Metagenomic Next-Generation Sequencing for Pulmonary Fungal Infection Diagnosis: Lung Biopsy versus Bronchoalveolar Lavage Fluid

Purpose: Metagenomic next-generation sequencing (mNGS) is widely used for pulmonary infection; nonetheless, the experience from its clinical use in diagnosing pulmonary fungal infections is sparse. This study aimed to compare mNGS results from lung biopsy and bronchoalveolar lavage fluid (BALF) and determine their clinical diagnostic efficacy. Patients and Methods: A total of 106 patients with suspected pulmonary fungal infection from May 2018 to January 2020 were included in this retrospective study. All patients' lung biopsy and BALF specimens were collected through bronchoscopy. Overall, 45 (42.5%) patients had pulmonary fungal infection. The performance of lung biopsy and BALF used for mNGS in diagnosing pulmonary fungal infections and identifying pathogens was compared. Additionally, mNGS was compared with conventional tests (pathology, galactomannan test, and cultures) with respect to the diagnosis of pulmonary fungal infections. Results: Lung biopsy-mNGS and BALF-mNGS exhibited no difference in terms of sensitivity (80.0% vs 84.4%, P=0.754) and specificity (91.8% vs 85.3%, P=0.39). Additionally, there was no difference in specificity between mNGS and conventional tests; however, the sensitivity of mNGS (lung biopsy, BALF) in diagnosing pulmonary fungal infections was significantly higher than that of conventional tests (conventional tests vs biopsy-mNGS: 44.4% vs 80.0%, P<0.05; conventional tests vs BALF-mNGS: 44.4% vs 84.4%, P<0.05). Among 32 patients with positive mNGS results for both biopsy and BALF specimens, 23 (71.9%) cases of consistency between the two tests for the detected fungi and nine (28.1%) cases of a partial match were identified. Receiver operating curve analysis revealed that the area under the curve for the combination of biopsy and BALF was significantly higher than that for BALF-mNGS (P=0.018). Conclusion: We recommend biopsy-based or BALF-based mNGS for diagnosing pulmonary fungal infections because of their diagnostic advantages over conventional tests. The combination of biopsy and BALF for mNGS can be considered when higher diagnostic efficacy is required.