宏基因组下一代测序（mNGS）在严重风湿性患者的呼吸道病原体检测和临床决策中的有效性仍未被探索。
一项单中心回顾性研究，对58名因疑似肺炎合并急性呼吸衰竭而入住ICU的风湿病患者进行了支气管肺泡灌洗液标本mNGS和微生物联合检测（CMT），以比较其诊断表现。以临床综合诊断为金标准。还审查了基于mNGS结果的治疗修改。
43例患者被诊断为微生物确认的肺炎，15例被认为是非感染性疾病。mNGS在感染性和非感染性肺浸润的准确诊断方面优于CMT(98.1%[57/58]与87.9%[51/58]，P=0.031)。金标准共定义了94个病原体，27名患者患有微生物肺炎。病原体检测的灵敏度和mNGS与金标准的完全一致超过了CMT(92.6%[87/94]vs.76.6%[72/94]，P<0.001和72.1%[31/43]vs.51.2%[22/43]，分别为P=0.004)。此外，仅通过mNGS检测到22种病原体，并通过正交试验证实。因此，19例病因诊断改变，14例经验治疗有所改善，包括8例抢救治疗和11例抗生素降级。在病原体类型的水平上，两种方法对细菌具有可比性，但mNGS有利于识别病毒(准确率：100%vs.81%,P=0.004)。对于肺孢子虫jirovecii检测，mNGS与Gomori'smethenaminesilverspacing(91.7%vs.4.2%，P<0.001），高于聚合酶链反应（79.2％），但差异无统计学意义(P=0.289)。就曲霉而言，发现培养和半乳甘露聚糖测试的组合比mNGS的灵敏度更好(100%vs.66.7%,P=0.033)。
mNGS在危重风湿性疾病患者疑似肺炎的病因诊断和病原体检测方面具有出色的准确性，这对临床决策具有潜在的意义。它对不同类型病原体的优越性取决于CMT的全面性。
The effectiveness of metagenomic next-generation sequencing (mNGS) in respiratory pathogen detection and clinical decision-making in critically rheumatic patients remains largely unexplored.
A single-center retrospective
study of 58 rheumatic patients who were admitted to ICU due to suspected pneumonia with acute respiratory failure if they underwent both bronchoalveolar lavage fluid specimen mNGS and combined microbiological tests (CMTs) was conducted to compare their diagnostic performance, using clinical composite diagnosis as the gold standard. Treatment modifications based on mNGS results were also reviewed.
Forty-three patients were diagnosed with microbiologically confirmed pneumonia and 15 were considered as a non-infectious disease. mNGS outperformed CMTs in the accurate diagnosis of infectious and non-infectious lung infiltration (98.1% [57/58] vs. 87.9% [51/58], P = 0.031). A total of 94 causative pathogens were defined by the gold standard and 27 patients had polymicrobial pneumonia. The sensitivity of pathogen detection and complete concordance with the gold standard by mNGS exceeded those by CMTs (92.6% [87/94] vs. 76.6% [72/94], P < 0.001 and 72.1% [31/43] vs. 51.2% [22/43], P = 0.004, respectively). Moreover, 22 pathogens were detected only by mNGS and confirmed by orthogonal test. Accordingly, the etiological diagnosis changed in 19 cases, and the empirical treatment improved in 14 cases, including 8 cases of rescue treatment and 11 of antibiotics de-escalation. At the pathogen-type level, both methods were comparable for bacteria, but mNGS was advantageous to identify viruses (accuracy: 100% vs. 81%, P = 0.004). For Pneumocystis jirovecii detection, mNGS improved the sensitivity compared with Gomori\'s methenamine silver stain (91.7% vs. 4.2%, P < 0.001) and was higher than polymerase chain reaction (79.2%), but the difference was not significant (P = 0.289). In terms of Aspergillus, the better sensitivity with a combination of culture and galactomannan test than that with mNGS was found (100% vs. 66.7%, P = 0.033).
mNGS has an excellent accuracy in etiological diagnosis and pathogen detection of suspected pneumonia in critically rheumatic patients, which has potential significance for clinical decision-making. Its superiority to different types of pathogens depends on the comprehensiveness of CMTs.
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