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 knwon 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
