Diagnostic cut‐off value for Aspergillus fumigatus‐ and flavus‐specific IgG with clinical relevance in chronic pulmonary Aspergillus infection: A pilot study in Taiwan

Abstract

Background The diagnostic cut‐off value for chronic pulmonary Aspergillosis (CPA) by Aspergillus fumigatus‐specific IgG has never been evaluated In Taiwan. The cut‐off value for Aspergillus flavus‐specific IgG has not been evaluated worldwide. Objectives Evaluate diagnostic cut‐off value of Aspergillus IgG and its application characteristics. Patients/Methods Blood from control groups and treatment‐naïve patients with CPA infections was collected for Aspergillus‐specific IgG measurements. Controls were patients who had chest radiographic abnormalities and signs of respiratory tract infection, but were negative for Aspergillus and resolved without anti‐mould therapy. Confirmation and probability of CPA were defined according to radiological features and positivity for an Aspergillus or galactomannan index. Chest computer tomography patterns were recorded for the presence of aspergilloma or nodules, subacute invasive aspergillosis, chronic cavitary pulmonary aspergillosis and chronic fibrotic pulmonary aspergillosis. Results A total of 35 cases and 50 disease controls were included. The levels of A. fumigatus‐ and A. flavus‐specific IgG correlated with CPA progression (P < .05) but not with the presence of Aspergillus species from clinical specimens (P > .05). The best cut‐off value for A. fumigatus IgG was 21.7 mg/L with area under curve (AUC) for receiver operating characteristic curve (ROC) 0.934 and had 85.7% sensitivity and 92.0% specificity. For A. flavus IgG, the best cut‐off value was 22.1 mgA/L and the AUC was 0.928 with 88.2% sensitivity and 94.1% specificity. Conclusion The level of Aspergillus‐specific IgG correlated with radiographic characteristics in patients with CPA and the best cut‐off values compared to controls were 21.7 mgA/L for A. fumigatus‐specific IgG and 22.1 mgA/L for A. flavus‐specific IgG.

Establishing Aspergillus-Specific IgG Cut-Off Level for Chronic Pulmonary Aspergillosis Diagnosis: Multicenter Prospective Cohort Study

“…Among them, ImmunoCap Asp-IgG is one of the most commonly used kits with good performance. For ImmunoCap Asp-IgG, different cut-off points have been proposed, ranging from 20 to 50 mgA/L [13][14][15][16]. Table 2 summarizes previous reports and the performance of their proposed cut-off points in original and current study.…”

“…This raises concerns whether Asp-IgG could be used for diagnosing CPA in this setting and an optimal cut-off level is also not readily available. Furthermore, previous studies determining the cut-off level of Asp-IgG were mainly conducted with retrospective design, using cases from CPA databases and healthy control [13][14][15][16]. Prospective studies in a real-world clinical setting were scant and multicenter recruitment as well as validation was also lacking.…”

Chronic Pulmonary Aspergillosis: Disease Severity Using Image Analysis and Correlation with Systemic Proinflammation and Predictors of Clinical Outcome

“…In CCPA, the Th2 response is the main immune reaction, and the cytokines IL4, IL5, IL-15, TNF-α, and IL-10 were increased in peripheral blood [27]. One study showed that IL-1B in peripheral blood was associated with disease activity in CPA, and disease activity was evaluated by visual methods and by changes in the CCPA in chest images [25]. One case series showed that the administration of IFN-γ had a protective role in preventing invasive fungal infection; however, its downstream cytokine expression was not comprehensively evaluated [24].…”

“…Furthermore, lung fibrosis and collagen deposits are usually observed surrounding fungal hyphae [21]. Biomarkers, such as CRP, ESR, fibrinogen [22], TNF-α, IL-6, IL-8 [23], IFN-γ [24], and IL-1B [25], have been correlated with disease activity or treatment response in pulmonary aspergillosis patients.…”

Cytomegalovirus viral interleukin‐10 in patients with Aspergillus infection and effects on clinical outcome

“…CPA was defined according to national guidelines. 21 The cut-off value for Aspergillus fumigatus IgG was applied according to our previous study, 22,23 and Aspergillus niger IgG was determined according to the manufacturer's suggestion. Patients with a blood sample positive for A. fumigatus or A. niger IgG with coexisting abnormal chest imaging findings and clinical symptoms fulfilling the CPA criteria 21 were diagnosed with CPA.…”