Transient deficiency of peripheral blood accessory cells in supporting T cell mitogenesis in patients suffering from chronic idiopathic thrombocytopenic purpura after intravenous gammaglobulin treatment

Mitogenic response of blood lymphocytes to phytohemagglutinin (PHA) and to OKT3 monoclonal antibodies was investigated in 7 patients suffering from chronic idiopathic thrombocytopenic purpura (ITP) before, during and after high-dose intravenous (i.v.) immunogammaglobulin (IgG) infusion. The platelet count rose above the pre-treatment values during infusion therapy in all patients but one. Five out of seven patients presented elevated platelet-associated IgG (PA-IgG) levels at the time of the first infusion; four of these showed an increase in platelet count and a transient reduction or normalization of PA-IgG after IgG infusion. Five out of seven patients showed an impairment of T lymphocyte mitogenic response to PHA and OKT3 before therapy. All patients responded to IgG therapy with a transient deficiency of FcR mediated monocytes (Mo) in supporting T cell mitogenesis induced by both mitogens during and after IgG infusion. This reduced cooperative capability of Mo disappeared at various times after the end of therapy (range 3-12 days). The transient alteration of Mo function, possibly due to a modification in the surface number or in the affinity of Fc-receptors, can explain in part, the increase in platelet count during and after IgSRK infusion.     

Effects of immunotherapy and chemotherapy on immunocompetence. A study of patients with acute myeloblastic leukemia in remission

Summary The immunocompetence of 33 patients with acute myeloblastic leukemia in remission and treated with cytostatics (CT) was studied. In addition to cytostatics some of the patients were given immunotherapy (CT+IT).In an attempt to demonstrate immunization against allogeneic leukemic blast cells (or their extracts) or immunostimulation after immunotherapy or, alternatively, immunodepression after maintenance chemotherapy without immunotherapy, delayed hypersensitivity tests and lymphocyte stimulation tests were performed. In most cases PHA seemed to be a stronger stimulator than allogeneic lymphocytes and these seemed to be stronger than allogeneic blasts, although no difference was statisically significant.No significant differences were found in vitro or in vivo between the reactions of CT and CT+IT patients or their lymphocytes to allogeneic myeloblasts or to allogeneic lymphocytes. However, numerically, in vitro and in vivo CT+IT patients reacted more to myeloblasts, CT patients more to lymphocytes. This could suggest antigens on leukemic myeloblasts that are not found on lymphocytes. With present methods we could demonstrate neither immunodepression in patients given only chemotherapy nor nonspecific immunostimulation after immunotherapy. There was no significant difference between the two treatment groups in lymphocyte reactivity against PHA and allogeneic lymphocytes. Nor was the lymphocyte reactivity different from that in a group of healthy persons.Decreasing lymphocyte reactivity to PHA and allogeneic lymphocytes seemed to herald relapse.     

Blood leukocyte responses to extracorporal circulation. III. Long term extracorporeal circulation without and with irradiation in normal and splenectomized dogs

Long term (12-48 h) extracorporeal circulation without and with irradiation of the blood was performed in normal and splenectomized dogs in order to observe the effect of these procedures on blood leukocyte counts including CFU-C. A transient granulocytopenia and a decrease of lymphocyte count were observed. The blood CFU-C level diminished to a very low level and remained low for the whole time of the experiments. There was no significant difference between the results of procedures with or without irradiation. The similar effect of a shortened tubing system on the blood leukocyte count is also reported. Heparin infusion alone did not decrease the peripheral CFU-C concentration. The possible explanations for the observed phenomena are discussed.     

Circadian rhythm of 5-fluorouracil (FU) pharmacokinetics and tolerance

In 28 adult patients with unresectable, disseminated gastrointestinal cancer FU pharmacokinetics as well as hematological and gastrointestinal side-effects of the therapy were evaluated to determine it they were circadian-stage dependent. FU was given as a bolus i.v. injection (15 mg/kg) 4 times at 0100, 0700, 1300, and 1900 at intervals of at least 96h in a changing sequence. Pharmacokinetic parameters were calculated on the basis of drug concentration in the serum, measured by the gas-chromatography method. Hematological side-effects were evaluated on the basis of white blood cell and thrombocyte count. Gastrointestinal toxicity (nausea, vomiting and diarrhoea graded in own 0-2 scale) was evaluated after the therapy. The single-cosinor analysis was applied for both detection and characterization of circadian rhythms. The results of the study were as follows: 1. Pharmacokinetic parameters of FU depend on the time of injection with the highest drug biotransformation at midday and early afternoon. 2. The highest white blood cell count following FU administration was noted after the night injection (0100), though the time of administration did not affect thrombocyte count and gastrointestinal side-effects.     

Recombinant interleukin-2 (rIL-2) after autologous bone marrow transplantation (BMT): a pilot study in 19 patients.

In vivo use of rIL-2 autologous BMT may be the means of reproducing a kind of "adoptive immunotherapy" from grafted cells after allogeneic BMT. This approach may enhance the spontaneous generation of cytotoxic T-cells and NK cells which are presumably involved in this immunotherapy. Potential risks of such an approach would be to increase the usual toxicity of rIL-2 and to jeopardize the hemopoietic reconstitution. To determine the feasibility of this approach we have treated 19 poor prognosis patients with a succession of autologous BMT followed 78 +/- 12 days later by a continuous infusion of rIL-2. Eighteen million international units (IU) per m2 per day of Proleukine (CETUS, Amsterdam, The Netherlands) were administrated over 6 or 12 days. No patient died of the procedure. Clinical toxicity related to rIL-2 was not increased. Hemopoietic toxicity, significant both for platelets and granulocytes, was transient. Immune stimulation was dramatic for lymphocytes and subpopulations (CD3+ and NK cells) and for cytolytic functions (NK and LAK activity). This trial establishes the feasibility of administration of high doses of rIL-2, 2 months after autologous BMT. In this setting a 6 day period of continuous infusion of 18 million per m2 per day of Proleukine appears to be a regularly tolerable dosage conducting to a major immune activation and invites further studies to determine the clinical impact of such an approach.     

White blood cell count and adherence in sportsmen and non-training subjects

The white blood cell count and differential white blood cell count as well as the adherence of these cells were determined in 31 young clinically healthy men not participating actively in any sports and in 32 footballers belonging to third league sports clubs. In the group of footballers the determinations were carried out twice: in the initial period and then at the end of the highest-form period of the one-year training cycle. In the footballers in relation to the control group the total white blood cell count was raised, the differential count showed a shift in favour of neutrophils, eosinophils and monocytes at the expense of lymphocytes. The lymphocyte adherence was significantly decreased.     

Lymphocyte reactions at early periods after heart transplantation]

The authors determined the quantitative and qualitative composition of the white blood and dehydrogenase activity of lymphocytes in the blood from the afferent and afferent vessels of the transplanted heart at the early postoperative periods in dogs. There was noted a reduction of the lymphocyte count in the blood flowing from the transplanted heart on account of retention of these cells in the transplant, and also an inversion of the mitochondrial dehydrogenases activity due to the lymphocyte contact with foreign antigens of the transplanted heart. A hypothesis is put forward that the inversion mechanism was connected with the lymphocyte functions in the capacity of immunocompetent cells.     

Variation in the WBC differential count and other factors associated with reporting of herpes labialis: a population-based study of adults

Reactivation of latent herpes virus has been linked to triggers of mild immunosupression, such as stress or UV-exposure. Despite having predictive value in severe immunodeficiency, the white blood cell (WBC) differential count has not been examined in relation to risk of herpes reactivation in population studies. The WBC differential count and other risk factors for herpes labialis were examined in 5687 adults (ages 18-64) from the Third National Health and Nutrition Examination Survey, who had WBC 3.5-11 x 10(6) cells mL(-1) and reported no acute infections in the past month. The association between self-reported herpes labialis in the past year and the WBC differential count was modeled, adjusting for age, sex, race/ethnicity, education, smoking, upper respiratory infections (URI), and HSV-1 antibodies. Herpes labialis was significantly associated with white race/ethnicity, being a nonsmoker, and frequent URI. Compared with the highest quartile, being in the lowest quartile of granulocytes was associated with herpes labialis, adjusted odds ratio=1.82 (95% confidence interval 1.20, 2.28). At the same time, there was a trend towards an inverse association of lower lymphocyte count and herpes labialis. These findings suggest that moderate differences in the WBC differential count are related to reactivation of HSV-1. Prospective studies may help to show whether such differences indicate susceptibility to loss of latency or represent a consequence of reactivated infection.     

A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR

Nonmyeloablative allogeneic stem cell transplantation (SCT) can induce remission in patients with renal cell carcinoma (RCC), but this graft-versus-tumor (GVT) effect is often accompanied by graft-versus-host disease (GVHD). Here, we evaluated minor histocompatibility antigen (MiHA)-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI). One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT.     

Long-term clinical remission of a patient with chronic lymphocytic leukemia using alternative treatment option: Cottonseed oil (gossypol)

Chronic lymphocytic leukaemia (CLL) results from the accumulation of malignant immunologically incompetent lymphocytes.A routine full blood count of a single patient revealed that he had CLL. The daily intake of 700 ml of fresh bovine milk resulted in a decrease in the lymphocyte count from 85.5×10⁹/l to 12.5×10⁹/l over a period of 5 years.The aim was to establish which constituent(s) in milk would be responsible for the decline of the lymphocyte count. It was found that the higher vitamin D constituent in the milk, the lower the lymphocyte count.Whilst the milk from large dairy farms which use supplements in the feed in order to increase milk production, considerably decreased the lymphocyte count, the milk from small dairy farms, which do not supplement, had hardly any effect.The present study indicates that gossypol in cottonseed cake and oil are potentially responsible for the decrease in white blood cell count. It appears that gossypol is a very powerful anti-neoplastic agent.Free gossypol (Fig. 1) is a toxic phenolic compound which becomes detoxified in ruminants by binding to milk proteins, but gossypol is still an active inhibitor of tumour growth in the excreted milk.     

Cardiorespiratory and cellular changes with interleukin 2 infusion in sheep

Recombinant interleukin 2 (rIL-2) administration, a new form of therapy for patients with far-advanced cancer, is associated with a "third space" syndrome, i.e., pulmonary edema, respiratory distress, and hypoxemia, which limits the dose and duration of treatment. To extend our knowledge regarding this toxicity, we established a sheep chronic lung lymph fistula model and measured hemodynamics, arterial blood gases, caudal mediastinal (lung) lymph flow (QL), and blood and lung lymph cellular changes before, during, and after (recovery) a 3-day continuous rIL-2 infusion (9 x 10(5) U/kg). Moderate systemic hypotension, mild pulmonary hypertension, and an increase in alveolar-arterial PO2 gradient was present on day 3 of rIL-2 infusion. QL increased from a base line of 1.9 +/- 0.2 to a maximum of 4.3 +/- 1.1 ml/15 min on day 3 of rIL-2 infusion. At no time was there a change in lymph-to-plasma protein ratio. The leukocyte count increased significantly to 16.1 +/- 4.5 x 10(3) cells/mm3 at recovery day 1. The percentage of blood lymphocytes decreased significantly by day 1 of rIL-2 infusion, returned to base-line levels on day 3, and significantly increased on day 2 of recovery. Lung lymph lymphocytes decreased significantly on days 1 and 2 of rIL-2 infusion. There was a shift in their size; i.e., their area increased from 32 +/- 7 to 57 +/- 19 micron 2 (P less than 0.05) by day 2 of rIL-2 infusion. By day 1 of recovery, lung lymph lymphocyte counts increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

A model for experimental bacterial cystitis in the dog

To induce an experimental model of bacterial cystitis, ten preconditioned dogs underwent bladder irritation with a 0.1% alcoholic solution of salicylic acid followed in 24 hours by an intravesicular infusion of Proteus mirabilis. The dogs were observed for the following 14 days (five dogs) and 17 days (five dogs) and then euthanatized and necropsied. Tenesmus, dysuria, hematuria, and pollakiuria occurred in all dogs, but the severity of these signs diminished with time. The total white cell, neutrophil, and monocyte counts in the peripheral blood increased and urinalysis results were consistent with infection and severe inflammation. The infection persisted for the duration of the study, although the average quantitative bacterial count in urine progressively declined. No changes occurred in the measured clinical chemistry values. Severe inflammation was present on gross examination of the bladder and microscopic examination of the bladder, prostate, and renal pelvis. Less severe inflammation was present on microscopic examination of the urethra and ureter.     

Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study

Purpose Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma (RCC), adoptive immunotherapy using gamma-delta (γδ) T cells has not yet been tried. In this study, we designed a pilot study of adoptive immunotherapy using in vitro activated γδ T cells against advanced RCC to evaluate the safety profile and possible anti-tumor effects of this study. Experimental design Patients with advanced RCC after radical nephrectomy were administered via intravenous infusion in vitro-activated autologous γδ T cells every week or every 2 weeks, 6–12 times, with 70 JRU of teceleukin. Adverse events, anti-tumor effects and immunomonitoring were assessed. The anti-tumor effects were evaluated according to tumor doubling time (DT) by computed tomography (CT) and immunomonitoring was performed by flow cytometric analysis. Results Seven advanced RCC patients were entered in this study. The most common adverse events were fever, general fatigue and elevation of hepatobiliary enzymes, but no severe adverse events were seen. Prolongation of tumor DT was seen in three out of five patients; these three patients showed an increase in the number of γδ T cells in peripheral blood and also a high response to the antigen in vitro. Conclusions The results indicated that adoptive immunotherapy using in vitro-activated autologous γδ T cells was well tolerated and induced anti-tumor effects.     

外周血中常见血液学参数对乳腺癌预后评估价值的研究进展

在世界范围内,乳腺癌是最常见的女性恶性肿瘤,严重危害人民健康。最近的流行病学和临床研究发现炎性反应与乳腺肿瘤有着一定的联系。炎症构成肿瘤微环境的一部分,炎性细胞的变化影响着肿瘤的进展,包括乳腺癌细胞增殖,侵袭,免疫力降低,转移等。检验外周静脉血中的白细胞、中性粒细胞、淋巴细胞、单核细胞、血小板以及衍生出的中性粒细胞/淋巴细胞比值(NLR)、派生中性粒细胞/淋巴细胞(d-NLR)、血小板/淋巴细胞比值(PLR)、淋巴细胞/单核细胞比值(LMR)等可以反映许多恶性肿瘤细胞的炎性状态。深入研究外周血中常见的标记物与乳腺癌的治疗及预后的关系,为临床医师提供有价值的参考信息,将具有重要的临床意义和应用前景。本文就外周血中常见的标记物进行相关论述,以期为乳腺癌的治疗及预后提供一个新的方法。     

Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies

Clinical effects and side effects were studied in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of normal donors by means of initial stimulation with pokeweed mitogen (PWM). Six of 15 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastasis, pleural effusion and primary tumor. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Generally toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently except one patient who showed preshock like symptom accompanied with leukocytopenia and continuous hypotension immediately after infusion but was finally rescued. In the patients who received more than 10¹¹ of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies appeared in the patients. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells.Abbreviations PWM pokeweed mitogen - LAK lymphokine-activated killer - IL-2 interleukin 2 - PEL peripheral blood lymphocytes - TIL tumor-infiltrating lymphocytes - GVHD graft-versus-host disease - HLA human leukocyte antigen     

Effect of Beta-Adrenergic Stimulation on the Circulatory Lymphocyte Count: Studies in Normals and in Patients with Chronic Airflow Obstruction

In eight non-allergic patients with chronic airflow obstruction (CAO) and eight age and sex matched, healthy control subjects the circadian variation in circulatory lymphocyte count was studied in relation to serum Cortisol and urinary epinephrine levels. In addition, we investigated the effect of the beta-adrenergic agent terbutaline on the lymphocyte count in two ways: as a long-term effect after 8 days of oral slow-release terbutaline with constant diurnal and nocturnal serum levels in patients, and as a short-term effect by a constant rate infusion of 0.2μg/min over 4hr in normals. Both patients and controls showed similar circadian patterns of urinary epinephrine excretion and lymphocyte counts. Patients with CAO, however, had significantly lower epinephrine levels and significantly higher lymphocyte counts at all hours of observation (every 4 hr from 0800 to 0800 hr the next day), as compared with normal controls. After 8 days of slow-release terbutaline the lymphocyte count in the patient group decreased to levels not significantly different from that of normals. The circadian rhythm of the lymphocytes, however, persisted under terbutaline therapy. No correlation existed between the lymphocyte count modulating factor, serum Cortisol and the lymphocyte count over 24 hr. On placebo infusion in the control persons an increase of lymphocytes over 4hr occurred, as a consequence of circadian rhythmicity. On terbutaline infusion a significant increase of lymphocytes after 1hr was follwed by a decrease to levels significantly below those on the placebo day. The same pattern was found in the leucocyte count. From this study it is concluded that beta-adrenergic stimulation corrects the relative lymphocytosis to counts comparable with normals. Other coinciding factors must regulate, however, the circadian rhythmicity.     

Clinical characteristics and co-infections of 354 hospitalized patients with COVID-19 in Wuhan,China: a retrospective cohort study

From December 2019, a novel coronavirus, SARS-CoV-2, caused an outbreak of pneumonia in Wuhan city and rapidly spread throughout China and globally. However, the clinical characteristics and co-infection with other respiratory pathogens of patients with COVID-19 and the factors associated with severity of COVID-19 are still limited. In this retrospective cohort study, we included 354 inpatients with COVID-19 admitted to Renmin Hospital of Wuhan University from February 4, 2020 to February 28, 2020. We found levels of interleukin-6, interleukin-10, C-reactive protein, D-dimer, white blood cell count and neutrophil count were clearly elevated in males and critical cases compared with females and severe and mild cases, respectively. However, lymphopenia was more severe in males than females and levels of tumor necrosis factor alpha were reduced significantly in critical cases than severe and mild cases. 23.5% of severe cases and 24.4% of critical cases were co-infected with other respiratory pathogens. Additionally, stepwise multivariable regression analysis suggested that co-infection, lymphocyte count and levels of D-dimer were associated with severity of COVID-19.These findings provide crucial clues for further identification of the mechanisms, characteristics and treatments of patients with COVID-19.     

Observations on neutropenia associated with haemodialysis

In the first 30 minutes of haemodialysis, in patients with chronic renal failure, there is a dramatic fall in total neutrophil count in the peripheral blood. An hour after the start of dialysis this has returned to normal.We have carried out a series of experiments in an attempt to elucidate the cause of this neutropenia. Both the patient and the membranes of the dialyser appeared to be a necessary combination to produce these changes, which could not be induced by the infusion of blood or saline that had previously been in contact with the dialyser. The composition of the dialysing fluid was not related to the fall of white count, and this fall was repeated when the patient was connected to a second dialyser after recovering from the neutropenia caused by the first. It was only when reusing a kidney, by rinsing it out and resterilizing it, that the neutropenia could be modified, but this was not a constant finding.     

Effect of Beta-Adrenergic Stimulation on the Circulatory Lymphocyte Count: Studies in Normals and in Patients with Chronic Airflow Obstruction

In eight non-allergic patients with chronic airflow obstruction (CAO) and eight age and sex matched, healthy control subjects the circadian variation in circulatory lymphocyte count was studied in relation to serum Cortisol and urinary epinephrine levels. In addition, we investigated the effect of the beta-adrenergic agent terbutaline on the lymphocyte count in two ways: as a long-term effect after 8 days of oral slow-release terbutaline with constant diurnal and nocturnal serum levels in patients, and as a short-term effect by a constant rate infusion of 0.2μg/min over 4hr in normals. Both patients and controls showed similar circadian patterns of urinary epinephrine excretion and lymphocyte counts. Patients with CAO, however, had significantly lower epinephrine levels and significantly higher lymphocyte counts at all hours of observation (every 4 hr from 0800 to 0800 hr the next day), as compared with normal controls. After 8 days of slow-release terbutaline the lymphocyte count in the patient group decreased to levels not significantly different from that of normals. The circadian rhythm of the lymphocytes, however, persisted under terbutaline therapy. No correlation existed between the lymphocyte count modulating factor, serum Cortisol and the lymphocyte count over 24 hr. On placebo infusion in the control persons an increase of lymphocytes over 4hr occurred, as a consequence of circadian rhythmicity. On terbutaline infusion a significant increase of lymphocytes after 1hr was follwed by a decrease to levels significantly below those on the placebo day. The same pattern was found in the leucocyte count. From this study it is concluded that beta-adrenergic stimulation corrects the relative lymphocytosis to counts comparable with normals. Other coinciding factors must regulate, however, the circadian rhythmicity.     

AECOPD并重度呼吸衰竭患者有创机械通气的治疗时机探讨及其预后的影响因素分析

摘要 目的：探讨慢性阻塞性肺疾病急性加重（AECOPD）合并重度呼吸衰竭患者有创机械通气的治疗时机,并分析其预后的影响因素。方法：选取2020年3月~2021年12月期间于首都医科大学附属北京世纪坛医院治疗的161例AECOPD合并重度呼吸衰竭患者,按照气管插管时间分为早期组（n=89）和延期组（n=72）,对比两组治疗后临床指标、血气分析指标及28 d内病死率（预后）。根据预后的不同将患者分为死亡组（n=29）和存活组（n=132）,收集患者的一般资料和实验室资料,采用Logistic回归分析预后的影响因素。结果：早期组的总机械通气时间、有创通气时间、重症监护室（ICU）住院时间均短于延期组（P<0.05）。两组治疗后动脉血二氧化碳分压（PaCO₂）较治疗前下降,氧合指数（OI）、动脉血氧分压（PaO₂）较治疗前升高,且早期组变化程度大于延期组（P<0.05）。延期组28 d内病死率为15/72（20.83%）。早期组28 d内病死率为14/89（15.73%）,两组患者的28 d病死率对比无差异（P>0.05）。单因素分析结果显示,AECOPD合并重度呼吸衰竭患者的预后影响因素与并发呼吸机相关肺炎、并发多脏器功能不全综合征、年龄、PaCO₂、血红蛋白（Hb）、血尿素氮（BUN）、白细胞计数（WBC）、pH值、中性粒细胞计数/淋巴细胞计数比值（NLR）、血小板计数/淋巴细胞计数（PLR）、C反应蛋白（CRP）、D-二聚体（D-D）、B型尿钠肽有关（P<0.05）。AECOPD合并重度呼吸衰竭患者预后不良的危险因素主要有并发呼吸机相关肺炎、并发多脏器功能不全综合征、PaCO₂偏高、年龄偏大、Hb偏低、pH值偏低、D-D偏高（P<0.05）。结论：AECOPD合并重度呼吸衰竭患者早期使用有创机械通气,可有效改善血气分析,缩短有创通气时间、总机械通气时间、ICU住院时间。并发呼吸机相关肺炎、并发多脏器功能不全综合征、PaCO₂偏高、年龄偏大、Hb偏低、pH值偏低、D-D偏高均是导致AECOPD合并重度呼吸衰竭患者预后不良的危险因素。