College Answer

a)
Inavsive pulmonary aspergillosis is an important diagnosis to make as the mortality of the disease is
high.
In ICU patients it is more difficult due to;

• symptoms and signs difficult in these patients
• classic radiology signs difficult in ventilated patients
• biopsy often not able to be done
• Occurs in immune competent patients where there may be a low index of suspicion for this diagnosis
• Colonisation is common in patients, and so distinguishing colonisation from invasive disease may be difficult

b)
Background history

• Neutropenia > 10 days and immunosuppressed
• HIV,
• Haematological or oncological malignancy treated with cytotoxics
• Congenital or acquired immunodeficiency
• Prolonged steroid use,
• Chronic airflow limitation
• Bone marrow transplant,
• Cirrhosis or acute hepatic failure,
• Solid organ transplant,
• Chronic renal failure

Acute clinical features

• Fever refractory > 3 days Rx
• Pleuritic chest pain
• Pleural rub
• Dyspnea
• Haemoptysis
• Worsening respiratory insufficiency in spite of adequate antibiotic and ventilator support

c)
Radiology

• CT scan:
• Halo sign (pulmonary mass surrounded by ground glass)
• Air crescent sign (crescentic radiolucencies around a nodular consolidation)

Respiratory secretions-BAL

• Microscopy showing branched hyphae
• Galactomannan antigen
• PCR
• MALDI tof

Blood

• PCR
• Galactomannan Ag; low sensitivity and difficult to interpret in immune competent patients and
• interaction with Tazocin
• MALDI tof

Biopsy

Discussion

Invasive aspergillosis is discussed at greater lengths in the Required Reading section.

Briefly,

a) Discuss the difficulties in confirming a diagnosis of invasive pulmonary aspergillosis (IPA) in this patient. (applied in general, to all ICU patients)

• ICU patients will have nonspecific signs, buried under other signs, and often no history.
• Radiological diagnosis may be obscured by othr pathology, or may be logistically difficult
• Biopsy is frequently impossible
• Immunocompetent individuals are not suspected, yet may still develop the disease
• Clinically insignificant colonisation is common, but will yield the same positive diagnostic results as active invasive disease.
• Diagnostic test accuracy may be confounded by many factors, eg. concurrent β-lactam therapy.

b) What findings on history and examination are associated with increased risk of IPA?

c) What investigations are used to confirm a diagnosis of IPA?

• Serum galactomannan (poor sensitivity/specificity, many false positives)
• BAL galactomannan (better sensitivity and specificity
• BAL PCR (more sensisitve but less specific than BAL galactomannan)
• Microscopy, to identify hyphae
• Radiological findings:
  • "Halo sign" on CT
  • Pulmonary nodule on CXR
  • Wedge-like haemorrhagic pulmonary infarcts
  • Air crescents following resolution