Diagnosing aspergillus infection in human lung fluid to enable early intervention

Magda Swedrowska


Early identification of pulmonary fungal infection is critical to effective treatment. Delayed in therapy increases overall mortality, making early diagnosis essential. European Organisation for Research and Treatment of Cancer/ Invasive Fungal Infections Cooperative Group defines invasive aspergillus in terms of mycological diagnosis through positive microscopy, culture, histopathology, detection of galactomannan in plasma, serum, bronchoalveolar lavage (BAL) fluid or cerebral spinal fluid and detection of (1,3)-β-d-glucan in serum. These diagnostic tools have several limitations in terms of being time consuming, expensive, expressing low sensitivity and specificity. Thus, Aspergillus Lateral Flow Device (AspLFD) was developed for point-of-care diagnosis of invasive aspergillus consisting of a single-test, self-contained immuno-chromatographic assay. However, the lateral flow device was initially validated using PBS, as BAL samples are difficult to obtain, even from healthy patients. A synthetic simulated lung fluid (SLF) with composition similar to respiratory tract lining fluid obtained from the alveolar region of healthy subjects was used as a PBS / BAL fluid substitute. The study aims to assess the performance of AspLFD in SLF samples as a biorelevant model for validate the diagnostic technology. Various concentration of Aspergillus antigen in phosphate buffered saline (PBS) and SLF were tested using AspLFD. The detection limit of AspLFD was found by testing for antigen in PBS. The minimum concentration of Aspergillus antigen that AspLFD can detect in PBS was 40 ng/mL All concentrations in SLF gave negative results. When EDTA was added to SLF, Aspergillus antigen concentration of 0 and 10 ng/mL gave false positive results, while intermediate concentrations gave false negative results. Further investigations are required using BAL samples to develop a reliable method for processing lung fluid samples to allow detection of the Aspergillus antigen.     

Key Message

Early diagnosis and identification of fungal lung infections will allow better treatment and may indicate a patient population for which inhaled antifungal medication would be beneficial

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