Respiratory Flashcards
COPD severity criteria and category
GOLD - by FEV1 %
- 1 >80
- 2 50-79
- 3 30-49
- 4 <30
A for asymptomatic
B for symptomatic
E for exacerbations - 2 or more, or 1 leading to hospital
A 70yo man with severe COPD is admitted to hospital with an exacerbation of COPD requiring 24hrs of non-invasive ventilation, oxygen therapy, oral steroids and oral antibiotics. After four days, he is discharged home with outpatient follow-up. What is his approximate 12-month mortality risk after this episode?
- 5% * 10% * 25% * 50% * 70%
25% - mortality
65% - readmission
A 73yo male with moderate COPD presents to clinic for review. He has symptoms on exertion but no history of exacerbations. He is on no inhaled therapy currently. He has no history suggestive of asthma and his peripheral eosinophil count is 0.1. Which of the following inhalers would be expected to have the greatest effect on AECOPD, hospitalization and symptoms.
- LAMA monotherapy
- ICS/LABA
- ICS monotherapy
- LABA/LAMA
- LABA monotherapy
- LABA/LAMA
Factors favouring use of ICS in COPD (3)
Hospitalisation for exacerbation
2 or more exacerbations
Eosinophils >300 (or >0.3)
History of asthma
mortality benefit demonstrated with triple therapy
Which of the following therapies are not associated with a reduction in mortality in people with COPD?
- Smoking cessation
- Long-term oxygen therapy
- Pulmonary rehabilitation
- Non-invasive ventilation
- LABA+LAMA+ICS
- Long-term macrolide antibiotic
- Long-term macrolide antibiotic
lung volume reduction also has mortality benefit
A 50yo man attends your clinic and you discuss his current smoking habit and strategies to quit. You outline options for smoking cessation pharmacotherapy for him. Which of the following comorbidities would preclude the use of combination nicotine replacement therapy?
* Unstable ischaemic heart disease
* Bipolar disorder
* Schizophrenia
* Suicidal ideation
* Stable ischaemic heart disease
- Unstable ischaemic heart disease
Evidence based smoking cessation strategies
Brief counselling RR 1.86 v usual care
Combination NRT (short + long) + behaviour intervention is the best
Combo NRT = Varenicline > bupropion (antidepressant with weak norepinephrine and dopamine uptake inhibition)
Acute NIV can be used to treat respiratory failure. Which of the following scenarios should NIV be considered “off-label” therapy?
* Post-extubation respiratory failure
* Hypercapnic respiratory failure due to AECOPD * Acute severe asthma
* Acute cardiogenic pulmonary oedema
* None of the above
- Acute severe asthma
What is the most likely diagnosis?
A 67yo woman presents to clinic with cough and some exertional dyspnoea. She is an ex-smoker with 30 pack year history. She has been started on LAMA therapy by her GP for presumed COPD
Spirometry is performed (flow-volume loop normal, both pre and post salbutamol)
- COPD
- Interstitial lung disease
- Asthma
- Malingering
- Uninterpretable spirometry due to lack of effor
- Asthma
COPD/ ILD are out because of normal loop
It is interpretable
Asthma is very common
Z-score cut-off for “normal” in spirometry
-1.645
Which of the following statements regarding asthma and/or cough are most correct?
- negative mannitol bronchoprovication test excludes asthma
- A low FeNO (<10ppb) excludes asthma
- Cough that is caused by ACE inhibitor occurs within 4 weeks of commencing therapy
- A low PEFR confirms asthma as the most likely diagnosis
- negative methacholine bronchoprovocation test excludes asthma
Negative methacholine bronchoprovocation test excludes asthma
- positive test would mean >20% fall in FEV1
Manitol or hypertonic saline
- positive would mean >15% fall in FEV1
- better positive predictive value (i.e. diagnose rather than exclude)
PEFR - peak expiratory flow rate, usually monitored over a few weeks, if variable then identifies Asthma, good to identify triggers
FeNO - correlates with increased Eosinophilic inflammation > predicts steroid responsiveness; diagnostic value not demonstrated
Bronchodilator reversibility
> 12% AND >200mL increase in FEV1
Asthma categories (4)
INTERMITTENT ASTHMA
– normal FEV1, symptoms/SABA <2/week, no limitations
PERSISTENT ASTHMA
MILD – normal FEV1, symptoms/SABA >2/week, minor limitation
MODERATE – mildly abnormal FEV1 (60-80%), daily symptoms, some limitation
SEVERE – abnormal FEV1 <60%, daily symptoms + nocturnal, limited function
Asthma treatment
PRN ICS/ LABA for mild
- better than SABA alone
- non-inferior to regular to ICS with 17% of steroid exposure
Then regular with increasing dose
Then add on LAMA
Then advanced therapies
Biological therapy targeng which of the following molecular targets would be unlikely to improve asthma control?
- IgE
- IL-5
- Eosinophilic aromatase
- IL-5 receptor
- thymic stromal lymphopoien (TSLP)
- IL-4 and IL-13
*Eosinophilic aromatase
Omalizumab - IgE
Mepolizumab - IL-5
Benralizumab - IL-5 receptor
Tezepelumab - TSLP (may be effective in those without eosinophilic inflammation)
Dupilimab - IL-4 and IL-13
Severe asthma definition
Either maximal therapy or symptoms on maximal therapy
Main issue is adherence 15-54%
- 25% increase would lead to 10% reduction in exacerbations
Inhaler technique is optimal in only 31%
Omalizumab
Binds IgE - prevents binding to mast cells, basophils, eosinophils, T cells
25% less exacerbations
Less SABA
Less oral and inhaled steroids
Less symptoms
Better QoL
Mepolizumab and Benralizumab
IL-5 and IL-5R - blocks eosinophil growth, differentiation, recruitment and activation
Eosinophil count >150 but ideal >300/uL
Reduced hospital presentation
50% reduction in oral corticosteroids
Better QoL
Dupilimab
IL-4 + IL-13
- original use in atopic dermatitis
- elevated IgE or eosinophils
Reduced severe asthma exacerbations
Improvement in FEV1
Some benefit in those with lower eosinophils
Tezepelumab
Thymic stromal lymphopoietin (TSLP) is upstream of IL-4, IL-5, IL-13, and IgE
Less exacerbation
Better FEV1
Better symptoms + QoL
Similar effect regardless of eosinophils
A 68yo ex-smoker presents with gradually increasing dyspnea over the past 12 months. He has crackles on examinaon and is clubbed. He has no history of occupaonal exposures or clinical features of connecve ssue disease. He is referred for HRCT which is reviewed in a muldisciplinary meeng and a diagnosis of idiopathic pulmonary fibrosis is reached. Which of the following features on HRCT is least likely to be present?
- Honeycombing
- Subpleural reticular opacity
- Traction bronchiectasis
- Basal reticular opacity
- Widespread ground glass opacity
- Widespread ground glass opacity
Usual interstitial pneumonitis pattern = all four of
1. Honeycombing
2. Traction bronchiectasis
3. Reticular opacities - lower and peripheral
4. No atypical features
When to consider biopsy for interstitial lung disease (3)
carries 1-2% mortality
age <50yo
atypical HRCT
rapidly progressive
transbronchial only helpful for centrilobular pathology
A 60 year old non-smoker has been recently diagnosed with idiopathic pulmonary Bbrosis. You conduct a literature search to determine treatment opons for him. Which of the following would not be appropriate?
- Pirfenidone
- Referral to lung transplant team
- Nintendanib
- Prednisolone
- Oxygen therapy
Prednisolone
- increases mortality and hospitalisation with no benefit
Nintedanib (multiple TK inhibitor) and pirfinedone (TGF-b inhibitor) = anti-fibrotic
- mild/ moderate IPF
- slow rate of decline in FVC (no clear survival benefit)
- SE = diarrhoea, nausea
alternative indication for nintendanib
non-ipf pattern progressive fibrosis
- known or unknown etiology ILD with fibrosis on HRCT and 2/3 of:
1. Worsening symptoms
2. Worsening PFTs
3. Worsening HRCT
non-specific interstitial pneumonitis pattern (4)
- Ground glass opacity
- Traction bronchiectasis
- Apical to basal gradient
- Subpleural sparing
NSIP pattern tends to indicate a potential for response to immunosuppression (but also a better prognosis than UIP pattern)
What is NSIP associated with? (4)
- CTD ( 88% in one study had laboratory or clinical features of undifferentiated CTD - lung disease may precede clinical CTD features)
- HIV
- Drugs: amiodarone, methotrexate, flecanide, nitrofurantoin
- Hypersensitivity pneumonitis
Treatment for NSIP (3 line agents)
- First line agent: Glucocoricoids (long taper over 6-9 months assuming clinical response)
- Second line agents: Mycophenolate or Azathioprine (implemented initially with more severe disease; those that fail to respond to first line agents; and those that worsen as steroids reduce
- Third line agents: IV Cyclophosmamide monthly, Rituximab, lung transplant
A 60yo pigeon breeder presents for a roune health assessment. He is an ex-smoker of 30 pack years. He is asymptomac with good exercise tolerance. His lungs are clear, oxygen sats are normal on room air and his PFTs demonstrate mild fixed airflow obstruction with a normal DLCO. His HRCT is reported as normal. Serum precipins are posive for IgG to pigeons. The most likely diagnosis is:
A) Hypersensitivity pneumonitis (pigeon fanciers lung)
B) Asthma
C) COPD
D) Sarcoidosis
E) Idiopathic Pulmonary fibrosis
C - PFTs are suggestive of COPD, precipitins are common in bird handlers even without disease
Risk factors/Clinical history clues for Hypersensitivity Pneumonitis
Agricultural dusts
- Recurrent ‘atypical’ pneumonia
- Symptoms after moving to a new job or home
- Exposure to pets (birds especially)
- Water damage to home/office–moulds
- Hot tub/sauna/swimming pool exposure
- Other people with similar symptoms
- Improvement when on holiday or over weekends
Common aetiology:
# Bioaerosols
# Microorganisms
# Reactive chemical species
Diagnosis of hypersensitivity pneumonitis
THERE IS NO DIAGNOSTIC TEST
The principle pathophysiological aetiology is around precipitins (specific IgG)
Precipitans can be avian, fungal, or thermophilic actinomyces
- Precipitins don’t rule in (30-40% asymptomatic
farmers have + precipitins to common causes of HP) - Precipitins don’t rule out (tests can be nonreactive even if the causative antigen is included)
1) HRCT
2) Bronchoscopy, surgical lung biopsy
3) BAL - lymphocytic pattern suggestive (~30% lymphocytes)
4) TBBx can demonstrate non-caseating granulomas
5) Surgical lung biopsy or cryobiopsy where imaging, exposure, or BAL are inconclusive (after balancing risks vs benefits)
HRCT features of hypersensitivity pneumonitis (3)
Typical features:
1) Centrilobular nodules and/or ground glass opacities
2) Mosaic attenuation (inspiratory), three density pattern, gas trapping (expiratory)
3) Fibrosis – linear opacities, coarse reticulation and lung distortion, traction bronchiectasis, honeycombing (relative sparing of lower zones, random involvement both axially and craniocaudally)
Some HP will have a radiological pattern that is consistent with UIP => reinforces that the diagnosis of idiopathic pulmonary fibrosis is generally only reached if there are no features that suggest an alternative Dx
Sarcoidosis - age
Multisystem granulomatous disorder – with 90% lung involvement
- Peak incidence 20-39yrs
- T cell mediated with granuloma formation and fibrosis due to Th2
HRCT findings of sarcoidosis
HRCT findings are variable
- Bilateral hilar and mediastinal LAD
- Nodular (upper zone) + hilar and mediastinal LAD * Parenchymal = at least stage II disease
SARCOIDOSIS IS A DIAGNOSIS OF EXCLUSION
Non-caseating granulomas DDx – TB (demographics), lymphoma, other ILD, cancer
A 50yo woman is referred to you with asymptomatic HRCT abnormalities including some bilateral upper zone nodular interstitial changes and bilateral hilar and mediastinal lymphadenopathy. After obtaining a history, examination and basic investigations you suspect sarcoidosis. Which of the following tests test is most likely to confirm your clinical diagnosis?
A) Serum ACE level
B) Spirometry and TLCO
C) Bronchoscopy with broncho-alveolar lavage for elevated CD4:CD8 rao
D) Bronchoscopy with transbronchial and endobronchial biopsy
E) Endobronchial ultrasound guided transbronchial needle aspiraon of hilar lymph nodes
E
Tissue diagnosis:
* BAL–elevated CD4:CD8 is supportive(>3.5:1)
* Endobronchial biopsy–positive in 40-70%
* Transbronchial biopsy 50-75%
* EBUS–80-90%
Combined approach may have the highest yield (>90%)
** Mediastinoscopy or lung biopsy uncommonly required **
Extrapulmonary complications/involvement of Sarcoidosis (4)
1) Ocular: requires ophthalmology review
2) Calcium: urinary calcium excretion rate, serum Ca2+, vit D (1,25)
3) Cardiac: ECG, ECHO -> MRI or PET
4) Brain: no routine investigation required, but can do MRI + LP
When do you treat sarcoidosis? (7)
** 70% of those with sarcoidosis require NO TREATMENT **
However, the condition is more aggressive in non-Caucasian populations)
Indications for treatment:
1) Progressive symptomatic pulmonary disease
2) Asymptomatic pulmonary disease with persistent infiltrates or progressive loss of lung function
3) Cardiac disease
4) Neurological disease
5) Eye disease not responding to topical therapy
6) Symptomatic hypercalcaemia
7) Other symptomatic/progressive extrapulmonary disease
- Sometimes measuring functional tests (6MWD, CPET) helps with treatment decision (and objectively measuring response)
Treatment of Sarcoidosis
1) Inhaled corticosteroids – possibly helpful for cough, useful if co-morbid asthma
2) Oral corticosteroids – first line therapy for sarcoidosis: long taper over 12 months
Other agents (primarily as steroid sparing agents):
Methotrexate
Hydroxychloroquine
Azathioprine
Mycophenolate
Others rarely used: Infliximab, Adalimumab, Rituximab
A 38 yo man presents with 18 months of cough and mild dyspnoea. His GP has arranged chest imaging that has been reported as demonstrating egg-shell calcification. What occupational exposure should be specifically sought?
A) Asbestos
B) Flour
C) Beryllium
D) Silica
E) Birds
D
What is silicosis
- Disease progression can occur even after exposure ceases
- Accelerated silicosis assumed if lung function deteriorates at
>10x expected age related decline - Uncertain how much exposure is required to develop
disease - Grinding, cutting or polishing of artificial stone surfaces are
the key risk area identified – generates fine respirable dust
particles - No known treatments or disease modifiers
- Screening with spiro/TLCO and imaging
- Avoidance of exposure is the only strategy
- Monitoring and referral for transplant for severely affected
Ventilation strategies in ARDS (3)
- Ventilate with low tidal volumes and inspiratory pressures
- Prone positioning for severe
- Higher PEEP can be tried (reduces atelectrauma)
Predictors of NIV failure (4)
- Acidosis <7.25
- Marked acute hypoxemia PaO2/FiO2 <200
- RR >25
- Non-pulmonary organ failure
NIV indications for neuromuscular disease (4)
- Paradox or othopnea
- Vital capacity <50%
- SNIP <30cm H2O
- pCO2 >56 mmHg
OSA diagnosis - via sleep study, and severity
AHI >5 + symptoms
OR
AHI >15
5-15 is mild and >30 is severe
OSA pathophysiology (4)
- Narrow + collapsible upper airway
- Low arousal threshold
- Ineffective dilator muscles
- Oversensitive ventilatory system
Obesity hypoventilation syndrome triad and pathophysiology
- Awake hypercapnia >45
- BMI >30
- Sleep disordered breathing
Leptin resistance + increased load = blunted ventilatory response
CPAP v NIV in OHS and OSA
OHS - mortality benefit of both, choose modality based on whether the phenotype is more OSA vs respiratory failure
OSA - no cardiac mortality benefit, but improves everything else
Narcolepsy type 1 and 2 and treatment
Type 1
- 3 months of sleepiness
- cataplexy and MSLT <8mins or low CSF hypocretin
Type 2
- 3 months sleepiness
- NO cataplexy and MSLT or normal hypocretin
Treatment = dexamphetamine, armodafinil, for cataplexy SSRI
Bronchiectasis treatments (5)
- Airway clearance - improves QOL - refer to physio
- Inhaled hypertonic saline - reduces exacerbations
- Infections for at least 10 days
- Airway obstructions - no/low evidence - salbutamol and possible trial of ICS
- Chronic inflammation - macrolides - erythromycin reduce exacerbation in frequent
MAC treatment
Ethambutol, Rifampicin and Clarithromycin
CF diagnosis
CFTR (1/25 carrier frequency)
heel prick for trypsinogen
chloride sweat test >60
CF therapies (5)
- CFTR modulators
- Inhaled DNAse - increases FEV1
- Macrolide - azithromycin
- Hypertonic saline - increases FEV1
- Lung transplantation
CFTR modulators
Ivacaftor is a potentiator that opens channel
Tezacaftor and Elexacaftor are correctors that move the protein to the cell surface
Homozygous DF508 mut = ivacaftor/ tezacaftor
Heterozygous = elexacaftor/ ivacaftor/ tezacaftor
Major organ complications with CF (5)
- Pancreatic insufficiency (85-90%)
- GI: obstruction, reflux, prolapse, intussusception
- Bone disease
- Infertility
- Psychiatric due to disease
Demographics impacting lung cancer outcomes (3)
- Remoteness
- low SES
- Indigenous status
Benefit of CT scan screening for lung cancer
1-2 yearly
- 50-80yo
- 20+ pack years - current or quit within 15 years
20-33% reduction in mortality
Early stage lunch cancer treatment
- Surgical resection up to IIIA - VATS leads to less complications and shorter stay than thoracotomy
OR radiotherapy - Adjuvant platinum chemo II-IIIA
Locally advanced lung cancer treatment
- Concurrent chemoradiotherapy
- Follow with immunotherapy - first line if identified EGFR, ALK, ROS1
Lung cancer targeted therapy
EGFR (10-30%) = gefitinib, erlotinib, afatinib, or osimertinib - Asian
ALK (5%) = crizotinib, certinib, alecetinib, brigatinib, loratinib
ROS1 (1-2%) = cirzotinib, entrectinib
Lung cancer immunotherapy - 3 PD1 and 2 PDL1
PD1
Pembrolizumab - initial treatment single or combined with chemo
Nivolumab - after progression on platinum
Nivolumab + ipilimumab - first line stage 4
PDL1
Atezolizumab - initial with platinum and bevacizumab
Durvalumab - stage III after platinum
SCLC
- paraneoplastic: SIADH, Cushing, LEMS, encephalomyelitis, dermatomyositis
- no benefit of screening CT
- higher stage with poorer outcome
- 50% brain mets»_space; prophylactic cranial irradiation
- very responsive to cytotoxic - transient however
Poor prognosis in mesothelioma (3)
- Age
- Male
- Sarcomatoid subtype
Mean survival 9-12 months (so generally poor anyways)
No benefit of screening or following-up plaques
Mesothelioma treatment
platinum based - 3 month improvement
nivolumab + ipilimumab - additional 4 months
PE treatment duration (4)
Provoked - 3 months unless permanent risk factors then consider indefinite
Unprovoked 3-6 months
Sub-massive 6-12 months
Massive indefinite
CTEPH after PE - when, who, what
6 months
after massive PE OR if still symptomatic do a CTPA or V/Q and an echo
PAH workup - main echo finding and decision making
TR 2.9-3.4 m/s
- above is likely, below is unlikely
- other echo features, risk factors, and associated conditions can make you consider repeating echo if below or further investigations if intermediate
Follow with right heart Cath
Group 1 PAH treatment pathways (3) and choice of therapy
- Endothelin - receptor antagonists - ambriesantan, bosentan, macitentan
- NO - PDE 5 inhibitors preventing breakdown of cGMP - sildenafil, tadalafil, riociguat
- Prostacyclin derivatives - epoprostenol, iloprost, selexipag
Initial therapy = combination oral therapy 1+2
Severe - add in 3
Group 2 and 3 PAH - what happens if we use vasodilator therapy
Group 2 - vasodilation of pre capillary whilst there is already a high back pressure»_space; pulmonary edema
Group 3 - tight V/Q match is disrupted leading to shunting and hypoxemia
Slow vital capacity on spirometry
Eliminates dynamic airway collapse (cartilage weakness or membrane bowing) and would be higher than FVC if this is the case
Fixed vs variable intrathoracic vs variable extra thoracic obstruction - PFT loop pattern - in other words which phase
Fixed - affects both
Intrathoracic - affects exhalation
Extrathoracic - affects inhalation
Compensation in respiratory acidosis, respiratory alkalosis, metabolic alkalosis, and metabolic acidosis
Resp Acidosis
- Acute response: HCO3 increase 1mmol/L for every 10mmHg rise in PaCO2
- Chronic: 4 for 10
Resp Alkalosis
- Acute: decrease 2 for 10
- Chronic: 5 for 10
Metabolic Alkalosis
- CO2 increases by 0.7 for 1 of HCO3
Metabolic Acidosis
- CO2 decreases by 1.2 for 1
ABG formulas
- Aa
- Anion gap
Aa = (FiO2x713 - 1.25xCO2) - a
normal Aa = Age/4 + 4
Anion gap = Na + K - Cl - HCO3 = 11
Risk factors for IPF (5)
- Older age
- Male
- Smoking history
- GORD
- Family history
A 32 year old lifelong non-smoking woman, with a history of 2 previous pneumothoraces, presents with progressive dyspnoea over 2 months and infrequent haemoptysis. Family history is remarkable for tuberous sclerosis. A CT chest (shown below) demonstrates multiple cystic changes throughout both lung fields.
What is the most likely diagnosis?
A. Cystic fibrosis
B. Bronchiectasis
C. Lymphangioleiomyomatosis
D. Pulmonary Langerhan’s cell histiocytosis
Answer = C
Lymphangioleiomyomatosis (LAM)
- women of childbearing age - risk with oestrogen
- strong association with tuberous sclerosis
- Other features include renal angiomyolipoma, thoracic or abdominal chylous effusion, lymphangioleiomyoma or lymph-node
- Treat with puffers + rehab + sirolomus - stabilises FEV1
Pulmonary Langerhan’s cell histiocytosis is a rare disorder that affects young adults who smoke with CT
findings of nodules and small irregular shaped cysts.
CF and bronchiectasis will have bronchiectatic changes.
