Introduction. Inappropriate use of antibiotics and inadequate therapeutic regimens for early-stage pulmonary infections are major contributors to increased prevalence of complications and mortality. Moreover, due to the limitations in sensitivity of conventional testing, there is an urgent need for more diagnostically efficient methods for the detection and characterization of pathogens in pulmonary infections. Hypothesis/Gap Statement. Metagenomic next-generation sequencing (mNGS) can contribute to the diagnosis and management of pulmonary infections. Aim. This study aimed to evaluate the clinical application and value of mNGS in the diagnosis of clinically suspected pulmonary infections by comparing with conventional testing. Methodology. In this study, the diagnosis performance of mNGS was evaluated using bronchoalveolar lavage fluid (BALF) samples from 143 patients with suspected lung infections. First, we conducted a prospective study on 31 patients admitted to Yuebei People’s Hospital Affiliated to Shantou University Medical College to investigate the clinical value. Then a retrospective analysis was performed by including more patients (n=112) to reduce the random error. Pathogens were detected by mNGS and conventional methods (culture and PCR). Then, the types and cases of detected pathogens, as well as the specificity and sensitivity, were compared between the two methods. We evaluated the performance of mNGS in detecting bacterial, fungal, viral and mixed infections in BALF. The effect of disease severity in pulmonary infections on the integrity of mNGS pathogen detection was also explored. Results. The mNGS provided an earlier and more comprehensive pathogen profile than conventional testing, which in turn prompted a change in clinical medication, which led to improvement in eight patients (8/31=25.81 %) in the presence of other serious comorbidities. In a retrospective analysis, mNGS was much more sensitive than conventional testing in the diagnosis of pulmonary infections (95.33 % vs. 55.56 %; P<0.001), with a 39.77 % increase in sensitivity. The detection rate of mNGS for mixed infections was significantly higher than that of conventional testing methods for both common and severe pneumonia (48/67=71.64 % vs. 12/52=23.08 %, P<0.001; 44/59=74.58 % vs. 11/59=18.64 %, P<0.0001). Conclusion. The sensitivity of mNGS in the diagnosis of pathogenic microorganisms in pulmonary infections far exceeds that of conventional culture tests. As a complementary method to conventional methods, mNGS can help improve the diagnosis of pulmonary infections. In addition, mNGS pathogen integrity detection rate was similar in common and severe pneumonia. We recommend the prompt use of mNGS when mixed or rare pathogen infections are suspected, especially in immunocompromised individuals and/or critically ill individuals.

中文翻译：

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通过支气管肺泡灌洗液宏基因组下一代测序改善肺部感染诊断

介绍。抗生素使用不当和早期肺部感染治疗方案不足是并发症发生率和死亡率增加的主要原因。此外，由于常规检测灵敏度的限制，迫切需要诊断更有效的方法来检测和表征肺部感染的病原体。 假设/差距陈述。宏基因组下一代测序（mNGS）有助于肺部感染的诊断和管理。 目的。本研究旨在通过与常规检测的比较，评价mNGS在诊断临床疑似肺部感染中的临床应用和价值。 方法。在这项研究中，使用来自 143 名疑似肺部感染患者的支气管肺泡灌洗液 (BALF) 样本评估了 mNGS 的诊断性能。首先，我们对汕头大学医学院附属粤北人民医院收治的31例患者进行前瞻性研究，探讨其临床价值。然后通过纳入更多患者（ n =112）进行回顾性分析，以减少随机误差。通过 mNGS 和常规方法（培养和 PCR）检测病原体。然后比较两种方法检测病原体的类型和病例以及特异性和敏感性。我们评估了 mNGS 在检测 BALF 中细菌、真菌、病毒和混合感染方面的性能。还探讨了肺部感染疾病严重程度对 mNGS 病原体检测完整性的影响。 结果。mNGS 提供了比传统检测更早、更全面的病原体谱，这反过来又促使临床用药发生变化，导致 8 名存在其他严重合并症的患者 (8/31=25.81%) 得到改善。回顾性分析显示，mNGS 诊断肺部感染的灵敏度比常规检测灵敏得多（95.33 % vs. 55.56 %；P <0.001），灵敏度提高了 39.77 %。mNGS对混合感染的检出率均显着高于常规检测方法对普通肺炎和重症肺炎的检出率（48/67=71.64% vs. 12/52=23.08%，P < 0.001；44/59=74.58% vs. .11/59=18.64%，P <0.0001）。 结论。mNGS诊断肺部感染病原微生物的敏感性远远超过传统培养检测。作为传统方法的补充方法，mNGS 可以帮助改善肺部感染的诊断。此外，普通肺炎和重症肺炎的mNGS病原体完整性检出率相似。当怀疑混合或罕见病原体感染时，我们建议立即使用 mNGS，特别是在免疫功能低下的个体和/或危重患者中。