造血干细胞移植早期发生呼吸道感染的危险因素分析

发布时间：2018-03-22 07:08

本文选题：造血干细胞移植　切入点：呼吸道感染　出处：《中山大学》2012年硕士论文　论文类型：学位论文

【摘要】：研究背景造血干细胞移植（hematopoietic stem cell transplantation，HSCT）已成为治疗血液系统病、实体瘤、自身免疫性疾病和基因缺陷等疾病的重要手段之一。HSCT可增加呼吸道感染的发生几率，其发生率可高达64.9%。HSCT后下呼吸道感染，尤其是真菌性肺炎的危险因素研究较为多见，但对HSCT后上呼吸道感染与下呼吸道感染的危险因素进行分层对比分析的文献则较少。近年来人们关注到，HSCT后上呼吸道感染更易进展为下呼吸道感染，进而可危及移植后患者的生命，建议加强早期抗感染措施。近年来，HSCT的临床应用正在逐渐扩大，其疗效已得到肯定。但是，HSCT前后各种因素使得患者的机体防御能力受到损坏，易于发生各种感染，呼吸道组织结构脆弱、血供丰富，因而成为移植后感染最常见的发生部位。HSCT后呼吸道感染的原因主要包括三方面：一、基础疾病导致呼吸道感染的发生率增高；二、干细胞移植免疫抑制状态导致呼吸道感染的发生率增高：移植预处理方案大剂量放-化疗使患者的造血和免疫功能受到明显破坏，在其骨髓恢复正常造血功能前，患者外周血细胞数极低，抵抗力差，使得机体对病原体高度易感，即使骨髓恢复造血功能后，免疫功能的重建也需要较长时间；三、移植物抗宿主反应的发生使HSCT后呼吸道感染的发生率增高。移植物抗宿主病（graft versus host disease，GVHD）患者免疫失调和免疫重建延迟，使GVHD患者对病原体的抵抗力减弱，感染的发生率增高； GVHD对呼吸道粘膜完整性的损伤可使机体的固有免疫屏障损伤，病原体易于定植；GVHD的患者还可能因异体反应淋巴细胞攻击受者支气管腺体，使其腺体分泌作用逐渐减弱，导致气道干燥、免疫球蛋白分泌减少，对病原体的抵抗能力进一步下降，从而易发生呼吸道感染。本文收集我院168例HSCT患者的资料，统计HSCT早期呼吸道感染率、呼吸道感染时间、呼吸道感染与造血重建的关系，并进行呼吸道感染、上呼吸道感染、下呼吸道感染危险因素的分析，希望对HSCT后呼吸道感染的早期诊断、治疗起到一定的作用。移植早期是指HSCT后1至30天。HSCT后1至30天内发生的呼吸道感染定义为移植早期呼吸道感染。研究目的 1.总结HSCT早期呼吸道感染的发病情况； 2.探讨HSCT早期造血重建情况与呼吸道感染的关系； 3.分析HSCT早期呼吸道感染的危险因素； 4.分层分析HSCT早期上、下呼吸道感染的危险因素。研究对象与方法 1.研究对象 2000年-2010年在我院行HSCT的患者共168例。原发病类型包括：急性淋巴细胞白血病32例，急性非淋巴细胞白血病49例，地中海贫血44例，再生障碍性贫血12例，慢性淋巴细胞白血病3例，慢性粒细胞白血病9例，淋巴瘤5例，骨髓异常增生综合症2例，多发性骨髓瘤2例，复发性多软骨炎4例，系统性红斑狼疮2例，假肥大性肌营养不良2例，粘多糖贮积病2例。年龄范围为1岁至63岁，，其中儿童（＜14岁）101例，成年(≥14岁)67例，儿童与成年的比例约为1.51：1。男性患者104例，女性64例，男女比例约为1.63：1。经统计分析，男女比例、年龄比例均存在可比性。 2.研究方法 2.1收集病例 2.1.1记录造血干细胞移植患者的年龄、性别、疾病类型等基本资料； 2.1.1对患者的移植时间、移植方式、预处理方案、移植后造血恢复情况及HSCT早期呼吸道感染的发生情况进行回顾性病例对照研究。 2.2病例分组将168例患者按照是否发生呼吸道感染分为呼吸道感染组和无呼吸道感染组，其中呼吸道感染组122人，无呼吸道感染组46人；呼吸道感染患者进一步分为上呼吸道感染组和下呼吸道感染组，其中上呼吸道感染组74人，下呼吸道感染组48人。 2.3统计分析对符合正态分布的计量资料用均数±标准差（X|-±s）表示，两组均数比较采用独立样本t检验；对不符合正态分布连续性计量资料用中位数及四分位数间距表示。计数资料应用率或比表示，采用χ~2检验进行比较。危险因素分析先采用单因素分析筛选出有统计意义的可能危险因素，然后采用逐步前进法Logistic回归分析得出独立的危险因素。样本量较少不宜进行危险因素分析的资料采用Spearson相关系数分析。所有数据统计分析均使用SPSS16.0软件包进行分析，所以统计结果均以P0.05为有统计学差异。结果 1.HSCT早期呼吸道感染率 2000年-2010年在我院接受HSCT的患者共168例，有122例患者在HSCT早期发生了呼吸道感染，呼吸道感染率为72.6%。上呼吸道感染共计74例，HSCT早期上呼吸道感染率为44.0%；下呼吸道感染共计48例，HSCT早期下呼吸道感染率为28.6%。2000年-2005年在我院接受HSCT的患者共59例，HSCT早期发生呼吸道感染的患者共52例，呼吸道感染率为88.1%；2006-2010在我院接受HSCT的患者共109例， HSCT早期发生呼吸道感染的患者共70例，呼吸道感染率为64.2%。将2000年-2005年与2006年-2010年患者HSCT早期呼吸道感染率比较，P值0.05，差异有统计学意义，近5年（2005-2010年）患者HSCT早期呼吸道感染率比前5年（2000-2005年）低。 2.HSCT早期造血重建情况及呼吸道感染时间患者在HSCT早期造血重建的平均时间为移植后第14.5±5.4天。HSCT早期呼吸道感染时间的中位数为HSCT后第7天，四分位数间距为6.5天。发生呼吸道感染的122例患者中，99例患者呼吸道感染发生于造血重建前，占HSCT早期呼吸道感染的81.1%；23例患者呼吸道感染发生于造血重建后，占HSCT早期呼吸道感染的18.9%。 3. HSCT早期呼吸道感染的危险因素分析根据单因素分析，年龄、干细胞来源、预处理方式、非亲缘移植、HLA不匹配移植、血象恢复时间是HSCT早期呼吸道感染的危险因素（P＜0.05）。选择单因素分析差异有统计意义的可能危险因素进行逐步前进法Logistic回归分析，得出影响HSCT早期呼吸道感染的独立危险因素有年龄、非亲缘移植。 4. HSCT早期上呼吸道感染的危险因素分析根据单因素分析，年龄、干细胞来源、非亲缘移植、HLA不匹配移植、血象恢复时间是HSCT早期上呼吸道感染的危险因素（P＜0.05）。选择单因素分析差异有统计意义的可能危险因素进行逐步前进法Logistic回归分析，得出影响HSCT早期上呼吸道感染的独立危险因素有年龄、非亲缘移植。 5． HSCT早期下呼吸道感染的危险因素分析根据单因素分析，干细胞来源、非亲缘移植、HLA不匹配移植、aGVHD、真菌性肺炎病史是HSCT早期下呼吸道感染的危险因素（P＜0.05）。选择单因素分析差异有统计意义的可能危险因素进行逐步前进法Logistic回归分析，得出影响HSCT早期下呼吸道感染的独立危险因素有真菌性肺炎病史、HLA不匹配移植。 6． HSCT早期下呼吸道感染的其他相关因素分析经Spearson相关系数分析得出，口腔溃疡与下呼吸道感染存在正相关，相关系数r_s=0.178(P=0.047)。败血症与下呼吸道感染存在正相关，相关系数r_s=0.261(P=0.001)，但因病例数量较少，未能纳入此次危险因素分析中。结论 1.168例患者HSCT早期呼吸道感染率为72.6%，前5年患者HSCT早期呼吸道感染率比近5年高，感染率分别为88.1%和64.2%。 2. HSCT后患者造血重建的平均时间为移植后第14.5±5.4天。HSCT早期呼吸道感染的中位时间为移植后第7天。HSCT早期大多数呼吸道感染发生在造血重建恢复前。 3. HSCT早期呼吸道感染单因素分析的危险因素有年龄、干细胞来源、预处理方式、非亲缘移植、HLA不匹配移植、血象恢复时间；多因素分析后独立危险因素有年龄、非亲缘移植。 4. HSCT早期上呼吸道感染单因素分析的危险因素有年龄、干细胞来源、非亲缘移植、HLA不匹配移植、血象恢复时间；多因素分析后独立危险因素有年龄、非亲缘移植。 5. HSCT早期下呼吸道感染单因素分析的危险因素有干细胞来源、非亲缘移植、HLA不匹配移植、发生aGVHD、真菌性肺炎病史；多因素分析后独立的危险因素有HLA不匹配移植、真菌性肺炎病史。 6.败血症、口腔溃疡的发生与HSCT早期下呼吸道感染存在正相关。
[Abstract]:Research background
Hematopoietic stem cell transplantation (hematopoietic stem cell transplantation, HSCT) has become the treatment of blood system disease, tumor, autoimmune diseases and genetic defects and other diseases is one of the important means of.HSCT can increase the probability of occurrence of respiratory tract infection, the incidence of lower respiratory tract infection can be as high as 64.9%.HSCT, especially the study of risk factors of fungal pneumonia the more common, but the hierarchical contrast analysis and risk factors of lower respiratory tract infection is less HSCT after upper respiratory tract infection. In recent years, people pay attention to HSCT after upper respiratory tract infection in lower respiratory tract infection more easily, and the quality and the life of patients after transplantation, proposed to strengthen the anti infection measures early.
In recent years, the clinical application of HSCT is gradually expanding, its efficacy has been confirmed. However, various factors of HSCT before and after the damage defense ability of the body makes patients, prone to infections, respiratory structure vulnerability, abundant blood supply, and thus become mainly includes three aspects of respiratory tract infection occurred after.HSCT. The most common cause of infection after transplantation: a basic disease causes respiratory tract infection rate increased; two, stem cell transplantation, immunosuppression resulted in increased incidence of respiratory tract infection: transplantation pretreatment regimen of high-dose chemotherapy and hematopoietic - make the immune function of the patients was significantly damaged in the recovery of bone marrow of normal hematopoietic function, peripheral blood of patients with the number of cells is extremely low, poor resistance, makes the body highly susceptible to pathogens, even if the recovery of bone marrow hematopoietic function after the reconstruction of the immune function also needs a long time. Three; incidence of graft-versus-host reaction to HSCT infection rate increased. Graft-versus-host disease (graft versus host disease, GVHD) in patients with immune disorders and delayed immune reconstitution, the GVHD patients with weakened resistance to pathogens, the infection rate increased; GVHD damage to the respiratory tract mucosa integrity the innate immune barrier can make damage to the body, easy to GVHD patients pathogen colonization; allogeneic lymphocyte response may also be due to attack by bronchial glands, the glands secretion gradually weakened, resulting in airway free drying, reduce the secretion of immunoglobulin, the resistance to pathogens decreased further, thus prone to respiratory infections.
This paper collected data of 168 cases with HSCT, statistical HSCT early infection rate of respiratory tract, respiratory tract infection time, the relationship between respiratory infection and hematopoietic reconstitution, and respiratory tract infection, upper respiratory tract infection, risk factors of lower respiratory tract infection, hope for the early diagnosis of respiratory tract infection after HSCT treatment, play a certain role. Refers to the definition of early transplantation occurred in 1 to 30 days after.HSCT for 1 to 30 days after HSCT transplantation for respiratory tract infection of respiratory tract infection early.
research objective
1. to summarize the incidence of early respiratory tract infection in HSCT.
2. to investigate the relationship between the early hematopoietic reconstitution of HSCT and the respiratory tract infection.
3. the risk factors of early respiratory tract infection in HSCT were analyzed.
4. stratified analysis of the risk factors for lower respiratory tract infection at the early stage of HSCT.
Research objects and methods
1. research objects
In 2000 -2010 years in our hospital 168 cases of HSCT. The primary disease types include: 32 cases of acute lymphocytic leukemia, 49 cases of acute non lymphocytic leukemia, 44 cases of thalassemia, 12 cases of aplastic anemia, 3 cases of chronic lymphocytic leukemia, chronic myeloid leukemia in 9 cases, 5 cases of lymphoma, 2 cases of myelodysplastic syndrome, 2 cases of multiple myeloma, 4 cases of relapsing polychondritis, 2 cases of systemic lupus erythematosus, Duchenne muscular dystrophy in 2 cases, 2 cases with mucopolysaccharidosis. The age range was 1 to 63 years old, the children (< 14 years) 101 cases that adult (over 14 years) in 67 cases, the proportion of children and adults about 104 cases of 1.51:1. patients, 64 cases were female, male to female ratio is about 1.63:1. by statistical analysis, the proportion of men and women, there are comparable in age.
2. research methods
2.1 collection of cases
2.1.1 records the basic data of age, sex, and type of disease in patients with hematopoietic stem cell transplantation.
2.1.1 retrospective analysis was performed on the time of transplantation, the way of transplantation, pretreatment plan, hematopoietic recovery after transplantation and the incidence of HSCT early respiratory infection.
2.2 cases group
The 168 patients with respiratory tract infection is divided into respiratory infection group and non respiratory infection group, respiratory tract infection group 122, group 46 without respiratory tract infection; patients were divided into group and group of lower respiratory tract infection of upper respiratory tract infection of respiratory tract infection, 74 of them were upper respiratory tract infection, 48 groups of lower respiratory tract infections..
2.3 statistical analysis
According to the measurement data of normal distribution with mean standard deviation (X|- + s) said that the two groups were compared using independent sample t test; do not conform to the normal distribution of continuous measurement data with a median and four percentile interval. Count data or application rate than that using X ~2 test comparative analysis of risk factors. By using single factor analysis to identify the possible risk factors with statistical significance, then using stepwise forward method Logistic regression analysis showed that independent risk factors. The small sample amount should not be carried out to analyze the risk factors of the data was analyzed by Spearson correlation statistical analysis. All data were analyzed using SPSS16.0 software package, so the statistical results are P0.05 as statistically significant.
Result
Early respiratory tract infection rate of 1.HSCT
In 2000 -2010 years in our hospital 168 cases of HSCT, 122 cases occurred in patients with respiratory tract infection in the early stage of HSCT, respiratory tract infection rate for a total of 74 cases of upper respiratory tract infection 72.6%., HSCT early upper respiratory tract infection rate was 44%; a total of 48 cases of lower respiratory tract infection, HSCT in the early stage of lower respiratory tract infection rate was 28.6%.2000 -2005 years in our hospital 59 cases of HSCT, HSCT in the early stage of respiratory tract infection occurred in patients with a total of 52 cases of respiratory tract infection rate was 88.1%; 2006-2010 in our hospital 109 cases of HSCT, HSCT in the early stage of respiratory tract infection occurred in patients with a total of 70 cases of respiratory tract infection rate was 64.2%. in 2000 -2005 and 2006 -2010 in patients with early HSCT respiratory tract infection rate, the P value is 0.05, the difference was statistically significant, nearly 5 years (2005-2010 years) in patients with early HSCT infection rate than the previous 5 years (2000-2005 years).
Early reconstruction of hematopoiesis and time of respiratory tract infection in 2.HSCT
The average HSCT in early hematopoietic reconstitution time for patients after transplantation, 14.5 + 5.4 days early.HSCT respiratory tract infection time for a median of seventh days after HSCT, the four percentile interval for 6.5 days. 122 cases of respiratory tract infection patients, 99 cases of patients with respiratory tract infection in hematopoietic reconstruction, early respiratory tract infection accounted for HSCT 81.1%; 23 cases of patients with respiratory tract infection in hematopoietic reconstruction after respiratory tract infection early 18.9%. accounted for HSCT
Analysis of risk factors for 3. HSCT early respiratory tract infection
According to the univariate analysis, age, source of stem cells, pretreatment, non genetic transplantation, HLA, transplantation, blood recovery time is a risk factor for respiratory tract infection early HSCT (P < 0.05). Univariate analysis the possible risk factors for statistically significant differences in the stepwise forward Logistic regression analysis, factors that influence independent risk HSCT respiratory tract infection early age, non genetic transplantation.
Analysis of risk factors for early upper respiratory tract infection in 4. HSCT
According to the univariate analysis, age, source of stem cells, non genetic transplantation, HLA, transplantation, blood recovery time are risk factors of HSCT infection of the upper respiratory tract early (P < 0.05). Univariate analysis the possible risk factors for statistically significant differences in the stepwise forward Logistic regression analysis, the independent risk factors for HSCT upper respiratory tract infection in early age, unrelated transplantation.
Analysis of risk factors for early lower respiratory tract infection in 5.HSCT
According to the analysis of single factor, stem cell source, unrelated transplantation, HLA, transplantation, aGVHD, history of fungal pneumonia was HSCT early in the risk factors of respiratory tract infection (P < 0.05). Univariate analysis the possible risk factors for statistically significant differences in the stepwise forward Logistic regression analysis, the independent risk factors HSCT in the early stage of lower respiratory tract infection in patients with a history of fungal pneumonia, HLA mismatched transplantation.
Analysis of other related factors of lower respiratory tract infection in early 6.HSCT
The Spearson correlation coefficient analysis, oral ulcer and lower respiratory tract infection were positively correlated, the correlation coefficient r_s=0.178 (P=0.047) and lower respiratory tract infection. Sepsis has a positive correlation, the correlation coefficient r_s=0.261 (P=0.001), but the number of cases is less, not included in the analysis of the risk factors.
conclusion
The early respiratory infection rate of HSCT in 1.168 patients was 72.6%. The early respiratory infection rate of HSCT in the first 5 years was higher than that of nearly 5 years, and the infection rate was 88.1% and 64.2%., respectively.
After 2. HSCT, the average time of hematopoietic reconstitution was 14.5 + 5.4 days after transplantation. The median time of.HSCT infection was seventh days after transplantation. Most respiratory infections occurred before hematopoietic reconstitution in.HSCT.
3., the risk factors for single factor analysis of early respiratory tract infections in HSCT were age, stem cell origin, pretreatment, non related transplantation, HLA mismatch and hematologic recovery time. After multivariate analysis, the independent risk factors were age and non related transplantation.
4., the risk factors for single factor analysis of early HSCT upper respiratory tract infection were age, stem cell origin, non related transplantation, HLA mismatch and hematologic recovery time. After multivariate analysis, the independent risk factors were age and non related transplantation.
5., the risk factors of single factor analysis of HSCT early lower respiratory tract infection were stem cell origin, non related transplantation, HLA mismatch transplantation, aGVHD and fungal pneumonia history. Independent risk factors were HLA mismatched transplantation and fungal pneumonia history after multifactorial analysis.
6. septicemia, the occurrence of oral ulcers is positively related to the early lower respiratory tract infection in HSCT.

【学位授予单位】：中山大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R56

【相似文献】