Respiratory Flashcards
1
Q
Describe constituents and production of surfactants
A
Lipoprotein composed mainly of dipalmitoyl phosphatidylcholine.
Secreted by type 2 pneumocytes
Functions to increase compliance of alveoli
Fetuses begin production of surfactant between 24-28 weeks with maximum level at 36 weeks
2
Q
Management approach for pulmonary hypertension
Specific therapeutic recommendations for Class I PAH
A
For all classes, treat the underlying cause.
Also:
- Pulmonary rehabilitation - improves QoL, VO2max
- Exercise training - improves endurance and aerobic capacity
- O2 if hypoxic
- Anticoagulation for IPAH, drug induced PAH, hereditary PAH and CTEPH (but not for CTD associated PAH as they bleed more)
For class I PAH, If positive vasoreactivity test on RHC, trial CCB (although large doses are often needed, eg nifedipine upto 240mg, diltiazem upto 900mg etc) Trial ERA, PDE5 inhibitors, GC stimulators, prostacyclin analogues
3
Q
Role of tiotropium in COPD
A
Improves exacerbations, FEV1, symptom scores and QoL.
It however does NOT slow the rate of loss of lung function
4
Q
Haldane effect
A
Increase in PO2 means CO2 binds less well to Hb
5
Q
Name 5 strongest risk factors for VTE (OR >10)
A
- Fracture of lower limb
- Hip/knee replacement
- Heart related issues (admission for heart failure or AF or MI within last 3 months)
- Previous VTE
- Spinal cord injury
6
Q
Action of Ivacaftor
A
CFTR potentiator, indicated in CF patients with G551D mutation in the CFTR gene.
7
Q
Management of HACE?
A
- Descent
2. Dexamethasone
8
Q
What is the risk of VTE recurrence after 12 months?
A
Around 10%
Recurrence risk is higher in unprovoked VTE and after multiple VTE episodes, continuing OCP, PE, proximal DVT, elevated d dimer
9
Q
Which types of cancers are associated with highest risk of VTE? (name 5)
A
- Haematological Ca
- Lung
- GI
- Pancreatic
- Brain
10
Q
Vareniciline
A
Nicotine receptor partial agonist.
Most effective - compared to placebo, NRT, bupropion.
Main SE is nausea in 30%, NOT dose dependent.
Also possible neuropsychiatric side effects such as suicidal ideation.
11
Q
Classification of alpha 1 antitripsyn deficiency
A
Inherited in codominant fashion
Alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow
normal = PiMM
homozygous PiSS (50% normal A1AT levels)
homozygous PiZZ (10% normal A1AT levels)
Patients who manifest disease have PiZZ.
12
Q
Indications for home O2 therapy
A
PO2 <7.3 kPa
PO2 7.3-8 kPa and:
Secondary polycythaemia
Nocturnal hypoxemia
Cor pulmonale
13
Q
Efficacy of triple therapy in COPD
A
OPTIMAL study in 2007 showed addition of seretide to tiotropium significantly improved disease specific QoL, frequency of all cause hospitalizations, lung function.
14
Q
Efficacy of ICS in COPD - pros and cons
A
ICS + LABA reduced the rate of exacerbations RR 0.7, improved QoL and daily symptoms. One exacerbation was prevented for every 2-4 years of treatment.
However the caveat is:
- Increased oral candidiasis and skin bruising RR ~2
- Increased risk of pneumonia (OR 1.78 with fluticasone, less with budesonide OR 1.62)
15
Q
Risk factors for pneumothorax recurrence?
A
- Male
- Tall
- Low body weight
- Persistent smoking
- Emphysematous lung blebs
16
Q
What is the efficacy of PDE 5 inhibitors?
A
Includes sildenafil, tadalafil, vardenafil.
Improves haemodynamics, exercise capacity, WHO functional class and QoL, but actual mortality benefit is unknown.
17
Q
What options of airway secretion management are available in CF?
A
- Inhaled Dornase alpha (DNase)
Improves FEV1 by 6%, reduces exacerbation - Inhaled hypertonic saline - no impact on FEV1 but reduces exacerbation frequency and absenteeism
- PEP therapy (positive expiratory pressure) - reduces exacerbation frequency.
18
Q
Epidemiology of PE according to age, sex and race
A
- Increased risk with increasing age - risk doubles every decade after 40 years of age
- Females have lower recurrence rates of PE
- Males have higher incidence of PE
- Higher incidence in African Americans, but lower incidence in Asians and Pacific Islanders
19
Q
5 Secondary causes of restless leg syndrome
A
- Iron deficiency
- Neurological disorders - spinal cord, peripheral nerve, vertebral disc
- Pregnancy
- Uraemia
- Drug induced -TCA, SSRI, dopamine antagonist, lithium
20
Q
What is the role of inhaled antibiotics in bronchiectasis?
- CF associated
- Non - CF associated
A
In CF-associated bronchiectasis, inhaled antibiotics have been associated with reduced exacerbation, reduced airway inflammation and reduced bacterial load.
Current role is uncertain in non-CF bronchiectasis.
21
Q
Indications for LTOT in COPD
A
- PaO2 <55 mmHg or
- PaO2 <60mmHg with pulmonary hypertension/RHF
Mortality benefit only with usage of more than 16 hours a day
22
Q
Approximate carriage rate for CF gene
A
1:25
23
Q
In CF, why do people undergo double lung transplant vs single lung transplant?
A
Contamination of the transplanted lung occur from the native lung as CF causes purulent disease.
24
Q
Which is the only drug that has been proven ‘prospectively’ to have mortality benefit in class I PAH?
A
IV epoprostenol (prostacyclin) Improved symptoms, exercise tolerance and haemodynamics.
2 other drugs which have shown mortality benefit are Bosentan (against historical controls) and Macitentan (as a composite end point of mortality and morbidity)
25
6 causes of raised DLCO
1. Asthma
2. Polycythaemia
3. Pulmonary haemorrhage
4. Severe obesity
5. Mild heart failure with increased pulmonary capillary blood volume
6. Exercise prior to testing causing increased cardiac output
26
Causes of methaemoglobinaemia
Oxidization of Ferrous Fe2+ to Fe3+ (Ferric)
1. Dapsone
2. Topical anaesthetic agents such as lidocaine
3. Inhaled NO
4. Aniline dye
Methemoglobinemia is strongly suggested when there is clinical cyanosis in the presence of a calculated normal arterial pO2 (PaO2) as obtained by arterial blood gases. Arterial blood gas analysis is deceptive because the partial pressure of oxygen is normal in subjects with excessive levels of methemoglobin.
27
Indications for NIV in COPD exacerbation
1. Hypercapnic respiratory failure
Consider instituting early when RR >30 and pH 7.35
Aim of reducing RR and increasing pH within an hour with repeat ABG to monitor.
28
What does a REDUCED TLC in the presence of ELEVATED RV/TLC ratio indicate?
Mixed obstructive/restrictive defect, or neuromuscular disease.
29
What is the purpose of BAL in diagnostic investigation of ILD?
To exclude chronic hypersensitivity pneumonitis
Retrospective data suggests that 8% with HRCT UIP pattern have BAL findings of an alternative diagnosis
30
Adverse prognostic factors for VTE on the basis of imaging findings?
1. RV dysfunction on echo - 2x mortality
2. RV thrombus - doubles 14 day mortality and 3 month mortality
3. Coexistent DVT - increase in all cause mortality and PE specific mortality
31
Antibiotic rules for treatment of CF infections
One antibiotic for each organism isolated on culture
2 antibiotics for each gram negatives isolated if possible
Higher dose of antibiotics often required due to poor tissue penetration.
32
4 pathways targeted in PAH
1. Endothelin pathway - prevents vasoconstriction
2. NO pathway - NO produces vasodilation and inhibits proliferation
3. Prostacyclin pathway - prostaglandins produce vasodilation and anti proliferation
4. Soluble guanylate cyclase pathway
33
5 major causes of ILD
1. Drug induced
2. Granulomatous lung disease - sarcoidosis, hypersensitivity pneumonitis
3. Connective tissue disease
4. Others (pLAM, histiocytosis X)
5. Idiopathic:
Idiopathic causes include: IPF, NSIP, COP, AIP, RBILD, DIP, LIP
34
5 treatment approach to bronchiectasis
1. Screen and treat potentially treatable cause (eg: ABPA, CVID, MAC, AAT deficiency)
2. Aid sputum clearance
3. Pulmonary rehab - will reduce exacerbation and improve 6MWT
4. Sputum culture - monitor future cultures for MAC, and attempt eradication of pseudomonas if first culture
5. Macrolide therapy if frequent exacerbation - 3 ore more exacerbations in a year or 2x hospitalization in 12 months (modulation of inflammation)
35
What is the significance of mediastinal lymph node involvement in lung cancer?
If mediastinal lymph nodes are pathologically involved by tumour, then the patient has at least stage III disease and a combined modality therapy approach is most appropriate.
If mediastinal lymph nodes are negative by pathologic evaluation, then the patient has clinical stage I or II disease and resection of the primary tumour along with further mediastinal lymph node assessment at surgery is in order.
36
Bohr vs Haldane effect
Bohr effect - under the conditions of acidity, O2 binds less well to Hb facilitating unloading of O2
Haldane effect - increasing PO2 at the lungs lead to better unloading of CO2.
37
What is the role of PESI score?
Identifies very low risk to very high mortality risk at 30 days to determine who would be suitable for outpatient management.
If intermediate or high risk, requires further investigations such as echo to define RV function and to consider primary reperfusion.
Lancet study 2011 showed that PESI class 1/2 patients can be safely treated in outpatient setting without significance increase in VTE rates at 3 months or differences in bleeding rates.
38
Paraneoplastic syndromes associated with squamous cell carcinoma of the lung
1. Parathyroid hormone-related protein (PTH-rp) secretion causing hypercalcaemia
2. Clubbing
3. Hypertrophic pulmonary osteoarthropathy (HPOA)
4. Hyperthyroidism due to ectopic TSH secretion
39
Paraneoplastic phenomena associated with adenocarcinoma
Gynaecomastia
40
Mechanism of action of Riociguat?
Stimulates soluble guanylate cyclase and has 2 modes of action:
1. Increases the sensitivity of sGC to endogenous NO and causes vasodilation
2. Direct stimulation of NO receptor.
Improves 6MWT, WHO functional class, symptoms and PVR.
Has shown similar benefit in both class I PAH and CTEPH.
Mortality impact unknown.
41
Effect of long term macrolide therapy in bronchiectasis
Reduces exacerbation frequency
However increased macrolide resistance, no changes in FEV1, no changes in QoL, and benefit appears to be temporary.
42
Treatment of restless leg syndrome?
1. Narcotics such as codeine
2. Pregabalin - most useful, start at low dose
3. Dopamine agonist such as sinemet or pramipexole
43
5 factors which affect TLCO measurements
1. Anaemia decreases TLCO and vice versa
2. COHb - decrease in TLCO due to decreased diffusiong radient and anaemia like effect caused by COHb
3. Alveolar pCO2 - increased TLCO due to reduction in PAO2 and less competition for CO to bind to Hb
4. Pulmonary capillary blood volume
5. Body position - supine causes increased TLCO due to changes in blood flow distribution.
44
Why is pseudomonas colonization important in bronchiectasis?
Associated with more rapid FEV1 decline.
Upon being identified for the FIRST TIME, eradication with ciprofloxacin +/- nebulized colistin therapy or IV therapy can reduce exacerbation frequency.
At median 14 month follow up after eradication, 50% remain pseudomonas free.
45
Classification of pulmonary hypertension
1. Pulmonary arterial hypertension (idiopathic, heritable PAH eg BMPR2 mutation, drugs or toxin induced, associated diseases such as CTD, HIV, schistosomiasis)
2. PH due to left heart disease
3. PH due to lung disease/hypoxia
4. CTEPH
5. PH due to multifactorial mechanisms - haematological, systemic disorders such as sarcoidosis
46
What does a normal TLC with increased RV on a lung volume measurement suggest?
1. Gas trapping due to airflow limitation
2. Neuromuscular disease (TLC often reduced as well)
If you have a normal TLC and increased FRC and RV, it means lungs are hyperinflated due to airflow limitation, and require breathing at higher resting lung volume to reduce airways resistance.
47
What is the role of ICS in bronchiectasis?
Not much evidence of benefit...
ICS may reduce sputum volume
However do not reduce exacerbation frequency or alter rate of FEV1 decline.
48
When should thrombophilia screen be undertaken?
1. Positive family history (1 or more 1st degree relatives with VTE age <45)
If family history is -ve:
2. Recurrent VTEs in patients <45 years
3. Unusual sites of thrombosis or multiple sites (eg: portal, hepatic, mesenteric, cerebral veins)
4. Warfarin induced skin necrosis
5. Patients with arterial thrombosis
49
6 absolute contraindications in thrombolysis
1. Haemorrhagic stroke or stroke of unknown origin at any time
2. Ischaemic stroke within the last 6 months
3. CNS neoplasm
4. Recent major trauma/surgery/head injury in the preceding 3 weeks
5. GI bleed within the last 1 month
6. Known bleeding risk
50
What is the expected rate of FEV1 decline per year for CF?
2% per year
51
Endothelin 1 in PAH
Implicated in pathogenesis of PAH.
ET-A/ET-B receptors are present on smooth muscles - causes vasoconstriction and proliferation
ET-B receptors only are present on endothelium - causes NO release and vasodilation
Endothelin-1 levels are increased in plasma and lung in PAH and higher level correlates with disease activity and mortality.
52
Characteristics of UIP
1. Lower zone and subpleural predominance
2. Reticular pattern with honeycombing
3. Traction bronchiectasis and architectural distortions
4. Temporal heterogeneity on pathology with fibroblastic foci in 'old' collagen
53
Diagnostic criteria for ABPA?
Predisposing condition - asthma or CF (1 needs to be present)
Obligatory criteria - Positive skin prick test or Aspergillus specific IgE, PLUS elevated IgE needs to be present (both)
Other criteria: (at least 2)
Raised eosinophil >0.5 in steroid naïve individual
Radiology consistent with ABPA (CT normal in 20%)
Positive aspergillus precipitant or IgG to A fumigatus1
54
Paraneoplastic syndromes associated with SCLC
1. SIADH
2. ACTH - not typical, hypertension, hyperglycaemia, hypokalaemia, alkalosis and muscle weakness are more common than buffalo hump etc
3. Lambert-Eaton syndrome
55
Benefits of pulmonary rehabilitation in COPD
Benefit extends across all COPD spectrums.
Most benefit seen following acute exacerbation.
Benefits extend to patients recovering from other post-critical illnesses.
Effects are lost in 2-3 months unless you keep up with the exercise.
56
Role of antibiotics in COPD
60% of AECOPD are secondary to bacterial infections.
AB use reduces mortality and 30 day readmission rates for COPD. Rates of C diff colitis did not differ.
Therefore USE antibiotics in AECOPD.
57
Calculation of A-a gradient
PAO2 = FiO2 (PB - PH2O) - (PaCO2/0.8)
Usual FiO2 at ground level is 21%
PB is 760 mmHg at ground
PH2O inside the airway is 47 mmHg
Therefore at sea level, can be assumed at 150mmHg.
In normal diet, 0.8 CO2 is produced for every 1 O2.
Normal A-a gradient <15mmHg
>15mmHg = abnormal.
58
Cardinal features of narcolepsy
Pathogenesis?
HLA associations?
1. Cataplexy - diagnostic. REM inhibition of muscles. emotion induced
2. Sleep paralysis in 4%
3. Hypnagogic hallucination - dreaming at sleep onset
Due to marked reduction in hypocretin at the hypothalamus
Associated with HLA DR2 and HLADQB1*0602
59
3 major features of sarcoidosis
1. Nodular lung infiltrate in mid/upper zones
2. Mediastinal/hilar LAD
3. Extrapulmonary manifestations - ocular, hepatic, hypercalcaemia, rarely CNS and cardiac
60
5 factors commonly associated with development of Group 1 PAH?
1. CTD eg scleroderma
2. HIV
3. Portal hypertension
4. Congenital heart disease
5. Schistosomiasis
61
How would you manage unprovoked PE?
If first episode, needs at least 3 months of treatment.
If high risk of bleeding complication - stop at 3 months.
If low/moderate risk of bleeding - indefinite therapy (as unprovoked PEs have 30% recurrence at 5 years)
Higher risk patients (eg recurrent VTEs, APLS, hereditary thrombophilia) - may need indefinite treatment but evidence is not conclusive.
62
3 important respiratory infections in CF
1. Pseudomonas - unlike non-CF population, mucoid phenotype develops with biofilm formation. Need to reduce transmission between CF patients by contact precautions, masks, single room for inpatient care etc
2. Burkholderia cepacia complex - chronic infection is associated with accelerated lung function decline. Usually multi-drug resistant and worse outcomes with transplantation. Infection control is essential to prevent cross infection between CF patients
3. NTM - MAC is not associated with worse transplant outcomes but M abscessus is.
Only treat NTM if clinical symptoms, worsening lung function, or nodular/cavitating disease.
63
Bohr effect
Increasing acidity means O2 binds less well to Hb
64
Chemotherapy in advanced stage NSCLC?
Chemotherapy can improve QoL but gains in survival compared to best supportive cares are modest at best (33% vs 12-15% in terms of one year survival)
More is not better - 2 combination is better than 1, 3 is worse than 2.
Platinum based combinations are the best - cisplat/paclitaxel or doxitaxel, or cisplat/gemcytabine
65
Describe action of omalizumab
Humanized recombinant mAb to form complexes with free IgE preventing binding to mast cells.
Improves asthma symptom control, allows patients to be managed with lower doses of ICS, reduces frequency of exacerbation.
66
ILD associated with smoking?
Features on HRCT?
DIP and RB-ILD
Features of ground glass attenuation, basal and peripheral, diffusely spread.
67
5 features of pLAM
1. Premenopausal female
2. Cystic lung disease
3. Hyperinflation
4. Pneumothorax
5. Extrapulmonary manifestations such as angiomyolipoma, chylous effusions
68
3 endothelin receptor antagonist currently available?
Bosentan - non selective ERA. Limited by hepatotoxicity in 10%. Improves 6MWT, WHO functional class, symptoms, echo, time to clinical worsening.
Only showed survival benefit when compared against historical controls.
Macitentan - no-selective ERA. Can cause nasopharyngitis and anaemia. Improves 6MWT, WHO functional class, AND improved composite end point of morbidity and mortality.
Ambrisentan - selective endothelin A antagonist.
Less hepatotoxicity than Bosentan. Improves symptoms, 6MWT, WHO functional class, QoL, pulmonary vascular haemodynamics.
69
Features of NSIP?
1. Bilateral patchy ground glass changes
2. Lower zone predominant
3. Subpleural areas
4. Absence of honeycombing
5. Features of fibrosis such as anatomical distortions and traction bronchiectasis but no gross honeycombing
NSIP is a single hit disease - no progression over time
70
Describe MIST-2 trial regarding empyema
Investeigated effectiveness of fibrinolytic therapy for pleural empyema with primary end point being RADIOLOGICAL improvement and not mortality.
This study observed that when tPA/DNAse was used as a rescue therapy (after drainage was deemed ineffective at controlling the pleural disease) it showed reduction in ened for surgery and reduced hospital stay of 6.7 days compared to placebo.
Drains were smaller seldinger drains which supports the use of small bore ICDs in the management of pleural infection.
Use of DNAse alone was associated with higher incidence of surgical referrals therefore omission of tPA is not recommended.
Currently no mortality benefit of tPA + DNAse has been demonstrated in study however.
Thoracotomy remains the gold standard of treatment but is associated with considerable mortality.
71
Mechanism of action of ivacaftor
Efficacy?
CFTR potentiator in those with G551D mutation.
G551D mutation results in defective channel opening.
4% of CF patients have this mutation.
Ivacaftor increases chloride secretion and reduces excessive Na and fluid absorption.
Improves FEV1 by 10%
55% exacerbation risk reduction
Weight gain
Reduced hospitalization.
NOT effective in delta508 mutation.
72
Interpretation of DLCO and importance of DL/VA ratio (which is the same thing as KCO)
Because the DLCO is directly proportional to VA (the single-breath dilutional estimate of TLC), nonpulmonary processes that reduce the TLC cause reductions in the DLCO. If VA can be assessed accurately, these reductions produce a normal or elevated DL/VA ratio. Examples of this include lung resection, thoracic cage abnormalities (eg, kyphoscoliosis), and small lungs.
A reduced DLCO and a reduced DL/VA ratio suggest a true interstitial disease such as pulmonary fibrosis or pulmonary vascular disease.
73
Association between ICS and cataracts
Risk of developing cataracts increase by 25% for each 1000 ug/day increase in dose.
74
Describe actions of Pirfenidone and Nintedanib.
Effect in IPF?
Pirfenidone - anti-fibrotic.
Nintedanib - TKI 1,2 inhibitor which targets VEGF, FGF and PDGFR.
Pirfenidone has been shown to reduce decline in FVC and 6MWT and improves progression free survival, but no reduction in dyspnoea scores or death.
Nintedanib significantly reduces FVC decline, no changes in time to first exacerbation, no difference in QoL scores.
75
Role of BMPR2 in pulmonary arterial hypertension
BMPR2 inhibits smooth muscle proliferation and induces apoptosis. Abnormalities of BMPR2 results in proliferation of pulmonary vascular cells resulting in vascular remodelling.
Note: only 25% of patients with BMPR2 mutation actually develop PAH.
However 70-80% of patients with familial PAH have BMPR2 mutation.
76
What is the relationship between TLCO and KCO?
TLCO = KCO x alveolar volume
KCO is a measure of efficiency of gas exchange into blood stream. It is reduced if there is lung damage and increased if there are additional blood in the lungs to remove carbon monoxide.
In asbestosis, both KCO and TLCO are reduced as alveolar volume and gas exchange is impaired.
However in neuromuscular disease, gas exchange itself is not affected (thereby KCO will be normal) but TLCO will be elevated as alveolar volume taking part in gas exchange is reduced.
77
Management of High Altitude Pulmonary Oedema?
1. Descent
2. O2 if available
3. Medications including nifedipine, dexamethasone, acetazolamide, phosphodiesterase type V inhibitors. All reduce systolic pulmonary artery pressure
78
Bupropion
Dopamine and NA reuptake inhibitor.
Unknown mechanism of action that promotes smoking cessation.
Effective compared to placebo.
Can cause seizures 1:1000 by lowering seizure threshold, and possible increase in suicidal ideation.
79
What does reduced TLC, FRC and RV in proportion indicate?
Restrictive defect such as ILD, chest wall abnormalities, or external constraints (obesity, chest pain, poor volition)
80
What is the role of Well's score in assessment of VTE?
Determines the pre-test probability.
| Prevalence of VTE increases with increase in pre-test probability.
81
What is the test of choice to safely exclude PE in a HIGH pre-test probability of VTE?
VQ scan - if it is normal.
Unfortunately it is non-diagnostic in 50%.
82
2 main causes of reduced FVC in spirometry
1. True restrictive disease
| 2. Inappropriately shortened expiration
83
4 adverse prognostic factors in pulmonary hypertension
1. Male
2. CTD associated PHTN
3. Older age group >51
4. Worse NYHA functional class
84
What causes the following:
Upper lung fibrosis (5)
Lower lung fibrosis (4)
Upper lung fibrosis:
1. Hypersensitivity pneumonitis (extrinsic allergic alveolitis)
2. Pneumoconioses due to coal, silica
3. Sarcoidosis
4. Histiocytosis
5. TB
Lower lung fibrosis:
1. IPF
2. Drug induced - MTX, amiodarone, bleomycin
3. Most CTD related fibrosis
4. Asbestosis
85
Definition of reversibility on spirometry
Demonstration of an increase of at least 12% and 0.2 L in either FVC (provided the expiratory time for both sessions agree within 10%) or FEV1 on a spirogram performed 10-15 minutes after inhalation of a therapeutic dose of a bronchodilating agent
86
What is the role of aspirin in VTE secondary prevention
It does help! 30-35% reduction in risk of recurrence after unprovoked VTE... however this is less than half of the risk reduction achieved with other anticoagulants. It however is associated with less bleeding rates.
If you were to stop anticoagulation, aspirin is recommended as a continuation therapy in unprovoked VTE.
87
What is the role of routine screening for PAH in high risk individuals such as in scleroderma or HIV?
It is effective with improved 8 year survival compared to routine practice.
88
What needs to be screened for before commencing long term macrolide therapy?
1. NTM colonization - macrolide resistant MAC can rarely be cured
2. QTc prolongation
89
5 treatable cause of bronchiectasis
1. Immune deficiency (CVID)
2. ABPA
3. MAC infection
4. COPD
5. Associated inflammatory conditions (RA, IBD)
90
What is BODE index?
Estimates 2 year mortality rate. Consists of:
BMI
Obstruction (% FEV1 predicted)
Dyspnoea scale (MRC)
Exercise Capacity 6MWD
91
Treatment of ABPA?
Mainly steroids for 12+ weeks to suppress immune response to aspergillus and induce remission acutely during an exacerbation.
If steroid dependent, itraconazole for 16+ weeks which reduces prednisone use, improves IgE, and radiology, QoL and symptoms.
92
3 causes of UIP 'pattern' on HRCT
1. Asbestosis
2. IPF
3. CTD related ILD such as RA
93
Management of spontaneous pneumothorax
PSP or SSP and significant dyspnoea of any size should have active intervention - either needle aspiration or chest drain
If failed NA - small bore chest drain
Observation only for small
94
What are the poor prognostic factors in CF?
1. Female (males tend to survive better than females at lower FEV1)
2. Low FEV1
3. High CO2
4. High WBC
95
What is the role of screening in lung cancer?
Most lung cancer patients die due to the disease
However if detected and resected early, expected survival at Stage 1A is 80%
National lung cancer screening trial showed definitive improvement in mortality with RR reduction 20%
But only 27% of the initial LDCT detected nodules were >4mm, which can provoke anxiety in patients with nodules and false positives which can increase complications secondary to investigations
96
Management of diabetes in CF
Contrary to other causes of diabetes, weight loss is of major concern in patients with CF as low weight has a serious impact on respiratory function. Therefore diabetic diets are not used and patients are encouraged to maintain normal weight. Insulin is used.
97
5 Non CF but CFTR related diseases
1. Chronic rhinosinusitis
2. Idiopathic bronchiectasis
3. Acute and chronic idiopathic pancreatitis
4. ABPA
5. Congenital bilateral absence of vas deferens.
CF patients may present with above conditions in childhood therefore important to screen for CF mutations.
98
How do you diagnose narcolepsy?
Treatment?
With MSLT (multiple sleep latency test)
Sleep latency of LESS than 8 minutes, with >2 sleep onsets are REM periods.
Cataplexy can be treated with SSRI/TCA
Sleepiness can be treated with methylphenidate or modafinil.
99
Carriage rate of CFTR gene mutation
1/25
Autosomal recessive
CF seen in 1/2500 births
100
What is the role of BAL galactomannan in febrile neutropenia?
Galactomannan is in the cell wall of aspergillus. Can be found in both BAL and in blood of invasive aspergillosis.
BAL GM and CT can guide treatment in febrile neutropenia - effective in identifying IA with Sn88%/sp87%.
101
Typical HRCT changes in PCP
Ground glass opacification without centrilobular nodules or cavities.
102
3 diseases which can give the UIP pattern
1. IPF
2. Asbestosis
3. CTD related ILD such as RA
103
Compare and contrast indirect vs direct airway hyperresponsiveness testing
Indirect - activates mast cells to release histamine and other bronchoconstrictor mediators by using mannitol, hypertonic saline. Greater reflection of INFLAMMATORY component of AHR. High specificity, low sensitivity. a RULE IN TEST.
Direct - directly constricts airway smooth muscles via receptors on smooth muscle by using methacholine or histamine. Greater reflection of persistent AIRWAY REMODELLING of AHR. High sensitivity, fair specificity. RULE OUT TEST.
104
How do you calculate peak flow variability and what is its significance?
%PF variability = Highest-Lowest/Highest.
>20% variability is significant and is diagnostic of asthma of symptoms are also present.
As you treat asthma, variability becomes less.
105
Diagnosis of cryptogenic organizing pneumonia on HRCT, lung function test and histology
Causes of COP
1. Multiple ground-glass or consolidative opacities.
2. Pulmonary function tests usually show a restrictive pattern with an associated gas transfer defect.
3. Histopathologic lesions characteristic of COP include excessive proliferation or "plugs" of granulation tissue within alveolar ducts and alveoli, associated with chronic inflammation in the surrounding alveoli
Causes:
1. Infection - anything... TB, viral, PJP, mycoplasma
2. CTD
3. Drugs - namely amiodarone and cocaine
4. Aspiration
5. Hypersensitivity pneumonitis
106
Cut off for 'hyperinflation' on lung function test
Cut off for 'normal' DLCO
>120%
Usually >80% for DLCO
107
What is the main differential diagnosis to think of in context of isolated decrease in DLCO with normal spirometry and lung volume?
The finding of an isolated decreased in the DLCO (i.e. normal spirometry and lung volumes) is highly suggestive of a pulmonary vascular process such as pulmonary hypertension.
108
Severity of OSA on the basis of AHI
AHI index: 5-15 is mild, 16-30 moderate, 30+ severe
109
Respiratory changes in pregnancy
VC and TLC are preserved due to increased mobility and flaring of the ribs and unimpaired diaphragmatic excursion.
RV and FRC decrease during gestation due to diaphragm elevation from enlarging uterus.
FEV1 and FVC are not greatly affected by pregnancy as airway mechanics remain similar to non pregnant status.
Minute ventilation increases during pregnancy with increased tidal volume presumably related to increased level of progesterone. This leads to compensated respiratory alkalosis.
110
2 types of asbestos and their significance
1. Serpentine fibres - chrysotile. Long curly strands. Less toxic than amphibole fibres
2. Amphibole fibres - long, straight, rod like structures (crocidolite exposure)
Amphibole fibres are more toxic and are associated with most frequent progression
111
Describe the effect of PaO2 and PaCO2 level and respiration.
Two chemoreceptors are present - peripheral and central.
Central chemoreceptors are present in medulla and accounts for 80% of respiratory drive. Responds indirectly to rise in PaCO2 as detected via rise in H+.
Peripheral chemoreceptors are present in carotid bodies and aortic arch. Responds both to PaO2 and PaCO2. Accounts for 20% of respiratory drive.
In most cases, it is the rise in PaCO2 above 40mmHg which stimulates respiration (both peripheral and central).
PaO2 <60mmHg starts to stimulate peripheral chemoreceptors to increase respiration.
112
Lung nodules - high risk features and management
High risk features:
1. Increasing age - >60 years: >50%
2. Size of the nodule - nodules >20mm have >50% chance of being malignant
3. Nodule attenuation - either solid or subsolid (pure subsolid aka ground glass, or part solid). Part solid lesions have a higher likelihood of being malignant.
4. Volume doubling time - most malignant nodules have VDT of 20-400 days
5. Risk of malignancy is higher with irregular borders
6. Hounsfield unit >164
In a patient at low risk for malignancy, no follow up is required for incidental nodule <4mm. If patients are at risk of malignancy, then CT scan repeated in 12 months time.
Attenuation coefficient of a pulmonary nodule is a measure of its density and is expressed in Hounsfield units. Enhancement after contrast reflects nodule vascularity and is an indicator of malignancy or active inflammation. A nodule that shows less than 15 Hounsfield units of enhancement on contrast study is highly likely to be benign - 97% NPV.
113
Management of methaemoglobinaemia
1. Methylene blue if no concurrent G6PDH deficiency or is not on medication that could cause serotonin syndrome
2. In patients with known G6PDH deficiency, MB is dangerous as reduction of methaemoglobin by MB is dependent upon NADPH generated by G6PD. As a result, MB may induce haemolysis.
If MB is contraindicated, use ascorbic acid. However MB has a more rapid onset of action compared to ascorbic acid.
114
Differential diagnosis of exudative effusion with >10% eosinophilia
ABCDEF
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Asbestos
Bad hodgkins lymphoma
Churg Strauss Syndrome
Drugs - dantrolene, bromocriptine, nitrofurantoin, valproate
Embolism - PE
Fungus - coccidiodomycosis
```
115
Medications which exacerbate restless leg syndrome
selective serotonin reuptake inhibitors (SSRIs)
serotonin-norepinepherine reuptake inhibitors (SNRIs)
diphenhydramine
dopamine antagonists
116
When is NIV indicated in COPD exacerbation?
Hypercapnic respiratory failure
Consider instituting early when RR >30 and blood pH <7.35
Improves RR, PaO2, PaCO2 and pH
Decreases treatment failure intubation, mortality and length of stay.
117
Who benefits from lung volume reduction surgery?
Predominant upper lobe emphysema.
| Overall increase in early mortality but no changes at 2 years. Also increase exercise capacity
118
Efficacy of long term macrolide therapy in COPD
Daily azithromycin for 1 year significantly increased time to first exacerbation, however no changes in hospitalization and increased macrolide resistant organisms. NOT A STANDARD OF CARE.
119
Eosinophilic bronchitis
NOT synonymous with asthma - airway hyperresponsiveness is absent.
Diagnosed by eosinophil count >2.5% in induced sputum.
A cause of steroid responsive cough.
Responds to ICS and oral steroids.
Atopy is at same frequency as the general population.
120
How is IgE produced?
IgE is produced by B lymphocytes under the direction of two cytokines: interleukin-4 (IL-4) and the closely related interleukin-13 (IL-13), which are produced by several cell types including T helper type 2 (Th2) cells (a subset of T helper lymphocytes prevalent in atopy)
121
What is the strongest risk factor for development of asthma?
Atopy.
122
5 criterias which need to be met for omalizumab therapy
1. Age >6 years
2. Moderate-to-severe persistent asthma
3. Asthma symptoms that are inadequately controlled with inhaled glucocorticoids
4. High serum IgE
5. Allergic sensitization demonstrated by positive skin testing or in vitro testing for allergen-specific IgE to an allergen that is present year round (a perennial allergen), such as dust mites, animal danders, cockroach, or molds.
123
Efficacy of omalizumab
1. Improves asthma symptom control
2. Allows patients to be managed with lower doses of ICS
3. Reduces frequency of exacerbation
124
MoA of Lebrikizumab
Anti IL-13 inhibitor.
IL13 is important mediator of inflammation in Th2 response.
Improvement in FEV1 in Lebrikizumab compared to placebo (in active asthma on mod/high doses of ICS +/- LABA).
High FeNO (which is a Th2 biomarker) predicted response.
125
MoA of mepolizumab and resilizumab
Anti-IL 5 inhibitor.
| Reduced exacerbation, improved FEV1, symptom control and QoL.
126
Mechanism of action of dupilumab
monoclonal antibody which blocks IL-4R.
| Blocks both IL4 and IL13 signalling, and improves FEV1 and reduces exacerbations in mod/severe eosinophilic asthma.
127
What constitutes massive PE? (haemodynamic instability)
BP <90 mmHg. Carries a high mortality risk.
128
When should D dimer be used in diagnosis/exclusion of PE?
Has a high NPV making it a useful test to EXCLUDE PE in patients with low-intermediate pre-test probability.
Should not be used for patients with high pre-test probability.
129
Recurrence risk of VTE after unprovoked PE
What about VTE in cancer?
30% at 5 years
15% per annum
130
When is anticoagulation recommended in pulmonary hypertension?
1. Idiopathic PAH
2. Drug induced PAH
3. Hereditary PAH
4. CTEPH
Not recommended in CTD associated PH - bleeds more
131
Role of calcium channel blocker in pulmonary hypertension
CCBs can be trialled in patients with positive vasoreactivity test - only 10-25% respond to vasodilators.
CCBs improve survival in IPAH, but not in CTD associated PAH (as they are usually non-vasoreactive)
132
When should lung transplantation be considered in IPAH?
Medically refractory IPAH providing normal LV function.
Usually bilateral lung transplantation performed
Severe RV dysfunction often improves.
Higher incidence of obliterative bronchiolitis in IPAH patients.
133
Cause of death in acute leukaemia patients after 100 days
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Relapse of leukaemia - 48%
GVHD - 23%
New Cancer - 10%
Organ Failure - 9%
Infection without GVHD - 4%
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