支气管肺泡灌洗液及其mNGS对血液系统疾病造血干细胞移植后肺部感染的临床应用

Clinical Application of Bronchoalveolar Lavage Fluid and Its mNGS in Pulmonary Infection after Hematopoietic Stem Cell Transplantation for Hematopoietic Diseases

白血病是起源于造血干细胞的恶性克隆性疾病,白血病细胞大量的增值后抑制了骨髓中正常的白细胞、血小板和红细胞的生成。粒细胞缺乏所致的感染常见感染部位有上呼吸道、肺部、口腔、肛周及全身(败血症)。最常见的致病菌为革兰氏阴性杆菌,其次为革兰氏阳性球菌,还可能出现病毒、真菌(含卡氏肺孢子菌)感染等。造血干细胞移植(Hematopoietic stem cell transplantation, HSCT)是指对患者进行放疗、化疗及免疫抑制预处理,消除异常造血与免疫系统后,将供者或自身造血干细胞(HSC)经血管输注到患者体内,使之重建正常造血和免疫系统的一种治疗方法。自1959年美国E. D. Thomas医师实行全球首例同卵孪生提供造血干细胞进行HSCT后,HSCT已成为治疗多种血液系统恶性疾病有效乃至唯一的耿直方法。骨髓移植后由于全血细胞减少、粒细胞缺乏、留置导管、粘膜屏障受损及免疫功能低下等,感染相当常见。由于HSCT患者的特殊性导致抗生素的滥用以及感染病原体的不断产生、进化和编译,导致其脓毒血症、呼吸衰竭死亡的患者病死率高。临床常用检测方法为分离、生化、核酸等操作相对简单,成本较低的方式方法,然而这些传统方法检测耗时较长,且仅能对常见病原体检测,并且所送项目及标本更依赖临床医师执业水准和判断,因此对像HSCT这种免疫力低下的患者可能感染到的未知及罕见病原体识别困难。宏基因二代测序技术(metagenomics next generation sequencing, mNGS)比较上一代测序方法通量更高,测序速度更快,理论上能无偏倚地检测出细菌、真菌、病毒以及罕见致病微生物,因此,mNGS对疑难甚至复合感染的早期诊断,指导临床抗生素的合理使用和精准治疗提供了重大参考意见。

Leukemia is a malignant clonal disease originating from hematopoietic stem cells. The proliferation of leukemia cells inhibits the production of normal white blood cells, platelets, and red blood cells in the bone marrow. The common sites of infection caused by granulocyte deficiency include the upper respiratory tract, lungs, oral cavity, perianal area, and systemic (sepsis). The most common pathogenic bacteria are Gram negative bacilli, followed by Gram positive cocci, and there may also be viral, fungal (including Pneumocystis carinii) infections. Hematopoietic stem cell transplantation (HSCT) refers to a treatment method in which a patient undergoes radiotherapy, chemotherapy, and immunosuppressive pretreatment to eliminate abnormal hematopoiesis and immune systems. After that, donor or autologous hematopoietic stem cells (HSCs) are transfused into the patient’s body through blood vessels to rebuild normal hematopoiesis and immune systems. Since 1959, Dr. E. D. Thomas implemented the world’s first homozygous twin to provide hematopoietic stem cells for HSCT, HSCT has become an effective and even the only straightforward method for treating various hematological malignancies. After bone marrow transplantation, infections are quite common due to decreased whole blood cells, lack of granulocytes, indwelling catheters, damaged mucosal barriers, and weakened immune function. Due to the particularity of HSCT patients, the abuse of antibiotics and the continuous generation, evolution, and compilation of infectious pathogens lead to a high mortality rate in patients with sepsis and respiratory failure. The commonly used clinical testing methods include isolation, biochemistry, nucleic acid, and other relatively simple and low-cost methods. However, these traditional methods take a long time to detect and can only detect common pathogens. Moreover, the items and specimens sent rely more on the professional level and judgment of clinical physicians. Therefore, it is difficult to identify unknown and rare pathogens that may be infected by patients with low immunity, such as HSCT. Metagenomics next generation sequencing (mNGS) technology has a higher throughput and faster sequencing speed compared to the previous generation of sequencing methods. In theory, it can detect bacteria, fungi, viruses, and rare pathogenic microorganisms without bias. Therefore, mNGS provides significant reference opinions for the early diagnosis of suspected or even complex infections, guiding the rational use and precise treatment of clinical antibiotics.