Trial Information

Early Diagnosis of Invasive Aspergillosis in a High Risk Group of Patients Using Serum and Bronchoalveolar Lavage Fluid Real Time PCR and Galactomannan ELISA

OBJECTIVES:

Primary

- Determine the test characteristics of galactomannan (GM) ELISA using serum and
bronchoalveolar lavage fluid (BALF) collected from patients at high risk of invasive
fungal infection.

- Determine the test characteristics of aspergillus PCR using blood and BALF samples
collected from these patients.

- Evaluate the role of noninvasive exhaled breath condensate (EBC) in detecting invasive
aspergillosis (IA).

- Determine whether repeated measures over time or a combination of markers improves the
test characteristics.

- Establish cutoff points for the diagnosis of IA.

Secondary

- Determine the inflammatory marker and cytokine profile of EBC in fungal infection and
after bone marrow transplantation as a marker of acute lung injury.

- Assess the role of bronchoscopy with bronchoalveolar lavage in identifying the causal
pathogen early in the disease course of febrile neutropenic patients.

- Assess the role of GM ELISA in prognosis and response to treatment for IA.

- Assess the role of aspergillus PCR in prognosis and response to treatment for IA.

OUTLINE: This is a prospective study.

Patients are assessed for early diagnosis of invasive aspergillosis (IA) using serum and
bronchoalveolar lavage fluid (BALF) evaluated by ELISA for galactomannan (GM) antigen and
real time PCR for fungal DNA. Serum samples are collected at baseline and periodically
during study, beginning with the onset of neutropenia and continuing until resolution of
fever or recovery of neutrophil count. BALF samples are collected in patients with abnormal
chest radiology evaluated by bronchoscopy and bronchoalveolar lavage. BALF is analyzed for
GM antigen, fungal DNA, inflammatory markers, and cytokines.

Patients are also assessed using exhaled breath condensate (EBC) evaluated by GM ELISA and
real time PCR. EBC is collected at baseline and periodically during study to detect GM
antigen or fungal DNA and to measure markers of pulmonary inflammation and oxidative stress
(e.g., pH, hydrogen peroxide, and leukotriene B4).

PROJECTED ACCRUAL: A total of 200 patients will be accrued for this study.