Research published this week has explored several different aspects of aspergillosis, including complications of chronic pulmonary aspergillosis, CT findings in ABPA, antifungal resistance and the challenges of adjusting voriconazole treatment.
There were no findings likely to change treatment immediately, but several papers provide useful insights into how these conditions are diagnosed and monitored.
Paper of the week: treating an abscess inside a CPA cavity
A case report describes a person with chronic pulmonary aspergillosis who developed a lung abscess inside an existing pulmonary cavity.
The abscess was successfully treated using percutaneous drainage, a procedure in which a catheter is passed through the chest wall into the infected area to allow the contents to drain. This was used alongside antifungal treatment.
Most people with CPA do not develop this complication. However, the report illustrates how the appearance of a cavity can change over time and why new symptoms or changes on scans may require further investigation.
A worsening cavity does not always mean that antifungal treatment has simply failed. There may be an additional problem, such as an abscess, bacterial infection or obstruction, requiring a different treatment approach.
This was a single case report, so it cannot tell us how often this approach will be useful. It does, however, show that drainage may occasionally provide an additional treatment option when infection becomes trapped within a cavity.
Read the case report on PubMed
Dense mucus on CT may help identify ABPA
A radiology report has highlighted the importance of high-attenuation mucus in allergic bronchopulmonary aspergillosis.
In ABPA, thick mucus can collect inside widened airways. On a CT scan, some mucus appears unusually dense or bright. This is called high-attenuation mucus.
Although it is not present in every person with ABPA, this finding can be a useful clue, particularly when someone has difficult-to-control asthma, bronchiectasis, eosinophilia or evidence of sensitisation to Aspergillus.
The finding is important because mucus plugging can contribute to:
- worsening cough and wheeze;
- repeated chest infections;
- blocked airways;
- temporary or permanent changes in lung function; and
- the development or progression of bronchiectasis.
A CT scan is only one part of the diagnostic process. High-attenuation mucus does not diagnose ABPA on its own, and its absence does not exclude ABPA. Doctors also consider symptoms, asthma or bronchiectasis, blood tests and the overall pattern on imaging.
Read the radiology report on PubMed
Genetic variants did not predict viral-associated aspergillosis
A multicentre study investigated whether common genetic variants in two immune-related genes—PTX3 and CLEC7A, also known as Dectin-1—were associated with invasive pulmonary aspergillosis following severe influenza or COVID-19.
The study did not find an association between these genetic variants and either the occurrence or outcome of invasive pulmonary aspergillosis.
This is useful information, but it does not mean that genetics are irrelevant to aspergillosis. The immune system involves many genes, and susceptibility may depend on combinations of genetic variants, the type of underlying illness, immune treatments and the particular form of aspergillosis.
It does show that testing one or two common genetic variants is unlikely to provide a simple way of predicting who will develop viral-associated aspergillosis.
Early signs of resistance to olorofim
Olorofim is a newer antifungal drug being developed for difficult-to-treat fungal infections. Laboratory researchers have identified amino-acid changes in Aspergillus flavus that can reduce susceptibility to olorofim.
This is laboratory research rather than evidence that olorofim resistance is already widespread in patients. Nevertheless, it is important because antifungal resistance can reduce the effectiveness of treatment.
Whenever a new antifungal becomes available, doctors and laboratories need to monitor:
- whether resistant strains are already present;
- whether resistance develops during treatment;
- how resistance is detected; and
- whether a different antifungal is needed.
The study involved Aspergillus flavus, whereas many chronic lung infections are caused by Aspergillus fumigatus. The findings therefore cannot be applied directly to every person with aspergillosis. They are an early warning that resistance testing will remain important as new treatments are introduced.
Why voriconazole blood tests remain important
Voriconazole is affected by genetic differences in an enzyme called CYP2C19. Some people process the drug quickly, while others process it more slowly.
A case report describes a patient with a CYP2C19 result expected to indicate normal metabolism. Despite this, she required a much higher-than-usual dose of voriconazole to achieve therapeutic blood concentrations.
The authors also noted that increased C-reactive protein, or CRP, appeared to be associated with reduced CYP2C19 activity. Inflammation may therefore alter how the body processes voriconazole, even when genetic testing suggests that metabolism should be normal.
This is one reason why a genetic result cannot replace therapeutic drug monitoring. Blood tests can show whether enough voriconazole is present to be effective without reaching unnecessarily high concentrations.
The report does not mean that people with inflammation should automatically receive higher doses. It describes one patient, and dose changes must be guided by clinical review and blood-level monitoring.
Read the case report on PubMed
What does this mean for patients?
The papers published this week reinforce several practical points:
- New or worsening symptoms during CPA may need investigation for complications rather than being assumed to represent simple treatment failure.
- CT findings can provide important clues in ABPA, especially when thick mucus blocks widened airways.
- Genetic testing is unlikely to give a complete answer about susceptibility to aspergillosis.
- Resistance to new antifungals must be monitored as these drugs enter clinical use.
- Voriconazole doses cannot always be predicted accurately from genetics alone, which is why therapeutic drug monitoring is so valuable.
As usual, these studies add to our understanding but do not replace individual medical assessment. Decisions about antifungal treatment, drainage procedures or drug doses should be made by the clinical team caring for the patient.
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