Aspergillosis

Fungal infection by the Aspergillus mould family with a broad spectrum of clinical disease from:

Epidemiology and Risk Factors

Major risk factors for both disease and severity are essentially surrogates of immunosuppression as well as underlying lung disease. They include:

Respiratory disease significantly ↑ rate of aspergillus colonisation, and risk of subsequent infection if immunocompromise occurs.

  • Patient
    • Extremes of age
      <1 and >70.
    • Malnutrition
    • Alcohol misuse
  • Disease
    • Respiratory
      • COPD
      • CF
      • Interstitial lung disease
    • Immunocompromise
      • Diabetes
      • Burns
      • HIV
      • Prolonged neutropenia
      • Bone marrow transplant
      • Solid organ transplant
        Lung most significant.
      • Complicated abdominal surgery
      • Decompensated CLD
  • Treatment factors
    • Prolonged ICU stay
    • Mechanical ventilation
    • Broad spectrum antibiotics
    • Indwelling catheters
    • PN
    • Steroid
      >1mg/kg for >2 weeks.
    • Chemotherapy
  • Environmental
    • Construction site exposure

Pathophysiology

Fungal pneumonia:

  • Peri-vascular predominance in the immunocompromised
    • ↑ Rate of pulmonary infarction
      Leads to:
      • Haemoptysis
      • Cavity formation
  • Bronchoalveolar pneumonia in the immunocompetent
    • Similar to other pneumonias
    • “Classical” features of cavitation and aspergilloma formation are rarer

Clinical Features

Features include:

The majority of cases are secondary mycoses of the immunosuppressed, although can occur in otherwise immunocompetent patients with intercurrent illness.

  • Respiratory failure
    • Resting hypoxaemia
  • Persistent infection
    • Pneumonia refractory to antibiotics
    • Refractory fever
  • Pulmonary infarction
    • Cough
    • Pleuritic chest pain
    • Haemoptysis
      May be massive.
    • Pneumothorax
      Rare.
  • Distant infection
    • Abscesses
    • Skin lesions

In the immunocompromised, haematogenous dissemination and rampant infection can lead to:

  • Endocarditis
  • Endophthalmitis
  • Abscesses

Investigations

Cultures, stain, and specific testing (galactomannan, PCR) are unable to discriminate between colonisation and infection.

Laboratory:

Galactomannan is a cell wall polysaccharide found in aspergillus, ice cream, salad dressings, and cream cheese.

  • Blood
    • FBE
      • Eosinophilia
      • Neutropenia
    • Serum galactomannan
      • Moderately sensitive (75%) and specific (85%) at a cutoff of >0.5
        Higher cutoffs ↑ specificity and ↓ sensitivity.
      • Lower sensitivity in the immunocompetent and those receiving prophylaxis
    • (1→3)-β-D-glucan antigen
      Cell wall component of most fungi. Improves sensitivity and specificity in combination with galactomannan.
    • Serum PCR
      Similar diagnostic properties to serum galactomannan.
  • Bronchoscopy
    BAL is an integral part of adequate sampling.
    • Visual inspection
    • Fungal culture and stain
      • Difficult to culture, with correspondingly low sensitivity and long culture times
      • Loss of specificity with aspergillus colonisation
    • Aspergillus PCR
      • Highly sensitive - negative result persuasive for no infection
    • BAL galactomannan
      • Better than serum galactomannan in the immunocompetent
        More likely to have contained pulmonary disease.
    • Transbronchial biopsy
      • Definitive diagnostic test
      • Risk of bleeding and pneumothorax often precludes this, particularly in the critically unwell
  • Sputum
    Significantly ↓ yield compared with BAL.
    • Aspergillus radioallergosorbent assay
    • Silver staining
    • Aspergillus IgG/IgE

Imaging:

  • CXR
    • Aspergilloma cavities
  • CT
    • Aspergilloma cavities
    • Nodules
    • Monod sign
      Free-moving (i.e. positional and dependent) aspergilloma in a pulmonary cavity.
    • Halo sign
      Ground-glass opacity around a nodule or mass, usually indicating haemorrhage secondary to pulmonary infarction.
    • Air crescent sign
      Halo of air around a region of necrosis; indicates recovery.
Monod

Air Crescent Sign

Other:

  • Open lung biopsy
    Rarely indicated due to risk of procedure.

Diagnostic Approach and DDx

Management

Aggressiveness of antifungal treatment depends on the severity of clinical presentation, and usually begins prior to diagnostic confirmation due to the long lead time of specific investigations.

Specific therapy:

  • Pharmacological
    • Allergic Bronchopulmonary Aspergillosis
      • Corticosteroids
      • PO itraconazole
    • Aspergilloma
      • PO itraconazole
    • Pneumonia and invasive disease
      • IV antifungal
        • Voriconazole
          1st line for efficacy.
        • Echinocandins
          Synergistic when combined with azoles. Combination therapy may be appropriate with:
          • Known or likely azole resistance
            From culture findings, treatment failure, or local microbial patterns.
          • Severe disease
            Profound immunosuppression.
        • Amphotericin B
          Generally not preferred due to nephrotoxicity. Indicated for:
          • Hepatic failure
          • Azole-resistant
      • Altering immunosuppression
        Consideration should be given to ↓ exogenous immunosuppression.
      • G-CSF
        For neutropenia.
  • Procedural
    • Aspergilloma
      • Surgical resection
      • Percutaneous amphotericin injection
  • Physical
    • Respiratory isolation

Supportive care:

Disposition:

Marginal and Ineffective Therapies

Anaesthetic Considerations

Complications

  • Death
  • B
    • Pneumothorax
  • I
    • Disseminated infection

Prognosis

High mortality with invasive disease:

  • 50-90%
    Highest in the immunosuppressed.

Key Studies

References

  1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  2. Case courtesy of Frank Gaillard, Radiopaedia.org, rID: 8684.
  3. Case courtesy of Ian Bickle, Radiopaedia.org, rID: 26223.