Evaluation of Galactomannan Testing, the Aspergillus-Specific Lateral-Flow Device Test and Levels of Cytokines in Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis

Abstract

Background: Diagnosis of chronic pulmonary aspergillosis (CPA) is challenging. Symptoms are unspecific or missing, radiological findings are variable and proof of mycological evidence is limited by the accuracy of diagnostic tests. The goal of this study was to investigate diagnostic performance of galactomannan (GM), the newly formatted Aspergillus-specific lateral-flow-device test (LFD), and a number of cytokines in bronchoalveolar lavage fluid (BALF) samples obtained from patients with CPA, patients with respiratory disorders without CPA and healthy individuals.Methods: Patients with CPA (n = 27) and controls (n = 27 with underlying respiratory diseases but without CPA, and n = 27 healthy volunteers) were recruited at the Medical University of Graz, Austria and the Research Center Borstel, Germany between 2010 and 2018. GM, LFD and cytokine testing was performed retrospectively at the Research Center Borstel.Results: Sensitivity and specificity of GM testing from BALF with a cut off level of ≥0.5 optical density index (ODI) was 41 and 100% and 30 and 100% with a cut off level of ≥1.0 ODI. ROC curve analysis showed an AUC 0.718 (95% CI 0.581–0.855) for GM for differentiating CPA patients to patients with other respiratory diseases without CPA. The LFD resulted positive in only three patients with CPA (7%) and was highly specific. CPA patients did not differ significantly in the BALF cytokine profile compared to patients with respiratory disorders without CPA, but showed significant higher values for IFN-γ, IL-1b, IL-6, IL-8, and TNF-α compared to healthy individuals.Conclusion: Both GM and LFD showed insufficient performance for diagnosing CPA, with sensitivities of BALF GM below 50%, and sensitivity of the LFD below 10%. The high specificities may, however, result in a high positive predictive value and thereby help to identify semi-invasive or invasive disease.

Galactomannan detection in bronchoalveolar lavage fluids: A diagnostic approach for fungus ball in patients with pulmonary tuberculosis?

“…In this present study, the statistical analysis of the sensitivity, specificity, PPV, NPV, correlation coefficient, likelihood ratios and AUC for GM detection (index ≥ 0.5) in BAL samples from old PTB patients with fungus ball also showed a significant correlation. Several previous studies 9,25–27 have reported a range of 41%‐100% of sensitivity and 76.3%‐100% of specificity for the detection of GM (index ≥ 0.5) in BAL samples of patients with CPA including aspergilloma which were relatively consistent with the results of the present study. It is worth noting that a new Aspergillus GM lateral flow assay (LFA) on BAL samples has recently shown a considerable sensitivity and specificity for the diagnosis of invasive pulmonary aspergillosis in non‐neutropenic patients 28,29 .…”

Efficiency of A fumigatus‐specific IgG and galactomannan testing in the diagnosis of simple aspergilloma

“…Serum and BALF‐GM are other frequently used investigations for diagnosing CPA . In a previous study, we have shown that serum and BALF‐GM at a cut‐off value of 0.55 and 1.4, respectively, provided the best sensitivity and specificity in diagnosing CPA .…”

“…But this study included only six subjects (2 each with IA, SAIA and SA) . In a recent study, the sensitivity and specificity of BALF‐GM at ODI of 0.5 for the diagnosis of CPA were 41 and 100%, respectively . However, the study included only six subjects with SA.…”

“…21 Serum and BALF-GM are other frequently used investigations for diagnosing CPA. 6,[9][10][11][22][23][24][25] In a previous study, we have shown that serum and BALF-GM at a cut-off value of 0.55 and 1.4, respectively, provided the best sensitivity and specificity in diagnosing CPA. 6 The values of serum and BALF-GM for diagnosing SA were also different in this study, as CPA is minimally invasive compared to acute or subacute invasive pulmonary aspergillosis.…”

“…10 In a recent study, the sensitivity and specificity of BALF-GM at ODI of 0.5 for the diagnosis of CPA were 41 and 100%, respectively. 25 However, the study included only six subjects with SA. Sputum culture may be of use in susceptibility testing, which is of value in chronic infections like CPA.…”