Differential Treatment Of Aecopd Respiratory Failure Evaluation And Monocyte Toll-like Receptors And Cytokines In Peripheral Blood

Objectivechronic obstructive pulmonary disease (COPD) combined with acute respiratory failure are key drivers of morbidity and mortality, which results in an economic and social burden that is both substantial and increasing. It is reported that treatment with Traditional Chinese Medicine(TCM) may do some benefit to the disease, but the quality of evidence is poor, and mechanism about TCM treatment is not so clear. Inflamation induced by inflammatory cells appears to be amplified in patients who develop COPD. TLRs (Toll-like receptors) comprise a family of proteins whose function is principally to facilitate the detection of, and response to pathogens, viruses, bacteria and fungi can all activate TLR signaling pathway, and these signals have important roles in the activation of COPD host defence. But most of our knowledge of TLRs has emerged from studies of animals. The contribution of TLRs function to human COPD is less advanced.To investigate clinical therapeutic effect of patients with AECOPD and respiratory failure by treatment of syndromes differentiation of TCM, and the pathogenesis of treatment of syndromes differentiation of TCM, their cellular and molecular mechanisms, and how these underlie physiologic abnormalities and symptoms characteristic of the disease.MethodsOf a total of 104 patients, we randomly assigned 52 to the control group and 52 to the experimental group. The control group were treated by conventional medicine treatment, the experimental group were treated by TCM besides conventional medicine treatment. The primary efficacy endpoint was mortality, intubation and extubation rate and VAP rate. Secondary endpoints included health status measured by symptomes scores, APACHEâ…¡scores, blood rutine examination, blood gas analysis and MMRC scores (measured the 0,4,7,14 day after study medication). The expression of TLR4 surface molecules on human CD 14⁺ monocytes was assessed using FACS analysis by flow cytometry (measured the 0 and 14 day), so is CD4⁺,CD8+T cells. The TLR4mRNA,CD14mRNA,NF-κBp65 mRNA of human CD 14⁺ monocytes was assessed by Reverse Transcriptase Polymerase Chain Reaction method(measured the 0,7,14 day)..β-EP,IL-1b,IL-6,IL-8,TNF-α,IFN-γin peripheral blood of patients were assessed by means of enzyme linked immunosorbent assay method(measured the 0,7,14 day). Safety was assessed by documenting all adverse events. Routine examination of blood, urine, stools, liver and renal function, electrocardiograms were performed at days 0 and 14.ResultsOf a total of 104 patients,52 were assigned to the control group and 52 to the experimental group.3 in experimental group and 4 in the control group drop out. 1 2(3.85%) of patients in experimental group died compared with 3 (5.77%) in the control group (P=0.6467).8 (15.38%) of patients in experimental group intubated compared with 11 (21.15%) in the control group(P=0.6118).6(75.0%) extubated in experimental group compared with 4(36.36%) in the control group(P=0.0959). More ventilator-associated pneumonia were reported in the control group relative to experimental group (P=0.0397).2 The clinical status in experimental groups decreased significantly compared to the control group during the study period(P=0.041), and so was the symptomes scores(P=0.016). There was no significant difference about scores of signs between the two groups (P=0.322).Score of the independent item such as cough, expectoration, gasping, short breath, lack of power, palpitation, upset, abdominal distension and edema decreased significantly compared to the control group during the study period. Dyspnea, sweating, headache, paraphasia, anorexia, wheezing, cyanosis and mental status scores of TCM patients showed no difference to the control group.3 APACHEâ…¡score were decreased in both the two groups at days 14, it was lower in the experimental treatment group than the control group during the study period (P=0.040)4 Total white cell count in peripheral blood and the neutrophil percentage decreased in the two groups at days 14, it was lower in the experimental treatment group during the study period, there was no major difference between the two groups(P=0.336, P=0.517).5 Arterial oxygen tension(PaO₂) increased in both the two groups during the study period, it was higher in the experimental treatment group, and there was significant difference between the two groups(P=0.002). Partial pressure of carbon dioxide (PaCO2) in the experimental treatment group showed no significant difference to the conventional treated patients (P=0.988).6 CD4(+) T cells and ratio of CD4⁺/CD8⁺ increased in AECOPD patients, CD8(+) T cells in experimental group increased over the study period(P<0.01), CD4(+), CD8(+) T cells in control group increased too ratio of CD4⁺/CD8+ decreaced. there were no significant difference between the two groups(P>0.05).7 The MMRC dyspnoea scale scores decreased in both group during the study period (P=0.000), it was lower in the experimental treatment group than the control group during the study period (P=0.007)8 CD 14 on AECOPD patients peripheral blood monouclear cell were little lower compared to normal using FACS analysis, and decreased significantly compared to the stable COPD patients (P<0.05). the CD 14 X-mean expressed elevated in stable COPD patients and decreased in severe AECOPD patients, there were no significant difference between them. TLR4 was elevated in stable and AECOPD patients as compared to normal ones, there was significant difference between COPD patients and normals (P<0.05). TLR4 X-mean expressed elevated in stable and AECOPD patients, there was no significant difference between three groups. 9 CD 14 expression were elevated in the experimental(P>0.05) and down-regulated in control group(P>0.05) after treatment. CD14 X-mean expression were not changed much in both groups, and there was no significant difference between them. Expression of TLR4 on monouclear cell were similar in the two groups, and reduced over the treatment period, there was no significant difference as compared to before treatment. TLR4 X-mean expression down-regulated in experimental group and control group, there was no significant difference as compared to before treatment and between them(P>0.05).10 Compared with the control group, TLR4mRNA,CD14mRNA. NF-κBp65mRNA in monocyte of the experimental group decreased after treatment, The expression levels of CD14mRNA decreased significantly(P=0.020)11 C-reactive protein in serum was reduced in both the two groups after treatment, CRP in the experimental group reduced more compare to the control group (P=0.045).12 The level ofβ-EP,IL-1b,IL-6,IL-8,TNF-αin serum was reduced in the experimental group after treatment, all the cytokines in the experimental group reduced more than the control group, especially the IL-8 (P=0.047) and TNF-α(P=0.032). IFN-γin serum was increased gently in the experimental group, but no more than the control group (P<0.05).13 Safety evaluation, treatment by syndromes differentiation of TCM is safe and effective, no severe adverse reaction reported. Only a few reporting some adverse event, the most frequent of which were diarrhea and abdominal distension.Conclusion1 Treatment by syndromes differentiation of TCM to patients with COPD exacerbations and respiratory failure have obvious therapeutic effect. It can relieve clinical symptoms, decrease APACHEâ…¡score and the MMRC dyspnea scale outcome. The mechanism of action may related to the following reason.2 CD 14 and TLR4 expression on monouclear cell increaced in patients with AECOPD and respiratory failure, so peripheral blood monouclear cell may related to the disease.3 TCM may have the role cf inhibiting activation of TLR4 and nuclear factor-kappaB signaling pathway on peripheral blood monoeytes in patients with AECOPD with respiratory failure, which may associated with reduced cytokine concentration, then relieving the sytemic inflammatory responses. The concentration of CRP,IL-8,TNF-αrelevant to severity of the disease, and maybe it can be take as a biomarker for AECOPD.4 The experimental group have some advantage in VAP rate. The experimental group have less in intubation and more extubation patients, given more sample, it might be a difference conclusion. There were no significant difference in death rate in the two groups,...