Presentation
Jan is being treated for COPD at her local hospital. Despite using a steroid inhaler, she has had multiple exacerbations and chest infections per year, which sometimes require hospitalization. Her lung function has declined over the past 18 months and she has started to occasionally produce blood-tinged sputum. A chest X-ray last year revealed a right-upper lobe cavity but no obvious sign of an aspergilloma. Recently Aspergillus grew in her sputum cultures.
Her respiratory consultant referred her to the National Aspergillosis Centre for assessment and a treatment plan. During her initial appointment you notice that she recently has lost 3 kg and appears generally unwell.
Notes, obs & scans
| Referred from | Respiratory consultant |
| Diagnoses |
|
| Demographics |
|
| Vital signs |
|
| Recent radiology | Chest X-ray showed cavity in the right upper lobe |
CT scan reproduced from Graham & Nasir (2019)
Which tests would you order?
Culture & sensitivity
Correct
Antifungal susceptibility testing is vital because azole resistance is common in Aspergillus
Biopsy & histopathology
Possibly
Biopsy is an invasive procedure but it may be considered if initial tests are inconclusive
Galactomannan & BDG
Incorrect
CPA patients are generally non-neutropaenic and will clear fungal antigens from the blood rapidly. These tests are more relevant to invasive fungal infections.
Total IgE & Aspergillus IgE
Correct
IgE antibodies are a measure of allergic sensitisation and are primarily used for diagnosing ABPA/SAFS.
At NAC, they are also measured at the initial intake for suspected CPA
Aspergillus IgG
Correct
Aspergillus IgG antibody is key to diagnosing CPA and monitoring response to treatment.
Titres vary widely, but sensitivity is >90% (Baxter et al, 2013).
Please note that patients with cystic fibrosis tend to have a slightly raised baseline Aspergillus IgG
Aspergillus PCR
Correct
Quantitative PCR on BAL provides an estimate of how much Aspergillus is present in the lungs (the ‘fungal burden’). It can be useful for monitoring response to treatment and in some cases can provide an early warning that antifungal resistance has developed.
This test is generally not performed by local laboratories, but it can be ordered through a regional one such as the Mycology Reference Centre Manchester
Test results
| Test | Result (range) |
| Culture & ID |
Aspergillus fumigatus |
| Susceptibility | Azole susceptible |
| Aspergillus IgG | 98 mg/L (0-40 mg/L) |
| Total IgE, Aspergillus IgE | Normal |
| LFTs, FBC, ECG | Normal |
What are the subtypes of CPA?
Nodule
Aspergillus occasionally forms nodules resembling lung cancer, which are identified when hyphae are seen in the biopsy tissue.
Aspergilloma
A fungal ball made of hyphae and extracellular matrix, seen late in infection as the fungal growth inside a cavity collapses. A single ‘simple’ aspergilloma may be suitable for surgical removal (lobectomy).
Necrotising
Chronic necrotising pulmonary aspergillosis (CNPA; also known as sub-acute invasive aspergillosis, SAIA) is more often seen in patients with some degree of immunosuppression (e.g. diabetes, corticosteroids, alcoholism). Nodules and consolidation with or without a thin-walled cavity form over the course of several weeks.
Cavitary / complex
Chronic cavitary pulmonary aspergillosis (CCPA) involves fungal growth in multiple cavities, with pulmonary symptoms and raised inflammatory markers. Cavities may enlarge over time if left untreated over the course of some years. A fungal ball may or may not be present.
Fibrosing
Chronic fibrosing pulmonary aspergillosis (CFPA) can occur when an infection is left untreated. Extensive fibrosis and significant loss of lung function.
What is her diagnosis?
Chronic cavitary pulmonary aspergillosis
Correct
Her results show growth of Aspergillus within a cavity, without necrosis or fibrosis
Chronic necrotising aspergillosis
Incorrect
There is no evidence of invasion/necrosis and she is not known to be immunosuppressed
Aspergilloma
Incorrect
There is currently no sign of a mobile mass within the cavity on the CT scan
Treatment
Jan was started on 200 mg BD voriconazole as per ERS guidelines (Denning et al, 2016). Therapeutic drug monitoring at 2 weeks showed that her serum voriconazole levels were within the correct range. Follow-up at 6 months showed that her Aspergillus IgG had fallen from 92 to 75 (range 0-40) and she no longer produced blood-tinged sputum. After ~18 months at NAC, her condition had stabilized enough that she was discharged back to her consultant. If her CPA worsens then she may be re-referred in future.
Anything else?
Smoking cessation
Smoke reduces mucociliary clearance, which prevents fungal spores and bacteria from being cleared from the lungs. Many CPA patients are former or even current smokers. It can be awkward to ask about someone’s smoking habits, but it is worth checking whether they would like any help with quitting or cutting down.
NHS Stop Smoking services can give advice even to patients who are currently very reluctant or anxious about stopping. More types of treatment and support have become available in recent years, so quitting may not be as hard as people fear.
- Carbon monoxide breath test
- Personal advisor and tailored plan
- Discounted nicotine replacement gum/patches
- Other medications where appropriate (e.g. varenicline, bupropion)
- Out-of-hours helpline
- Some areas offer group or drop-in sessions
- More info on their website or call Smokefree on 03001231044
Support groups
CPA is a frightening diagnosis and many patients find comfort from joining a support group. The CARES team at NAC organises lots of activities, which are open to all UK aspergillosis patients and their carers. As well as practical tips on managing symptoms, we also invite scientists to share their cutting-edge research and even hold an annual Christmas quiz.
Each year we hold an online symposium and social media splash for #WorldAspergillosisDay on 1st Feb. This brings together patients/carers, clinicians and scientists. Find out about upcoming activities on the website
- www.aspergillosis.org
- Facebook: information page and private support group
- Twitter: @MFT_NAC
- YouTube: National Aspergillosis Centre
- Contact us to have a patient added to our private Telegram chat group and/or Zoom groups
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