Respiratory Flashcards
What does ground glass opacities (GGO) refer to?
Focal or diffuse veil-like opacification of the lung which does not obscure vascular structures, anatomic detail or yield air-bronchograms
What acute diseases manifest with diffuse ground-glass opacities?
Pulmonary oedema
Pulmonary haemorrhage
Pneumocystis jirovecii pneumonia (PJP)
Mycoplasma pneumonia
Viral pneumonia incl COVID019
Acute interstitial pneumonia
Acute eosinophilic lung disease
Early hypersensitivity pneumonitis
Among HIV-positive patients with PJP have ground-glass opacities on their chest CT?
90%
What chronic diseases cause ground-glass opacities?
Hypersensitivity pneumonitis
Desquamative interstitial pneumonia
Respiratory bronchiolitis-associated ILD
Non-specific interstitial pneumonia (NSIP)
Pulmonary alveolar proteinosis (PAP)
Bronchioalvecolar carcinoma/adenocardinoma-in situ
Organising pneumonia
Sarcoidosis
What do focal ground-glass opacities usually represent?
Focal atelectasis
Focal fibrosis
Focal inflammation
Atypical alveolar hyperplasia
Bronchioalveolar carcinoma (adenocarcinoma-in-situ)
If a focal ground glass opacity >10mm diameter fails to clear in 3 months time on repeat imaging, what should you suspect?
Bronchioalveolar carcinoma (adenocarcinoma-in-situ)
Ddx atypical alveolar hyperplasia
How can you differentiate consolidation (airspace filling) from ground-glass opacities on imaging?
Consolidation obscures vascular structures and is accompanied by air bronchograms
This is due to replacement of alveolar gas with pus/oedema/blood/surfactant/cells
What is Birt-Hogg-Dubé syndrome?
An inherited syndrome due to pathogenic variants in folliculin (FLCN gene - also known as BHD gene) on short arm of chromosome 17
Patients with Birt-Hogg-Dube syndrome are at risk of:
1) Bilateral multifocal kidney cancer
2) Lung findings
- multiple pulmonary cysts
- Spontaneous pneumothorax - it is the most common cause of familial spontaneous pneumothorax
3) Dermatological findings
- fibrofolliculomas - benign hamartomatous tumours of hair follicles which appear as white papules on nose and cheeks
What is pneumocystis jirovecii?
It is an atypical fungus
- atypical because it does not grown in fungal culture
How is PJP transmitted?
Via airborne route - it exists almost exclusively in alveoli of the lung
75% of transmission/PJP acquisition believed to occur in first 4 years of life
What are some of the immune deficiencies responsible for PJP in HIV-positive patients?
In healthy individuals, immune control of PJP is achieved by clearance of the organism from the lung by alveolar phagocytes. This process is organised by CD4+ T cells (which among other things recruit and activate monocytes and macrophages). In HIV, CD4+ depletion as well as acquired impairments in phagocytosis/macrophage activation may contribute to infection
How common is PJP colonisation?
In healthy adults ranges from 0-20%
The significance of this is not well understood - may be at risk of developing pneumonia or transmitting infection
- if receiving PJP prophylaxis may be at risk for developing drug resistance mutations
- may trigger inflammation and local alveolar damage leading to lung diseases eg COPD
Which HIV-positive patients are most at risk for PJP?
Those with advanced immunosuppression in patients not taking anteretroviral therapy (ART) ie undiagnosed or not receiving care
ie it is rare in those who are on ART, are virologically suppressed and have CD4 counts >100 - independent of PJP prophylaxis
Other risk factors:
A CD4 count <200
High HIV RNA levels
Previous episodes of PJP
Oral candidiasis
Recurrent bacterial pneumonia
What are the clinical manifestations of PJP?
Gradual onset (over days to weeks) of:
Fever
Cough - generally non-productive
Dyspnoea
May report chills, fatigue, chest pain, weight loss
~10% asymptomatic
O/e febrile + tachypnoea
Hypoxaemia with exercise characteristic
Oral thrush
Crackles and rhonchi - however 50% normal chest exam
Is it common in PJP to have haemoptysis and/or pleural effusions?
No
What laboratory findings may be found in HIV-positive patients with PJP?
1) Low CD4 counts (ie <200 cells/microL)
2) Widened A-a gradient
3) Elevated LDH
4) Elevated 1-3-beta-D-glucan plasma level (component of cell wall of PJP)
What abnormality on lung function testing would you expect in a patient with PJP?
Reduced DLCO
- rare in those with normal DLCO
How does PJP in HIV-positive patients appear on chest imaging?
CXR can be normal in 25% initially or have diffuse interstitial or alveolar infiltrates
May have upper lobe infiltrates or pneumothoraces
CT typically shows bilateral patchy or nodular ground glass opacities
HRCT 100% sens and 89% spec
- therefore if HRCT negative -> makes diagnosis of PJP unlikely
FDG-PET may show increased FDG uptake throughout both lungs especially in perihilar region
When should you start empiric treatment in an acutely ill patient with a high suspicion of PJP?
Immediately - can take days to obtain appropriate specimens and process tests and definitive diagnosis still possible after empiric therapy
What specimens may be appropriate to obtain for PJP diagnosis?
Induced sputum for Direct fluorescent antibody staining or PJP PCR - but may be non-diagnostic and does not rule out PJP
(note the ability to detect pneumocystis may be reduced in patients receiving prophylactic therapy especially aerosolised pentamidine)
Bronchoalveolar lavage and bronchoscopic sampling - often required to make definitive diagnosis
Endotracheal aspirate if intubated
Note even if negative induced sputum +/- BAL may treat empirically in patients with risk factors if characteristic presentation + other positive non-specific tests (e.g. beta-D-glucan, LDH)
Lung biopsy or transthoracic needle biopsy have high diagnostic yield but rarely performed due to risks
What is the main disadvantage with PCR testing for PJP?
Cannot distinguish between colonisation and disease
However, if PCR readily available, still the preferred diagnostic test
If patient has HIV, low CD4 count, clinical presentation with PJP and positive PCR -> most likely acute infection rather than colonisation
Is 1,3-beta-D-glucan specific for PJP?
No - it is a cell wall component of many fungi (eg histoplasmosis)
Also can get false positives after albumin infusion, infections with certain bacteria, use of cellulose filters/membranes with haemodialysis)
However, it can help distinguish true infection from colonisation in patients with atypical clinical presentations
i.e. positive PCR + elevated beta-D-glucan level = infection
positive PCR + low beta-D-glucan level = colonisation/alternative diagnosis
negative PCR + elevated beta-D-glucan level = non-PJP cause of elevated beta-D-glucan
Do you have to be concerned about co-infection in PJP?
Yes, occurs in approx 15% of patients especially low-resource settings where co-infection with TB is common; therefore need to consider in work-up and monitor for response to therapy - if poor response and definitive diagnosis, may indicate co-infection
What other pulmonary infections do you have to consider in the differential diagnosis of PJP, especially in HIV-positive patients with CD4 counts <200?
TB
Nontuberculous mycobacteria (NTM)
Toxoplasma
CMV
COVID
Influenza
Kaposi sarcoma
How might you differentiate PJP from TB in HIV-positive patients with low CD4 counts?
TB often associated with more severe constitutional symptoms eg fever, night sweats, malaise
Chest imaging may range from being clear to miliary pattern
Note as immunity declines, so too does the frequency of pulmonary cavitation which is the hallmark of pulmonary TB
What are the differences in presentation between PJP and NTM in HIV-positive patients with low CD4 counts?
NTM tends to present as disseminated disease without respiratory symptoms or pulmonary involvement (especially in cases of MAC) in HIV -> quite different from how NTM presents in immunocompetent patients with bronchiectasis
How might you differentiate between PJP and Disseminated histoplasmosis in HIV positive patients?
Both may present with fever, cough and diffuse interstitial infiltrates
Both may have elevated beta-glucan levels
Findings suggestive of histoplasmosis include:
- adenopathy
- hepatosplenomegaly
- oral or mucosal ulcerations
(diagnosis made with histoplasmosis antigen testing)
How might you differentiate between Toxoplasmosis and PJP clinically?
Quite often they are indistinguishable in patients with HIV and low CD4 counts
Toxoplasmosis is less common
Can identify responsible organism in BAL fluid
Any distinguishing features between CMV pneumonitis, influenza, COVID-19 infection and PJP in patients with HIV?
No
CMV less common - but similar presentation - definitive diagnosis of CMV requires observing CMV inclusion bodies on biopsy
Influenza more acute onset with myalgias and headaches cf PJP more subacute
COVID-19 often have more peripheral distribution and lower lobe involvement on CT than PJP but nothing pathognomonic
What feature may distinguish Kaposi sarcoma from PJP in HIV-positive patient with low CD4 count?
Skin findings commonly present in Kaposi sacroma and absent in PJP
- however 20% of patients with KS may have no evidence of cutaneous disease
- diagnosis (gold standard) consists of direct visualisation of characteristic lesions on bronchoscopy
- failing that, nuclear scans may help differentiate KS from PJP
Is extrapulmonary disease common in HIV+ve patients with PJP?
No, it is very rare and only usually in very advanced HIV or those receiving second-line PJP prophylaxis like dapsone or aerosolised pentamidine
Most often involves the eye - typically the choroid layer
A 50-year-old man is admitted to ICU with acute respiratory distress syndrome. High flow
nasal cannula oxygen is administered but, despite this, persistent hypoxic respiratory failure develops and he is intubated.
Which of the following strategies is recommended to improve oxygenation in severe
ARDS?
A. Extracorporeal membrane oxygenation
B. Prone positioning for 12-16 hours per day
C. High frequency oscillatory ventilation
D. Invasive ventilation strategy aiming for tidal volumes of 10-15 ml/kg
B - Prone positioning for 12-16 hours per day
Prone positioning >12hr / day shown to reduce mortality
Complications: increased rates of pressure sores and ET obstruction
The rest haven’t been shown to reduce mortality
Supportive care with mechanical ventilation remains the cornerstone
of ARDS management.
* Mechanical ventilation itself can cause and potentiate lung injury
* Mixed evidence, but overall research suggests up to a 30% reduction
in mortality risk with low tidal volumes and low inspiratory pressures
* Recommendation: We recommend that adult patients with ARDS
receive mechanical ventilation with strategies that limit tidal volumes
(4–8 ml/kg predicted body weight) and inspiratory pressures (plateau
pressure < 30 cm H2O) (strong recommendation, moderate
confidence in effect estimates)
Which of the following is an absolute contraindication to prone positioning?
A. Haemodynamic instability
B. Obesity
C. Ventilator associated pneumonia
D. Unstable vertebral fracture
D - unstable vertebral fracture
Absolute contraindications to prone positioning:
-Acute bleeding
-Multiple #
-Spinal instability
-Raised ICP or CPP
-Tracheal surgery or sternotomy within 2 weeks
A 50-year-old female non-smoker presents with 8 weeks of dry cough, low-grade fever, malaise and dyspnoea on exertion. There has been no clinical response to a one-week course of oral antibiotics (amoxycillin with clavulanate and doxycycline). On examination her oxygen saturation is 94% on room air. There is no clubbing. Chest auscultation reveals inspiratory crackles. Chest X-ray shows multifocal consolidation. CRP is elevated at 40. Connective tissue disease screen on serum is unremarkable. Her lung function results are provided below:
Pre- vs Post-bronchodilator
FEV1 3.6 L 67 (% predicted) 3.65L
FVC 3.8 L 69 (% predicted) 3.7L
DLCO 20 ml/min/mmHg 65 (% predicted)
Which of the following is the next step in her diagnosis?
A. High resolution CT Chest
B. Bronchoscopy
C. Video assisted thorascopic lung biopsy (VATS)
D. Plethysmographic lung volumes
A - High res CT to identify Idiopathic Interstitial Pneumonia
In this case, organising pneumonia is suspected
OP = Rare disease which often mimics community acquired pneumonia
* Idiopathic form of organizing pneumonia (aka bronchiolitis obliterans
organizing pneumonia [BOOP])
* A diffuse interstitial lung disease arising from injury to the alveolar wall.
* Characterised by peripheral lung infiltrates & responsiveness to systemic
glucocorticoids
* Presenting symptoms generally include
* Persistent nonproductive cough (71%)
* Dyspnea (62%)
* Fever (44%)
* Malaise (48%)
* Weight loss of greater than 5 kg (57 percent)
When should you suspect an Organising Pneumonia?
- Subacute cough (weeks to months)
- Dyspnoea
- Flu like illness at disease onset in ~50%
- Chest imaging with patchy or diffuse
ground-glass infiltrate or consolidation - Lack of response to (often multiple
courses of) antibiotics - Investigations for other causes
unremarkable
What is the differential diagnosis of an organising pneumonia (OP)?
- CAP – Antibiotic responsive
- Chronic eosinophilic pneumonia – High BAL eosinophil count >25% and more rapid response to steroids (over hours to days)
- Hypersensitivity pneumonitis – known exposure agent, micronodules and GGO, higher lymphocyte count on BAL, poorly formed granulomas
- Pulmonary lymphoma and
lymphomatoid granulomatosis –
different histopathology and
immunohistochemical appearance - Organizing Pneumonia – can occur in
other lung diseases including
interstitial idiopathic pneumonias
What are the typical HRCT findings in Cryptogenic Organising Pneumonia?
Often more extensive disease on
HRCT than expected from CXR.
Radiographic patterns include:
* Patchy air-space consolidation
* Ground-glass opacities
* Small nodular opacities
* Bronchial wall thickening with dilation
* Peripheral distribution, often in the
lower lung zones (as occurs with
chronic eosinophilic pneumonia)
* Less commonly, nodules, masses with
cavitation, irregular reticular opacities,
crescent shaped opacities
How do you best treat Cryptogenic Organising Pneumonia?
1) Prednisolone 0.5-1mg/kg/day (up to 60mg) for 4 weeks then wean over 4-6 months
Alternatively can trial macrolides OR observation (but only <10% spontaneously resolve)
A 45-year-old male presents with a 10-year history of cough productive of sputum. He is a non-smoker. His other past medical history is significant for rhinosinusitis, hypertension and hyperlipidaemia. He is a married father of 2 children and works as a civil engineer.
Sputum cultures are negative for atypical bacteria. Lung function and computed tomography (CT) chest are demonstrated below:
Pre-bronchodilator FEV1 4.39 L 95 (% predicted) Post = 4.45 L
Pre-FVC 5.10 L = 95 (% predicted) post = 5.23 L
DLCO 34 ml/min/mmHg = 130 (% predicted)
CT demonstrates:
- bronchiectasis
- tree in bud
- GGO
- mucous plugging
Which of the following the MOST likely diagnosis?
A. Cystic fibrosis
B. Alpha-1 antitrypsin deficiency
C. Allergic bronchopulmonary aspergillosis
D. Primary ciliary dyskinesis
C = ABPA
What is ABPA?
Allergic Bronchopulmonary Aspergillosis
- Complex hypersensitivity
reaction to colonization of the
airways by Aspergillus fumigatus - Occurs almost exclusively in patients with Asthma or Cystic fibrosis
- Episodes of repeated bronchial
obstruction, mucoid impaction
and inflammation resulting in bronchiectasis and Fibrosis - Elevated TLCO is seen in
hyperaemia of the airways and
frequently occurs in asthma
How do you diagnose Allergic Bronchopulmonary Aspergillosis (ABPA)?
No prospectively validated diagnostic criteria
1) Predisposing condition - asthma or CF
2) Positive skin prick test or increased IgE levels to Aspergillus fumigatus
AND
elevated IgE concentration (>1000 IU)
3) positive aspergillus precipitants or IgA to aspergillus fumigatus +/- radiology consistent with ABPA +/- total eosinophil count >0.5x10^6 in steroid naive patients
What are the radiological features of ABPA?
Proximal cyclindrical bronchiectasis
Mucous plugging
Tree in bud opacity
Atelectasis
Peripheral consolidation
GGO
Mosaic attenutation with gas trapping
However CT is normal in 20%
What is Primary Ciliary Dyskinesia (immotile cilia syndrome)?
A heterogenous syndrome caused by defects in proteins that make up the inner and outer dynein arms of cilia
How does primary ciliary dyskinesia manifest?
Pulmonary - chronic bronchitis and bronchiectasis
Rhinosinusitis
Otitis media (more common in children)
Situs inversus (although most with situs inversus do not have PCD)
Infertility - men infertile, women reduced fertility
Patients with heart failure are at high risk for symptomatic sleep disordered breathing.
The presence of which of the following would make you suspect that a patient was at a high risk of central sleep apnoea with Cheyne-Stokes breathing?
A. Female sex
B. Non-sustained ventricular tachycardia
C. Hypersomnolence
D. Hypocapnia
D - Hypocapnia
OSA is more common than central sleep apnoea (CSA) in the general population
* CSA with Cheyne-Stokes Breathing (CSA-CSB) may be more common in patients with
heart failure (esp with reduced ejection fraction)
* Observational studies suggest CSA-CSB prevalence of 50 – 70% in heart failure
patients
* Sleep disordered breathing is common in patients with optimally managed heart
failure – 61%
What is the pathophysiology of Central Sleep Apnoea
The respiratory control centre has a serum CO2 level below which apnoea results (ie the apnoea threshold)
CSB had consistently low pCO2 levels (ie chronic hypocapnia
- Low CO2 results in increased CSF pH, decreased central chemoreceptor stimulation and decreased RR and apnoea
Patients with HF have prolonged circulation time rendering the PCO2-ventilatory relationship unstable
During an apnoea in px with advanced HF - PCO2 increases but takes a while for the respiratory control centre to sense this due to increased circulation time (ie lag in ability of brain to respond to elevated CO2); when it eventually does it overcompensates with tachypnoea and hyperpnoea which drives PCO2 down so the cycle repeats (ie loop gain)
A 35-year-old non-smoking woman presents with dyspnoea on exertion. On examination her oxygen saturation is 87% on room air. Lung function is given below:
Pre (% pred)
FEV1 1.95 (96%) post - 208 (102%)
FVC 2.65 (100%) post 2.98 (112%)
DLCO 5.6 (30%)
KCO 1.2 (32%)
Which of the following diagnoses might explain her presentation?
A. Bronchiectasis
B. Emphysema
C. Pulmonary arterial hypertension
D. Alpha-1 antitrypsin deficiency
C - Pulmonary arterial hypertension
On the basis you have disproportionately low DLCO with normal spirometry
What are the typical lung function abnormalities in Bronchiectasis?
Obstructive ventilatory defects most commonly
Can get restrictive ventilatory defects in severe disease with lung destruction
Variable normal or reduced DLCO
What are the lung function test abnormalities in patient with emphysema?
Obstructive ventilatory defects + reduction in DLCO often in proportion to severity of emphysema so
What are the lung function test abnormalities in Alpha-1 antitrypsin deficiency?
In smokers - airflow obstruction with reduced DLCO is expected
In non-smokers - lung function should be normal
Which of the following statements regarding never-smokers with chronic obstructive pulmonary disease are true?
A. Never smokers with COPD have the same risk of lung cancer as smokers with
COPD
B. Never smokers with COPD have more severe symptoms than smokers with COPD
C. Never smokers with COPD have an increased risk of pneumonia compared to the general population
D. Never smokers with COPD have a higher burden of systemic inflammation than smokers with COPD
C
Compared to smokers with COPD, non-smokers with chronic airflow
limitation have fewer symptoms, milder disease and lower burden of
systemic inflammation.
* Never smokers do NOT appear to have an increased risk of lung cancer or cardiovascular disease, compared to those without chronic airflow
limitation.
* Compared to the general population never smokers have an increased
risk of pneumonia and mortality from respiratory failure
70-year-old man presents for his yearly respiratory review. He has been admitted to hospital for exacerbations of his chronic obstructive pulmonary disease twice in the last 12 months. He describes daily cough productive of white sputum. His exercise tolerance is measured at 400m on flat ground. He is currently managed on a combination longacting beta agonist and long-acting muscarinic antagonist.
Which of the following is the strongest indication to consider adding an inhaled
corticosteroid to his medications?
A. Repeated pneumonia events
B. Blood eosinophils >300 cells per microlitre
C. A single hospitalisation for exacerbation of COPD per year
D. Increased sputum production
B
Several studies have shown that blood eosinophil counts predict the
magnitude of the effect of ICS (added on top of regular maintenance
bronchodilator treatment) in preventing future exacerbations.
* Continuous relationship between blood eosinophil counts and ICS effects
* Nil/small effects are observed at lower eosinophil counts
* Increasing effects observed at higher eosinophil counts
* Blood eosinophil count ≥ 300 cells/μL identifies patients with the greatest
likelihood of treatment benefit with ICS.
* Data modelling indicates that ICS containing regimens have little or no
effect at a blood eosinophil count < 100 cells/μL
When is triple inhaler therapy indicated in patients with COPD?
Reduces mortality + reduces exacerbations + improves lung function, symptoms and health status in symptomatic COPD patients with a history of frequent and/or severe exacerbations
BUT increases risk of pneumonia
eTG:
Consider adding an inhaled corticosteroid (ICS) to long-acting bronchodilator dual therapy if both of the following apply:
- the patient has had a severe exacerbation (requiring hospitalisation) or at least two moderate exacerbations in the previous 12 months
AND
- the patient has significant symptoms despite dual therapy with a LAMA and LABA
What is the role of long-term low dose oral macrolides in COPD management?
Long-term low-dose oral macrolides may reduce the frequency of exacerbations
HOWEVER There are many potential significant adverse effects of long-term, low-dose macrolide therapy, including cardiac toxicity, ototoxicity, diarrhoea, and the development of antibiotic resistance
Important to first exclude NTM infection prior to starting
A previously well 60-year-old male is brought in by ambulance to the Emergency Department. He suffered a collapse at work and hit his head on a concrete floor with a brief loss of consciousness. On arrival to hospital his resting oxygen saturation is 94%
and he is noted to be febrile with a temperature of 38.8 C. A COVID PCR is performed, which is positive. On examination 2 hours later his oxygen saturation is 88% and this
persists despite being transitioned from nasal cannula 2 L/min to a non-rebreathing bag.
Which of the following could explain his hypoxia?
A. Hypoventilation
B. Decreased VQ mismatch
C. PFO on transthoracic echocardiogram with Valsalva manoeuvre
D. Non-sustained VT
A
Raised intracranial pressure following head injury
* Symptoms include headache, depressed consciousness and vomiting
* Signs include CN VI palsy, papilledema, periorbital bruising and the triad of
bradycardia, respiratory depression and hypertension (known as Cushing’s
Triad)
Which of the following interstitial lung diseases occur most commonly in people who
have never smoked?
A. Respiratory bronchiolitis interstitial lung disease (RB-ILD)
B. Pulmonary Langerhan’s Cell histiocytosis
C. Idiopathic pulmonary fibrosis (IPF)
D. Hypersensitivity pneumonitis
D
RB-ILD = smoking-related, usually seen in px 30-40yo with >30pk yr hx; SOB + cough + inspiratory crackles + GGO (upper zones) + centrilobar nodules + subpleural fibrosis + patchy opacification +/- emphysema
What is the typical clinical scenario and features of Pulmonary Langerhan’s Cell Histiocytosis?
Young smoking adults 20-40yo
Equal sex distribution
HRCT shows small periobronchiolar nodular opacities, multiple irregularly-shaped CYSTS, mid and upper zone predominance, GGO, mosaic attenuation, interlobular septal thickening
When and how does IPF typically present?
In patients >60yo with progressive exertional dyspnoea and non-productive cough
Smokers are at increased risk of IPF and have worse survival than never smokers
What are the HRCT features of IPF?
Subpleural distribution with reticular opacities - peripheral and lower lobe predominant
Traction bronchiectasis
Honeycombing
UIP pattern
What is hypersensitivity pneumonitis?
Previously called allergic alveolitis
A group of immune-mediated pulmonary disorders with inflammation and/or fibrosis affecting parenchyma and small airways (split into fibrotic and non-fibrotic HP)
Usually has a history of exposure to an offending antigen eg bird fanciers or farmers lung
Smoking is associated REDUCED risk of HP but more chronic and severe course
What are the HRCT features of Hypersensitivity Pneumonitis?
Coarse reticulations and lung distortion
Traction bronchiectasis
Honeycoming
Ill-defined centrilobar nodules
GGO
Mosaic attenuation and/or air trapping
Mid-zone predominant OR randomly distributed
Related lower zone sparing
How do you treat clinically stable patients with first episode of Small Primary Spontaneous Pneumothorax?
If pneumothorax is small (ie <3cm at apex, 2cm at hilum) and patient stable (ie RR <24, HR 60-120, BP normal, SpO2 >90%, can speak full sentences
Can treat with observation (with repeat CXR in 4 hours) +/- oxygen and discharged
In patients with bronchiectasis, which of the following has been most strongly associated
with increased mortality?
A. Colonisation with Pseudomonas aeruginosa
B. Class 2 obesity
C. FEV1/FVC ratio of > 70%
D. Chronic treatment with azithromycin
A - Pseudomonas colonisation
Which of the following is the likely cause of these arterial blood gas results taken from a
60-year-old?
A. Ventilation perfusion (VQ) mismatch
B. High altitude
C. Hypoventilation
D. Respiratory muscle weakness
ABG - pH 7.54, PCO2 25, HCO 22, PO2 65
A
Increased A-a gradient = V/Q mismatch or shunt
High altitude + hypoventilation (incl respiratory muscle weakness) = reduced A-a gradient
The A-a gradient is a nonspecific indicator of the integrity of the alveolocapillary
membrane.
* Any pathology of the alveolocapillary unit widens the gradient.
* Hypoxemia due to ventilation-perfusion (V/Q) mismatch, diffusion limitation, and
shunt are associated with a widened gradient, whereas hypoxemia due to
hypoventilation has a normal gradient
* Normal A-a gradient ~ (Age/4) + 4
Which of the following indicates the poorest prognosis in pulmonary arterial
hypertension?
A. NYHA functional class III
B. Mean right atrial pressure > 20 mmHg
C. Female sex
D. Supplemental oxygen use
B
Patients with IPAH and a mean right atrial pressure ≥20 mmHg have a median survival of ~ one month
Other prognostic factors =
Age >50
Male sex
Severe PAH/RHF
Hypocapnia
Comorbid
CTD-associated PAH
SSRI
Low VWF levels
BMPR2 mutations
Episode of acute PH crisis
What is DLCO and what does it measure?
DLCO = diffusion capacity of the lungs for carbon monoxide (or transfer capacity)
Measures the ability of the lungs to transfer gas from inhaled air to RBCs
Easy to perform - requires patient to hold their breath for 10 seconds
Diseases in which the uptake of οхygeո is reduced cause parallel decreases in the uptake of CO, as measured by the DԼСΟ. Older textbooks suggest that thickening of the alveolar-capillary membrane (in interstitial lung disease) and loss of alveolar membrane surface area (in еmрhysеma) are the primary causes of a low DLCՕ. However, subsequent experimental data suggest these and most other diseases that influence the DԼСΟ do so by reducing the volume of red blood cells in the pulmonary capillaries. The total volume of blood in the lungs in healthy adults at rest is less than 150 mL. Diseases in which the alveolar-capillary surface area is reduced (eg, idiopathic pulmonary fibrosis and еmрhyѕema) lead to a reduction in the blood volume in the lungs.
What conditions are associated with an increased DLCO (ie increased volume of blood in the pulmonary capillaries)?
- Exercise
- Supine position
- During reverse Valsalva manevoure
- Left-to-right cardiac shunt is present
- high altitude
- obesity
- polycythaemia
What conditions are associated with reduced DLCO?
- Emphysema (correlates with degree of anatomic emphysema; loss of DLCО usually occurs after the decline in FEV1)
- Interstitial lung disease
- Sarcoidosis
- Hypersensitivity pneumonitis
- Chest irradiation and cancer chemotherapy
- Rheumatic diseases
- Pulmonary vascular disease eg recurrent PE or CTEPH
- Idiopathic pulmonary arterial hypertension
- Pulmonary vascular involvement from rheumatic disease or vasculitides
- Heart failure
- Anaemia
- Smoking/increased carboxyhaemoglobin
What conditions do you have to consider in patients with low DLCO but normal spirometry?
1) Pulmonary vascular disease
2) Early interstitial lung disease
3) Anaemia
4) Hepatopulmonary syndrome
5) Increased carboxyhaemoglobin level due to smoking
What biologic would you use in severe asthma if the patient also required systemic atopic dermatitis treatment?
Dupiliumab - an anti-IL4Ra antibody
What is the biologic agent of choice for someone with severe asthma and comorbid chronic rhinosinusitis and nasal polyposis?
Dupilumab - anti-IL4Ra antibody - has the best evidence but could also use mepolizumab or omalizumab
Not benralizumab - studies show no improvement in symptoms, time to surgery or chronic steroid use
What is bronchiectasis?
The abnormal dilation of bronchi due to the destruction of the elastic and muscular components of the bronchial wall
When does bronchiectasis typically start?
More than 60% of adults with bronchiectasis report symptoms from childhood
- these patients have worse disease and a poorer prognosis compared with patients with adult-onset bronchiectasis
What are the causes of bronchiectasis?
1) Post-infectious
- e.g. post childhood resp viral infections eg measles, influenza, pertussis; prior mycobacterial infections, COVID-19 infection
2) COPD
3) Asthma
4) Connective tissue disease
- especially RA and Sjogren’s syndrome
5) ABPA
6) Immunodeficiency
- Immunoglobulin deficiency OR HIV infection
7) Aspiration or inhalation injury
8) Genetic conditions
- Cystic fibrosis
- Ciliary dyskinesia or immotile cilia syndrome with or without Kartagener syndrome
- alpha-1-antitrypsin deficiency
9) Inflammatory Bowel Disease
10) Focal bronchial obstruction
- e.g. foreign body, stenosis, tumour, extrinsic compression
11) Other rarer causes incl Young syndrome, ANCA-assoc vasculitides, Marfan syndrome etc
12) Idiopathic
What is Swyer-Jones or Macleod syndrome?
A chronic manifestation of bronchiolitis or pneumonitis in childhood characterised by unilateral pulmonary hypoplasia and radiographic hyperlucency
What is Kartagener syndrome?
An autosomal recessive condition characterised by the clinical triad of bronchiectasis, situs inversus and chronic sinusitis
What is Young Syndrome?
A condition (believed to be genetic) characterised by obstructive azoospermia with normal sperm production plus chronic or recurrent sinus and lung infections
Describe the pathophysiology of bronchiectasis?
An initial insult (e.g. primary infection) leads to airway inflammation and bronchial damage which then serves as a nidus for subsequent colonisation of the airways.
A viscous cycle then ensues predisposing to persistent bacterial colonisation and a subsequent chronic inflammatory reaction that leads to progressive airway damage (including the classical dilation and thickening of the bronchi) and recurrent infections
The factors that predispose individuals with an initial infection to go on and develop bronchiectasis remain unclear
Which morphological subtype of bronchiectasis is more likely to be associated with Pseudomonas colonisation and more sputum production?
Cystic
- it is the most severe form
- often found in CF patients
What is the diagnostic test of choice for diagnosing bronchiectasis?
High-resolution CT chest
How do patients with bronchiectasis typically present?
Persistent productive cough
Daily mucopurulent sputum
Dyspnoea
Fatigue
Rhinosinusitis
Haemoptysis/blood tinged sputum - less common
Intermittent fevers
Weight loss
Require a high degree of suspicion if above symptoms/signs accompany an underlying disorder (e.g. CTD, IBD etc)
What are the classical examination findings in bronchiectasis?
Digital clubbing
Crackles
High-pitched inspiratory squeaks or wheeze
What tests should be undertaken in a patient suspected of having bronchiectasis and why?
1) FBC
- elevated WCC may indicate superimposed infection/exac OR eosinophilia may indicate underlying ABPA
- elevated platelet count linked to higher mortality
2) Sputum MCS + AFBs
- aids in guiding antibiotic selection
3) Sweat sodium chloride concentration and genetic testing for CFTR mutation analysis
- to identify cystic fibrosis
4) Serum alpha-1 antitrypsin phenotype and level
- to identify alpha-1 antitrypsin disease as underlying cause esp in those with co-existing basal panacinar emphysema (in which case you may consider replacement therapy)
5) Immunoglobulin levels and IgG subclasses and response to pneumovax with strep pneumo 23 serotype titres
- to identify individual immunoglobulin deficiencies (which could be treated to reduce frequency of exac)
6) Specific IgE or skin prick test for Aspergillus fumigatus
- to evaluate for ABPA
7) HIV
- to identify HIV (which predisposes to bronchiectasis due to abnormal B-lymphocyte function)
8) Rheumatoid factor
- bronchiectasis more common in RA population
9) Nasal nitric oxide test
- if low (<100 parts per billion) indicates a diagnosis of Primary ciliary dyskinesia (if CF excluded)
10) RFTs
- obstructive airway disease (ie reduced FEV1/FVC) + may get increased RV/TLC due to air trapping + reduced DLCO in severe disease
What features raise the index of suspicion for underlying cystic fibrosis as the cause of bronchiectasis?
Early age at onset
Persistent isolation of Staphylococcus aureus on sputum culture
Features of malabsorption
Male primary infertility
Upper lobe bronchiectasis
A history of childhood steatorrhoea
What concentration of sodium chloride in a patient’s sweat is considered high / makes CF likely?
≥60 mmol/L
What is the diagnostic threshold for the CT diagnosis of bronchiectasis?
Broncho-arterial dilation ratio of >1 to 1.5
How might you differentiate COPD from bronchiectasis?
On examination - reduced intensity of bs characterise COPD but are not found in bronchiectasis
On CT - may be normal or show emphysema in COPD cf characteristic abnormalities in bronchiectasis eg thickened, dilated airways +/- air fluid levels, varicose constrictions, ballooned cysts, tree-in-bud pattern
How might you differentiate asthma from bronchiectasis?
On examination - inspiratory squeaks and crackles may be present in bronchiectasis but are not present in asthma
On CT - in asthma lack airway dilatation or signet ring sign
On RFTs - airway obstruction often reversible in asthma
What are main treatment measures in bronchiectasis?
1) Exercise
2) Improve nutrition
3) Airway clearance therapy
4) Self-management plan
5) Inhaled bronchodilator
6) Mucoactive agent
Why is a healthy diet and exercise recommended for bronchiectasis patients?
1) because exercise is a form of airway clearance - exercise improves exercise capacity + QOL + cough-related QOL + psychological symptoms
2) higher BMI correlates with beneficial outcomes
What does airway clearance involve in bronchiectasis?
1) Maintaining oral hydration
2) Percussion techniques
3) Breathing techniques
4) Coughing techniques
5) Positioning/postural drainage
6) Positive expiratory pressure devices
7) Oscillatory devices
Recommended 15-30mins 2-3 times per day
What bronchodilator therapy should be used in bronchiectasis patients?
If co-existent COPD or asthma - follow guidelines for COPD or asthma
If not - may benefit from nebulised salbutamol prior to mucoactive therapy
What mucoactive agents are available/recommended for bronchiectasis patients?
Nebulised/humidified sterile water or normal saline
Nebulised hypertonic saline - promotes mucus clearance by inducing coughing, shown to reduce inflammatory mediators, improve sputum bacteriology and QOL BUT may cause chest tightness and wheeze (can try bronchodilator before + add hyaluronic acid to improve tolerability)
Others eg bromhexine may be considered
What is the recommended treatment for a non-severe acute exacerbations of bronchiectasis NOT colonised by pseudomonas?
1) Oral antibiotics
- amoxicillin 1g TDS OR doxycycline 100mg BD
OR
- IF infection with beta-lactamase producing strain of Haemophilus or Moraxella suspected (eg because the patient had a recent exacerbation caused by one of these pathogens) -> Augmentin DF BD
How can you assess severity of underlying bronchiectasis / severity of acute exacerbation?
Using a validated severity score eg. Bronchiectasis severity index (BSI)
Or assessing for features of severe exacerbation including:
- worsening respiratory distress
- worsening hypoxaemia from the patient’s baseline state
- acute-onset confusion
- signs of sepsis or septic shock
When are antibiotics indicated for an acute bronchiectasis exacerbation?
ONLY if all three of the following clinical features are present:
1) increased sputum volume or change in sputum viscosity
2) increased sputum purulence
3) increased cough, which may be associated with wheeze, breathlessness or haemoptysis.
What is the recommended treatment of patients with severe acute bronchiectasis exacerbation NOT colonised with pseudmonas?
IV Ceftriaxone/cefotaxime OR IV Augmentin
What is the recommended antibiotic treatment for non-severe acute exacerbation of bronchiectasis in a patient colonised with pseudomonas?
Amoxicillin or doxycycline
Only if the patient is not improving on initial therapy AND you isolate pseudomonas on sputum change to Ciprofloxacin 750mg BD for 14 days
How do you treat a severe exacerbation of bronchiectasis in a patient with longstanding pseudomonas colonisation?
Use the results of susceptibility tests if available
1) Ceftazidime 2g Q8H
OR
2) Piptaz 4.5g Q6H
+
Gentamicin (preferred), Tobramycin OR ciprofloxacin
(this is called combination therapy - note there is limited evidence to inform the optimal empirical regimen and whether combination antipseudomonal therapy is required)
What does an uncomplicated or simple parapneumonic effusion refer to?
A free flowing pleural effusion adjacent to an area of pneumonia that is sterile; free flowing means it lacks internal loculations/septae
What does a complicated parapneumonic effusion refer to?
An exudative effusion that has been infected with bacteria or other microorganisms (ie pH <7.2 OR glucose <40 and/or positive gram stain or biochemical evidence of marked inflammation)
What does a complex parapneumonic effusion refer to?
A parapneumonic effusion that contains internal septations/loculated effusion
What does empyema refer to?
A collection of pus within the pleural space due to direct invasion by pyogenic bacteria from an adjacent pneumonia OR from blunt trauma or from another source
It is a type of complicated pleural effusion
Should you drain parapneumonic effusions?
If small uncomplicated (ie sterile effusions) - not required unless the effusion is sizeable enough to impair respiratory function
For large uncomplicated effusions, complicated effusions OR empyema - drainage should be performed ASAP for source control (especially in cases of empyema)
In what circumstances may you defer antibiotic therapy until microbiologic testing yields a diagnosis in cases of parapneumonic effusions?
In stable patients with long-standing effusions (since the pathogens that cause subacute/chronic empyema differ from those assoc with acute pneumonia eg myobacteria and fungi)
Otherwise, should commence empirical antibiotics that mirrors treatment for underlying pneumonia EXCEPT that should pay attention to ensuring appropriate anaerobic bacterial coverage (especially with empyema) and antibiotics that have good penetration into the pleural space (nearly all do EXCEPT aminoglycosides)
Which antibiotics do not penetrate the pleural space adequately?
Aminoglycosides eg gentamicin, tobramycin, amikacin
How long do you typically need to prescribe antibiotics for patients with parapneumonic effusions?
Uncomplicated - 1 to 2 weeks
Complicated - 2-3 weeks
Empyema - 4-6 weeks
Do you use radiographic response to guide antibiotic duration/
No - worth taking into account but complete radiographic resolution may take weeks to months and residual pleural thickening can last longer
What can you do with a patient who fails to improve after antibiotics and tube thoracostomy drainage for parapneumonic effusion (i.e. effusion persists or worsens, persistent or new fevers, persistent or worsening leukocytosis)?
May indicate antibiotic coverage or drainage is inadequate therefore:
1) adjusting antibiotics
2) additional drainage procedures
3) intrapleural tissue plasminogen activator (tPA) with deoxyribonuclease (DNase)
4) Video-assisted thoracic surgery
What is the risk of not being aggressive with cases of apparent treatment failure in parapneumonic effusions?
Possibility of residual trapped lung
What are the indications for intrapleural tPA/DNase?
Patients with complicated parapneumonic effusion OR empyema who fail antibiotic therapy and initial drainage
Patients who are not candidates for OR do not want surgery
What are the side effects of intrapleural fibrinolysis?
Chest pain
Fever
Allergic reactions
Pleural haemorrhage - 1-7%, most worrisome, more common in those with underlying risk factors for bleeding
What do you do with a patient with an infected malignant effusion with indwelling catheter?
Often you can leave the catheter in situ and treat with prolonged course of antibiotics (often infection due to staph species) and it will resolve
What are the complications of pleural space infections?
- residual pleural thickening
- fibrothorax
- pleural calcification
- bronchopleural fistula
- empyema necessitans (rupture of the empyema through the chest wall)
- pleural lymphoma (especially in Japanese patients)
What is the preferred initial test to identify Chronic Thromboembolic Pulmonary Hypertension (CTEPH)?
V/Q scan
It is more sensitive (and therefore higher negative predictive value) than CTPA although often performed as complementary studies
What is the preferred initial test to identify Chronic Thromboembolic Pulmonary Hypertension (CTEPH)?
V/Q scan
It is more sensitive (and therefore higher negative predictive value) than CTPA although often performed as complementary studies. CTPA is particularly poor at identifying PE at the level of the segmental level - which is amenable to surgery
In a patient suspected of having CTEPH based on V/Q scan, what is the benefit of performing a CTPA?
V/Q scan is not specific
Therefore CTPA will a) confirm the obstruction and b) exclude alternative causes of pulmonary artery obstruction specifically: pulmonary artery tumour, pulmonary artery stenosis, fibrosing mediastinitis
What is the gold standard test for diagnosing CTEPH?
Digital Subtraction Pulmonary Angiography
Also helpful for evaluating surgical eligibility
What is the diagnostic criteria for Pulmonary Hypertension on Right Heart Catheterisation?
Mean Pulmonary artery pressure >20mmHg at rest with vascular resistance of >= 2 Wood units in the absence of an elevated pulmonary capillary wedge pressure (PCWP <15mmHg)
How do you treat CTEPH?
1) lifelong anticoagulation
Plus
2) referral to a PH / CTEPH centre of excellence for consideration of Surgical Pulmonary ThromboEndarterectomy (PTE)
If operable candidate - lifelong anticoagulation plus surgical PTE (only curative therapy)
If inoperable - lifelong anticoagulation plus PH-medical therapy
- WHO functional class 2-3 - riociguat
- WHO class 4 - parenteral prostanoid (intravenous epoprostenol or treprostinil)
Alternatives / second line agents if medical monotherapy not effective incl sildenafil,
What is the mechanism of action of Riociguat?
It is a Soluble guanylate cyclase (sGC) stimulator that targets the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway, resulting in vasodilation and reduced pulmonary artery pressure.
What effect does smoking have on Riociguat therapy in CTEPH/PH?
Tobacco smoking decreases Riociguat concentrations by 50% therefore if patient is a smoker on Riociguat then stops smoking you may need to reduce dose by 50%
What medications should you not co-administer in patients on Riociguat?
Nitrates
Phosphodiesterase inhibitors eg sildenafil
What are the main adverse effects of Riociguat?
Hypotension
Peripheral (& pulmonary) oedema
Bleeding
What is the only curative therapy for CTEPH?
Surgical Pulmonary Thromboendarterectomy
What is the main focus of evaluation for surgical pulmonary thromboendarterectomy (PTE) for treatment of CTEPH?
Themain focus of the evaluation is to determine whether removal of thromboembolic material would sufficiently reduce the pulmonary artery vascular resistance (PVR). The latter assessment is critical since outcomes are dependent upon the effect of PTE on PVR. Outcomes are favorable when PVR decreases. In contrast, failure of the PVR to decrease following PTE is associated with poor short-term outcome
Is distal disease amenable to surgical PTE for the treatment of CTEPH?
No. Only thromboembolic disease located proximally in the main, lobar, or segmental pulmonary arteries are amenable to surgical removal while distal disease is not typically surgically accessible
Which patients are most likely to benefit from surgical PTE for CTEPH?
Those with significant haemodynamic abnormalities at rest eg elevated PVR (wood units 2-15).
High PVR better response but also potentially higher risk
What are the benefits of surgical PTE for CTEPH?
Only curative treatment modality - assoc with improved pulmonary hemodynamics, functional status, and long-term survival
