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Basic Physician Training Written Prep > Respiratory Disease > Flashcards

Respiratory Disease Flashcards

1
Q

Diagnosis of COPD

A

Persistent airflow limitation demonstrated by:

FER = FEV1/FVC = <0.7

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2
Q

GOLD Classification for COPD severity:

A

Takes into account symptom severity (based on mMRC score, or CAT score) and exacerbation frequency.

0 or 1 (not leading to hospital admission)
A
B

2 exacerbations, or 1 leading to hospital admission.
C
D

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3
Q

Principals of management in COPD?

A

Think about it in terms of symptom symptoms reduction and exacerbation reduction.

Reducing Symptoms:
LABA and LAMA effective for symptom reduction (and exacerbation therapy):
- LAMA is more effective than LABA for monotherapy (therefore tiotropium first line)
- combination LAMA/LABA therapy is more effective than mono-therapy but more expensive.

Preventing Exacerbations:
- Once someone has exacerbated, monotherapy no longer sufficient.
- 1st line is LABA/ICS or LABA/LAMA
- Most people will get LABA/LAMA, unless there is a reason to give steroid:
- Eosinophil count >0.3
- Asthma history

Once hospital admission – Triple therapy.

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4
Q

Contra-indications for smoking cessation therapy?

A

NRT
- Avoid in unstable coronary heart disease, ok to use in stable disease.

Vareniclne
- avoid in patients with suicidal ideation

Bupropion
- Avoid in bipolar disorder

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5
Q

Options for smoking cessation?

A

Combination NRT with behavioural intervention is more effective than either alone.

Combination NRT RR 1.34

Varenicline (nicotine receptor partial agonist)
- Avoid with unstable psychiatric symptoms and suicidal ideation. Ok in stable psychiatric disease.

Bupropion
- Similar efficacy to mono-therapy NRT, less efficacy than varenacline
- Preferred in those with mild untreated depression, avoid in bipolar disease and seizure disorders.

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6
Q

Basic steps to interpret spirometry?

A

1 - is there obstruction? FER <0.7

2 - is there restriction? FVC < LLN

This is all you can answer from basic spirometry.
Obstructive
Restrictive
Mixed

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7
Q

Gas Transfer and Diffusing Capacity

A

DLCO = gas exchange (total)

VA = Alveolar volume

KCO = index of efficiency of CO transfer (DLCO per unit alveolar volume)

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8
Q

Asthma Definition

A

History of respiratory symptoms (wheeze, SOB, chest tightness, cough
That VARY over time and in intensity
Together with variable expiratory airflow limitation

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9
Q

Investigating asthma

A

Mannitol bronchoprovocation testing
- highly specific, used to rule in.

Methacholine bronchoprovocation testing
- highly sensitive and used to rule out. Methacholine more provoking than mannitol.

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10
Q

Testing for asthma:

A

Step 1 - Spirometry

If normal spirometry without bronchodilator response. Move to Bronchoprovocation testing,

Step 2 - DIrect Methacholine testing looking for fall in FEV1 >20%, highly sensitive, good for ruling out

Step 3 Indirect Mannitol or hypertonic saline, testing looking for fall in FEV1>15%
Exercise or eucapnic voluntary hyperventilation.

Other:
- FeNO

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11
Q

Eosinophilic pneumonia

A

Ket feature is rapid radiological clearance with steroids.

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12
Q

SYGMA Trial in Asthma

A
  • Symptoms controlled best with regular ICS.
  • Symptoms controlled better with PRN ICS/LABA (eformoterol = fast acting LABA) than SABA
  • ICS/LABA was non-inferior to regular ICS for reduction in exacerbations.

Therefore intermittent LABA/ICS is the first line, rather than SABA.

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13
Q

What do when not controlled on regular ICS?

A

OPTIMA Trial - increased dose ICS vs ICS/LABA combination therapy.

Combination therapy superior to increasing dose of ICS.

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14
Q

Biologic therapy options for asthma?

A

Omalizumab - Anti IgE
Mepolizumab - IL 5
Benralizumab - IL5R
Dupilimab - IL 4 / 13
Tezepelumab - targets TSLP (thymic stromal lymphopoitin)

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15
Q

Classification for asthma phenotypes?

A

T2 high:
- Allergic: IgE, Aspergillis fumigatus IgE
- Eosinophilic: Blood and sputum eosinophilia, FeNO

T2 Low:
- Lack of T2 inflammation

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16
Q

Omalizumab

A

Anti - IgE
- SC injection every 2-4 weeks
- Benefit in patients: Elevated IgE + Atopy + Asthma

Major benefit in allergic asthma:
IgE needs to be elevated 30-700IU/ml with positive skin prick testing to at least 1 antigen.

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17
Q

Mepolizumab and Benralizumab

A

Mepo (IL 5) 4 weekly injection and Benza (IL 5 R) 8 weekly injections.

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18
Q

Dupilimab

A

IL 4 + IL 13
Fortnightly injection
Also used for eczema.

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19
Q

Tezepelumab

A

Up stream TSLP inhibitor.

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20
Q

Management of T2 Low severe asthma

A

Inflammation is often neutrophilic.
Treatment options more limited.
- LABA and LAMA
- Theophylline
- ?Macrolides

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21
Q

Radiological features of UIP

A

Definite UIP needs all 4 criteria:

1 Honeycombing
2 Reticular opacity with sub-pleural and basal predominance.
3 Traction bronchiectasis
4 And NO atypical features

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22
Q

ILD Categories:

A

ILD of known causes (can usually diagnose on history)
- Dusts, CTD, hypersensivity pneumonitis, radiation induced, drug induced.

Granulomatous ILD - sarcoidosis

Idiopathic ILD
- Smoking related: respiratory bronchiolitis ILD, desquamative
- Acute/Subacute: cryptogenic organising pneumonia, acute interstitial pneumonia
- Chronic/Fibrosing: IPF, idiopathic NSIP

Other

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23
Q

Treatment of IPF?

A

Prednisolone/Azathioprine/NAC associated with increased death.

Anti-fibrotic therapy (nintedanib and pirfinedone)
- IPF diagnosed with MDM
- FVC>50%
- FER > 0.7
- DLCO > 30%
- No other causes.

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24
Q

Nintendanib

A

MOA: multiple tyrosine kinase inhibitor

Slows rate of decline in FVC

S/E:
- Diarrhoea
- Nausea
- LFT derangement

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25
Q

Pirfenidone

A

MOA: Inhibits TGF beta and fibroblast proliferation.

Slows rate of FVC decline

S/E
- Rash
- Nausea
- Diarrhoea

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26
Q

NSIP Pattern

A

GGO
Reticular opacity, but diffuse and can have sub-pleural sparing.
Traction Bronchiectasis

NO honeycombing.

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27
Q

NSIP DDx:

A

CTD
HIV
Drugs (amiodorone, MTX, flecainide, nitrofurantoin)
Hypersensitivity pneumonitis
Idiopathic NSIP

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28
Q

Treatment of NSIP:

A

Considered treatable with corticosteroids.

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29
Q

Hypersensitivity Pneumonitis

A

Not a single disease.
Need a history of exposure + clinical features.

HRCT features:
- Centrilobular nodules or GGO
- mosaic hyper-attenulation

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30
Q

Silicosis

A
31
Q

Mepolizumab and Benralizumab

A

Mepo (IL 5) 4 weekly injection and Benza (IL 5 R) 8 weekly injections.
Major benefit in eosinophilic asthma
Indicated in those with moderate to severe asthma and serum eosinophil counts 150-300cells/ml.

IL5 is the major cytokine for growth, differentiation, recruitment, activation and survival of eosinophils.

32
Q

Bronchiectasis management:

A

Effective airway clearance is the cornerstone:
- Physiotherapy
- Inhaled saline and mannitol

Macrolides - reduce exacerbation frequency

What not to use:
- Inhaled antibiotics have no evidence.
- Recombinant human deoxyribonuclease - only used in Cystic fibrosis, trials showed harm in non-cystic fibrosis.
- Long term corticosteroids or bronchodilators (only if co-comitant COPD or asthma)

33
Q

Cystic Fibrosis Mutations

A

CFTR = CF transmembrane conductance regulator

del508 causes misfolding and retention of protein in ER.

50% homozygous for del508
- LUMACAFTOR partly rescues CFTR transport and therefore is effective in this group.

40% compound heterozygous for del508 and another mutation

10% have Gly511Asp mutation which results in abnormal gating of a normally inserted protein (Arg117His is similar)
- These respond to IVACAFTOR which is a CFTR potentiator.

34
Q

Bronchiectasis Imaging findings:

A

Bronchoarterial ratio of >1
Lack of airway tapering
Airway visible within 1cm of pleura

35
Q

Cystic Fibrosis Management:

A

Airway secretion management:
- Inhaled DNase alpha
- hypertonic saline
- Positive expiratory pressure therapy

Anti-inflammatory therapy:
- Macrolide antibiotics (ensure no NTM, ECG before starting)

36
Q

Important respiratory infections in CF

A

Burkholderia cepacia complex:
- Chronic infection associated with faster decline in lung function and short survival
- Multi-drug resistant
- Lung transplant with B cepacia associated with poor outcome

NTM:
- Lung transplant with NTM not associated with worse outcome
- M Abscessus associated with poor outcome and transplant complications
- Only treat NTM infections if associated with evidence of clinical symptoms, nodular infiltrates or cavitating lesions.

37
Q

Classes of CFTR mutation

A

Normal
Class 1 - no functional CFTR produced .
Class 2 - CFTR is misfolded and does not reach cell surface (d508)
Class 3 - CFTR reaches the surface but does not open properly.
Class 4 - CFTR does not conduct ions properly (R117H)
Class 5 - Normal CFTR but created in insufficient quantities.
Class 6 - reduced half life of CFTR

38
Q

IVACAFTOR

A

CFTR Potentiator
- G551D (Gly551Asp)
- CFTR does not open correctly (gating defect), Ivacaftor increases Cl transport
- Not effective for del508

39
Q

LUMACAFTOR

A

CFTR Corrector
Partially corrects the mis-folding and therefore improved transport to cell surface.

Given in combination with IVACAFTOR which improved ion transport once at cell surface.

LUMACAFTOR/IVACAFTOR is beneficial for del508 HOMOZYGOTES, but has is not of clinical benefit to del508 heterozygotes.

40
Q

Contraindications for Lung Transplant in CF:

A

Age >65
Significantly limited functional status
Colonisation with Burkolderia cepacia (cenocepacia) or Mycobacterium abscessus

Transplant survival outcomes:
- 1 year 88%
- 5 year 67%
- 10 year 50%

41
Q

TEZACAFTOR

A

Tezacaftor + Ivacafotr was shown to be effective in both d508 heterozygotes and homozygotes.

42
Q

ELEXACAFTOR/TEZACAFTOR/IVACAFTOR (triple therapy)

A

Now first line for del508 homozygotes and heterozygotes.

43
Q

ABPA

A

Complex hyper-sensitivity reaction to colonisation with aspergillus fumigtatis

Occurs exclusively in those with asthma or CF

44
Q

Diagnostic criteria for ABPA

A

1 - must have predisposing condition (asthma or CF)

2 - Must have both of:
- elevated igE levels
- Positive skin prick test or elevated IgE to Aspergillus fumigatus

3 - at least 2 of the following:
- Positive aspergiluus precipitans or elevated igG to A fumigatus
- radiology consistent with ABPA
- Total eosinophil count of > 0.5

45
Q

Radiological features of ABPA:

A

Proximal cylindrical bronchiectasis
Mucus pluggins
Tree in bud opacity
Atelectasis
GGO
Mosaic attenuation

46
Q

Management of ABPA exacerbations:

A

Doubling of IgE + new radiological infiltrates:

Treat with:
- Prednisolone 0.5mg/kg for 2 weeks and then wean over 2 months.
- Itraconazole for 16 weeks

Be aware of -azole CYP3A4 inhibition and Cushings syndrome

47
Q

Biological therapy for ABPA:

A

Omalizumab
Mepolizumab and Benralizumab
Dupilumab

48
Q

Clinical Phenotypes of OSA:

A

Sleepy (43%)
- Increased risk of Cardiovascular disease
- Best response to PAP therapy

Minimally symptomatic (25%)
- Some response to PAP

Disturbed sleep (33%)
- Less response to PAP

49
Q

Definition of Sleep Apnoea

A

Mild OSA - AHI 5-15
Moderate OSA - AHI 15-30
Severe OSA - AHI >30

Obstructive Apnoea = 90% reduction in respiratory nasal flow for 10 seconds WITH respiratory effort (No flow but ongoing respiratory effort = obstructive)

Hypopnoea = 30% reduction in nasal flow for 10 seconds with a 4% desat.

Central Apnoea = no effort.

50
Q

Management of Sleep Apnoea

A

PAP therapy
Mandibular advancement therapy - only mild/moderate, or if unable to tolerate PAP.
Sleep position modification
Surgery
Weight Loss
Smoking cessation.

Proven Benefits:
- Improved symptoms
- Hypertension (reduction of 1.7mmHg 24 hour mean BP)
- Reduction in CVD and mortality
- Improved insulin resistance
- Improved QOL, reduced motor vehicle accidents.

51
Q

Management of Restless Leg Syndrome

A

Non-pharmacological
- Ensure ferritin is >100microg/L

Pharmacological (dopamine agonists)
- Pramipexole
- Ropinirole
- Rotigotine Patch

But augmentation is common, worsening RLS with increasing doses of medications.

Impulse control disorders - 9 months after therapy.

Second line:
Pregabalin or Pregabaline

52
Q

Definition of CTEPH

A

Persistence of pulmonary hypertension secondary to pulmonary emboli despite effective anti-coagulation for 3 months.

Important to perform VQ scan and TTE on patients with ongoing dyspnoea secondary to PE (incidence of 3.4% after acute PE)

VQ preferred imaging modality for diagnosis, but CTPA is preferred to characterise lesion and assess if suitable for surgery.

53
Q

Management of CTEPH

A

First line in Pulmonary endarterectomy (PEA), however 40% of patients will not be suitable.

If unable to have PEA, medical therapy:
1 - Riociguat
2 - Bosentan
3 - Sildenafil

54
Q

Genetic defect in familial PAH?

A

BMPR mutation

55
Q

Best therapy for group 1 PAH?

A

Combination therapy with:
- Ambrisentan (Selective Endothelin A R antagonist)
- Tadalafil (PDE5 inhibitor)

56
Q

Legionella Facts

A

Over 50 specific of legionella in Aus, but 2 most common pathogenic are:
- longbeachae (commonly found in potting mix)
- pneumophila

Gram NEGATIVE, strict growth requirements that will not grow in usual media.

Intracellular pathogens, will respond well to macrolide, tetracyclines, and quinolones.

They are ubiquitous and found in water and wet areas. No human to human transmission.

Legionnaires Disease:
- Atypical pneumonia
- Gastrointestinal symptoms
- Neurological Symptoms
- Hyponatraemia
- elevated LFTs and CK

The urinary legionella antigen test is the most rapid and sensitive test available but will only test for L pnuemophila serotype 1 and may only be positive after day 5 of the illness.

57
Q

Narcolepsy Pathophysiology:

A

Type 1 Narcolepsy:
- Loss of the Orexin secreting neurons in the hypothalamas
- Orexin is responsible for promoting wakefulness during daytime hours and surpresses REM sleep
- thought to be Autoimmune, associated with HLA DQB1*06

58
Q

Narcolepsy Clinical features:

A

Sleep is still refreshing
Sleep paralysis
Hyponogogic and Hypnopompic hallucinations
Cataplexy (sudden loss of muscle tone induced by emotional trigger) - In type 1 Narcolepsy

59
Q

Narcolepsy Diagnosis

A

Sleep Studies:
- Early REM transition and disrupted sleep cycle

Multiple sleep latency test:
- Mean sleep latency of < 8 minutes
- 2 or more sleep onset REM periods (SOREMP)

Management:
- Behavioural
- Psychostimulants may be needed

60
Q

Lights Criteria

A

Sensitive but not specific for exudate, positive if one or more of:
1 - Pleural fluid protein to serum protein >0.5
2 - PF LDH to Serum LDH > 0.6
3 - Pleural fluid LDH more than 2/3 ULN for serum LDH (LDH > 200)

61
Q

Asbestos related diseases:

A

Asbestosis
Benign asbestos pleural effusion
Pleural Plaques - these are benign, and are NOT a premalignant condition, they do not require any follow-up. They may grow over time.
Rounded Atelectasis
Mesothelioma
Non-Small cell lung Ca

62
Q

Differential Ddx for asthma symptoms and significant eosinophilia (5)

A

1 - T2 high asthma
2 -Pulmonary strongyloidiasis
3 - ABPA
4 - Chronic eosinophilic pneumonia
5 - EGPA

Note Hypersensitivity Pneumonitis is a type 3 hypersensitivity reaction that does not cause eosinophilia but is more associated with restrictive deficits and reduced gas transfer.

63
Q

Types of hypersensitivity reaction?

A

T1 - IgE mediated, atopy
T2 - Cytotoxic/IgG or IgM mediated. Direct binding of antibody to cellular antigen causes destruction of cell via ADCC, NK cell or Macrophage activation.
T3 - Immune complex mediated
T4 - Delayed T cell mediated

63
Q

Types of hypersensitivity reaction?

A

T1 - IgE mediated, atopy
T2 - Cytotoxic/IgG or IgM mediated. Direct binding of antibody to cellular antigen causes destruction of cell via ADCC, NK cell or Macrophage activation.
T3 - Immune complex mediated
T4 - Delayed T cell mediated

64
Q

Lofgren Syndrome

A

Trial of:
- Bilateral Hilar Lymphadenopathy
- Erythema Nodosum
- Arthritis (typically ankles)

LS is an acute form of Sarcoidosis, it may also present with malaise and fevers.
It has a favourable prognosis with usually complete resolution in 6 months.

65
Q

Cryptogenic Organising Pneumonia

A

Previously called BOOP.

Alveolar injury caused by unknown insult –> formation of organised granulation tissue within the alveoli lumen and bronchioles leading to respiratory failure.

Presentation:
Weeks of fever, malaise, cough. Often failed treatment for presumed bacterial pneumonia.

Imaging:
Asymmetrical, bilateral patchy peripherally located consolidation and GGO.

COP is a diagnosis of exclusion..
BAL to exclude infection, haemorrhage, malignancy.
Biopsy often required to make diagnosis.

Treatment 1mg/kg Prednisolone weaned over 6-12 months.
Good prognosis if treated.

66
Q

Compensation rule for acute metabolic acidosis

A

PaC02 = (1.5 x HCO3) + 8 (+/-2)

For example if HCO3 is 16
PaC02 should be 24+8 = 32

If HC03 is 10
PaC02 should be 10+5+8 = 23

67
Q

Compensation rule for ACUTE Respiratory Acidosis:

A

Increase in HC03 should be = DeltaPaC02 / 10

Normal PaC02 is 40
Normal Bicarb is 24

PaC02 is 60
Increase in HC03 should be 2
Therefore HC03 should be 24+2 = 26

68
Q

Compensation rule for CHRONIC (3-5days) respiratory acidosis:

A

Increase in HC03 should be 4 x delta PCO2/10

PC02 is 60 (chronic)
HC03 increase should be 8
HC03 should be 24+ 8 = 32

69
Q

Compensation rule for acute respiratory alkalosis

A

Decrease in HC03 should be 2 x delta PCO2/10

69
Q

Compensation rule for Chronic respiratory alkalosis

A

Decrease in HC03 should be 5 x delta PCO2/10

69
Q

Compensation rule for Metabolic Alkalosis

A

PC02 = 40 + (0.7 x Delta HCO3)

70
Q

Delta Ratio

A

Delta ratio should be calculated in a metabolic acidosis to determine if mixed.

Delta anion gap = change in anion gap / change in HC03

<1 - likely mixed HAGMA/NAGMA
1-2 normal pattern for HAGMA
>2 likely mixed chronic metabolic alkalosis or chronic respiratory acidosis (which would increase the HC03).

71
Q

Management of spontaneous pneumothorax:

A

Primary (young, no lung disease)
- If <2cm and asymptomatic - consider discharge
- If >2cm or symptomatic, attempt needle aspiration, if able to reduce to <2cm and improve symptoms then consider discharge with OPD in 2-4 weeks.

Secondary (Age >50, or lung disease)
- If >2cm or breathless then insert size 8-14Fr chest drain and admit
- If 1-2cm and not breathless then attempt needle aspiration
- If <1cm then admit for high flow oxygen and observation 24 hours

NOTE:
- Any bilateral or unstable gets chest drain
- measure the inter-pleural distance at the level of the hilum, large pneumothorax is defined as >2cm at hilum or > 3cm at apex.

Basic Physician Training Written Prep (20 decks)

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