Clinical evaluation of droplet digital PCR in suspected invasive pulmonary aspergillosis.

Invasive pulmonary aspergillosis (IPA), the most common fungal infection, is associated with high mortality of affected patients. Traditional diagnostic methods exhibit limited sensitivity and specificity, raising big challenges for precise management of the patients. There is thus an urgent need to find out a timely and accurate diagnostic method in clinical practice. In this study, 163 patients suspected with IPA were enrolled. The medical data of the patients were retrieved from hospital information system. The 158 patients with complete data were classified into an IPA group with 122 cases (58 putative IPA, 19 probable IPA, and 45 possible IPA cases) and a non-IPA group with 36 cases. Cell-free DNA (cfDNA) of bronchoalveolar lavage fluid (BALF) or plasma samples was detected via a droplet digital PCR (ddPCR) assay targeting Aspergillus spp. Overall, this ddPCR assay demonstrated a higher sensitivity of 50.8 % for IPA diagnosis, compared with that of fungal culture (44.3 %) and smear test (10.7 %). Moreover, its sensitivity was higher in the IPA group (73.1 %) and putative IPA subgroup (88.2 %) when using BALF samples, compared with those using plasma samples (P < 0.01). It achieved a high specificity of 94.4 % for IPA diagnosis, with significant variations in cfDNA copy numbers across the subgroups (P < 0.05). In addition, the ddPCR results were associated with the prognosis of the patients at the discharge (P < 0.05). In conclusion, ddPCR assay demonstrated a good performance for IPA diagnosis when using BALF samples, especially for putative IPA. The ddPCR results could be integrated with clinical data to improve prognostic prediction.