THE ROLE OF IMMUNOLOGICAL FACTORS IN THE UNFAVORABLE OUTCOME OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

L. M. Karzakova, Evgeniya P. Alekseeva, S. Kudryashov, N. Zhuravleva, N. D. Ukhterova, Natalia P. Andreeva
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Abstract

Aim. The aim of the research was to study the role of immunological mechanisms in the unfavorable outcome of chronic obstructive pulmonary disease (COPD). Material and methods. The research included 116 patients hospitalized in 2005-2006 in the pulmonology department of patients with the exacerbation of mild and moderate COPD. Research protocol: general clinical and special (immunological) methods of examination were performed in patients with COPD. Instrumental research methods included: spirography, ECG, EchoCG, fibrobronchoscopy, chest X-ray. After diagnostic bronchoscopy, bronchoalveolar fluid (BAF) was taken for cytological and immunological examination. On the first and second days of inpatient treatment, patients underwent immunological studies: immunophenotyping of mononuclear cells (MNC), assessment of phagocytic activity of leukocytes (latex test, nitroblue tetrazolium (NBT) test) in blood and BAF, determination of the content of immunoglobulins in blood serum and BAF, study of cytokine levels in blood serum, BAF and MNC culture supernatant under conditions of their spontaneous production and activation in the mitogen-stimulated (phytohemagglutinin "Difco" 5 mg/ml) proliferation. Statistical data processing was carried out using the Statistica 10.0 program. In 2020, the long-term survival of COPD patients was assessed. The cohort of patients was divided into two groups. Survivors were included in the first group (n=44), and patients who died by 2020 were included in the other group (n=72). The retrospective comparison of the studied indicators was determined at the time of COPD exacerbation in 2005- 2006 in these patient groups. Results and discussion. In the surviving patients, the BAF cytogram was distinguished by the higher macrophage content and the increased number of NBT-positive cells in this population with the reduced neutrophil content in both blood and BAF. The deceased had elevated levels of IgM and IgA in the blood serum and BAF. The results of the study of cytokine production in MNC cultures in vitro indicate that the ratio of IFN-γ/IL-4 in the conditions of spontaneous cytokine production was higher in the deceased compared with the indicators of the surviving patients. This fact indicates the polarization of the immune response of the deceased in the direction of the cell type mediated by Th1 cells, which is confirmed by the peculiarities of the BAF cytokine profile in the deceased – the significant increase in the value of IFN-γ/IL-4 relative to the indicators in the survivors. Conclusion. The unfavorable outcome of COPD is associated with the increase in the number of neutrophil cells in BAF, in the blood, with the predominance of Th1-type activation of adaptive immunity at the local level and activation of both cellular and humoral mechanisms of adaptive immunity at the systemic level. The increased activity of innate immunity in COPD exacerbation, manifested by the increase in the number and metabolic activity of macrophages, is associated with the long-term survival of patients.
免疫因素在慢性阻塞性肺疾病不良预后中的作用
的目标。本研究的目的是研究免疫机制在慢性阻塞性肺疾病(COPD)不良结局中的作用。材料和方法。该研究纳入了2005-2006年在肺科住院的116例轻中度COPD加重患者。研究方案:对COPD患者进行一般临床检查和特殊(免疫学)检查。仪器研究方法包括:肺活图、心电图、超声心动图、纤维支气管镜、胸部x线片。诊断性支气管镜检查后取支气管肺泡液(BAF)进行细胞学和免疫学检查。在住院治疗的第一天和第二天,患者进行免疫学研究:单核细胞(MNC)的免疫分型,血液和BAF中白细胞吞噬活性(乳胶试验、硝基蓝四唑(NBT)试验)的评估,血清和BAF中免疫球蛋白含量的测定,血清、BAF和MNC培养上清中细胞因子水平的研究,在有丝分裂原刺激下(植物血凝素“Difco”5 mg/ml)增殖的自发产生和激活条件下。统计数据处理采用Statistica 10.0软件。2020年,对COPD患者的长期生存进行了评估。患者队列被分为两组。第一组纳入幸存者(n=44),另一组纳入到2020年死亡的患者(n=72)。回顾性比较这些患者组在2005- 2006年COPD加重时所研究的指标。结果和讨论。在存活的患者中,BAF细胞图的特点是巨噬细胞含量较高,nbt阳性细胞数量增加,血液和BAF中中性粒细胞含量降低。死者血清和BAF中IgM和IgA水平升高。体外培养MNC细胞因子产生的研究结果表明,在自发细胞因子产生条件下,死者的IFN-γ/IL-4比值高于存活患者。这一事实表明,死者的免疫反应向Th1细胞介导的细胞类型方向极化,死者体内BAF细胞因子谱的特殊性证实了这一点——相对于幸存者的指标,IFN-γ/IL-4的值显着增加。结论。COPD的不利结果与血液中BAF中中性粒细胞数量的增加有关,在局部水平以th1型活化的适应性免疫为主,在全身水平以细胞和体液活化的适应性免疫机制为主。慢性阻塞性肺病加重时先天免疫活性的增加,表现为巨噬细胞数量和代谢活性的增加,与患者的长期生存有关。
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