gms | German Medical Science

Background: Early diagnosis and prompt initiation of antifungal therapy increases survival of patients (pts) with invasive aspergillosis (IA). New strategies for diagnosis and management of IA include the use of non-invasive biomarkers [i.e.: galactomannan (GM) and 1,3 beta-d-glucan (1,3BDG)]. The role of serum and bronchoalveolar lavage (BAL) GM for the diagnosis of IA has been best established in pts with hematologic malignancies (HEM). Conversely, these biomarkers have significant variation in performance in other patient populations at risk for IA, such as solid organ recipients (SOT). Moreover, factors such as cost and outsourcing to reference labs limits testing frequency and timely result availability. Aspergillus immuno-chromatographic lateral-flow device (LFD) is a novel technique that uses an Aspergillus-specific monoclonal antibody (MAb JF5) for the point of care diagnosis of IA [1]. LFD is a rapid, simple and inexpensive test that may overcome the limitations of current diagnostic tests.

Objective: We sought to determine the utility of the LFD using BAL for the diagnosis of pulmonary IA in pts at high risk (HR) of IA within the Henry Ford Health System (HFHS). Secondly, we compared the performance of LFD to that of GM.

Material and Methods: We prospectively collected all BAL specimens obtained from bronchoscopies performed at HFHS from 1/2013 to 5/2013. Clinical information regarding risk factors and diagnostic criteria for IA was collected by retrospective chart review. Pts were classified as HR for IA according to the European Organization for Research and Treatment of Cancer /Mycoses Study Group 2008 guidelines. Pts were classified based on their underlying risk factor for IA into HEM group and non-HEM groups. The non-HEM included SOT recipients [further subdivided into Lung transplant (LungTx) and non-Lung SOT]; chronic steroid use (CSU); solid tumor (STU) and others. We compared the diagnostic performance of LFD and GM in BAL fluid from pts at HR for IA. BAL-LFD results were blindly analyzed by one of the investigators in this study.

Results: BAL samples from 311 pts were collected during the study period. Of these 96 pts were identified at HR for IA. Only 3 pts met the criteria for IA (2 probable; 1 possible IA). Mean patient age was 61 years (range: 35-81), 59 were female. Most pts 89/96 (93%) were in the non-HEM groups: SOT 57 (LungTx, 46, non-Lung SOT, 11); CSU 21; STU 6, other 5. Overall sensitivity (SS) and specificity (SP) of GM was 66% and 74%, respectively. SS of LFD 33% and SP was 95.6%. Test performance was similar for LFD and GM in the HEM group (SS 100% for both and SP 83% vs.100%, respectively). However, LFD showed a better performance than GM in the non-HEM groups, particularly in the SOT group (p 0.002). False-positive GM results were more frequent in the SOT group (29/57 pts; 50.8%), especially among Lung TX pts (26/46 pts; 56.5%). False-positive GM results were associated with lower OD index values (average 1.49; range: 0.5-7.18) compared to true-positive results (average: 5.86; range 4.02-7.7). Using a GM OD index ≥1.0 improved the SP compared to GM OD index ≥0.5 (74% vs. 52%). Conversely, LFD performance was superior with an overall SP of 95.6%, particularly among SOT pts and Lung Tx pts (p<0.002 and 0.0007, respectively). Results are summarized in Table 1 [Tab. 1].

Conclusions: This is the first report of the comparative performance of LFD and GM done on BAL obtained from a large group pts at risk for IA. Specificity of LFD was superior to GM, particularly among non-HEM patients. A high rate of false-positive results using GM was seen in SOT patients, particularly in LungTx recipients. Based on these preliminary results, LFD is a promising tool for the diagnosis of IA. LFD is a rapid, simple and cheap test performed on BAL that could help to rule out pulmonary IA in high-risk population, particularly LungTx recipients. More studies are needed to further determine the role of LFD in patients suspected diagnosis of IA.