Diagnostic Value of the Serum Galactomannan and (1, 3)-β-D-glucan Assays for Invasive Pulmonary Aspergillosis in Non-neutropenic Patients

Abstract

Objective Galactomannan (GM) and (1, 3)-β-D-glucan (BG) are considered useful seromarkers for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with neutropenia. However, there is still limited data on these seromarkers for testing non-neutropenic patients who are at the risk of IPA. The aim of this study was to evaluate the value of these two serum antigen assays for the early diagnosis of IPA in patients without neutropenia. Methods Between January 2011 and December 2012, 97 patients with suspected IPA admitted to the department of respiratory diseases and the respiratory intensive care unit were prospectively monitored. Serum GM and BG assays were performed before the patients received antifungal therapy. Results Patients were classified as proven IPA (n=11), probable IPA (n=16), possible IPA (n=4), or non-IPA (n=66). The most common underlying disease of patients with IPA was chronic obstructive pulmonary disease (18.5%), and 22.2% patients with IPA had no known diseases. The sensitivities, specificities, and positive and negative predictive values of the GM and BG assays and at least one positive on both assays were 40.7%/89.4%/61.1%/78.7%, 48.1%/78.8%/48.1%/78.8%, and 70.4%/75.8%/54.3%/86.2%, respectively. Conclusion Compared with the testing of neutropenic patients, the serum GM or BG assay alone was less useful for the diagnosis of IPA in non-neutropenic patients. However, at least one positive result of the two serum assays appeared to be useful in the diagnosis of IPA in non-neutropenic patients.

Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis with Nonneutropenic Patients

“…With the in-depth studies, hematologic diseases [ 9 , 17 ], COPD [ 18 ], liver cirrhosis [ 19 ], and intensive care unit patients [ 20 ] are also susceptible individuals. Furthermore, in recent researches [ 4 , 5 ], organ failure, pulmonary tuberculosis, bronchiectasis, and diabetes patients and even those with no underlying diseases can be infected by Aspergillus , which is similar to our study. Notably, in our small sample, 29.0% of 31 probable/possible IPA patients were void of underlying diseases.…”

“…In recent years, critically ill patients with COPD [ 2 ] and patients with cirrhosis [ 13 ] were also host factors. Moreover, diabetes mellitus, rheumatologic disease, and bronchiectasis had been reported as the underlying diseases for IPA [ 4 ]. Patients with above diseases were considered as host factors, except for neutropenic patients.…”

“…However, recent studies reported neutropenia was absent in a number of IPA patients [ 4 , 5 ]. In nonneutropenic patients, chronic obstructive pulmonary disease (COPD) was the most common underlying disease [ 4 ]. Besides, 19.2%–22.2% patients with IPA had no diseases, whose fatality rate was as high as 33.3% to 39%.…”

A Mortality Prediction Rule for Hematology Patients with Invasive Aspergillosis Based on Serum Galactomannan Kinetics

“…Besides, clearance of sGM occurs through several mechanisms, including elimination via neutrophils, hepatic uptake through macrophages (Kuppfer cells), and renal clearance [14]. Furthermore, the class-specific mechanism of action of the different antifungal drugs could also alter the release of GM (e.g., echinocandins induce cell wall lysis), whereas all mold active agents interfere with the test performance [8,15]. This demonstrates a complex interplay between sGM levels, fungal burden, antifungal therapy, and several host factors such as neutropenia and comorbidities.…”

The role of galactomannan testing to diagnose invasive pulmonary aspergillosis in critically ill patients

“…Finally, the combination of several biomarkers could provide an even more accurate diagnostic approach to identify IPA in such patients. [1][2][3]-β-D-glucan offered similar diagnostic accuracy as serum GM in two different studies, but lower accuracy than the GM BAL detection (25,26) and cannot be considered as a valuable alternative in this setting. Although promising, PCR techniques showed only moderate diagnostic accuracy when used as screening tests for IPA in high-risk patients and could be integrated in a diagnostic algorithm to exclude the diagnosis of IPA only when repeated at least twice, as a single PCR test may have around 20% of missed diagnosis (27).…”