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Published on: March 22, 2012
Concordance of Noninvasive Plasma Cell-free DNA With Invasive Diagnostics for Diagnosis of Invasive Fungal Disease
Anthony Lieu1,2,3, Alex N Zimmet1, Joseph Pozdol4
1Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, USA.
Background:
Mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) is a promising noninvasive diagnostic modality for early diagnosis of invasive mold disease (IMD) in immunocompromised patients. Although mold cfDNA PCR has been shown to be highly accurate, the value of invasive procedures to collect specimens for conventional fungal diagnostics following plasma cfDNA testing remains unclear.
Methods:
This retrospective single-center cohort study included patients with mold plasma cfDNA PCR performed 7 days before or 2 days after invasive specimen collection. Mold PCR detected Aspergillus species, Mucorales agents, Fusarium species, and Scedosporium species. Invasive procedures included tissue biopsy and bronchoscopy. The primary endpoint was the concordance of mold plasma cfDNA PCR results with results of conventional fungal tests performed on tissue and bronchoalveolar lavage fluid.
Results:
Five hundred and six patients with mold plasma cfDNA PCR resulting ahead of invasive specimen (123 tissue and 426 bronchoalveolar lavage fluid) results were included, and 437 (86.4%) were immunocompromised. After adjudicating discordant results based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium definitions for IMD, mold plasma cfDNA PCR and invasive test results were 88.5% (448/506) concordant. In proven cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results occurred in patients with fungal sinusitis (8) and limb infection (3). Nonhematologic malignancy and nonneutropenic state were statistically associated with negative mold plasma cfDNA PCR in patients with proven or probable IMD.
Conclusions:
Noninvasive mold plasma cfDNA PCR results were highly concordant with invasive specimen fungal test results, indicating risk-prone invasive specimen collection can be safely curtailed in immunocompromised patients with suspected IMD.
Insights
Noninvasive mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) testing shows high accuracy for diagnosing invasive mold disease (IMD). This suggests that invasive specimen collection can be reduced in immunocompromised patients.
Area of Science:
- Mycology
- Infectious Diseases
- Molecular Diagnostics
Background:
- Invasive mold disease (IMD) diagnosis in immunocompromised patients often relies on invasive procedures.
- Mold plasma cell-free DNA (cfDNA) polymerase chain reaction (PCR) offers a promising noninvasive alternative for early IMD detection.
- The clinical utility of invasive specimen collection after plasma cfDNA PCR testing remains uncertain.
Purpose of the Study:
- To evaluate the concordance between mold plasma cfDNA PCR results and conventional fungal diagnostic tests from invasive specimens.
- To determine if invasive procedures can be safely reduced following noninvasive cfDNA PCR testing.
Main Methods:
- Retrospective cohort study of 506 patients with mold plasma cfDNA PCR performed around the time of invasive specimen collection.
- Invasive procedures included tissue biopsy and bronchoscopy.
- Concordance was assessed between mold plasma cfDNA PCR and fungal tests on tissue/bronchoalveolar lavage fluid, adjudicated by EORTC/MSC guidelines.
Main Results:
- Overall concordance between mold plasma cfDNA PCR and invasive tests was 88.5% (448/506).
- In proven IMD cases, 64.7% (11/17) of negative mold plasma cfDNA PCR results were observed in patients with fungal sinusitis or limb infections.
- Nonhematologic malignancy and nonneutropenic status were linked to negative mold plasma cfDNA PCR in proven/probable IMD.
Conclusions:
- Noninvasive mold plasma cfDNA PCR demonstrates high concordance with results from invasive fungal diagnostic tests.
- These findings support curtailing high-risk invasive specimen collection in immunocompromised patients suspected of IMD.
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