Aspergillus lung disease

Question 1

What is Aspergillus lung disease?

Answer 1

• Filamentous fungi of the Aspergillus species are ubiquitously found as soil inhabitants.
• Inhalation of the aerosolised conidia (spores) causes the infection.
• The clinical spectrum varies from colonisation, allergy (e.g., allergic bronchopulmonary aspergillosis), asthma, or aspergilloma (fungal ball) to invasive disease, depending on host immune impairment.
• Neutropenia and compromised T-lymphocyte/macrophage function are key immune deficiencies predisposing to tissue invasion

Question 2

What are the different classifications of aspergillosis?

Answer 2

• Invasive aspergillosis (IA)
• Chronic necrotising aspergillosis
• Allergic bronchopulmonary aspergillosis (ABPA)
• Aspergilloma (fungal ball)

Question 3

What is Invasive aspergillosis (IA)?

Answer 3

• Invasive sino-pulmonary aspergillosis: inhalation of conidia most commonly results in sinus and pulmonary involvement.
• Disseminated aspergillosis: in profoundly immunocompromised patients, focal disease may spread to multiple organ sites.
• Single-organ IA: common sites include skin (via trauma), bone, and brain.

Question 4

What is chronic necrotising aspergillosis?

Answer 4

• An indolent destructive process due to invasion by Aspergillus.
• Usually seen in patients with lung disease such as COPD, pneumoconiosis, or cystic fibrosis, and in patients with mild immunosuppression.

Question 5

What is allergic bronchopulmonary aspergillosis (ABPA)?

Answer 5

• Hypersensitivity reaction to Aspergillus antigens, mostly due to A fumigatus.
• Typically seen in patients with long-standing asthma or cystic fibrosis.

Question 6

What is aspergilloma?

Answer 6

• The intracavitary mass lesion in the lung consists of masses of Aspergillus mycelia, inflammatory cells, fibrin, mucus, and tissue debris.
• The growth of Aspergillus on the walls of the cavity is facilitated by inadequate drainage. (Occurs in pre-existing lung cavities; it is commonly secondary to TB)
• Bleeding is uncommon; however, severe haemoptysis may sometimes occur secondary to erosion of bronchial blood vessels lining the cavity and mechanical friction of the fungal ball against the blood vessels

Question 7

What is the aetiology of Aspergillus lung disease?

Answer 7

Aspergillus is a ubiquitous environmental mould that grows in organic matter in the soil. The organism grows as a soil mycelium (filamentous form) and forms aerial hyphal stalks.

The conidia (spores) are about 2 to 10 micrometres in diameter. They are formed at the tips of the stalks (conidiophores) by asexual reproduction. Their hydrophobic nature aids in aerosolisation.

Humans routinely inhale the aerosolised conidia. The conidia are promptly eliminated from the respiratory tract, or may lead to colonisation or infection dependent on the underlying local and general immune status of the host.

Approximately 34 of 180 Aspergillus species are known to cause disease in humans. Aspergillus fumigatus is the most common pathogenic species, accounting for 50% to 70% of the aspergillosis syndromes

Rarely, the organism gains entry via direct cutaneous inoculation, particularly after trauma

In aspergilloma, A fumigatus remains the most common species.

Question 8

Name some risk factors for Aspergillus lung disease

Answer 8

• allogeneic stem cell transplantation
• prolonged severe neutropenia (>10 days)
• immunosuppressive therapy
• chronic granulomatous disease (CGD)
• acute leukaemia
• aplastic anaemia
• solid organ transplantation - invasive aspergillosis
• presence of pre-existing cavities - aspergilloma

Question 9

What are some weak risk factors for aspergillus lung disease?

Answer 9

• advanced chronic lung disease
• primary immunodeficiency
• HIV infection
• diabetes mellitus
• cystic fibrosis
• severe burns
• malnutrition
• multiple myeloma
• immunocompetent patients
• age >55 years
• smoking

Question 10

Summarise the epidemiology of Aspergillus lung disease

Answer 10

Aspergillus species are ubiquitous, invasive aspergillosis (IA) is seen in all geographical regions, usually in immunocompromised hosts such as cancer and transplant patients. IA occurs in the following settings:

• Allogeneic stem cell transplantation (25%)
• Haematological malignancy (28%)
• Solid organ transplantation (9%)
• Pulmonary disease (9%)
• AIDS (8%)
• Autologous stem cell transplantation (7%)
• Immunosuppressive therapy (6%)
• Other underlying conditions (6%)
• Non-compromised hosts (2%)

According to one study, 11% of patients with pulmonary cavities secondary to tuberculosis have radiological evidence of aspergilloma. In most cases the lesions remain stable without invasion of the pulmonary parenchyma or blood vessels

Question 11

What are the presenting symptoms of Aspergillus lung disease?

Answer 11

• cough
• pleuritic chest pain
• pleural rub
• headache
• fever
• skin rash

Invasive aspergillosis

• fever
• mild to moderate non-productive cough
• pleuritic chest pain
• haemoptysis
  
  • suggest the presence of a lung lesion eroding into a neighbouring blood vessel
• dyspnoea
• rapid deterioration
• septic picture
• Single or multiple discrete, erythematous, mildly tender nodules of varying sizes with a necrotic and often ulcerated centre (ecthyma gangrenosum) are common in immunocompromised patients

Invasive sinus disease

• headache
• congestion
• facial pain with or without sinus drainage
• sinus tenderness
• nasal ulcer

​Allergic Bronchopulmonary Aspergillosis (ABPA)

• mostly asymptomatic
• self-limiting mild haemoptysis
• ~ weight loss
• ~ chronic cough
• ~ malaise
• fever is rare

Aspergilloma

• Difficult to control asthma
• Recurrent episodes of pneumonia with wheeze, cough, fever and malaise

Question 12

What are some uncommon presenting symptoms of aspergillus lung disease?

Answer 12

• haemoptysis
• dyspnoea
• facial pain
• seizure
• altered mental status
• cranial nerve palsy
• malaise
• weight loss

Question 13

What are the signs of Aspergillus lung disease O/E?

Answer 13

cough =

• Invasive aspergillosis: usually non-productive, mild to moderate in severity, and frequently absent. Rejection of transplanted lung may present as cough.
• Aspergilloma: cough is an uncommon finding in these patients. If present, is non-productive.
• Tracheal deviation (only with very large aspergillomas)
• Dullness in affected lung on percussion
• Reduced breath sounds O/A
• Wheeze (in ABPA) O/A
• Cyanosis (possible in invasive aspergillosis)

Question 14

What are some primary investigations for ?Aspergilloma

Answer 14

• CXR
  
  • Single upper lobe lesions are the most common finding on CXR.
  • Multiple lesions are rarely seen.
  • An upper lobe, mobile, intracavitary mass with an air-crescent in the periphery (Monod’s sign) is strongly suggestive of aspergilloma
  • Plain x-rays are usually adequate
• Occasionally chest CT is required
• bloods: Serum IgG antibodies to Aspergillus

Question 15

What are some possible secondary investigations for ?Aspergilloma

Question 16

What are some primary investigations for ?ABPA

Answer 16

• Immediate skin test reactivity to Aspergillus antigens
• Bloods:
  
  • Eosinophilia
  • Raised total serum IgE
  • Raised specific serum IgE and IgG to A. fumigatus
• CXR
  
  • Transient patchy shadows Collapse
  • Distended mucous-filled bronchi Signs of complications:
  • May show a round mass with a crescent of air around it
  • Fibrosis in upper lobes Bronchiectasis
• CT
• Lung Function Tests
  
  • Reversible airflow limitation
  • Reduced lung volumes/gas transfer

Question 17

What are some primary investigations for ?Invasive Aspergillosis

Answer 17

• CXR
  
  • may reveal nodules, consolidation, or frequently non-specific infiltrates.
  • Often CXR shows no abnormalities.
  • If index of suspicion is high, chest CT scan should be obtained
• High resolution CT
  
  • ​preferred radiological method
  • useful in detecting early lesions suggestive of pulmonary aspergillosis
  • may show single or multiple nodules scattered over one or both lungs, generally in the periphery of the lung fields.
  • Smaller nodules (<1 cm), ground-glass opacities, and consolidation are non-specific features and do not necessarily suggest pulmonary IA
  • macronodules (1 cm or larger) in a high-risk patient is highly suggestive of IA, and may be seen in other conditions including other invasive fungal infections, tuberculosis, nocardiosis, and bacterial infections
  • leukemic patient with neutropenia, early disease is characterised by a haziness representing haemorrhage/oedema surrounding the nodules (‘halo sign’)
    
    • ​indicative of early disease and thus is useful in early diagnosis
  • air-crescent sign’ - is indicative of a necrotic lesion contracting from viable lung tissue, creating a cavity within where the air is trapped
    
    • indicates disease has been present for >6 to 7 days.
• bloods: Galactomannan (GM) antigen, Serum (1-3)-beta-D-glucan]
• Bronchoscopy with bronchoalveolar lavage (BAL) and/or biopsy
• Percutaneous transthoracic CT-guided needle aspiration
• Video-assisted thoracoscopic biopsy.