Question 9

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?

Clinical Features and Associated Findings in Aspergillosis

Pulmonary: An asthma-like clinical picture Haemoptysis Chronic cough Extrapulmonary: immunocompromised host endopthalmitis endocarditis

Eosinophilia Elevated serum IgE Spherical lesions on CXR Incidental lesions on CT

Risk Factors for Invasive Aspergillosis
(from Meersseman et al, 2007)

Low risk	Intermediate risk	High risk
Heart, kidney, liver transplant Burns Stay in ICU > 21 days Malnutrition Cardiac surgery Short term steroids	Bone marrow transplant (auto) COPD Cirrhosis Solid malignancy HIV Lung transplant Chronic steroids Chronic immunesuppression	Bone marrow transplant (allo) Neutropenia Haem malignancy

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

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