Diagnostic Accuracy of PCR Alone Compared to Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis: a Systematic Review

Abstract

f PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed >80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions.

Biomarkers for Invasive Aspergillosis: The Challenges Continue

“…This is rather similar to the results of a second meta-analysis that analyzed studies published between 1993 and 2012 and recorded an overall sensitivity of 77.2% and a specificity of 93.5% [156]. This poor performance and variability is a general characteristic of other PCR assays aimed at diagnosing IA, with one study reporting a complete lack of sensitivity [157], another 33-100%, depending on DNA extraction procedure [158] and others anything around 50-58% [159], 64% (BAL) or 73% (serum) [147], 75% [160], 80% [161,162] or 91% [163].…”

“…There is also heterogeneity in the results of studies that compare the diagnostic performance of PCR to that of GM in BAL: one suggests that they are similar, with PCR being slightly more sensitive [156], another that GM is more sensitive and more specific [79]. Nevertheless, both conclude that positivity for both GM and Aspergillus PCR in BAL is highly suggestive of a pulmonary aspergillosis and that performing both tests results in optimal sensitivity with no loss of specificity [79,156].…”

Evaluation of Risk Factors for Invasive Pulmonary Aspergillosis and Detection of Diagnostic Values of Galactomannan and PCR Methods in Bronchoalveolar Lavage Samples From Non-Neutropenic Intensive Care Unit Patients

“…Reinwald ve arkadaşlarının 31 ça-lışmasında da, immünosüpresif hastalarda duyarlılık ve özgüllük sırasıyla %59 ve %87 olarak saptanmıştır. Bir başka meta-analizde de, GM ve PCR yöntemleri karşılaştırılmış; iki tanısal testin birlikte kullanımıyla, özgüllükte belirgin düşme olmadan duyarlılığın artırı-Nötropenik Olmayan Yoğun Bakım Hastalarında İnvazif Pulmoner Aspergilloz İçin Risk Faktörlerinin Değerlendirilmesi ve Bronkoalveoler Lavaj Örneklerinde Galaktomannan ve PCR Testlerinin Tanısal Değerinin Belirlenmesi labileceği vurgulanmış, ancak PCR yönteminin GM antijen testine tanısal bir üstünlüğü saptanmamıştır 32 . Aspergillus PCR çalışmalarında duyarlılık aralığının değişken olması, yöntemin standardize edilememesinden kaynaklanmaktadır.…”

Antifungal stewardship considerations for adults and pediatrics

“…61,77 In addition, serial positive PCR results are highly indicative of IA, 61,77 and the combination of PCR and BAL GM has been suggested for improved sensitivity without loss of specificity. 78 However, clinical studies are limited by the lack of methodologic standardization and multicenter validation; there are no commercially approved PCR assays to date. 78 One area of interest is whether non-culture-based tests can shift the emphasis away from empiric to preemptive antifungal therapy.…”

“…78 However, clinical studies are limited by the lack of methodologic standardization and multicenter validation; there are no commercially approved PCR assays to date. 78 One area of interest is whether non-culture-based tests can shift the emphasis away from empiric to preemptive antifungal therapy. Maertens et al conducted a feasibility study in which neutropenic patients undergoing myeloablative allogeneic HCT or chemotherapy for acute leukemia or myelodysplastic syndrome (MDS) received fluconazole prophylaxis and were screened daily for the presence of GM via enzyme immunoassay (EIA).…”