Key points
- CPA diagnosis remains challenging because symptoms and radiology overlap with tuberculosis, non-tuberculous mycobacterial disease, bronchiectasis, chronic obstructive pulmonary disease, malignancy and other chronic lung disorders.
- Aspergillus immunoglobulin G (IgG) testing is a cornerstone of CPA diagnosis, but performance varies between assays.
- Cut-off selection affects sensitivity and specificity, with important consequences for both missed CPA and overdiagnosis.
- Confirmatory or complementary testing, such as Western blot in selected situations, may help clarify difficult or borderline cases.
- The paper is directly relevant to specialist respiratory, infectious diseases and mycology services because diagnostic reliability affects referral pathways, antifungal prescribing and case definition.
The paper
Bigot J, Gibert C, Millet N, et al. Aspergillus serology for chronic pulmonary aspergillosis diagnosis: optimization of an enzyme-linked immunosorbent assay kit and assessment of a Western blot kit performance. Journal of Clinical Microbiology. Published 28 May 2026. doi:10.1128/jcm.00182-26.
Why this paper matters
CPA is a progressive and potentially fatal chronic lung infection that usually occurs in patients with underlying structural lung damage. Diagnosis depends on combining clinical symptoms, characteristic radiology and evidence of Aspergillus infection or immune response.
In practice, Aspergillus serology is often the decisive test. A positive Aspergillus IgG result can support the diagnosis when imaging and symptoms are compatible. A negative result can reduce diagnostic probability. But serology is not absolute. Different assays use different antigen preparations, platforms and reporting units. This means that results from one laboratory may not be directly comparable with results from another.
This paper is therefore important because it addresses a real-world diagnostic problem: how to optimise Aspergillus serological testing so that it performs reliably in the diagnosis of CPA.
Clinical background: why CPA serology is difficult
CPA often develops in patients with structurally abnormal lungs. Common underlying conditions include previous pulmonary tuberculosis, non-tuberculous mycobacterial infection, chronic obstructive pulmonary disease, bronchiectasis, sarcoidosis, prior lung surgery and other cavitary lung diseases.
These same conditions can also cause chronic symptoms and abnormal imaging without CPA. This creates a diagnostic grey zone. Patients may have cavities, pleural thickening, fibrosis, bronchiectasis, chronic cough, haemoptysis or weight loss for reasons other than Aspergillus disease.
Aspergillus IgG testing is therefore valuable because it provides evidence of an immune response to Aspergillus. However, it must be interpreted in context. A positive result does not, by itself, prove active CPA. A negative result does not always fully exclude CPA, particularly if clinical suspicion remains high.
What the study evaluates
The paper evaluates two related aspects of CPA serology:
- Optimisation of an enzyme-linked immunosorbent assay (ELISA) kit for Aspergillus serology in CPA diagnosis.
- Assessment of Western blot kit performance, potentially as a complementary or confirmatory approach.
This is clinically relevant because ELISA-based Aspergillus IgG testing is widely used in diagnostic pathways, while Western blot may offer additional qualitative information in selected cases. The practical question is whether assay optimisation and confirmatory testing improve diagnostic performance enough to change specialist practice.
Why assay cut-offs matter
The choice of diagnostic cut-off is not a technical detail; it changes clinical classification.
| Cut-off strategy | Likely effect | Clinical risk |
|---|---|---|
| Lower cut-off | Higher sensitivity | More false positives and possible overdiagnosis |
| Higher cut-off | Higher specificity | More false negatives and missed CPA |
| Population-specific cut-off | Potentially better clinical performance | May reduce comparability between centres |
| Single universal cut-off | Simpler implementation | May perform poorly across different populations |
In a specialist CPA service, false negatives may delay antifungal treatment and referral. False positives may lead to unnecessary anxiety, additional imaging, prolonged antifungal therapy and avoidable toxicity. The correct balance depends on the clinical setting, disease prevalence and consequences of diagnostic error.
Where Western blot may fit
Western blot testing may be useful where ELISA results are borderline, discordant with imaging, or difficult to interpret in patients with complex lung disease. It may also be useful as a complementary method in diagnostic algorithms, depending on availability and validated performance.
However, Western blot should not be seen as a simple replacement for ELISA. Its value depends on whether it adds diagnostic clarity beyond standard serology, whether it is reproducible between laboratories, and whether clinicians know how to act on the result.
Clinical interpretation: serology is supportive, not standalone
For specialists, the key principle remains:
Aspergillus serology supports the diagnosis of CPA but does not diagnose CPA in isolation.
A robust CPA diagnosis requires integration of:
- compatible symptoms, usually chronic cough, weight loss, fatigue, breathlessness or haemoptysis;
- compatible imaging, particularly cavities, pleural thickening, pericavitary infiltrates, fungal ball, nodules or progressive fibrosis;
- mycological or immunological evidence, especially Aspergillus IgG;
- exclusion or recognition of alternative and co-existing diagnoses, including active tuberculosis, non-tuberculous mycobacterial disease, malignancy and bacterial bronchiectasis.
Implications for specialist services
This paper supports the need for carefully governed CPA serology pathways. Specialist centres and diagnostic laboratories should consider:
- which Aspergillus IgG assay is used locally;
- what cut-off is applied and how it was validated;
- whether borderline zones should be reported rather than simple positive/negative categories;
- how results are interpreted in high-risk structural lung disease populations;
- whether confirmatory testing is available for selected cases;
- how serology is integrated with CT findings and microbiology;
- whether local reports include interpretive comments to reduce misuse.
Suggested diagnostic reporting approach
Rather than reporting Aspergillus serology as a binary answer, laboratories and specialist services may benefit from a more interpretive model:
| Result category | Possible interpretation | Suggested action |
|---|---|---|
| Clearly negative | CPA less likely, but not impossible if clinical suspicion is high | Review imaging and alternative diagnoses; repeat if disease evolves |
| Borderline or low positive | Uncertain significance | Correlate with CT, symptoms, cultures and prior results; consider repeat or confirmatory testing |
| Clearly positive | Supports CPA in the right clinical/radiological context | Assess full CPA criteria and consider specialist referral or treatment discussion |
| Discordant result | Serology conflicts with clinical picture | Reassess diagnosis, assay limitations and possibility of co-existing disease |
Relevance to post-tuberculosis lung disease
This paper is particularly relevant when considered alongside recent evidence that CPA may be detected during or soon after pulmonary tuberculosis treatment. In post-tuberculosis lung disease, cavities and chronic radiological abnormalities are common, but not all symptoms are due to active TB or permanent scarring.
Reliable Aspergillus serology is therefore essential. If the assay cut-off is poorly calibrated, clinicians may either miss CPA in symptomatic patients with cavities or overdiagnose CPA in patients with structural lung damage but no active Aspergillus disease.
Relevance to bronchiectasis and non-tuberculous mycobacterial disease
Patients with bronchiectasis or non-tuberculous mycobacterial lung disease may also have chronic symptoms, mucus production, recurrent infection, radiological change and occasional Aspergillus isolation. Aspergillus serology can be useful in identifying CPA, but positive results must be interpreted carefully because these patients often have complex chronic airway disease.
For this group, assay performance and cut-off choice may substantially affect diagnostic confidence.
Implications for antifungal stewardship
Improved CPA serology has direct stewardship implications. Antifungal treatment for CPA is often prolonged and requires monitoring for toxicity, drug interactions and therapeutic drug levels. Overdiagnosis can expose patients to unnecessary azoles. Underdiagnosis can allow progressive cavitary disease, haemoptysis and loss of lung function.
More reliable serological testing can therefore support both earlier treatment in true CPA and avoidance of unnecessary therapy in patients who do not meet diagnostic criteria.
Evidence strength
| Question | Evidence strength | Comment |
|---|---|---|
| Is Aspergillus IgG central to CPA diagnosis? | Strong | Recognised in major CPA diagnostic guidance |
| Do different assays and cut-offs affect performance? | Strong | Well-recognised practical issue in CPA serology |
| Can assay optimisation improve diagnostic classification? | Likely | This paper directly addresses optimisation, but local validation remains important |
| Should Western blot replace ELISA? | Not established | More likely to be complementary or confirmatory in selected cases |
| Should serology alone determine CPA treatment? | No | Must be interpreted with symptoms, imaging and microbiology |
Practical take-home messages for specialists
- Know which Aspergillus IgG assay your laboratory uses.
- Know the cut-off and whether it has been validated for CPA.
- Be cautious with borderline results.
- Do not diagnose CPA on serology alone.
- Do not dismiss CPA solely because one serological test is negative if the clinical and CT picture is highly suggestive.
- Consider repeat or complementary testing when results are discordant.
- Integrate serology with CT, symptoms, sputum fungal culture/PCR and assessment for tuberculosis or non-tuberculous mycobacteria.
Conclusion
This paper is a timely reminder that CPA diagnosis depends not only on whether Aspergillus serology is performed, but on how well the assay is optimised, how cut-offs are selected and how results are interpreted. For specialist services, improved serology can strengthen diagnostic confidence, support earlier recognition of CPA and reduce unnecessary antifungal treatment.
The broader implication is clear: CPA diagnostic pathways need standardised, validated and clinically interpreted Aspergillus serology, not isolated positive or negative blood test results.
References
- Bigot J, Gibert C, Millet N, et al. Aspergillus serology for chronic pulmonary aspergillosis diagnosis: optimization of an enzyme-linked immunosorbent assay kit and assessment of a Western blot kit performance.
Journal of Clinical Microbiology. Published 28 May 2026.
doi:10.1128/jcm.00182-26.
PubMed - Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management.
European Respiratory Journal. 2016;47(1):45-68.
doi:10.1183/13993003.00583-2015.
PubMed - Patterson TF, Thompson GR, Denning DW, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America.
Clinical Infectious Diseases. 2016;63(4):e1-e60.
doi:10.1093/cid/ciw326.
PubMed
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