

Question 105

Pulmonary HTN - definition

Answer 105

Mean arterial pressure >25mmHg at rest of pulmonary artery

Normal ~ 20mmHg

Question 106

Pulmonary Rehabilitation in COPD

Answer 106

• Multidisciplinary approach
• Optimum benefits achieved from programs lasting 6 - 8 weeks
• Supervised exercise training twice weekly is recommended
• Rehabilitation - shown to be the most effective therapeutic strategy to improve SOB, health status and exercise tolerance
• Education alone is not effective

Question 107

Relative contraindications to lung transplantation (9)

Answer 107

Question 108

Removal of inhaled particles from the body

Answer 108

• Large particles - filtered out in the nose
• Smaller particles - removed by muco-cillary escalator
• Even smaller particles that make it to alveoli - engulfed by macrophages –> removed via lymphatics/blood flow

Question 109

Risk factors for pneumothorax

Answer 109

Primary spontaneous

• SMOKING (biggest)
• male gender
• cannabis smoking
• FHx
• Marfans
• Homocystinuria
• Thoracic endometriosis

Question 110

Sg and Sx of pulmonary HTN

Answer 110

Symptoms - do not usually occur until pressure 2x normal (50mmHg)

• Initial - exterional dyspnoea, fatigue (because you can’t adequately increase CO during exercise)
• Later - develop evidence of severe PH with RVF - exertional CP/syncope (when O2 demand goes up), oedema, ascites, pleural effusion

Signs

• Initial - increased P2, palpable P2
• Later - as RV hypertrophy develops –> prominent a wave of JVP due to forceful contraction of RA
• Even later - wider splitting of S2, RV heave. Systolic ejection click, S4, pulmonary ejection murmur
• Systemically in very severe disease - tachypnoea, peripheral cyanosis, cold extremities
• Pulse - small volume (severe disease)

Question 111

Spirometry Interpretation

Answer 111

First look at FEV1/FVC

• if > LLN then look at FVC - if FVC > LLN = normal study,
• if > LLN then look at FVC - if FVC< LLN = possible restrictive defect
• if < LLN or <0.70 then look at FVC - if FVC > LLN = obstructive defect
• if < LLN or <0.70 then look at FVC - if FVC < LLN = mixed: obstructive defect with possible restrictive defect or gas trapping

NOTE: post bronchodilator fixed ratio of FEV1/FVC < 0.70 = COPD type airflow limitation

Question 112

Spirometry result which indicates air trapping and hyperventilation

Answer 112

• Airtrapping: FRC or RV increased >120% predicted
• Hyperventilation: TLC increased >120%

Question 113

Stepwise management of Asthma

Answer 113

Question 114

Stepwise Management of Stable COPD

Answer 114

Triple therapy may reduce rate of exac and reduce hospitalisations – for stable COPD patients

• In patients with a history of exacerbations during the previous year:
• Triple therapy with fluticasone furoate, umeclidinium and vilanterol (ICS/LABA/LAMA) resulted in:
  
  • Lower rate of moderate or severe COPD exacerbations than
    
    • Fluticasone furoate–vilanterol (ICS/LABA) or
    • Umeclidinium–vilanterol (LAMA/LABA)
  • Lower rate of hospitalisations due to COPD than
    
    • Umeclidinium–vilanterol (LAMA/LABA)

Question 115

The primary causes of death post lung transplantation

Answer 115

• Within 30 days: Primary graft dysfunction (PGD)
  
  • a form of ARDS/diffuse alveolar damage
• After the first year: Chronic lung allograft dysfunction (CLAD)
  
  • bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome
• Less but still common at all time points
  
  • infection EG bacterial bronchitis/pneumonia, also fungi, CMV, viral and mycobacteria
• Less common
  
  • malignancy (most common overall: non-melanoma skin cancer, most common after 1 year posttransplant lymphoproliferative disease (PTLD))

Question 116

The role of pharmacotherapy in stable COPD

Answer 116

There is no conclusive clinical trial evidence that any existing meds for COPD modify long-term decline in lung function

Question 117

Theophyllines

Answer 117

• Mech - unclear ?sm musc relaxation, anti-inflam, increase diaphragm contractility, and CNS stimulation
• Many, many precautions + narrow therapeutic range
• ADR - nausea, vom, diarhoea, GORD, headache, insomnia, anxiety, tremor
  
  • +Rarely seizures, arrhythmias, tachycardia

Question 118

Total ventilation, alveolar ventilation definitions, and physiological deadspace

Answer 118

• Total ventilation (total volume leaving lung/min) = TV x RR
• Alveolar ventilation (volume of air available for gas exchange/min) = (TV - anatomical deadspace) x RR
• Physiological dead space - volume of gas that does not eliminate CO2
  
  • Anatomical and physiological dead spaces are roughly equal in healthy pts
  • Physiological increases in lung disease

Question 119

TPA and DNase for empyema Mx

• name the 2 benefits
• what is the current role

Answer 119

TNA/Dnase may be an option for patients in whom standard therapy has failed and who are not a candidate for thoracic surgery

Question 120

Treatment of OSA

Answer 120

• Weight loss
• CPAP
• Oral appliances
• Upper airway surgery
• Hypoglossal nerve stimulation
• Devices - nasal splints, expiratory valves, chin straps

Question 121

Treatment of primary spontaneous pneumothorax

Answer 121

>2cm!

Question 122

Type 1 vs Type 2 Respiratory Failure

Answer 122

• Type 1 - Oxygenation failure
  
  • Examples: ARDS, Pneumonia, CCF
• Type 2 - Ventilation failure
  
  • Examples: COPD, Asthma

Question 123

Usual interstitial pneumonia - CT findings

Answer 123

UIP - RASH

1. Reticular abnormality
2. Absence of inconsistent features
3. Subpleural, basal predominance
4. Honeycombing with or without traction bronchiectasis

Question 124

Vaccinations for stable COPD

Answer 124

1. Influenza - reduces serious illness and death in COPD patients
2. 23-valent pneumococcal polysaccharide vaccine (PPSV23) reduces CAP in COPD pts <65yrs with FEV1 <40% predicted + have comorbidities

• In the general population of adults >65years the 13-valent conjugated pneumococcal vaccine (PCV13) reduces bacteraemia and serious invasive pneumococcal vaccines

Question 125

Value of FEF 25-75

Answer 125

• It is the mean forced expiratory flow between the 25% and 75% of the FVC
• Reflects flow in smaller, peripheral airways
• May be reduced in early obstructive disease

Question 126

VO2 max formula

Answer 126

VO2 = maximum rate of oxygen consumption measured during incremental exercise; that is, exercise of increasing intensity.

Question 127

What are the benefits of the different advanced therapies for pulmonary HTN?

Answer 127

Soluble Guanylate Cyclase (sGC) Stimulators

• Soluble guanylate cyclase (sGC) is an enzyme in the cardiopulmonary system and the receptor for nitric oxide (NO). Pulmonary arterial hypertension (PAH) is associated with endothelial dysfunction, impaired synthesis of NO, and insufficient stimulation of the NO-sGC-cGMP pathway.
• eg of GC simulatant riocguat

Question 128

What factors shifts O2 dissociation curve to the RIGHT

Answer 128

• *CADET face RIGHT**
  increased: CO2, Acidity (decreased pH), 2-3 DGP, Exercise, Temperature

Question 129

What is the airflow at FRC

Answer 129

No airflow

Question 130

What is the full Aa gradient formula

Answer 130

Question 131

Which genetic mutation is associated with PAH

Answer 131

BMPR2 - Bone morphogenetic protein receptor 2 inactivation = inhibition of vascular proliferation

Question 132

A patient presents with PFTs showing a mixed obstructive/restrictive deficit that resolves with bronchodilators

What is the likely aetiology?

Answer 132

Pure obstructive disease with air trapping

Question 133

Are ABGs and VBGs equivalent in COPD?

Answer 133

No evidence they’re an acceptable alternative, shouldn’t be used

Question 134

Are corticosteroids of benefit in CAP? In which group?

Answer 134

• Yes, demonstrated in a meta analysis of 13 RCTs
• Pneumonia severity index (PSI) 4 and 5 have been shown to most benefit
• NNT of 18 to prevent 1 death
• 3% reduced mortality, 5% reduced need for mechanical ventilation, LOS reduced by 1 day

Another study IPD (more thorough review – gold standard) of the same studies (minus a few that wouldn’t share their data)

• More conservative conclusions than Cochrane review regarding benefits of steroids
• No difference in mortality
• Reduces LOS ~ 1 day
• Reduced time to clinical stability
• Increased hyperglycaemia requiring insulin
• Increased CAP related readmissions (NNH 45)

So… steroids in CAP?

• Not at this stage

Question 135

Are steroid sparing agents of use in asthma?

Answer 135

No for the classic ones, multiple have been tried with no benefit

• methotrexate, cyclosporin, azathioprine, gold, IVIg

Omalizumab

• neutralises circulating IgE without binding to cell-bound IgE
• reduces exacerbations in severe asthma, allows lower dose ICS, improves symptom control
• requires high IgE levels to qualify
• very expensive
• may be continued in pregnancy

Mepolizumab/reslizumab

• anti IL-5 which blocks eosinophil recruitment and activation in steroid resistant eosinophilic asthma
• reduces exacerbations 50%, improves FEV1, symptom control, and QOL
• requires peripheral eosinophilia to qualify

Benralizumab (CALIMA, Lancet Sept 2016)

• anti IL-5r inducing rapid eosinophil depletion
• Phase III RCT in those with severe uncontrolled asthma on ICS/LABA with >=2 exac in last yr and peripheral eos >300 cell/uL
• Improves exacerbation rate, FEV1

Dupilumab (Wenzel et al, Lancet April 2016)

• anti IL-4r, inhibiting IL-4/13 signalling
• Phase IIb RCT in those with uncontrolled asthma already on ICS/LABA
• improves FEV1 and reduces exacerbations regardless of baseline eosinophil count

Question 136

By what is IPF mediated? What are the treatment considerations?

Answer 136

• Aberrant wound healing thought to be the important underlying cause
• Nintedanib and pirfenidone both slow disease progression but don’t affect dyspnoea or survival
• Supplemental oxygen and pulmonary rehabilitation improve QOL

Question 137

Describe the distribution of inflammation typical of asthma and the cells that mediate it

Answer 137

Trachea to terminal bronchioles with predominance in bronchi

Mediated by airway hyperresponsiveness

Chronic inflammation punctuated by episodes of acute inflammation

Mast cells

• Found in airway surface in asthmatics, where none are normally
• Initiate acute bronchoconstrictor response to allergens or other stimuli
• IgE dependent activation mechanism
• Histamine, prostaglanding D2, cysteinyl leukotreines, other cytokines, chemokines, growth factors

Macrophages/dendritic cells

• Present antigen to uncommitted T lymphocytes
• Usually promote TH2 differentiation, require IL-12 or TNFa to differentiate to TH1
• Thymic stromal lymphopoetin instructs dendritic cells to attract TH2 into airways

Eosinophils

• Infiltration a characteristic feature of asthmatic airways
• Oxygen derived free radicals and basic proteins drive hyperreactivity
• Survive longer by adhering to vascular endothelial walls

Neutrophils

• Increased activated neutrophils may be found in some with severe asthma
• Some with mild asthma can have neutrophil predominance

T Lymphocytes

• Coordinate inflammatory response by recruiitng eosinophils and mast cells with specific cytokines
• TH2 phenotype overexpressed in naive and asthmatic immune system, which release IL-5 for eosinophilic inflammation and IL-4/13 for IgE formation
• TH1 predominate in normal airways
• Regulatory T cells play a role in expression of other cells

Structural cells

• May be more important than immune cells in chronic inflammation due to predominance
• Important source of inflammatory mediators

Question 138

Does coal dust increase risk of lung cancer?

Answer 138

Nope

Question 139

Does CPAP alter cardiovascular outcomes in OSA?

Answer 139

No

SAVE study in Sept 2016 NEJM

45-75yo with mod-sev OSA + coronary or cerebrovascular disease
- CPAP + usual care vs usual care alone

Primary end point

• death from cardiovascular causes, MI, stroke
• hospitalisation for UA, HF, TIA

AHI decreased from 29.0 -> 3.7 events per hour in the CPAP group

• *No difference in primary endpoint** (1.10; 0.91-1.32)
• **significant reduction in snoring and daytime sleepiness
• improved health related QOL and mood**

Question 140

Does immunotherapy (desensitisation therapy) help in asthma?

Answer 140

Yes

Question 141

Does snoring necessitate the presence of OSA? What is the prevalence of OSA?

Answer 141

Not necessarily, but is correlated

~23% women
~50% men

Question 142

Go through PFT interpretation

Answer 142

• *?Obstruction**
• FEV1/FVC <70% = obstruction
• *?Severity**
• mild >70%
• mod 60-69%
• mod-sev 50-59%
• sev 35-49%
• very sev <35%
• *?Reversible**
• Increase in FEV1 or FVC >12% and 200mL
• no SABA for 4hrs, no LABA for 12hrs, no LAMA for >24hrs prior
• *?Inducible**
• Direct = MetacholinE = SensitivE. Positive if >20% reduction in FEV1 with <=4mg/mL
• Indirect = Mannitol = Specific. Positive if >15% reduction in FEV1 at <=635mg cumulative
• *- Exercise** = treadmill = specific and sensitive for exercise induced bronchconstriction but not asthma. Positive if >=10% reduction in FEV1 or FVC over any two consecutive time points

?Specific volume loop pattern
Variable Extrathoracic (pharynx, larynx, extrathroacic trachea)

Question 143

DLCO interpretation

Answer 143

​?Diffusion

• DLCO high = polycythaemia, asthma, increased blood volume, L->R shunt, alv haemorrhage
• DLCO low = thick membrane, decreased surface area, decreased blood volume, decreased lung volume
• DLCO:VA (KCO) = gas exchange per unit volume. Low in pulm causes, high in extrinsic causes
• DLCO very low compared with TLC -> think pulmonary hypertension

Question 144

Go through the algorithm for approach to treatment of pulmonary arterial hypertension (group 1)

Answer 144

Question 145

Go through the various anatomical locations of insterstitum in the lungs

Answer 145

Question 146

How are SCLC and NSCLC staged? Are they different? Why? What’s the mortality like for the two subtypes of SCLC?

Answer 146

Both require imaging and tissue sampling

NSCLC staged with TNM

• CTCAP first
• If mets then no PET. If no mets then PET
• PET upstages 20%, avoiding unnecessary surgery

Question 147

How are the interstitial lung diseases (ILD) subclassified? How might they behave?

Answer 147

Varying presentations/clinical course

• Self limiting inflammation
• Inflammation with risk of progression to fibrosis
• Stable fibrosis
• Progressive fibrosis with stabilisation posisble
• Inexorably progressive fibrosis

Question 148

How bad is second hand smoke?

Answer 148

Third leading cause of preventable death in the USA

• *Increases risk of:**
• *- heart disease** 23%
• *- lung cancer** 17-30%
• COPD; asthma exacerbations; meningococcal meningitis

All cause mortality increased by 15% in lifetime non-smokers who live with smokers

Question 149

How can central sleep apnoea (CSA) be differentiated from OSA on polysomnography?

Answer 149

CSA (due to instability of respiratory controller)

• minimal hypoxia
• minimal snore
• gets better in REM

OSA (due to anatomical obstruction)

• hypoxia
• loud snore
• gets worse during REM

>80% of apnoeas have to be central to diagnose
- i.e. no flow and no chest or abdo muscular effort

Question 150

How can severity of pneumonia be categorised? What is the mortality associated with various scores?

Answer 150

CURB65
• Confusion
• Urea >7mmol/L
• Respiratory rate >30
• BP <90mmHg systolic or 60mmHg diastolic
• Age >65

Risk of death at 30 days (0-1 = outpatient; 2 = consider short stay in hospital or close observation as OP; 3-5 requires hospitalisation and consideration of ICU)

• 0 – 0.6%
• 1 – 2.7%
• 2 – 6.8%
• 3 – 14%
• 4 – 27.8%
• 5 – 27.8%

SMART-COP is probably the better score to use as it identifies those which may deteriorate rather than those who are clinically obviously severe

Question 151

How can the severity of cystic fibrosis be predicted based on genetic abnormality?

Answer 151

Severe - F508del homozygotes

• more often associated with pancreatic insufficiency
• more often associated with OP
• more often associated with DM

Less severe - F508del + other

Least severe - other + other

Question 152

How can you think of the asthma epitypes and their management?

Answer 152

90-95% of asthmatics are sorted out by ICS +- LABA

Of that 5-10% separate into:

• refractory with eosinophilia or high IgE
  
  • in which case you go to the appropriate mab (omalizumab IgE, mepolizumab IL-5, with new ones coming)
• refractory non-eosinophilic
  
  • in which case no good treatment but maybe dupilumab against IL-4r will be the go to in coming years

Question 153

How do ICS work in asthma? When are they of benefit? What are their side effects?

Answer 153

Reduce inflammatory cells and their activation

• eosinophils, surface mast cells, activated T lymphocytes
• switch off transcription of multiple genes that encode inflammatory proteins

Of benefit in any age and severity

• prevent symptoms and exacerbations
• reduce AHR
• minimise irreversible changes
• don’t cure, only suppress

ADR: Hoarseness and oral candidiasis most common

• no convincing evidence of impaired growth in children or OP in adults

Question 154

How do inhaled anticholinergics act? Are they well tolerated?

Answer 154

Muscarinic receptor antagonists

• Prevent cholinergic induced bronchoconstriction and mucous secretion
• less effective than beta agonists as they only affect the cholinergic reflex aspect

Slower than SABAs so should be used only after

Well tolerated

• most commonly dry mouth
• the elderly more likley to get urinary retention or glaucoma

Question 155

How does chronic eosinophilic pneumonia differ from acute?

Answer 155

• More indolent, never presents with acute respiratory failure and hypoxaemia
• 90% have peripheral eosinophilia
• Classic ‘photographic negative pulmonary oedema’
• >50% relapse after treatment with corticosteroids

Question 156

How does hypersensitivity pneumonitis present? How is it diagnosed? What is the strongest predictor of HP?

Answer 156

Variable presentation, strongest predictor is exposure to an antigen known to cause HP

Acute

• 4-8hrs following exposure with intense fevers, chills, malaise, dyspnoea
• resolves within hours/days without further exposure
• note that usually no wheezing

Subacute

• Gradual onset over weeks
• May occur as culmination of intermittent episodes of acute HP
• Resolves over weeks/months without further exposure

Chronic

• Insidious onset makes diagnosis a challenge
• Progressive dyspnoea, cough, fatigue, weight loss, clubbing
• Can have irreversible component
• May mirror IPF
• Fibrotic phenotypes may be associated with bird antigens
• Emphysematous phenotypes may be seen in farmer’s lung (actinomycetes; fungus)

Chronic HP with parenchymal changes is associated with poorer prognosis

• Chronic pigeon breeder’s lung has similar mortality to IPF

Diagnosis

• Careful occupation and home exposure history
• May have ill defined micronodular or ground glass opacities on CXR
• HRCT may be normal in acute; subacute characterised by groundglassing and centrilobular nodules; chronic may show reticular changes and traction bronchiectasis
• May have subpleural honeycombing similar to IPF; but spares the bases unlike IPF
• PFTs can be restrictive or obstructive
  
  • Useful for categorising physiologic impairment and gauging response to therapy
  • DLCO may be significantly impaired, especially in chronic HP with fibrotic changes
• Serum precipitins
  
  • Assays for precipitating IgG antibodies against specific antigens
  • Often provide false negatives
• Bronchoscopy
  
  • For BAL, which may show lymphocytosis which is characteristic but not specific to HP
  • note that there’s no eosinophilia
• Biopsy
  
  • Not necessary
  • Loose and poorly defined non-caseating granulomas
  • Differ from sarcoid where the granulomas are well defined
  • Mixed cellular infiltrate with lymphocytic predominance in alveolar spaces/interstitium

Question 157

How does inhaled nitric oxide affect pulmonary physiology? In which conditions might it be useful? In which harmful?

Answer 157

• Localised dilation of vasculature associated with ventilated alveoli.
• Useful in pulmonary hypertension or in severe ARDS, where optimisation of V/Q mismatch can be helpful to improve oxygenation and ventilation.
• Can worsen oxygenation/ventilation in COPD due to significant number of partially ventilated alveoli to which flow is directed

Question 158

How does pulmonary sarcoidosis present?

Answer 158

>90% of those with sarcoidosis

CTchest more sensitive but CXR preferred for characterising and following up

• • peribronchial thickening, reticular nodular changes, predominantly subpleural

Stage 0 = normal
Stage 1 = hilar adenopathy alone
Stage 2 = hilar adenopathy plus infiltrates
Stage 3 = infiltrates alone
Stage 4 = fibrosis

PFTs

• DLCO the most sensitive test for ILD
• Restrictive defect can be seen but 1/3 with abnormal CXR and dyspnoea have normal volumes
• ~50% have obstructive defect

PAH in >=5%

• Found in 70% of those with end stage awaiting transplant
• Sarcoidosis related PAH can respond to therapy

Question 159

How does sleep progress throughout the night?

Answer 159

Normal sleep in adults is consistently organised from night to night

• Progress through stages of non-REM

Have bouts of REM in cycles of 90-110 minutes

• 4-6 episodes per night
• get progressively longer
• associated with dreaming if awoken

Slow wave = used to be called stage 3/4

• Slow wave sleep may be completely absent in older adults

Sleep duration associated with weight gain and mortality

• <6hrs associated with more weight gain at 4yrs compared to more sleep
• <6hrs associated with increased mortality, seems to be mediated by inflammation

Question 160

How is allergic bronchopulmonary aspergillosis (ABPA) managed?

Answer 160

• *Oral steroids for >=12 weeks**
• induce remission
• long term doesn’t prevent relapse
• slight increase in risk of invasive aspergillus
• *Itraconazole**
• improves IgE, radiology, QOL, symptoms
• reduces prednisolone use
• use for 4 months in those who’re steroid dependent
• *Omalizumab**
• overall limited evidence
• decreases exacerbations and steroid use; reduces IgE and FeNO

IgE level a marker of disease severity and treatment response

Question 161

How is bronchiectasis managed?

Answer 161

Manage underlying disease if modifiable

• nontuberculous mycobacteria
• IgG deficiency of whatever cause
• ABPA
• COPD

Acute exacerbations

• decisions made based on symptom changes rather than investigations
• increased sputum, more viscous, darker, dyspnoea, haemoptysis
• sputum MCS prior to abx to guide therapy
• consider eradication of pseudomonas when first isolated (80% successful initially; free at median 14months f/u in 50%)

Prevention

• Positive expiratory pressure therapy (chest physio): improves QOL/FEV1/FVC; reduces sputum/inflammatory markers
• azithromycin reduces rates of exacerbation (use in frequent exacerbators >=3/yr or 2 hosp in 12 months)
• need to ensure no MAC colonisation first
• immunisations
• inhaled aminoglycacides not clear in non-CF bronchiectasis
• nebulised saline improves sputum bacteriology and QOL
• nebulised dornase increases exacerbation frequency, hospitalisation, steroid/antibiotic use
• inhaled steroids only with concommitant asthma/wheeze

Question 162

How is COPD severity classified?

Answer 162

Severe complications without severe obstruction unlikley solely due to COPD

Question 163

How is eosinophilia with pulmonary infiltrates classified? Name some of the causes

Answer 163

Question 164

How is non-cardiogenic pulmonary oedema defined? What is its main underlying pathophysiology?

Answer 164

Radiographic evidence of alveolar fluid accumulation without haemodynamic evidence of cardiogenic aetiology (PAWP <= 18mmHg)

Question 165

How long is it recommended to wait before flying after pneumothorax?

Answer 165

Most airlines recommend 6 weeks, though it has been shown to be safe to fly 2 weeks after radiological resolution of pneumothorax.

Question 166

How may asthma be differentiated from COPD clinically and on PFTs?

Answer 166

Clinically

• COPD has less variability in symptoms
• COPD never completely remits
• COPD has less reversibility with bronchodilators
• ~10% of COPD have features of asthma: eosinophils and response to OCS

PFTs (>20% improvement psot bronchodilators quite specific for asthma over COPD)

• Asthma often fully reversible with bronchodilators
• COPD may have increased TLC and decreased RV, indicated gas trapping and hyperinflation

Question 167

How much does weight loss improve OSA? What effect does CPAP have on weight?

Answer 167

Improves symptoms but very few are cured of mod-sev OSA with weight loss

• degree of weight loss doesn’t predict
• significant improvement in sleep symptoms with weight loss
• weight loss better than CPAP for metabolic benefits (CRP, insulin resistance, TGs)
• both weight loss and CPAP improve hypertension in those with OSA

Mod-sev OSA patients treated with CPAP tend to gain weight

• thought due to feeling better -> more of an appetite

Note that weight loss is an important adjunctive treatment when initiating CPAP for the metabolic benefits

Question 168

How ought COPD exacerbations be managed?

Answer 168

Bronchodilators and corticosteroids the mainstay

Bronchodilators

• SABAs: No evidence nebuliser more efficacious than MDI and spacer in asthma. Not extended to COPD but makes sense.
• Neb = 10-12 puffs ventolin
• Evidence for adding ipratropium mixed

Systemic corticosteroids

• Improve symptoms, FEV1, PaO2 in mod-sev exac
• Reduced treatment failure, relapse, length of stay
• SEs: insomnia, anxiety, depression, BSLs
• 30-50mg/day
• No advantage to IV. May be useful in first 24hrs in those in extremis and unable to take orals
• No benefit beyond 2 weeks
• 5 days likely adequate (no tapering needed)

Antibiotics

• Controversy
• Most benefit in those with all 3 symptoms: SOB, volume, purulence
• More and more evidence that sputum purulence and ?CRP are the most important
• ?CRP >40 indication for antibiotics
• In severe exacerbations decreases mortality and length of stay
• Most only require oral antibiotics
• Not unreasonable to start intravenous in the most severe exacerbations

Oxygen

• Use low concentrations aiming 88-92% SaO2. Use Prongs at 0.5-2L/min
• ideally all patients with significant exacerbation need ABGs
• Risk of worsening hypercapnoea: Alter V/Q matching, haldane effet, decrease hypoxic drive
• High flow oxygen associated with increased HDU admission, NIV and LOS

NIV

• Indicated in hypercapnoeic respiratory failure
• Use early in RR >30 and pH <7.35
• Improves biochemical markers
• Decreases failure, length of stay, rates of intubation
• Needs experienced nurses +/- HDU
• Start at low pressures
• Aim to fix RR and pH within an hour

Intubation

• Mortality 10-50%. Varying with QOL, age, acuity, comorbidities, length of ventilation, previous episodes
• Weaning may be facilitated by NIV

Question 169

How should empyema be managed?

Answer 169

Thoracotomy the gold standard

• associated with considerable morbidity and mortality as patients usually unwell and with comorbidities

Drain size

• small bore drains effective
• bigger drains = more pain and lower patient satisfaction

DNAse/tPA

• MIST-2 showed that DNase + tPA intrapleurally decreases need for surgical intervention (study endpoint was radiological and not mortality)
• note that the study did this after standard drainage deemed ineffective
• DNase alone -> higher treatment failure

Question 170

How should patients with possible PAH be risk stratified based on PFT and TTE screening?

Answer 170

Question 171

In what forms is CO2 carried in the blood?

Answer 171

• *Dissolved**
• 10% of CO2 in alveoli from blood from dissolved form

Bicarbonate

• *Carbamino compounds**
• CO2 combined with terminal amine groups of blood proteins
• Most importan globin of Hb, giving carbaminohaemoglobin

Question 172

In which group with pulmonary hypertension is there a mortality benefit to oxygen?

Is exercise training of use? In whom should the pulmonary vasodilators be used?

Answer 172

Those with pulmonary cause have oxygen benefit

Exercise training improves 6MWT more than any other management option

• *Pulmonary vasodilators**
• Good for group 1 (pulmonary artery hypertension)
• Maybe in 3,4,5
• NEVER in group 2 (cardiac cause)

Question 173

In which patients is lung resection contraindicated due to mortality risk? What can indicate patients that will tolerate pneumonectomy and lobectomy?

Answer 173

MI within 3 months

• 20% will die of reinfarction
• within 6 months relative contraindication

Uncontrolled arrhythmia
FEV1 <1L
Hypercapnoea
Severe pulmonary htn
DLCO <40%

FEV1 >2L can tolerate pneumonectomy
FEV1 >1.5L can tolerate lobectomy

Question 174

Is adaptive servo ventilation (ASV) of benefit in those with central sleep apnoea and heart failure?

Answer 174

No, harmful (note that CPAP also doesn’t alter outcomes but is not harmful)

SERVE-HF trial in September 2015 NEJM

• LVEF <=45% + AHI >=15/hr and predominance of central events
• Treatment: ASV + usual care vs usual care alone
• Primary outcome - death from any cause, lifesaving cardiovascular intervention, unplanned hospitalisation for worsening HF

AHI -> 6.6/hr in ASV group

All cause mortality (1.28; 1.06-1.55) and Cardiovascular mortality (1.34; 1.09-1.65) significantly higher in ASV group

Question 175

Is drug induced liver injury more common in those with underlying CLD?

Answer 175

No, but severity of outcome may be amplified

Exceptions in presence of hepatitis C

• Aspirin
• Methotrexate
• Isoniazid
• HAART for HIV

Question 176

Is HRCT better than CXR in immunocompromised patients?

Answer 176

Yes, very much so

HRCT is a good, sensitive test. Not overly specific.

• can give clues as to the cause of the infiltrate, e.g. fungal

Question 177

Is immunosuppression of benefit in IPF?
What did the PANTHER trial show?

Answer 177

NOO - is harmful!

Landmark study in IPF

Question 178

Is nocturnal ventilation of benefit in neuromuscular Central Sleep Apnoea (CSA)?

Answer 178

E.g.

• muscular dystrophy
• MND
• Kyphoscoliosis
• Diaphragm paralysis

MIPS (maximal inspiratory pressure) on PFTs can be a good predictor of noctural hypoventilation
- MIPS <15-20 strongly predicts

Of benefit
- decreases mortality, hospitalisations, infections, symptoms

Question 179

Is smoking cessation of use in COPD? What about vaccinations? Long term antibiotic therapy?

Answer 179

Smoking = Intervention with the greatest mortality/FEV1 impact

Flu - Reduction in number/severity of exacerbations
Pneumococcal - Reduces invasive disease

• *Antibiotics**
• Azithromycin has not become standard of care
• Signficantly increases time to first exacerbation
• Increased macrolide resistance
• No change in hospitalisations

Simvastatin doesn’t reduce exacerbation frequency (NEJM 2014)

Question 180

Is there a difference between continuous and intermittent ICS in mild intermittent asthma? What about mild persistent asthma? What about moderate persistent asthma already on ICS?

Answer 180

No for mild intermittent

• Boushey et al NEJM 2005
• RCT of 225 pts
• 200 budesonide BD vs placebo vs 20 BD zafirlukast
• Exacerbation rescue: 800 budesonide BD for 10 days or 0.5mg/kg pred for 5 days
• No difference between groups
  
  • exacerbation rate, QOL, rate of FEV1 decline over a year

Yes for persistent

• Pauwels et al Lancet 2003
• RCT of 7241 pts
• • 400 daily >11yrs, 200 daily <11yrs budesonide vs placebo
• 44% reduction in risk of hospital or ED treatment of asthma
• Improved FEV1 from baseline prebronch 1.71% and postbronch 0.88% at 3yrs
• Fewer courses of oral steroids and more symptom free days

Addition of LABA for mod persistent already on ICS

O’Byrne et al Am J Respir Crit Care Med 2001

From POV of exacerbations per year

• bud 200 = bud 400
• bud 200 + eform ~30% reduction in exacerbations (vs 200 bud)
• bud 400 + eform ~60% reduction in exacerbations (vs 400 bud)

Question 181

List the main causes of obstructive pulmonary defect

Answer 181

Asthma
COPD
Bronchiectasis
Bronchiolitis obliterans
Alpha1 antitrypsin disease
Cystic fibrosis

Question 182

Name the major causes of non-cardiogenic pulmonary oedema

Answer 182

ARDS
Neurogenic
Altitude
Re-expansion
Opioid
PE
Eclampsia
TRALI

Question 183

Of what should you be suspicious with groundglass nodules?

Answer 183

Lung adenocarcinoma that is not yet apparent

• need to keep a close eye on them
• shouldn’t be dismissed as infection

Question 184

To what does primary and advanced therapy refer in the management of pulmonary hypertension and that are the options in the different groups?

Answer 184

All

• • Pulmonary rehab improves 6MWT, QOL, WHO class, VO2max but not haemodynamics
• • Exercise training improves aerobic capacity and endurance
• • Diuretics have no RCT evidence but are used
• • Oxygen if hypoxic has no evidence but is used
• • anticoagulation for (retro observational data): IPAH, drug induced PAH, hereditary PAH, CTEPH (not in CTD group)

Primary = at underlying disease

• • group 1: CTD and HIV if the cause
• • group 2: OMT of heart failure
• • group 3: underlying disease. Continuous oxygen (>16hrs/day) if baseline PaO2<55 confers survival benefit
• • group 4: anticoagulation for 3 months, if no improvement then surgical thrombendarterectomy which may result in dramatic and sustained response (both lacking good data)
• • group 5: variable at specific aetiologies

Advanced = pulmonary vasodilators

• • in WHO functional class II-IV despite treatment of underlying cause
• • definite in group 1, almost never in group 2, case-by-case in 3-5
• • group 1: Improved survival, 6MWT, functional class, delayed disease progression, improved pulmonary haemodynamics
• • group 2: increase mortality
• • group 3: thought to worsen due to worsened V/Q mismatch
• • group 4: could consider after thrombendarterectomy or if they’re not fit for it or to bridge to surgery
• • group 5: unknown role

Agents

• *- CCBs if vasoreactive on RHC**
• improved survival, function, haemodynamics

Prostacyclin pathway

• • epoprostenol IV: first line in class IV (only medication with prospective evidence of improved survival)
• • improves function, haemodynamics and survival in IPAH, unclear if in other group 1
• • iloprost inh: improves functional class and 6MWT but needs 6-9x/day
• • selexipag: improves progression free survival and decreases hospitalisations, no change in mortality
• Endothelin receptor antagonists
• • nonselectives: bosentan, macitentan
• • bos delays clinical worsening, improves haemodynamics and exercise capacity with mortality favourable to historical controls
• • maci delayed clinical worsening, improves functional class and exercise capacity, improves combined morbidity/mortality endpoint
• • selective against A: ambrisentan
• • improves exercise tolerance, functional class, haemodynamics and QOL

NO-cGMP enhancers

• PDE5 inhibitors: sildenafil, tadalafil
• sild: improves haemodynamics and exercise capacity
• tada: improves time to clinical worsening and exercise capacity

Riociguat

• Stimulates soluble guanylate cyclase
• increases sensitivity of sGC to endogenous NO; direct stimulation of NO receptor
• improves 6MWT, WHO class, symptoms, PVR
• unknown if mortality benefit

End stage

• • lung transplant and creation of R->L shunt

Question 185

To what does vasodilator response refer and how does it change management options in pulmonary hypertension?

Answer 185

During RHC

• • short duration vasodilator administered
• • decrease in PAMP >=10mmHg to an absolute level of <=40mmHg without decrease in CO or BP

In these patients long term treatment with a dihydropyridine or diltiazem CCB confer survival, functional, and haemodynamic benefit
- use outside of vasoreactivity worsens outcomes

Question 186

What are desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis interstitial lung disease (RBILD)?

Answer 186

DIP

• • Smoking related form of ILD (one of the rarest forms)
• • Diffuse groundglass opacities, usually basal and peripheral
• • pigment laden macrophages fill alveoli on histology
• • good prognosis with smoking cessation and steroids

RBILD

• • related to DIP, some feel that DIP is just end stage RBILD

Question 187

What are some of the infectious causes of pulmonary eosinophilia?

Answer 187

Question 188

What are the adverse effects of OSA?

Answer 188

Cardio/pulmonary/vascular risk
- doubles CV risk
Sleepiness and QOL
Noise pollution
Post-operative risk

Question 189

What are the age related changes to the respiratory system?

Answer 189

Loss of elastic tissue

• • enlarged alveolar ducts -> loss of surface area for gas exchange
• • decreased lung recoil -> maximal exercise limit to expiratory flow and produces dynamic lung hyperinflation

Increased stiffness of the chest wall
Flattened and less efficient diaphragm

Physiology

• • DLCO decreases 5%/decade
• • increased V/Q mismatching
• • increase in A-a gradient
• • decreased response to hypoxaemia and hypercapnoea
• • decreased mucociliary clearance

Question 190

What are the aims of asthma therapy? What are the features of controlled/partly controlled/uncontrolled asthma? Is education important?

Answer 190

Aims of asthma therapy

• minimal chronic symptoms, ncluding nocturnal
• minmal exacerbations
• no emergency visits
• minimal use of SABA
• no limitations on activities, inclduign exercise
• Peak exp flow circadian variation <20%
• normal peak flow exp flow
• minmal ADR from medicine

Education improves compliance, especially with ICS

• also helps to recognise worsening asthma and how to step up
• Written action plans reduce admissions and morbidity in adults and children

Question 191

What are the benefits of auto-CPAP compared to fixed pressure CPAP in OSA?

What about BiPAP vs CPAP in OHS?

Answer 191

Some studies show higher patient preference and adherence

• • no benefit regarding apnoea/hypopnoea and oxygen desaturations

CPAP equally effective compared with BiPAP in OHS

• • both improve daytime hypercapnoea in those without severe nocturnal hypoxaemia

Question 192

What are the broad categories of aetiology for bronchiectasis?

Answer 192

Bronchial obstruction

• • tumours
• • hilar lymphadenopathy
• • COPD
• • mucoid impaction (ABPA)

Immunodeficiency

• • IgG: bruton’s, CVID, subclass deficiency
• • IgA: selective, ataxia telangiectasia
• • CGD

Abnormal clearance

• • ciliary defects: ciliary dyskinesia
• • cystic fibrosis
• • Young’s: obstructive azoospermia with sinopulmonary infections

Miscellaneous

• • A1AT
• • infections: childhood, bacterial, viral, other
• • recurrent aspiration pneumonia
• • CTD: RA/Sjogren’s
• • IBD
• • chronic rejection post transplantation

Question 193

What are the categories of causes of restrictive lung defects? Name some examples from each category

Answer 193

Parenchymal

• IPF
• Drugs
• Amiodarone, bleomycin, methotrexate, nitrofuraontoin
• CTD
• SLE, systemic sclerosis, RA, sarcoid, vasculitidis
• Environmental
• Asbestosis, silicosis, hypersensitivity pneumonitis
• Radiation

Neuromuscular Weakness
- GBS, ALS, muscular dystrophy, myasthenia gravis

Chest wall/pleural

• Kyphoscoliosis
• Ankylosing spondylitis
• Effusion
• Morbid obesity

Question 194

What are the causes of a fixed obstructive defect on flow-volume loop? What is its appearance?

Answer 194

Tracheal stenosis and goitre

Question 195

What are the causes of clubbing?

Answer 195

Idiopathic
- pachydermoperiostosis, familial clubbing, hypertrophic osteoarthropathy

Pulmonary

• lung cancer, pulmonary metastases, pleural mesothelioma
• ILDs, sarcoidosis, cryptogenic fibrosing alveolitis
• lung hydatids

Cardiac

• cyanotic congenital heart disease
• any right to left shunt
• IE

Gastrointestinal

• IBD
• PBC, cirrhosis, hepatopulmonary syndrome
• achalasia, peptic ulceration of the oesophagus

Skin
- Bureau-Barrière-Thomas syndrome, Fischer syndrome, palmoplantar keratoderma, and Volavsek syndrome

Malignancies

• Thyroid
• Hodgkins, disseminated CML, POEMS

Miscellaneous

• acromegaly, thyroid acropachy, severe secondary hyperparathyroidism
• sickle cell
• pregnancy

Question 196

What are the changes to pulmonary function testing (PFT) with aging?

Answer 196

Increased:

• residual volume and FRC
• V/Q mismatching
• airway reactivity
• compliance

Decreased

• FEV1
• FVC
• DLCO
• respiratory drive in response to hypoxia and hypercapnoea

Unchanged
- TLC

Question 197

What are the characteristic radiographic findings in silicosis, coal worker’s pneumoconiosis, and asbestosis?

Answer 197

• *Asbestosis**
• Irregular linear opacities in lower lung fields
• Groundglassing
• Curvilinear lines parallel to the pleural surface
• Pleural thickening
• *Silicosis**
• Crazy paving pattern
• Calcified hilar nodes
• Small, rounded upper lobe opacities
• May coalesce as disease progresses and form large, non-segmental conglomerates of irregular masses
• Simple = small, rounded opacities without PFT change
• Complicated = coalescing
• Progressive massive fibrosis = large masses
• *Coal worker’s pneumoconiosis**
• Identified in 10% of all coal miners
• Nodules similar to silicosis
• May cause chronic bronchitis and COPD
• May progress to PMF as in silicosis

Question 198

What are the clinical features of bronchiectasis? Radiological? Distribution aetiology associations?

Answer 198

• *Cough with daily production of mucopurulent and tenacious sputum for months/years the classics**
• dyspnoea, wheeze, pleuritic chest pain less so
• urinary incontinence common
• *Look for some underlying cause**
• infective, obstructive, immunodeficiency, etc
• *Imaging**
• CT preferred
• airway dilatation (>1.5x diameter of adjacent vessel)
• *- signet ring** sign classic
• *Distribution**
• *- perihilar: ABPA**
• upper: cystic fibrosis
• ML/LL: primary ciliary dysfunction
• ML/lingular of LUL: nontuberculous mycobacteria
• LL: idiopathic

Question 199

What is physiological shunt and deadspace?

Answer 199

• Shunt: Perfusion to non-ventilated alveoli
• Deadspace: Ventilation to non-perfused areas

Question 200

What are the major risk factors for fatal asthma?

Answer 200

Question 201

What is the mechanism behind cyanosis?

Answer 201

Hb is purple, so decrease in bound O2 results in purple colour

Question 202

Why does 2,3 DPG have lower binding affinity to HbF?

Answer 202

2,3 DPG best binds to the beta subunit, so HbF has less 2,3 DPG.

• Results in an oxygen dissociation curve shifted to the left (HbF has higher affinity for oxygen)

** DPG - promotes hemoglobin transition from a high –> LOW-oxygen-affinity state (shifts curve to the right)

Question 203

What is the definition of an obstructive defect on PFT? How is severity categorised?

What is the definition of a reversible obstructive defect?

Answer 203

FEV1/FVC <70% predicted

Severity is categorised based on FEV1

• Mild >70%
• Mod 50-69%
• Severe <50%

Reversible

• Increase in FEV1 by >=12% and >=200mL after bronchodilators
• Asthma typically fully reversible, COPD not.

Question 204

Which medications need to be withheld prior to PFT?

Answer 204

SABA for 4hrs
LABA for 12hrs
Tiotropium for >24hrs

Question 205

What is inducibility PFT? When is it performed? What is used? What constitutes a positive test?

Answer 205

Either direct stimulation of bronchoconstriction, or activity to induce release of histamine.

Performed to rule out exercise or allergen induced asthma when standard PFTs normal

1. Inhaled metacholine (direct challenge: cause direct constriction via receptors on smooth muscle)

• Highly sensitive but not specific
• >=20% reduction in FEV1 with 4mg/mL metacholine is positive

2. Inhaled mannitol (indirect challenge: cause activation of mast cells -> histamine + bronchoconstrictor release)

• Highly specific but but not sensitive
• >=15% reduction in FEV1 with <=635mg inhaled mannitol

3. Exercise challenge

• Excellent spec and sens for exercise induced bronchoconstriction
• Baseline spirometry followed by 80-90% maximum HR treadmill held for 8mins
• >=10% decline in FEV1 or FVC over any two consecutive timepoints at 1, 3, 5, 10, 15, 20, 30, 45 mins

Question 206

What is the typical appearance of an extrathoracic obstruction on flow-volume loop? Why does it look the way it does?

Answer 206

NORMAL expiration flow

LIMITED inspiratory flow

Question 207

What is the typical appearance of intrathoracic obstruction on pfts? Why does it appear the way it does?

Answer 207

LIMITED expiratory flow (as the obstruction moves IN with expiratory as it INTRAthoracic pushs IN on it)

PRESERVED inspiratory flow (as the obstruction moves out with inspiration as it is INTRAthoracic)

Question 208

What is this flow-volume loop pattern indicative of? Differentials?

Answer 208

Indicative of fluctuating upper airway obstruction

• Neuromuscular weakness
• Parkinson’s disease
• OSA
• Upper airway burns
• Pedunculated tumours
• Laryngeal dyskinesia

Question 209

lable diagram

Answer 209

Question 210

What is the definition of a restrictive defect on PFT? What does RV:TLC tell you?

Answer 210

TLC<lln> defines a <strong>restrictive defect. </strong>FVC<lln>TLC is required in the definition</lln></lln>

RV (residual volume):TLC (Total lung capacity) tells you the ratio of unusable lung

• Increased RV:TLC points toward extrinsic restrictive defect
• normal RV:TLC points toward intrinsic restrictive defect

Question 211

What is DLCO in relation to PFTs? Name the categories and causes for increase and decrease

Answer 211

Amount of CO that can bind to Hb

Decrease

• Diffusion problem
  
  • Thickened membrane
    
    • Fibrosis, alveolitis, vasculitis
  • Decreased surface area
    
    • COPD
• Decreased capillary blood volume
  
  • Anaemia
  • PE
  • HF
• Decreased lung volume (previous lobectomy)

Increase

• Polycythemia
• Asthma
• Increased blood volume
• Left->right shunt
• Alveolar haemorrhage
  
  • Suspect if DLCO intially high then decreased subsequently

Question 212

What is DLCO:VA? What does it mean?

Answer 212

KCO shows gas exchange per unit volume of lung, accounting for change in lung volume

Low in pulmonary causes of decreased DLCO

• ILD, fibrosis, pulmonary vascular disease

High in extrapulmonary causes of decreased DLCO

• Resection, thoracic wall abnormalities

Question 213

Run through the algorithm to interpret PFTs

Answer 213

Question 214

What type of genetic disorder is cystic fibrosis? On which chromosomes are the mutations? What is the most common mutation? Does any drug target it? Are there any other common mutations for which medications are available?

Answer 214

Autosomal recessive exocrinopathy due to mutations on chromosome 7

F508del most common

• 70% defective alleles
• 90% individuals carry >=1 F508del mutation

Ivacaftor of benefit in individuals with G551D stop mutation (~4% of CF)

• ~8% have this mutation
• improves FEV1 7-10%, reduces exacerbation by 55%, reduces hospitalisation, gains BMI

Lumacaftor-ivacaftor of minor benefit in individuals homozygous for F508del

• lumacaftor partially corrects misfolding
• ivacaftor improves channel gating activity
• 3% increase in FEV1, reduced exacerbation freq by 39%, small improvements in BMI and QOL
• similar benefit to that of inhaled tobramycin

Question 215

What is the defective ion channel in cystic fibrosis? Where is it located? What happens when it’s defective?

Answer 215

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

• epithelial ion channel
• apical plasma membrane of acinar and epithelial cells

Inability to transport chloride ions, affecting different tissues in different ways

• Overriding principle is that of thickened secretions due to lack of periciliary layer caused by decrease in water

Question 216

How many classes of CFTR defects are there?

Answer 216

6

• Class I
  
  • Absence of synthesis
• Class II
  
  • Defective protein maturation and premature degradation
  • F508del accounts for ~70% of defective alleles
  • 90% individuals carry >=1 F508del mutation
• Class III
  
  • Disordered gating/regulation
• Class IV
  
  • Defective conductance through the ion channel pore
• Class V
  
  • Reduced number of CFTR transcripts due to promoter/splicing abnormality
• Class VI
  
  • Accelerated turnover from cell surface

Question 217

In whom is cystic fibrosis most common? What percentage carry a CF mutation? Incidence?

Answer 217

Caucasians

• 1/25 carry
• 1/3,300 live births in caucasians
• 1/33,000 live birth in asians

Question 218

Why do individuals with cystic fibrosis get lung injury? What particular pattern does it follow?

What can be done to assist with mucous clearance?

Answer 218

Thick sputum is difficult to clear which leads to chronic infection and inflammation.
This then leads to bronchiectasis, typically in the upper lobes.

Chest physiotherapy

• daily required

Mucolytics

• DNase and hypertonic saline of benefit
• inhaled steroids and bronchodilators only of benefit in those with asthma phenotype

Question 219

What are the extrapulmonary manifestations of cystic fibrosis? Their prevalence and treatment?

Answer 219

Pancreatic

• exocrine insufficiency
• 80-90% of those with CF
• due to blockage of ducts due to thickened and inspissated mucous
• fat soluble vitamin replacement
• pancreatic enzyme replacement
• requires PPI as they don’t function in acidic environment
• endocrine insufficiency
• >30% of adults with CF
• features of type 1 and 2
• yearly oral GTT recommended to screen (fasting BGL and HbA1c low sens)
• treated with insulin, never with diabetic diet
• decreased nutrition decreases BMI which worsens PFTs

Liver

• CF related liver disease usually develops before 18yrs of age
• ~10% CF patients develop cirrhosis
• hepatic steatosis most common at ~60%
• multilobar or focal biliary cirrhosis may be associated with portal hypertension and splenomegaly
• no benefit to ursodeoxycholic acid
• may progress to failure requiring transplantation

GORD

• requires aggressive treatment with PPI to reduce microaspirations

Gallbladder

• microgallbladder in 25-30%
• cholestasis and cystitis

Intestinal

• meconium ileus in 10-20% newborns with CF
• distal intestinal obstructive syndrome in adults
• c. difficile infection presents atypically, not usually with diarrhoea but with pain

Genitourinary

• involution of vas deferens in 99% males
• functioning spermatogenesis
• amenorrhoea and anovulation in females

Renal

• diabetic nephropathy
• oxalate nephrolithiasis

Haematological

• anaemia of chronic disease
• functional iron deficiency
• hypersplenism
• high INR

Musculoskeletal

• clubbing
• seronegative arthropathy
• pANCA positivity

Question 220

What are the major predictors of poor outcome in cystic fibrosis? What about predictors of decline?

When is lung transplantation indicated?

Answer 220

Major predictors

• FEV1. Expected decline 2%/yr
• WCC
• Low BMI
• High CO2
• Female gender

Decline

• new bacteria
  
  • especially pseudomonas, MRSA, MAC, burkholderia cepacia, stenotrophomonas
• diabetes
• ABPA
• poor social situation or poor compliance
• poor nutrition
• *Lung transplant indicated when 5yr survival <30%, best proxied by FEV1 <30%**
• 60% survival at 5yrs after transplant

May also be indicated with precipitous decline, especially when female or diabetic; massive haemoptysis or malnutrition; or pulmonary hypertension in the absence of hypoxaemic exacerbation

Question 221

What is the most common bacterial pathogen in cystic fibrosis? What percentage of adults with cystic fibrosis are chronically infected with p. aeruginosa? How should acute pseudomonal exacerbations of cystic fibrosis be treated? What if any prophylactic therapy is appropriate? What is significant about burkholderia cepacia complex and mycobacterium avium complex?

Answer 221

Staph aureus most common

• MRSA becoming increasingly common, up to 25% prevalence
• MRSA independent risk factor for death

~70% of adults chronically infected with p. aeruginosa

• prolonged infection results in conversion to mucoid phenotype due to production of alginate
• chronic infection an independent risk factor for <fev1></fev1>

</fev1>

Dual anti-pseudomonal cover

• antipseudomonal beta lactam + one of fluoroquinolone, aminoglycacide (tobramycin preferable), or colistin
• utilise past sensitivities

Azithromycin and inhaled anti-pseudomonals (aztreonam, tobramycin) have been demonstrated to improve number of exacerbations and FEV1 when administered chronically in those colonised with pseudomonas

Burkholderia cepacia complex is associated with accelerated decline in PFT and decreased survival

• treated with bactrim
• contraindication to transplant in some centres

Isolation of MAC should result in immediate cessation of azithromycin prophylactic therapy to preserve sensitivity

Question 222

What is the leading cause of cancer related death? What is the lifetime risk? How much risk does the largest risk factor confer?

Answer 222

Lung Ca

8% men, 6% women

• • note that incidence in men has fallen dramatically whereas woman is plateauing/slightly going up
• *10x risk smokers** compared to never smokers
• *20x risk in continuin**g smokers
• stopping in middle age ameliorates 90% of the additional risk

Question 223

What are the subsets of lung cancer? What are some basic pathological features?

Answer 223

Small Cell

• Neuroendocrine markers
• CD56, neural cell adhesion molecule, synaptophysin, chromogranin
• ~100% association with smoking

Non-Small Cell

• 90% of epithelial lung cancers
  
  • Adenocarcinoma
    
    • Most common subtype
    • Glandular differentiation or mucin production
    • Thyroid transcription factor-1 positve in 70%
    • Napsin-A positive in >90%
  • Squamous
    
    • Morpholigcally identical to those outside the lung
    • Sheets of cells with keratinisation or intercellular bridges arising from bronchial epithelium
    • more likely to be cavitating than the others
  • Large cell
    
    • <10% of all lung cancers

Question 224

Which subtypes of lung cancer are most associated with smoking?

Answer 224

Small cell and squamous

• ~100% of SCLC is associated with smoking

All lung cancer subtypes can occur in smokers

Question 225

Who should be screened for lung cancer?

Answer 225

Not currently recommended in Australia

High risk patients

• Current smokers 55-80yrs old with >30pck/yr smoking Hx
• Ex smokers of <15yrs and 55-80yrs old

As per the National Lung Screening Trial in NEJM 2011

• 53,454 pts 55-74yrs with >30pck/yr smoking and no symptoms
• 3x annual LDCT vs 3x annual CXR, primary endpoint all cause mortality
• Annual screening decreased mortality by 20%, despite 96% false positive rate
• 27% of initial LDCT had a nodule >4mm

Question 226

In which subtype of lung cancer is paraneoplastic syndrome most common? Is it exclusive to this subtype? What are the common syndromes and their natural history?

Answer 226

Common, especially in SCLC but not exclusive

PTH

• Mostly with squamous

ADH/ANP

• SIADH (classic for SCLC)
• Usually resolves within a month of chemotherapy
• Look for ANP if hyponatraemia doesn’t resolve with fluid restriction

ACTH (think SCLC)

• Usually with electrolyte disturbances rather than Cushing’s
• Usually resolves with chemo
• Can perform bilateral adrenalectomy if extreme

Skeletal/connective tissue

• Clubbing ~30%, HPOA 1-10% (think SCC)
• Neurologic-myopathic syndromes (think SCLC) ~1%

CNS

• Anti-hu, anti-CRMP5, ANNA-3

Anorexia, cachexia, immunosuppression, fever, weight loss

Question 227

How are SCLC and NSCLC staged? Are they different? Why? What’s the mortality like for the two subtypes of SCLC?

Answer 227

Both require imaging and tissue sampling

NSCLC staged with TNM

• CTCAP first
• If mets then no PET. If no mets then PET
• PET upstages 20%, avoiding unnecessary surgery

SCLC staged with limited vs extensive disease

• CTCAP + MRIB +/- bone scan
• hepatic/adrenal disease common
• CNS involvement in 10% asymptomatic
• MRI spine in those with cord compression signs/symptoms for consideration of palliative resection/radiotherapy

Limited disease confined to a ipsilateral thorax within a tolerable radiation port

• median survival 12-20months, 5yr ~10%

Extensive disease overt metastatic disease by imaging or clinical exam

• median survival 7-11months, 5yr ~1%

Significant implication for survival and cure rates

Question 228

Which lung cancers require surgical resection? What are the contraindications to curative lung resection in NSCLC?

Answer 228

Stage I-II NSCLC require resection if patient amenable and appropriate for surgery

IIIa NSCLC can be considered with mediastinal clearance in certain patients

Surgical resection not recommended in SCLC due to micrometastases even in early stage.
May be considered in clinical stage I when invasive mediastinal staging clear and with adjuvant chemotherapy

Contraindications to curative resection in NSCLC

• Extrathoracic metastases, metastases to supraclavicular node, contralateral lung/mediastinum
• SVC syndrome
• Malignant effusion
• Tamponade
• Tumour within 2cm of carina
• Involvment of main pulmonary artery

Question 229

Is adjuvant chemotherapy of benefit in NSCLC? In which populations? Is any particular chemotherapy regimen or duration recommended?

Answer 229

Worsens outcomes in Ia
Possibly improves in Ib

Definitely improves in II-IIIa

• • LACE study 5.4% improved survival at 5yrs with chemo + surgery compared to solo surgery
• No evidence of benefit to >4 cycles
• *Platinum based** but no particular regimen optimal
• *- Cisplatin or carboplatin** +/- other depending on subtype
• EGFR erlotinib or gefitinib
• ALK crizotinib
• If neither then bevacizumab (shouldn’t be used in squamous or CNS involement due to bleeding risk)

Question 230

What are the rough 5yr survival rates associated with NSCLC?

Answer 230

Question 231

What proportion of NSCLC present with metastatic disease? What is its median survival? What is the management of metastatic NSCLC?

Answer 231

~40% present with metastatic disease
Mean survival 4-6months

Symptom control very important

• *Chemotherapy** improves s**ymptoms, quality of life, and survival
• appropriate in ECOG <=2 with few comorbidities**

Look for specific mutation

• EGFR
  
  • gefitinib/erlotinib
  • Doesn’t work if RAS present
• ALK crizotinib
  
  • mutually exclusive with EGFR

Platinum based first line

• cisplatin/carboplatin + either vinorelbine, paclitaxel/docetaxel, gemcitabine
• response rate ~30%
• increases meadian survival from 6 to 9 months

Addition of anti-VEGF (bevacizumab) improves survival

• HTN (predicts response), haemorrhage (especially in squamous or CNS), impaired healing, GI, skin, leukopoenias

Non-squamous has better outcomes with cisplatin + pemetrexed
Squamous has better outcomes with cisplatin + gemcitabine

Question 232

What is the treatment for SCLC? Does it differ depending on staging? What are the median survival and 5 yr survival rates?

Answer 232

Surgical resection not recommended even in stage I disease due to prevalence of micrometastases

Chemotherapy

• platinum based
  
  • cisplatin/carboplatin + etoposide, ironotecan
  • or cyclophosphamide, doxorubicin, vincristine if not tolerated
  • Response rates ~80% but survival still abysmal (LD median 12-20months, 5yr 6-12%)(ED median 7-11months, 5yr ~1%)

Radiotherapy (60Gy in 30#)

• Standard part of induction in LD with good performance status
• Improves survival by 5% compared to sole chemo
• Better toxic profile with cisplatin + etoposide
• Prophylactic cranial given in complete response due to 100% 2yr CNS disease

Extended stage = palliative RTx and chemotherapy

Question 233

What symptoms are characteristic of hyperventilation syndrome? What breathing patterns?

Answer 233

Dizziness, dry mouth, parasthesias in hands/feet, chest pain

Rapid, shallow, irregular breathing with frequent sigh breaths

Question 234

When do respiratory symptoms tend to develop in myasthenia gravis? Is it a common presenting symptom?

Answer 234

Late in the disease process.

Very rare to present with respiratory weakness as the first symptom

Question 235

What is the prevalence of asthma? Does disease severity vary within patients? What are the main risk factors for death?

Answer 235

10-12% adults

Usually each patient sticks within their own severity

Risk factors for death:

• Poorly controlled
• Poor compliance with ICS
• Previous near fatal asthma
• ICU admission or intubations

Question 236

What are the main risk factors for developing asthma? What about triggers for those with asthma?

Answer 236

Risk factors

• Atopy the major one
  
  • Those without unlikely to develop asthma
• Genetics
  
  • Polygenic
  • ADAM-33, DPP-10, ORMDL3, Arg-Gly-16 for decreased beta ag response, 5-lipooxygenase repeats for decrease leukotreine antagonist response
• Hygeine hypothesis
  
  • Lack of exposure to infections pushes toward TH2 cell bias which is allergenic response
  • Exposure associated with TH1 cell bias
• Obesity
  
  • Independent risk factor for development
• Occupational
  
  • Common, 10% young adults
  • Suspect when symptoms abate on weekends and holidays
  • Removal from exposure within 6 months usually results in complete resolution without airway damage
• Intrinsic
  
  • ~10%
  • Normal IgE and negative skin prick
  • Usually more severe and persistent with later onset

Triggers

• Pollutants
• Allergens
  
  • Activate mast cells with bound IgE
• Exercise
• Physical
  
  • Cold air, hyperventilation, laughter, perfumes
• Infections
  
  • Rhinovirus, coronavirus, RSV most common triggers of acute exacerbations
• Occupational exposure
• Drugs
  
  • beta blockers, aspirin

Don’t make a difference

• diet
• GORD
• ACEI

Question 237

What are the structural changes to the airway associated with asthma?

Answer 237

Epithelial shedding

• Loss of barrier function and exposure of sensory neurons
• Loss of enzymes for degrading inflammatory mediators
• Loss of relaxant factors

Thickening of basement membrane

• subepithelial type III and V collagen deposition
  
  • feature of eosinophilia
• In severe the airway itself may be thickened, leading to irreversible narrowing

Oedematous and thickened airway wall

• especially in fatal

Mucous hypersecretion and plugging

• glycoproteins from increased number of goblet cells and plasma protein exudate
• Hyperplasia of submucosal glands in large airways

Vasodilation and angiogenesis

• VEGF involved

Airway smooth muscle hypertrophy/hyperplasia

• PDGF, endothelin 1
• Reduced response to beta agonism, likely resulting from uncoupling of receptors or chronic inflammation altering resting membrane potential

Altered neural regulation

• Secondary effect
• Reflexive cholinergic activation
• Inflammatory activation of sensory neurons
  
  • Reflex cholinergic bronchoconstriction, release of inflammatory neuropeptidases
• Hyperalgesia
• Neurotrophin release, sensitising and proliferating
• Release of substance P

Question 238

When might fractional exhaled NO (FENO) be useful in asthma?

Answer 238

NO is derived from airway epithelium and promotes dilation of blood vessels and airways

• vasodilation -> promotes oedema -> worsen obstruction

Measurement can be useful to determine compliance with ICS

• high NO implies active inflammation, which points toward non-compliant or not working

No convincing evidence that using NO to titrate ICS improves outcomes

Question 239

What is the stepwise approach to asthma therapy?

Answer 239

Biologicals for severe asthma

Asthma type

Target

Molecule

Allergic asthma

IgE

Omalizumab

Eosinophiliac asthma

Il-5 or Il-5 receptor

Mepolizumab, benralizumab

• These monoclonal Abs are used in addition to ICS + LABA.
• In appropriately selected patients, mABs induce ~50% reduction in exacerbations
• Oral steroid sparing
• Modest improvements in lung function

Add on therapies for severe asthma

• Long term oral steroids should be avoided where possible

Question 240

What do beta 2 agonists do? Do they affect inflammatory cells? What are their common side effects? Do patients develop tolerance? Are they safe?

Answer 240

Beta 2 receptors coupled via G proteins to adenyl cyclase, increasing intracellular cAMP

• relax SM, inhibit mast cells, reduce plasma exudate, reduce neural stimulation
• inflammatory cells rapidly downregulate their receptors, so little effect on AHR

SABAs

• 3-6hr duration
• Increased use indicates poor control

LABAs

• >=12hr duration
• Use without comcommitant ICS worsens outcome (doesn’t treat underlying inflammation)
• Improve control and reduce exacerbations when added to ICS

Side effect mainly tremors, mainly in the elderly

Large reserve of beta 2 receptors in smooth muscle means even with downregulation they’re still effective

• less so with mast cells, where ICS helps counteract downregulation

Question 241

When is theophylline used in asthma? How does it act? What are its common side effects?

Answer 241

• Non-selective PDE inhibitor relaxing smooth muscle
• Used rarely as an adjunct when on maximal other medications
• Arrhythmias associated with higher levels >10mg/L - rarely observed below this
• Most commonly nausea, vomiting, headaches
• Largely inactivated by the liver

Question 242

When are OCS required in asthma? How should they be dosed? What percentage of patients require maintenance treatment? What are their side effects?

Answer 242

During moderate-severe exacerbations

• oral equivalent to IV
• 30-45mg daily for 5-10days, no taper required

~1% require maintenance

• should be titrated to the minimum dose required to suppress symptoms and avoided when possible!

Multiple side effects

• truncal obesity, bruising, OP, diabetes, HTN, gastric ulcers, proximal myopathy, depression, cataracts
• monitoring of bone density allows for treatment with bisphosphonates

Question 243

When are antileukotreines used in asthma?

Answer 243

May be added in those not controlled on low dose ICS

• less effective than LABA

Inhibit cyc-LT1 receptors

Question 244

LUNG VOLUMES

Answer 244

Question 245

What shifts the oxygen dissociation curve left or right?

Answer 245

Question 246

What is aspirin sensitive asthma? Does it have a defined phenotype? How is it managed?

Answer 246

Called aspirin exacerbated respiratory disease (AERD)

7% of asthma sufferers get worse with COX inhibitors

• 14% with severe asthma
• need to ensure it’s not to a single agent, as that may be IgE mediated allergy

Phenotype (clinical diagnosis the rule)

• perennial rhinitis
• nasal polyps
• non atopic
• late onset

80% have upper or lower airway reactions to alcoholic drinks

NSAID reaction

• 30mins-3hrs after ingestion
• dose related, can be as bad as fatal
• urticaria/angioedema in 15%

Pathophysiology

• due to baseline dysregulation in arachidonic acid metabolism with balance shifted toward leukotrienes
• primary cell producing it is bronchial mast cells
• COX-1 inhibition exaggerates the dysregulation, thought to be by reducing PGE2 which is a ‘brake’ on leukotrienes

Triggered by COX inhibitors but present even in their absence

Safe to use COX2 inhibitors

• some exquisitely sensitive people may be triggered by them

Management

• Asthma as per usual guidelines
• COX-1 avoidance unless being desensitised
• leukotriene antagonists vastly improve airway symptoms and exacerbation rate

Question 247

What is the natural history of asthma in pregnancy?

Answer 247

1/3 get better, 1/3 stay the s with mod/sev asthma

Prednisone better than prednisolone as foetal liver can’t convert prednisone to prednisolone

Breastfeeding safe

Question 248

What percentage of asthmatics smoke? How bad is it?

Answer 248

~20%

More severe disease, more frequent admission, faster decline in PFTs, higher risk of death

Interferes with anti-inflammatory action of corticosteroids, requiring higher doses

Cessation improves PFTs and reduced steroid resistance

Question 249

What is hypersensitivity pneumonitis? Name some of the pathogens that cause it

Answer 249

Exposure and sensitisation to an antigen leading to inflammation of the alveoli and small airways.
Sensitisation is necessary but not sufficient for developing HP; many sensitised individuals don’t develop HP.
TH1 inflammatory pattern with emerging evidence of TH17 subsets involved

Fungal, bacterial, mycobacterial, bird-derived, and chemical causes.

Question 250

What is the treatment for hypersensitivity pneumonitis? Is any pharmacotherapy helpful?

Answer 250

• Antigen removal the mainstay
• Corticosteroids may help in decreasing duration of symptoms but don’t change outcomes
• • 0.5-1mg/kg for 1-2/52 followed by 2-6/52 taper
• Fibrotic changes associated with chronic HP may be irreversible

Question 251

What are the diagnostic criteria for acute eosinophilic pneumonia? Who is the prototypical patient? Is it associated with peripheral eosinophilia? What does HRCT show?

Answer 251

• Males 20-40 with no history of asthma
• Not associated with peripheral eosinophillia, not typically not until 7-30 days
• HRCT is always abnormal or reticular opacities with small pleural effusions
  
  • characterised by high pH with marked eosinophilia
  • bilateral groundglassing

Question 252

What are the general causes of an increased A-a gradient?

Answer 252

• *R->L intrapulmonary shunt**
• CCF
• ARDS
• Pneumonia
• *V/Q mismatch**
• PE
• Atelectasis
• Pneumonia
• Obstruction
• Pneumothorax
• *Alveolar hypoventolation**
• ILD
• *Hypoventilation**
• Neuromuscular disorders
• CNS disorders

Question 253

What is methaemoglobinaemia? Why does it matter?

Answer 253

• *Ferric (3+) iron in heme**
• due to oxidation of Fe2+ -> Fe3+
• Unable to bind O2
• Affinity of the remaining ferrous heme groups is increased
• Functional anaemia!
• *Congenital**
• May be asymptomatic
• Cyanotic, slate blue skin and mucous membranes
• *Acquired**
• Drugs usually

Acquired treated with cessation of the cause and methylene blue or hydroxycobalamin.
Congenital best treated by avoiding medications that induce methaemoglobin

Question 254

What are the risk factors for pulmonary embolism? What are the most common mutations causing prothrombotic states?

Answer 254

Prothrombotic states

• Common
  
  • Factor V leiden: causes resistance to activated protein C
  • Prothrombin gene mutation: increases plasma prothrombin concentration
  • Antiphospholipid syndrome - most common acquired cause of thrombophilia
• Rare
  
  • Deficiency of: antithrombin, protein C, protein S

Question 255

What is Well’s Criteria (wells score)?

Answer 255

d-dimer increased in those >70yrs

• not affected by smoking
• false positives in: sepsis, AMI, cancer, pneumonia, post-operative state, 2nd/3rd trimesters of pregnancy

Question 256

What is McConnell’s sign on TTE?

Answer 256

Describes a regional pattern of acute right ventricular dysfunction - Hypokinesis of RV free wall with normal or hyperkinetic RV apex.

Best known indirect sign of PE

Question 257

What percentage of adult asthma/COPD is a result of occupational factors?

Answer 257

15 - 20%

Question 258

What are the syndromes associated with organic and inorganic dusts?

Answer 258

Question 259

What is the risk of lung cancer in smokers with asbestos exposure? Is mesothelioma associated with smoking?

Answer 259

60 x baseline risk, synergistic risk

Mesothelioma doesn’t appear related to smoking. Even short term exposures of asbestos in the distant past can be associated with development of mesothelioma

Question 260

Does silicosis affect risk of infection? How? Which? Does it have any rheumatological associations?

Answer 260

Silica is toxic to alveolar macrophages

Result in higher risk of infections requiirng these as primary defence

• **TB, atypical mycobacteria, fungi
• Treatment of latent TB is longer**

May develop connective tissue disorder

• *- RA or systemic** sclerosis
• Caplan syndrome is the combination of seropositive RA with pneumoconiotic nodules in the lung
• First described in coal workers

Question 261

How does berylliosis present? How does it differ from sarcoidosis?

Answer 261

May present with acute pneumonitis

More commonly it presents with a chronic granulomatous disease similar to sarcoidosis

• Differs by evidence of specific cell mediated response to beryllium
• Delayed hypersensitivity reaction

Beryllium lymphocyte proliferation test

• Compares in vitro proliferation of lymphocytes from blood or BAL in the presence of beryllium salts to unstimulated cells
• Usually measured by uptake of radiolabelled thymidine

In beryllium sensitised individuals non-caseating granulomas or monocytic infiltration on lung biopsy establishes the diagnosis

Question 262

What is diacetyl used for? With what is it associated?

Answer 262

Used to provide butter flavour to popcorn

Has been associated with bronchiolitis obliterans

Question 263

What characterises COPD? What is its prevalence? What are the COPDX guidelines?

Answer 263

Progressive chronic airflow limitation which is not fully reversible

5th leading cause of death worldwide, almost equal burden between genders

Prevalaence by spirometry

• • 7.5% in >40yrs
• • 29% in >75yr

Prevalence by symptoms

• • 30% describe wheeze, 25% SOBOE in past 12 months

COPDX

• Confirm diagnosis
• Optimise function
• Prevent deterioration
• Develop support
• X - manage exacerbations

Question 264

What defines a COPD exacerbation? What are the underlying aetiologies? Who ought to be hospitalised?

Answer 264

No universally accepted definition

Change in symptoms out of keeping of their normal variation

• Dyspnoea
• Purulence
• Volume

No objective diagnosis in 50%

Respiratory infection (50-70%)

• Bacterial: h influenzae, s pneumo, m catarrahalis, mycoplasma, chlamydia; pseudomonas, staph in more advanced
• Viral: influenza, rhinovirus, RSV, metapneumovirus

Non-infectious:

• Pollution
• PE: ~1 in 4 exacerbations without clear cause
• CCF
• Pneumothorax
• Sedation
• Anxiety

Hospitalisation

• Failed OP management
• Unable to manage at home due to breathlessness: Mobilising, sleeping, eating
• Severe comorbidities
• Confusion
• Worsening gas exchange
• New arrhythmia

Question 265

What are the risk factors for developing COPD?

Answer 265

Cigarettes

• • Accounts for >95% burden of diease
• • Only 10-20% develop clinical disease
• • ~50% have some airflow limitation

Organic/inorganic dusts (cadmium, coal, cotton, cement, grain)
Smoke from cooking
Bronchial hyperresponsivenes
Genetics

• • alpha 1 antitrypsin
• • 1-2% of population

Infections/mucous hypersecretion

Question 266

What is the stepwise management of stable COPD? Do pharmacologic therapies improve survival or slow decline in FEV1?

Answer 266

Pharmacologic therapies useful in reducing symptoms, improving QOL, and reducing exacerbations but not improving survival or slowing decline of FEV1

Mild (FEV1 >60%)

• SABA only: terbutaline, salbutamol

Moderate (FEV1 <60%)

• Anticholinergic (LAMA): ipratropium; tiotropium, glycopyrronium, aclidinum, umeclidium
• LABA: salmeterol, eformeterol
• VLABA: indacterol, olodaterol
  
  • Reduced dyspnoea, improved QOL, reduced exacerbations
• Longer acting and newer medications probably better than salmeterol/eformeterol
• Some concerns about CV effects of tiotropium, with risk/benefit usually falling on benefit side
• Multiple combination medications: ICS + LABA, LAMA + LABA/VLABA

Mod/sev (FEV1 <50%) with frequent exacerbations

• Addition of inhaled corticosteroids (ICS) reduces symptoms, improves QOL, reduces exacerbations
• Combination with LABA may slow decline in FEV1
• SEs: increased pneumonia, easy bruising, cataracts, ?OP
• budesonide doesn’t seem to increase pneumonia, fluticasone dose

Others

• Theophylline: Modest bronchodilator effect. New data indicating low dose may have anti-inflammatory and immunomodulatory effects
• PDE4 inhibitors: Anti-inflammatory with moderate fficacy as add on to LABA. Not TGA approved
• Mucolytics: May improve clearance and decrease exacerbations. High dose NAC shows promise

Severe with respiratory failure

• Continuous oxygen therapy: Improves mortality
  
  • PO2 <55 or <60 with pulm HTN or RHF
  • Only beneficial if used >=16hrs a day
    
    • Portable oxygen not shown to have mortlaity benefit

Beta blockers are safe in COPD

• LVRS: Rarely in Australia. Predominant upper lobe emphysema benefit the most.
  
  • Overall early increased mortality with no change at 2yrs, with increased exercise capacity
• Bronchoscopic techniques: valves, plugs, steam, airway bypass
• Transplant: Young with severe disease casuing significant morbidity

Additional

• QOL: Questionnaires, self reported dyspnoea
• Exercise tolerance
• Bone density: Significant number of mod/sev COPD population have OP, and do worse

Question 267

What tend to be the causes of death in COPD? How does pulmonary hypertension and RHF affect this?

Answer 267

Generally don’t die of COPD, even in severe disease.

Top are CVS and cancer

Question 268

What are the distinctive clinical and radiological findings in legionella pneumonia?

Answer 268

• *pneumophila** = cooling towers and humidifiers
• *longbeachae** = potting mix

Risk factors

• older, smokers
• immunocompromised
• chronic cardiac, resp, renal disease
• Diarrhoea, neurologic findings,* and temp >39
• *Hyponatraemia,** elevated LFTs, haematuria

Distinctive rounded, nodular opacities

• Especially in the immunosuppressed

Management

• azithromycin, moxifloxacin

Question 269

What are the risk factors for developing non-tuberculous mycobacterial infection?

Answer 269

• Underlying lung diseases
• Bronchiectasis, pneumoconiosis, COPD, CF, alpha 1 antitrypsin deficiency, primary ciliary dyskinesia

Question 270

What is the pattern of resistance as you progress through the airway generations? Which have tracheal rings?

Answer 270

First 7 generations have cartilage rings

Question 271

What are the mechanisms of small airway narrowing?

Answer 271

Question 272

What are the defining characteristics of asthma?

Answer 272

Air flow variability

• diurnal and between day variability
• gold standard for diagnosis of occupational asthma is day to day variability with bad days while at work (measured with peak flow)

Reversibility

• pre and post bronchodilator
• >12% and 200mL

Airway tests of airway hyperresponsiveness

• direct = metacholine test, sensitive BUT NOT specific. Good to look for perisistent airway remodelling
• indirect = mannitol, hypertonic saline. good measure of the inflammatory component. specific BUT NOT sensitive

Question 273

What’s the definition of bronchiectasis? What’s it caused by?

Answer 273

Abnormal irreversible bronchial dilation

• • HRCT gold standard

>=1 dilated bronchi

• • internal luminal diameter exceeding diameter of adjacent arteries

Clinically characterised by small airway obstruction,

Causes - see list, but think ‘chronic infection and airway destruction’

Question 274

What is constrictive bronchiolitis? Pathology? Causes? Clinical?

Answer 274

Also known as obliterative bronchiolitis and bronchiolitis obliterans

Pathology

• peribronchiolar fibrosis
• cicatrization of the bronchiolar lumen
• fibrosing inflammatory process surrounding the lumen
• extrinsic compression and obliteration of the airway

Causes (result of immunological injury)

• Allograft (lung, heart-lung, SCT)
• Postinfectious
• Connective tissue
• Inhalational injury
• Drugs

Clinical

• Severe, progressive small airway obstruction with dynamic hyperinflation
• CXR is normal or nonspecific
• On HRCT mosaic decreased attenutation. Evidence of gas trapping variability between neighbouring airways on expiration

Question 275

What are the defenses against respiratory infection?

Answer 275

• Upper airway reflexes
• Cilia
  
  • nonspecific and specific. e.g. smoking vs cilia diskinesis syndrome
• Mucous
  
  • nonspecific and specific. e.g. chronic bronchitis from smoking vs CF
• Cough
• Immune

Question 276

What proportion of those with COPD who have a viral infection develop secondary bacterial infection over the next week?

Answer 276

36% - Experimental infection of COPD patients with rhinovirus induces bacterial infection

Coinfection causes greater decline in lung function and prolonged hospital stay

Question 277

What is a halo sign on HRCT? What does it represent?

Answer 277

• *Groundglass opacity** surrounding a pulmonary nodule/mass, representing haemorrhage
• *- Typically in fungal infection**
• *- May represent neoplasm or vasculitis**

Question 278

What are the problems with empiric treatment, especially in opportunistic infections?

Answer 278

Question 279

What is the yield on bronchoscopy in immunocompromised patients presenting with possible pneumonia?

Answer 279

Use of bronchoscopy in immunocompromised:

• diagnosis in 65%
• sensitivity 75% and spec 86%
• 80% accuracy

Question 280

What is galactomannan?

Answer 280

Found in the cell wall of aspergillus

• antigen can be done in BAL or blood. Better in BAL
• Sens 79%, spec 86%, accuracy 89%
• Get false positives in
• contamination
• tazocin, amoxicillin, plasmalyte*

Corss sensitive with:
- penicillium, alternari, cladosporium, trychphyton, histoplasmosis, cryptococcus

• *Get false negatives with antifungal treatment**
• sens 52% vs 89%

Question 281

What CT finding is characteristic of cystic fibrosis?

Answer 281

• Bronchiectasis that spares the peripheries
• Mosaic attenuation

Question 282

Is oestradiol related to pseudomonas? How?

Answer 282

Oestradiol levels are related to alginate production of pseudomonas

• - testosterone not, placed on OCP not

Exacerbations correlate with the cycle phase in patients with cystic fibrosis

Question 284

How is OSA classified?

Answer 284

CV risk begings to climb around 30 events/hr

Question 285

What is the physiology underlying Obesity Hypoventilation Syndrome (OHS)?

Answer 285

Question 286

What are the different types of Central Sleep Apnoea (CSA)? What are some examples of each subtype?

Answer 286

Question 287

What is a secondary pulmonary lobule?

Answer 287

Question 288

What are the key findings on HRCT in ILD?

Answer 288

• Honeycombing
• Traction bronchiectasis
• Reticulation

Question 289

What is the best predictor of mortality on PFT in IPF? What’s a significant change in FVC or DLCO?

Does 6MWT have a role in measuring chane in disease severity?

Answer 289

FVC trends predict mortality better than other parameters

10% change in FVC or 15% in DLCO is considered significant

6MWT has no role in measuring change in disease severity

Question 290

What are the diseases associated with specific BAL findings? When is it indicated?

Answer 290

Not indicated in the majority
- Most importantly to exclude hypersensivity pneumonitis

Question 291

When should lung biopsy be performed for ILD? Which type of biopsy?

Answer 291

Question 292

What is usual interstitial pneumonia (UIP)?

Answer 292

Describes a histopathological pattern on biopsy

• *- heterogeneity!**
• hallmark is fibroblastic foci (demonstrate ongoing damage)

Also used to describe a radiological pattern on HRCT.

Especially absence of groundglass

Causes

• IPF
• Asbestosis
• CT related ILD

Question 293

Why does IPF need to be differentiated from NSIP?

Answer 293

Different prognosis and treatment options

Basically if IPF and appropriate to should refer for transplant

Question 294

What did the ASCEND trial in IPF show?

Answer 294

NOT a CURE, slows down decline of RFT but minimal QoL benefit

Question 295

What did the IMPULSIS trial in IPF show?

Answer 295

RCT for nintedanib

Question 296

What is interstitial pnuemonia with autoimmune features?

Answer 296

ILD with features of CTD that don’t meet specific classification criteria for a given autoimmune disease

Question 297

What particular infections are those with lung transplant predisposed to?

Answer 297

Early

• Pneumonia very common. 66% in one series
  
  • Given prophylactic broad spectrum antibiotics in the initial days
• Mediastinitis more common than in cardiac transplant

Middle

• Incidence of CMV 75-100% if either donor or recipient is seropositive
  
  • Most severe in cardiac and lung transplant for unknown reasons
• High incidence of HSV pneumonitis

Late

• PCP incidence high in lung and cardiac transplant

Question 298

What is alpha-1 antitrypsin? What does it do?

What are the phenotypes of deficiency? With what other diseases is deficiency associated?

Answer 298

Glycoprotein in the family of serine protease inhibitors, controlling inflammatory cascades

• Produced in hepatocytes

Inherited in an autosomal co-dominant pattern

Phenotypes

• Normal
  
  • Normal alleles are classed M, normal genotype = MM/PiMM
• Deficient
  
  • Plasma AAT <35% of normal
  • Most common deficient allele associated with emphysema is Z, carried by 2-3% of Caucasians
• Null
  
  • No detectable AAT protein
  • Least common, highest risk of lung disease, no risk of liver disease
• Dysfunctional
  
  • Produce a normal quantity of protein that is defective
  • Z and M(malton) the two common ones

Hepatic Disease

• Chief cause of liver disease in children
• Z and M(malton) alleles most well known to confer risk, autosomal recessive
• Due to accumulation of dysfunctional AAT protein in the hepatocyte, seen as intrahepatocyte inclusions with +ve acid Schiff stain
• 10-15% of newborns and adults develop hepatic disease
• Most are PiZZ

Pulmonary Disease

• Loss of function and imbalance between neutrophil elastase and the elastase inhibitor AAT. Protects against proteolytic degradation of elastin
• Cigarette smoking and infection increase elastase production, therefore greatly increase risk of progression
• Polymers of Z antitrypsin are chemotactic to neutrophils
• Deficiency = early onset emphysema.
• Bullous changes more prominent in bases than apices. Can be apical or diffuse in 1/3
• Test in persistent obstruction despite bronchodilator, early onset emphysema in non-smoker, and family history of emphysema/liver disease

Other

• Necrotising panniculitis; vasculitis, psoriasis, urticarial, angiodema
• Aneurysms and arterial fibromuscular dysplasia
• IBD
• GN
• ANCA +ve vasculitis

Question 299

What underlies hepatopulmonary syndrome?

Answer 299

• Systemic vasodilation resulting in V/Q mismatch
• Presentation
  
  • orthodeoxea: decreased O2 saturation when upright, increased when lying
  • platypnoea: dyspnoea when upright, better when lying flat
• Above due to dilation resulting in worsening of V/Q mismatch when sitting upright (blood pools to poorly ventilated bases)

Question 300

What are the Fleischer Society Guidelines for incidental pulmonary nodules? What clinical and radiological features predict malignancy in pulmonary nodules?

Answer 300

• Clear growth = resect
• Groundglass = annual CT (higher risk of malignancy but usually slower growing)
• Stable over 2yrs without groundglassing = discharge
• PET in >=1cm with intermediate risk. Sensitivity 95%, specificity 75%

High risk features

• age > 60, current smoker, corona radiata or spiculated nodule margins
• volume doubling of mass 20-100 days, upper lobe calcification, spiculation.

What features carry the highest likelihood ratio of malignancy?

• >16mm cavity wall thickness
• spiculated edge
• Age > 70
• size > 3cm
• History of other malignancy
• Smoking > 40 ciggs/day

What carries a 0 likelihood ratio of being malignant?

• growth < 7 days and no growth > 465 days
• benign pattern of calcification

Question 301

What patient factors predict EGFR mutation in NSCLC? What can you do about it?

Answer 301

Mutation present in 15% of lung adenocarcinoma

• Women>men
• Non-smokers>smokers
• Asian>non-asian

EGFR TKIs approved for 1st line treatment of EGFR +ve NSCLC - shown to be equivalent to chemotherapy

1st generation: erlotinib, gefitin and 2nd gen Afatinib

• Acne, diarrhoea, rare: pneumonitis/hepatitis

3rd generation: osimertinib (less rahs, designed for drug resistance)

Question 302

What are the findings indicating mild/moderate, severe, or life threatening acute asthma? Go through the algorithm for approach to acute asthma, including secondary severity assessment

Answer 302

Question 303

What clinical sign would indicate diaphragmatic paralysis?

Answer 303

Paradoxical movement of the abdomen inward with inspiration

Bilateral -> has mod-sev restriction of TLC

This gets worse on lying down
- decrease in VC of 30-50% when supine supports the diagnosis

Question 304

What is the Bohr effect?

Answer 304

CO2 and acidosis preferentially stabilise the deoxygenated form of haemoglobin, resulting in release of oxygen from haemoglobin

This is desirable in the tissues

Question 305

What is the mutation associated with familial pulmonary arterial hypertension (PAH)?

Answer 305

• *Bone morphogenetic protein receptor type-2 (BMPR2)**
• BMPR2 inhibits smooth muscle proliferation and induces apoptosis
• abnormalities -> proliferation of pulmonary vascular cells -> remodelling
• mutation confers 15-20% chance of developing PAH during lifetime
• accounts for 70-80% of familial PAH

Question 306

What is the most sensitive test in one suspected to have active pulmonary tuberculosis?

Answer 306

Sputum culture

Question 307

What are the Light Criteria for differentiating transudate from exudate?

Answer 307

Pleural fluid:serum protein >0.5
Pleural fluid: serum LDH >0.6
Pleural fluid LDH >2/3ULN of serum LDH

If all false then transudate
If >=1 true then exudate

Question 308

What proportion of those post lung transplant develop brochiolitis obliterans (constrictive bronchiolitis)? Risk factors?

Answer 308

50% at 5yrs
75% at 10yrs

Major impediment to long term graft and patient survival

Hard to demonstrate on transbronchial biopsy
- decline in FEV1 used as a surrugate marker

Risk factors

• acute rejection the major one
• GORD or silent aspirations may contribute in some

Retransplant the only definitive management

• systemic immunosuppression doesn’t really work
• aerosolised cyclosporine has shown potential efficacy
• fundoplication to control reflux has been associated with improved PFTs in some with BOS

Question 309

What’s the classic presentation of allergic bronchopulmonary aspergillosis (ABPA)? What’s the pathognomonic chest xray finding?

Answer 309

Virtually all have long-standing atopic asthma

Classically in 4th-5th decade

• chronic asthma, recurrent pulmonary infiltrate, and bronchiectasis
• long Hx of intermittent wheezing with evolution into more chronic and symptomatic: fever, chills, pulmonary infiltrates, productive cough
• *Segmental infiltrate or atelectasis in the upper lobes**
• branching, finger-like shadows of mucoid impaction of dilated central bronchi are pathognomonic.

Question 310

What is pulmonary alveolar proteinosis?

Answer 310

Rare condition characterised by alveolar accumulation of surfactant

• several causes
• *Autoimmune in 90%**
• antibodies against GM-CSF -> no activation of alveolar macrophages -> accumulation of surfactant
• *Presentation varies considerably**
• everything from asymptomatic and spontaneously remiting to severe respiratory failure
• *HRCT**
• • crazy paving pattern*
• *Lavage**
• • grossly turbid exudate
• periodic acid-Schiff positive*

Whole lung lavage the most effective therapy

Question 311

With which genetic mutation is lymphangioleimyomatosis associated?

Answer 311

Occurs in ~30% of women with tuberous sclerosis

• TSC1 encodes hamartin, TSC2 encodes tuberin

Sporadic LAM also associated with mutation of tuberous sclerosis genes

Characterised by smooth muscle cell infiltration and cystic destruction of the lung

• express markers of smooth muscle and melanocytic differentiation

Presentation

• progressive SOBOE, recurrent pneumothoraces, abdominal/thoracic lymphadenopathy, abdominal tumours
• angiomyolipomas, lymphangiomyomas

May present with just abdominal disease, mimicing lymphoma/ovarian cancer

• very rare

Rx: sirolimus

Question 312

When is CTPA of greatest accuracy? When is V/Q helpful as an addition?

Answer 312

• Most sensitive for the main and lobar pulmonary arteries
  
  • decreases in the segmental and sub-segmental vessels
• Normal V/Q rules out pulmonary hypertenion due to chronic thromboembolic disease

Question 313

What’s tracheomalacia? What kind of airflow obstruction does it cause?

Answer 313

Variable intrathoracic obstruction

Question 314

What are the two types of alveolar cells and what do they do?

Answer 314

Type 1 = squamous

• cover 90-95% of alveolar surface
• involved in gas exchange
• unable to replicate, susceptible to toxic insults

Type 2 = surfactant secreting

• <5% of alveolar surface
• can divide and differentiate into type 1 cells if lung tissue is damaged

Question 315

When is elevated PaCO2 and low PaO2 expected in COPD?

Answer 315

PaO2 usually remains near normal until FEV1 <50% predicted

• ventilation-perfusion mismatching accounts for essentially all of the reduction

PaCO2 usually not elevated until FEV1 <25%

• may not even occur then

Question 316

Which disorders cause predominant upper zone vs lower zone fibrosis?

Answer 316

• *Upper (think allergens)**
• hypersensitivity pneumonitis
• coal worker’s pneumoconiosis (+ progressive massive fibrosis)
• silicosis
• sarcoidosis
• tuberculosis
• histiocytosis
• ankylosing spondylitis (rare)
• *Lower (think immune and drug)**
• IPF
• CTD related
• Drug: amiodarone, bleomycin, methotrexate
• Asbestosis (fibres are heavy)

Question 317

What are the main differential diagnoses for cavitating lung lesion?

Answer 317

• Abscess
  
  • s aureus, klebsiella, pseudomonas
• Squamous cell lung cancer (others can do but less common)
• Tuberculosis
• Granulomatosis with polyangiitis (GPA, Wegener’s)
• Rheumatoid arthritis
• Other infection
  
  • aspergillosis, histoplasmosis, coccidiodomycosis

Question 318

What is Kartegener’s Syndrome?

Answer 318

• Primary ciliary dyskinesia
  
  • respiratory tract (including eustachian tube and inner ear), fallopian tube, flagella of sperm = infertility
• Rare autosomal recessive disorder resulting in defective outer/inner dynein arms (give cilia motility)
• Only known as Kartagener’s when associated with situs inversus
  
  • ~50% of the time

Question 319

What are the presentations of the altitude related disorders?

Answer 319

Descent is a required part of management of all

Acute mountain sickness

• generally self limiting
• headache, nausea, fatigue
• starts above 2500m, develops gradually over 6-12hrs, may last days
• acetazolamide to prevent, gain altitude at <500m/day

High altitude pulmonary oedema

• classic pulmonary oedema features
• nifedipine, dexamethasone, acetazolamide, PDE5 inhibitors
• oxygen if available

High altitude cerebral oedema

• dexamethasone

Question 320

What makes up surfactant?

Answer 320

Dipalmitoyl phosphatidylcholine

Question 321

Which form of asbestos is most dangerous?

Answer 321

Crocidolite (blue)

Question 322

What is Combined Pulmonary Fibrosis and Emphysema Syndrome?

Answer 322

Usually patients have either disorder predominating

• as they have dissimilar physiologic effects
• emphysema: reduced recoil, increased compliance, increased volumes, reduced maximal exp flow
• fibrosis: increased recoil, decreased compliance, reduced volumes, normal/increased maximal exp flow

Features

• male (90%), smoking history (98%), dyspnoea, pulmonary hypertension
• upper lobe emphysema
• lower lobe fibrosis, predominance of UIP
• relatively normal spiro/lung volumes with severely impaired DLCO

Diagnosis

• consensus definition doesn’t exist
• HRCT showing typical features + above hx/RFs

Complications

• pulm HTN more frequent and severe than in IPF alone
• significantly increased risk of lung cancer, with worse outcomes if they get it

Prognosis

• median survival 2-8yrs
• if pulmn HTN 1yr survival 60%
• seem to have similar outcomes to pulm fibrosis alone

Management

• smoking cessation
• lung transplantation the only definitive

Question 323

What are the commonly isolated pathogens in bronchiectasis?

Answer 323

Viral

• • coronavirus, rhinovirus, influenza

Bacterial

• • haemophilus influenzae
• • moraxella catarrhalis
• • staph aureus
• • pseudomonas aeruginosa
• • strep pneumoniae

Question 324

What is the recommended diet for cystic fibrosis?

Answer 324

High calorie, high fat

• used to be low fat to reduce steatorrhoea
• now recognised important to get enough fat intake

Supplementation with vitamin A, D, E, K

90% need pancreatic enzymes

Question 325

Which supplements increase the risk of lung cancer in smokers?

Answer 325

Beta carotene and vitamin E

Question 326

What is graft survival like comparing the different transplanted organs?

Answer 326

Question 327

What’s the definition of Acute Respiratory Distress Syndrome (ARDS)?

Answer 327

Within 1 week of a known insult, or new/worsening respiratory symptoms

Bilateral opacities not explained by effusions, collapse/consolidation, nodules

Hypoxia not explained by CCF or overload

• do a TTE in those with no risk factors for ARDS to look at LV function

Phases

• acute exudative phase
• fibrosing alveolitis (days to weeks after)
• recovery phase

Management

• low volume ventilation (6mL/kg ideal bodyweight)
• prone ventilation decreases mortality (PROSEVA study NEJM 2013; 23.6% vs 41% 90 day mortality proning 16hrs/day vs not)
• supportive care
• nothing works to fix it

Question 328

What is eosinophilic bronchitis?

Answer 328

Not synonymous with asthma

• lacks airway hyperresponsiveness
• have the same frequency of atopy as the general population

Causes a steroid responsive chronic cough

• responds to oral or ICS

Diagnosed with >2.5% eosinophils in induced sputum

Question 329

What did the FLAME trial of ICS/LABA vs LAMA/LABA in COPD show? What about the LANTERN study?

Answer 329

Summary

• LABA/LAMA > LABA/ICS
• Fewer exacerbations in the LABA/LAMA group

LANTERN study in Int J Obstruct Pulm Dis 2015

• looked at the same population with <=1 exacerbation in the last 12 months
• showed non-inferiority

Question 330

What markers can help prognosticate in COPD?

Answer 330

• *BODE** Index - higer the score the worse prognosis
• Better predicts mortality, hospitalisation, survival post LVRS
• *BMI -** < 21 = 1 point
• *Obstruction -** FEV1
• *Dyspnoea -**on dyspnoea scale score
• *Exercise -** distance walked in 6 minutes

Question 331

What is acute interstital pneumonitis (AIP)?

Answer 331

Also known as Hamman-Rich syndrome

Rapidly progressive non-infectious ILD

• the only acute process of the idiopathic interstitial pneumonias
• effectively looks like and follows a similar course to ARDS

Typically occurs in middle aged adults without pre-existing lung disease

• presents with productive cough, fever, dyspnoea that often requires mechanical ventilation within weeks of onset

Radiology - same as ARDS

Question 332

What is the pulmonary embolism severity index (PESI)? What are the risk stratifying parameters in acute PE?

Answer 332

PESI useful to identify low risk patients suitable for outpatient management

Imaging

• RV dysfunction due to PE = 2x mortality
• RV thrombus = ~doubled mortality
• Co-existent DVT = 2x mortality

Laboratory

• low BNP predicts uncomplicated course
• raised troponin OR 5 for short term mortality
• hyponatraemia <130 OR 3 for mortality
• lactate >2 predicts mortality

Question 333

Who should be tested for inherited thrombophilia?

Answer 333

Routine screening for those presenting with VTE not recommended

Family history +ve

• 1st degree relative with VTE <45yrs
• protein C, S, antithrombin III deficiency, factor V leiden, prothrombin gene mutation

Family history -ve

• <45yrs and recurrent VTE = thrombophilias and APLS
• thrombosis in multiple or unusual sites (portal*, hepatic*, mesenteric, cerebral veins) = thrombophilias and APLS
• warfarin induced skin necrosis = look for protein C deficiency (rarely protein S or FVL)
• arterial thrombosis = look for APLS

* = also test for JAK2 mutation and PNH

Question 334

At what weight should NOACs be avoided?

Answer 334

BMI >=40 or weight >120kg
- lack of data to guide dosing

Question 335

When should those with pulmonary embolism (PE) be thrombolysed?

Answer 335

PE with hypotension (‘massive’) = thrombolyse

• RR 0.20 for mortality
• 9.4% vs 19% risk of recurrent VTE or death

PE without hypotension = don’t thrombolyse

• no difference in mortality

PE without hypotension but with RV dysfunction and elevated troponin (‘submassive’) = not standard

• no difference in mortality (Meyer et al NEJM 2014)
• reduced cardiovascular collapse but increased bleeding

Question 336

Which medications are associated with development of group 1 pulmonary hypertension?

Answer 336

Question 337

What are the important prognostic factors in pulmonary hypertension?

Answer 337

Poor prognosis

• male
• CTD
• older
• NYHA class

Question 338

What are the two types of endothelin receptor and what do they do?

Answer 338

• *Endothelin-1 has A and B receptors**
• levels increased in plasma and lungs in PAH
• levels correlate with disease activity and mortality

Both present on smooth muscle

• activation -> vasoconstriction

Endothelin B present on vascular endothelium

• activation -> NO release and vasodilation

Question 339

What are the mandatory minimum investigations on diagnosis of bronchiectasis?

Answer 339

• FBE + immunoglobulin level
• Culture of airway secretions, including for non-tuberculous mycobacteria
  
  • if first isolation of pseudomonas attempt eradication
• Spirometry
• Serological tests for aspergillus

Question 340

What should be the approach to respiratory infections in cystic fibrosis?

Answer 340

• *Routine sputum MCS 3 monthly to guide therapy**
• base antibiotic choice on prior isolates with exacerbations
• *Pseudomonas aeruginosa**
• initial isolation -> attempt to prevent colonisation with aggressive antibiotic therapy
• >70% of adults chronically infected, once mucoid phenotype develops impossible to eradicate
• mucoid -> worsening lung function
• in chronic infection antibiotic susceptibility doesn’t affect outcome
• chronic azithromycin beneficial (decreases exacerbations, increases FEV1)
• contact precautions and masks for healthcare workers; patients shouldn’t congregate together
• *Burkholderia cepacia complex**
• chronic infection -> accelerated decline in lung function
• usually multi drug resistant
• contraindication to lung transplantation (due to worse outcomes)
• *Non-tuberculous mycobacteria**
• MAC not associated with worse transplant outcomes
• Abscessus associated with worse transplant complications
• only treat is symptoms, worsening lung function, or nodular infiltrates/cavitating disease
• *Antibiotics**
• one antibiotic for each organism isolated on culture
• two antibiotics if possible for each gram -ve isolated
• no role for routine tune-ups
• no role for chronic/cyclical antibiotics other than azithromycin

Question 341

What are the two biggest predictors of cigarette dependence?

Answer 341

• Smoking within minutes of waking predicts stronger dependence
• Increased number of cigarettes smoked per day predicts stronger dependence

Question 342

Is there any evidence to support reduction of number of cigarettes smoked per day as a method of smoking cessation?

Answer 342

NO

Question 343

What are primary and secondary spontaneous pneumothorax (PSP; SSP), what are their risk factors and rates of recurrence? Management?

Answer 343

• *Primary =** no underlying lung disease. Recurrence 25-50%
• Smoking the biggest: >22cpd -> 102x RR; <12 cpd 7x RR
• FHx in 10%
• others: Marfan’s, homocystinuria, thoracic endometriosis
• *Secondary =** underlying lung disease. Recurrence >50% (depends on aetiology)
• usually more dangerous than PSP due to decreased reserve. M**ortality 16%
• COPD responsible for 50-70%**
• 5-10% of PCP will get SSP
• up to 20% of CF >18yo will develop SSP
• others: TB, lung cancer, necrotising pneumonia, ankylosing spondylitis, LAM, ILD, histiocytosis, CTD
• *Management** (2cm (at the level of hilum) the cutoff for small vs large; symptoms more important than size)
• SP of any size with significant dyspnoea -> active intervention
• SSP of any size should be intervened upon (only 60% spontaneously close)
• needle aspiration equivalent to large bore + reduced admission rates and LOS
• never repeat needle aspiration unless technical difficulties caused it to fail (insert small bore drain rather than repeat)\
• *Recurrence prevention**
• thoracotomy + pleurectomy -> 1% recurrence
• VATS pleuradesis -> <5% recurrence
• Talc pleuradesis -> 5-8% recurrence + 2% risk of ARDS
• smoking cessation

Question 344

What factors are associated with poor outcome in pleural infection?

Answer 344

RAPID score

Question 345

What did the REDUCE trial show with regard to use of glucocorticoids in exacerbations of COPD?

Answer 345

RCT of 5 days vs 14 days of 40mg prednisolone in those presenting with acute exacerbation of COPD
- 314 patients, 92% admitted to hospital

5 days non-inferior to 14 days

• • predefined non-inferiority criterion was upper limit of 15% increase in re-exacerbation rates
• • no difference in time to death; combined exacerbation, death, or both; recovery of lung function

Question 346

What is the concept of ‘frequent exacerbators’ in COPD?

Answer 346

Phenotype is distinct as some with COPD are prone to frequent exacerbations

• • Generally defined as >=2 exacerbations per year

Rate of exacerbation in the past year predicts risk in the next year

Frequent exacerbations lead to more rapid decline of lung function, more rapid functional decline, greatest risk of AMI

Targets for interventions to reduce exacerbations

• • LAMAs reduce exacerbations, most data for tiotropium
• • LABA/LAMA superior to LABA/ICS for exacerbation prevention
• • indacterol, vilanterol, olodaterol superior to salmeterol
• • add ICS in those with significant reversibility or frequent exacerbations
• • pneumonia risk least with budesonide

Question 347

What is the significance of OSA in those with COPD?

Answer 347

Those with both are more likely to have pulmonary hypertension or hypercapnoea than with either alone

OSA (untreated) in those with COPD predicts worse survival and severe exacerbations

• • risk abolished by treatment of the OSA

Question 348

What did the FLORALI study find when comparing high flow nasal oxygen with non-invasive ventilation in those with acute hypoxaemic respiratory failure?

Answer 348

HIGH FLOW BETTER!

• less required intubation at 28 days
• decreased rates of death at 90 days

Question 349

When is tiotropium of benefit in asthma?

Answer 349

RCT of addition of tiotropium vs placebo in those with poorly controlled asthma on ICS/LABA

• 912 patients

Outcomes (improves PFTs, symptoms, exacerbations)

Question 350

What is the dominant immune pattern in asthma vs COPD?

Answer 350

Asthma

• • eosinophilic and TH2 driven

COPD

• • neutrophilic and CD8 driven

Note that there’s an overlap

• • longstanding asthma can move toward a neutrophil/CD8 predominance
• • a portion with COPD have TH2 pathway and eosinophils

Question 351

What are the expected values to assess for degree of compensation in respiratory acidosis and alkalosis?

Answer 351

Question 352

When is pulmonary rehab useful?

Answer 352

Involve all with COPD early, even with mild symptoms

Grade A evidence

• improves exercise capacity
• reduces breathlessness
• improves health related QOL
• reduces hospitalisations and LOS
• improves recovery after hospitalisation for an exacerbation
• reduces anxiety/depression associated with COPD

Grade B evidence

• benefits extend well beyond immediate period of training
• improves survival
• enhances effect of LABA

Question 353

What are the complications and their associated mortality in IPF? When should they be referred for transplant?

Answer 353

• Progressive respiratory failure - 39%
• Cardiovascular disease - 24%
  
  • RV hypertrophy, cor pulmonale due to PH+RHF, LV due to concurrent IHD
• Bronchogenic carcinoma - 10%
  
  • 14:1 excess risk c/w general population
  • same histologic distribution as the general population
• Pulmonary embolism - 3-7%
• Pulmonary infection - 2-4%
• Pneumothorax
  
  • less often than in other ILDs
• Complications of therapy
• Referral for transplant
  
  • should be referred early if appropriate
  • DLCO <40%, FVC <80%, any dyspnoea or functional limitation due to IPF, decrease in sats to <89% even if only during exertion
  • decline in FVC >=10% or DLCO >=15% during 6 months of f/u, pulmonary hypertension