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- Y6 Respiratory > Aspergillus lung disease > Flashcards

Aspergillus lung disease Flashcards

1
Q

Define aspergillosis.

A

Infection with filamentous fungi of the Aspergillus species (which are soil inhabitants) caused by inhalation of the aerosolised conidia/spores.

The clinical spectrum varies from colonisation, allergy, asthma, or aspergilloma to invasive disease.

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2
Q

Broadly how is Aspergillus diagnosed?

A
  • Imaging
  • Sputum/BAL
  • Aspergillus Abs (precipitans)
  • Galactomannan - bronchial sample or circulating in blood
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3
Q

3 phenotypes of aspergillus lung infection?

A
  1. Allergic bronchopulmonary aspergillosis (ABPA)
    • Chronic wheeze
    • Eosinophilia
    • Bronchiectasis
  2. Aspergilloma
    • May cause haemoptysis
  3. Invasive aspergillosis
    • Immunocompromised
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4
Q

What is invasive aspergillosis?

A

Invasive aspergillosis is a systemic Aspergillus infection (A. fumigatus, flavus, and terreus) that is a leading cause of death in immunocompromised patients.

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5
Q

Describe aspergilloma. When does it occur?

A

An aspergilloma is a mycetoma (mass-like fungus ball) which often colonises an existing lung cavity (e.g. secondary to tuberculosis, lung cancer or cystic fibrosis).

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6
Q

Describe the pathophysiology of ABPA.

A

Hypersensitivity reaction to colonisation of airways/sinuses/lungs. Predominantly affects those with asthma, CF and bronchiectasis.

Aspergillus allergens induce IgE-mediated (type 1) and IgG-mediated (type 3) reactions that causes a severe asthma.

T-lymphocyte are mostly Th2 CD4+ cells, producing IL-4/5/13 that target eosinophils and B cells.

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7
Q

What is the difference between ABPA and EAA?.

A

Asthma - type I hypersensitivity reaction to fungal spores

EAA - broad term for a non-IgE mediated reaction to spores in sensitised individuals. Many types:

  • Malt worker’s lung (Aspergillus clavatus)
  • Sugar worker’s lung (Thermoactinomyces sacchari)
  • Bird-fancier’s and pigeon fancier’s lung (bird droppings)
  • Farmer’s and mushroom worker’s lung (Micropolyspora faeni, Thermoactinomyces vulgaris)
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8
Q

What are the risk factors for ABPA?

A
  • asthma
  • cystic fibrosis (CF)
  • atopy
  • HLA-DR2- and HLA-DR5-positive
  • IL-10 promoter polymorphisms
  • surfactant protein polymorphisms
  • CFTR gene
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9
Q

How is ABPA diagnosed?

A

Diagnosis is made on the basis of a deterioration in the patient’s clinical condition (the underlying asthma or CF symptoms worsen), being a susceptible patient and the presence of the following:

  • eosinophilia
  • flitting CXR changes
  • positive radioallergosorbent (RAST) test to Aspergillus
  • positive IgG precipitins (not as positive as in aspergilloma)
  • raised IgE
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10
Q

What are the clinical features of ABPA?

A
  • Chronic wheeze
  • Eosinophilia
  • Bronchiectasis

Other:

  • Fever.
  • Generalised malaise.
  • Severe headache.
  • Pleuritic chest pain.
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11
Q

What are the risk factors for invasive aspergillosis?

A

Risk factors include:

  • HIV
  • Leukaemia
  • Following broad-spectrum antibiotics
  • Allogeneic stem cell transplantation/ prolonged severe neutropenia (>10 days)/ immunosuppressive therapy/solid organ transplantation (SOT)
  • Multiple myeloma
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12
Q

Describe the presentation of invasive aspergillosis.

A
  • Usually the patient is immunocompromised.
  • Cough
  • Fever
  • SOB
  • Pleuritic chest pain
  • Haemoptysis
  • Nasal congestion and pain (if sinusitis develops)

The fungus may spread haematogenously and affect the kidneys, brain, heart, spleen, liver, thyroid, gastrointestinal tract, eyes and skin. Angioinvasion of hyphae can lead to vascular thrombosis, tissue infarction and coagulative necrosis

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13
Q

What is the management of ABPA?

A
  • oral glucocorticoids
  • itraconazole is sometimes introduced as a second-line agent
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14
Q

What investigations would you do for invasive aspergillosis?

A

Hard to diagnose so must be looked for specifically in symptomatic immunocompromised patients

  • CXR - nodules, consolidation, infiltrates or may be normal.
  • high resolution CT - nodules (1 cm or more in size) with or without halo sign or air-crescent sign.
  • Sputum, lung tissue biopsy, BAL may show hyphae using appropriate stains
  • serum Aspergillus galactomannan (GM) antigen EIA - 2 positive results of optical index ratio 0.5 or greater in the same blood sample (false positives are common because GM is found as a stabiliser in foods).
  • MRI brain and sinuses - space-occupying lesions with surrounding oedema, abscesses, haemorrhage, sinus opacity and/or bone erosion.
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15
Q

What is galactomannan and how can you test for it?

A
  • Part of the Aspergillus cell wall
  • Can be tested for in the serum by enzyme immunoassay
  • 2 positive results of optical index ratio 0.5 or greater in the same blood sample = positive

NB: False-positives may be due to intake of food containing GM (used as a stabiliser in ice cream, cream cheese, fruit preparations, and salad dressings), other fungal infections (e.g., histoplasmosis, cryptococcosis, and blastomycosis), and use of antibiotics such as piperacillin-tazobactam.

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16
Q

Descirbe the typical presentation of aspergilloma.

A
  • Presents with haemoptysis in up to 60% - sometimes severe enough to threaten life.
  • Cough or fever - less common.
  • Asymptomatic detected after CXR
17
Q

What investigations would you do to diagnose aspergilloma?

A

CXR shows a mass within a pulmonary cavity, often in the upper lobe. An air cresent outline may be seen to surround a solid mass. Usually helpful in diagnosis.

Serology - aspergillus precipitin antibody test results (ie, for IgG) are usually positive.

Other:

  • CT - may show mycetoma in more detail. Supine and prone should be performed to demonstrate the mobility of the mass.
  • Sinus CT will show space-occupying lesions without bone erosion.

Not many characteristic laboratory signs. Sputum negative.

18
Q

Describe the presentation of CNPA and the investigations you would do.

A
  • Affects those with mild-to-mod immunosuppression e.g. in alcoholism or steroid dependency. There may be pre-existing lung disease - eg, chronic obstructive pulmonary disease (COPD).
  • Symptoms include:
    • Fever.
    • Night sweats.
    • Cough.
    • Anorexia and weight loss.
  • Presents like pneumonia that doesn’t respond to usual antibiotic therapy. It may spread gradually and undergo cavitation.

Investigations:

  • CXR and CT
  • Diagnosis requires the demonstration of fungal hyphae in sputum/biopsy/BAL fluid.

CNPA = chronic necrotizing pulmonary aspergillosis

19
Q

Which stain is used to visualise Aspergillus fungi?

A

Visualization of the characteristic fungi using Gomori methenamine silver (GMS) stain –> fungal wall turns a grey-black colour

20
Q

What is the first line treatment for invasive aspergillosis?

A

Voriconazole

  1. Early antifungal agents - empirical amphotericin B or echinocandin first, then definitive voriconazole for 3 or more months
  2. Reverse immune deficiency e.g. CSF to reduce neutropenia
  3. Surgical resection of the infected focus
21
Q

Which organisms cause lung cavitation?

A
  1. Staph aureus
  2. Klebsiella
  3. Haemophilus
  4. TB
22
Q

What are the key immunodeficiencies predisposing to aspergillosis?

A
  • Neutropenia
  • Compromised T-lymphocyte/macrophage function
23
Q

What is the management of aspergilloma?

A

No evidence that aspergilloma responds to antifungal agents whether IV, inhaled or intracavitary. Can try these if disease is symptomatic only:

  1. IV high dose amphotericin B - must be monitored closely as nephrotoxic
  2. Bronchial artery embolisation to treat severe haemoptysis
  3. Surgical resection in life threatening haemoptysis
24
Q

Which type of aspergillus most commonly causes aspergillosis?

A

Aspergillus fumigatus

Others: A. clavatus, A. flavus, A. niger

25
Q

What is the prognosis with aspergillosis?

A

Better in early diagnosis and reversal of immunodeficiency

Mortality is 80% to 90% when Aspergillus involves the brain or infection disseminates.

Risk of relapse is 20%

26
Q

If relapse of aspergillosis likely, what prophylaxis may be offered?

A

Voriconazole

27
Q

What are the complications of aspergillus lung disease?

A
  • Life threatening haemoptysis
  • Disseminated infection - e.g. brain via haematogenous spread causing abscess with high mortality (tx: voriconazole)
  • Severe hypoxia
  • Obstructive pneumonia
  • Pericarditis
28
Q

Is aspergillus a yeast or mould?

A

Mould - just like mucormycoses and dermatophytes

Aspergillus culture
29
Q

What is shown?

A

TB cavity invaded by aspergillus

30
Q

What is ambisome?

A

Amphotericin B + phospholipid bilayer = more lipophilic so can enter CNS

- Y6 Respiratory (23 decks)

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