Validation of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for diagnosis of suspected pulmonary infections in patients with systemic autoimmune rheumatic diseases receiving immunosuppressant therapy

Sichun Wen; Siqi Peng; Xuejiao Hu; Nan Jiang; Bohou Li; Boxi Chen; Shuting Deng; Ye Yuan; Qiong Wu; Yiming Tao; Jianchao Ma; Sijia Li; Ting Lin; Feng Wen; Zhuo Li; Renwei Huang; Zhonglin Feng; Chaosheng He; Wenjian Wang; Xinling Liang; Wei Shi; Lixia Xu; Shuangxin Liu

doi:10.3389/fmed.2023.1161661

Validation of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for diagnosis of suspected pulmonary infections in patients with systemic autoimmune rheumatic diseases receiving immunosuppressant therapy

Front Med (Lausanne). 2023 Jul 6:10:1161661. doi: 10.3389/fmed.2023.1161661. eCollection 2023.

Authors

Sichun Wen^{1

2}, Siqi Peng^{2

3}, Xuejiao Hu⁴, Nan Jiang², Bohou Li², Boxi Chen², Shuting Deng², Ye Yuan², Qiong Wu², Yiming Tao², Jianchao Ma², Sijia Li², Ting Lin², Feng Wen², Zhuo Li², Renwei Huang², Zhonglin Feng², Chaosheng He², Wenjian Wang², Xinling Liang², Wei Shi², Lixia Xu², Shuangxin Liu^{1

2

3}

Affiliations

¹ School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
² Department of Nephrology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
³ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
⁴ Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

Abstract

Background: The accuracy and sensitivity of conventional microbiological tests (CMTs) are insufficient to identify opportunistic pathogens in patients with systemic autoimmune rheumatic diseases (SARDs). The study aimed to assess the usefulness of metagenomic next-generation sequencing (mNGS) vs. CMTs for the diagnosis of pulmonary infections in patients with SARDs receiving immunosuppressant therapy.

Methods: The medical records of 40 patients with pulmonary infections and SARDs treated with immunosuppressants or corticosteroids were reviewed retrospectively. Bronchoalveolar lavage fluid (BALF) samples were collected from all patients and examined by mNGS and CMTs. Diagnostic values of the CMTs and mNGS were compared with the clinical composite diagnosis as the reference standard.

Results: Of the 40 patients included for analysis, 37 (92.5%) were diagnosed with pulmonary infections and 3 (7.5%) with non-infectious diseases, of which two were considered primary diseases and one an asthma attack. In total, 15 pathogens (7 bacteria, 5 fungi, and 3 viruses) were detected by CMTs as compared to 58 (36 bacteria, 12 fungi, and 10 viruses) by mNGS. Diagnostic accuracy of mNGS was superior to that of the CMTs for the detection of co-infections with bacteria and fungi (95 vs. 53%, respectively, p < 0.01), and for the detection of single infections with fungi (97.5 vs. 55%, respectively, p < 0.01). Of the 31 patients diagnosed with co-infections, 4 (12.9%) were positive for two pathogens and 27 (87.1%) for three or more. The detection rate of co-infection was significantly higher for mNGS than CMTs (95 vs. 16%, respectively, p < 0.01).

Conclusion: The accuracy of mNGS was superior to that of the CMTs for the diagnosis of pulmonary infections in patients with SARDs treated with immunosuppressants. The rapid diagnosis by mNGS can ensure timely adjustment of treatment regimens to improve diagnosis and outcomes.

Keywords: antibiotics; bronchoalveolar lavage fluid; immunosuppressants; metagenomic next-generation sequencing; pulmonary infection; systemic autoimmune rheumatic diseases.