A 65-year-old male with a background history of chronic obstructive pulmonary disease has been ventilated for ten days for respiratory failure related to community-acquired pneumonia. He develops a new fever and a sputum sample is positive for Aspergillus spp.

a) Discuss the difficulties in confirming a diagnosis of invasive pulmonary aspergillosis (IPA) in this patient.

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?

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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

References

References

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Soubani, Ayman O., and Pranatharthi H. Chandrasekar. "The clinical spectrum of pulmonary aspergillosis." CHEST Journal 121.6 (2002): 1988-1999.

Sherif, Rami, and Brahm H. Segal. "Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications." Current opinion in pulmonary medicine 16.3 (2010): 242.

Meersseman, Wouter, et al. "Invasive aspergillosis in the intensive care unit."Clinical Infectious Diseases 45.2 (2007): 205-216.

Trof, R. J., et al. "Management of invasive pulmonary aspergillosis in non-neutropenic critically ill patients." Intensive care medicine 33.10 (2007): 1694-1703.

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