Effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor of chronic obstructive pulmonary disease rat

Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.

Predictive role of interleukin-6 and CAT score in mechanical ventilation in patients with chronic obstructive pulmonary disease at the acute exacerbation stage in the emergency department

BACKGROUND:The study aimed to evaluate the predictive role of interleukin-6(IL-6)and chronic obstructive pulmonary disease(COPD)assessment test(CAT)score in mechanical ventilation(MV)in COPD patients at the acute exacerbation stage in the emergency department(ED).METHODS:For a one-year period,among adult patients in the ED who met the criteria of acute exacerbation of COPD,158 who received MV within 48 hours after admission were compared to 294 who didn't require MV within the same period after admission.IL-6 level and CAT score were compared between the two groups.The predicted value of IL-6 and CAT score was assessed by logistic regression analysis and a receiver operating characteristic(ROC)curve.RESULTS:The IL-6 and CAT scores in the 158 MV patients were much higher than those without.IL-6 and CAT scores were independent predictors of MV within 48 hours using logistic regression analysis(IL-6:odds ratio[OR]1.053,95%confidence interval[CI]1.039–1.067,P<0.001;CAT score:OR 1.122,95%CI 1.086–1.159,P<0.001).The combination of IL-6 and CAT scores(area under ROC curve[AUC]0.826,95%CI 0.786–0.866,P<0.001)improved the accuracy of predicting MV within 48 hours when compared with IL-6(AUC 0.752,95%CI 0.703–0.800,P<0.001)and CAT scores alone(AUC 0.739,95%CI 0.692–0.786,P<0.001).The sensitivity and specificity were 69.6%,74.1%,75.32%and 63.6%,respectively.CONCLUSION:The combined of IL-6 and CAT scores is useful for evaluating the risk of COPD patients at acute exacerbation in ED,and can provide a predictive value for MV or not within 48 hours.

Effect of Yufeining (愈肺宁) on Induced Sputum Interleukin-8 in Patients with Chronic Obstructive Pulmonary Disease at the Stable Phase

Objective： To evaluate the effect of Yufeining （愈肺宁）, a traditional Chinese medicine, on induced sputum interleukin-8 ilL-8） in patients with chronic obstructive pulmonary disease （COPD） at the stable phase. Methods： Thirty-six patients with COPD were divided into trial group （18 cases） and control group （18 cases） randomly. The trial group was treated with Yufeining pills taken orally for half a year; the control group was not given any medicine. Routine lung function was recorded before and after treatment. Total cell count （TCC）, differential cell counts （DCCs） and IL-8 in induced sputum were determined at the baseline and 6 months later. Results： The indices of lung function improved significantly after 6 months＇ treatment in trial group （P〈0.05）; TCC and absolute neutrophil count decreased significantly compared with baseline in the trial group （P〈0.05） ; Sputum IL-8 concentration dropped significantly after 6 months＇ treatment, from a mean of 5. 216±2.914 μg/L to 4. 222±2. 140 μg/L （P〈0.05）. There were insignificant changes in the parameters in the control group between baseline and 6 months later. Conclusion： Yufeining could improve lung function, decrease sputum TCC, absolute neutrophil count and IL-8 concentration, and relieve airway inflammation in patients with COPD in the stable phase.

Research advances concerning the mechanism of glucocorticoid resistance in relation to traditional Chinese medicine for patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is a common,highly disabling,and burdensome disease.Anti-inflammatory glucocorticoid medication plays a key role in its treatment;however,glucocorticoid resistance in patients with chronic obstructive pulmonary disease considerably weakens the effects of the treatment.Despite recent advances in determining the mechanism of glucocorticoid resistance in patients with chronic obstructive pulmonary disease,the role of traditional Chinese medicine in treating such patients remains unclear.In this review,we reviewed the mechanism of chronic obstructive pulmonary disease-related glucocorticoid resistance with reference to the glucocorticoid receptor,the important signaling pathways(phosphatidylinositol-3-kinase/protein kinase B signaling pathway,p38 mitogen-activated protein kinase signaling pathway,and interferon-γ/Janus kinase/stransducer and activator of transcription signaling pathway),histone deacetylase,nuclear transcription factor-κB,exosomes,and microRNA.Moreover,the methods of establishing the glucocorticoid resistance model associated with chronic obstructive pulmonary disease and advances in therapeutic approaches including traditional Chinese medicine to restore chronic obstructive pulmonary disease glucocorticoid sensitivity have also been reviewed.This review shows that traditional Chinese medicine reverses glucocorticoid resistance mainly by regulating the expression of glucocorticoid receptor,p38 mitogen-activated protein kinase signaling,histone deacetylase 2,and nuclear transcription factor-κB in chronic obstructive pulmonary disease models.Future research is suggested to evaluate traditional Chinese medicine understanding of chronic obstructive pulmonary disease-related glucocorticoid resistance in relation to exosomes,microRNA,and other signaling pathways.

A new in ammation marker of chronic obstructive pulmonary disease– adiponectin

BACKGROUND： This study was undertaken to measure the concentration of adiponectin （APN） in serum and induced sputum in patients with chronic obstructive pulmonary disease （COPD during acute exacerbation （AECOPD） and at stable stage and to determine the role of APN as a marker of in？ ammation in the pathogenesis of COPD.METHODS： All the patients in this prospective study were enrolled from October 2008 to October 2009, including 30 male AECOPD patients from the emergency department, 30 male stable COPD patients from the department of respiratory diseases, and 30 healthy non-smoking male controls from the department of medical examination. The serum and induced sputum were collected from each patient. All of the patients had normal weight （BMI range 18.5-24.9 kg/m2）. Patients with severe bronchial asthma, bronchiectasis or autoimmune disease were excluded. Cell count and classi？ cation was performed for the induced sputum. The concentrations of APN, IL-8, IL-6 and TNF-α were measured by ELISA. Pulmonary function was tested among the three groups. Comparisons between the groups were conducted by Student＇s t test, ANOVA analysis or nonparametric test. Correlation analysis was carried out by Pearson＇s product-moment correlation coef？ cient test or Spearman＇s rank-order correlation coef？ cient test.RESULTS： The concentrations of APN in the serum or induced sputum in AECOPD patients were signi？ cantly higher than those in stable COPD patients or healthy non-smoking controls （P〈0.01）. The concentration of APN in stable COPD patients was signi？ cantly higher than that in healthy non-smoking controls （P〈0.01）. For the AECOPD patients, APN was positively correlated with IL-8 and TNF-α in the serum and induced sputum （r=0.739, 0.734, 0.852, 0.857 respectively, P〈0.05）. For the stable COPD patients, APN was also positively correlated with IL-8 and TNF-α in the serum and induced sputum （r=0.751, 0.659, 0.707, 0.867 respectively, P〈0.05）. In addition, for the AECOPD patients, APN was positively correlated with the percentage of neutrophils in the induced sputum （r=0.439, P〈0.05）.CONCLUSIONS： APN is involved in the process of systematic and airway inflammation ofCOPD. This process is related to neutrophils in the airway, IL-8 and TNF-α. APN could be used as a new marker for in？ ammation of COPD.

Effect of polymorphisms in the β2-adrenergic receptor on the susceptibility and pulmonary function of patients with chronic obstructive pulmonary disease： a meta analysis

Background Chronic obstructive pulmonary disease （COPD） is a heterogeneous and complex disease of which the pathogenesis remains largely unknown. Many factors could influence COPD development and progression. One of them is the genetic risk factor. A severe hereditary deficiency of alpha-1 antitrypsin is the best genetic proof. Four single nucleotide polymorphisms （SNPs） of beta2-adrenergic receptor （β2AR） result in single amino acid substitution. Two loci had been extensively studied and found that they could change the function of β2AR. Two SNPs consist of substitutions of glycine for arginine at amino acid position 16, glutamic acid for glutamine at position 27. Many studies proved that polymorphisms at position 16 and 27 altered the lung function of COPD patients or the patient＇s susceptibility to the development of COPD. However, there was no exclusive conclusion. Therefore, a meta analysis was done to investigate the effect of polymorphisms in the 62-adrenergic receptor （ADRB2） gene on the risk of COPD and lung function. Methods Comprehensive searches of MEDLINE, Embase, Ovid, HighWire, Cochrane Library, and Chinese databases （CBMdisc, VIP, CNKI, and Wanfang data） from January 1980 to September 2011 were performed, using the keywords： COPD OR chronic obstructive pulmonary disease AND adrenoreceptor OR adrenergic receptor AND polymorphism OR mutation OR variation. Case-control research or cross sectional studies in which diagnosis of COPD met the Global Initiative for Chronic Obstructive Lung Disease （GOLD） guidelines; all the studies reported the ADRB2 genotype at position 16 or 27. Outcomes measured were genotype frequency and forced expiratory volume in the first second （FEV1%） in both the case and control. Results Twelve case-control studies and eight cross-sectional studies were included. Compared to the control （n= 1225）, neither Gly/Gly （n=527） nor Arg/Arg （n=422） homozygotes at position 16 demonstrated increased susceptibility to COPD, with odds ratios （ORs） of 0.95 （95% CI （0.68, 1.31）, z=0.33, P=0.740） and 0.82 （95% CI （0.52, 1.28）, z=0.88, P=0.381）, respectively. Similar results were obtained for position 27, with ORs of 0.97 （95% CI （0.77, 1.23）, z=0.21, P=0.833） for Glu/Glu homozygotes （n=357） and 0.82 （95% CI （0.53, 1.29）, z=0.85, P=0.393） for Gin/Gin homozygotes （n=704） （control=1183）. In patients with COPD, Arg/Arg homozygotes （n=41） had a similar FEV1% compared with Gly/Gly homozygotes （n=102） （standardized mean difference （SMD）=0.88, 95% CI （-0.85, 2.62）, z=1.00, P=0.319）. The genotype distribution was different between Caucasian and Asian populations （all P 〈0.05 except the genotype Arg/Gly） for both position 16 and 27. Conclusions Polymorphisms of ADRB2 at positions 16 and 27 did not change the risk of COPD nor affect lung function or disease severity. The genotype distribution for these polymorphisms was different between Caucasian and Asian populations.

Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease

OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.

The relationship between the expression of transient receptor potential vanilloid 1 and the airway remodeling in elderly patients with chronic obstructive pulmonary disease

Objective To investigate the relationship between the expression of trannsient receptor potential vanilloid(TRPV1)and the severity of airway remodeling in elderly patients with chronic obstructive pulmonary disease(COPD).Methods According to airflow obstruction severity,totally 100 cases of elderly patients with

Expression and role of adrenomedullm and its receptor in patients with chronic obstructive pulmonary disease

Objective To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).Methods Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n =12) and those with PH were placed in Group B (n =10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted.Results The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD ( P < 0. 01). In situ hybridization showed that ADM mRNA and ADMR mRNA were expressed in the pulmonary artery walls of control subjects . The expression levels were significantly higher in those of COPD sufferers ( P < 0. 01). Statistically positive relationships were visible between ADM and ADMR, and the plasma ADM level of Group B was significantly higher than that of Group A (P < 0. 05). The plasma ADM level had a significantly positive correlation to mPAP and pulmonary vascular resistance (PVR), while being negatively correlated to levels of PaO2.Conclusion ADM may play an extremely protective role as a local autocrine/paracrine factor in COPD.

High levels of interleukin-6 and 8-iso-prostaglandin in the exhaled breath condensate and serum of patients with chronic obstructive pulmonary disease related pulmonary hypertension

Background Pulmonary hypertension （PH） is a common complication of chronic obstructive pulmonary disease （COPD）. Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD. Methods We measured the levels of interleukin-6 （IL-6） and 8-iso-prostaglandin （8-iso-PSG） in exhaled breath condensate （EBC） and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure （PASP） was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg. Results Compared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH （（8.27±2.14） ng/L vs. （4.95±1.19） ng/L, P 〈0.01）. The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group （（72.8±21.6） ng/L vs. （43.58±13.38） ng/L, P 〈0.01 ）. Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group （EBC： （9.00±2.49） ng/L vs. （5.96±2.31） ng/L, P 〈0.01 and serum： （41.87±9.75） ng/L vs. （27.79±11.09） ng/L, P 〈0.01）. Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum （r=0.477-0.589, P 〈0.05）. Conclusion The increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Association of gene polymorphisms of tumour necrosis factor-α and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing

Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α) has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-α and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-α gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.Methods A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction (PCR) to determine the polymorphism at -1055 in the IL-13 gene promoter region. PCR restriction fragment length polymorphism (RFLP) was used to determine polymorphisms in the TNF-α gene-308 position. The products were investigated by sequence analysis also. Results One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% (13/111) in the COPD group and 13.4% (13/97) in the controls (P=0.713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62-25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR=7.7 (95% CI 1.37-43.80). The frequencies of A allele in the TNF-α gene were 5.9% in COPD and 3.1% in controls (P=0.131). The OR value of A allele was 5.0 (95% CI 1.011 to 25.059) in smokers with COPD. Conclusions There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-α between Han Chinese patients with COPD versus control. Thus, it does not appear that theseSNPs are independent factors in COPD for Han nationality in (Beijing. However,)these SNPs may increase the risk of COPD among smokers.

Association between the interleukin-13 gene and development of chronic obstructive pulmonary disease in southern Chinese Han population： a case-control study

Background Interleukin-13 （IL-13） has been implicated to be responsible for recruitment of inflammatory cells from the blood to the lung,regulation of matrix metalloproteinase and induction of mucin production and secretion in chronic obstructive pulmonary disease （COPD）.We determined plasma IL-13 levels in patients with COPD and investigated its association with common polymorphisms of IL-13 gene in a case-control study.Methods We genotyped 160 cases and 175 control subjects in a local hospital using Mass-ArrayTM Technology Platform then tested the association of four SNPs in IL-13 （rs1295685,rs1800925,rs1881457,rs20541） with COPD,and then determined plasma IL-13 levels in patients with COPD and controls.Results Association was found between IL-13 gene SNPs （rs20541 and rs1800925） and an increased risk of COPD.By linkage disequilibrium （LD） analysis,two blocks （rs1881457 and rs1800925; rs20541 and rs1295685） were found.The risk of COPD was found associated with the IL-13 gene polymorphism among southern Chinese Han population.Plasma IL-13 level was increased in COPD patients compared with controls.Conclusions The polymorphism of the IL-13 gene is associated with an increased risk of COPD in southern Chinese Han population.Plasma IL-13 levels were found elevated in patients with COPD.

Cyclooxygenase 2 1195G〉A polymorphism is associated with chronic obstructive pulmonary disease in Japanese and Chinese patients

Background Cyclooxygenase-2 （COX-2） is overexpressed during airway inflammation in chronic obstructive pulmonary disease （COPD） patients.Single nucleotide polymorphisms （SNPs） in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to COPD.We investigated the association between COX-2 （-765G〉C,-1195G〉A） polymorphisms and COPD susceptibility in Japanese and Chinese patients.Methods COX-2 genotypes were determined by polymerase chain reaction,restriction fragment length polymorphism in 230 COPD patients （103 Japanese and 127 Chinese） and 273 healthy controls （129 Japanese and 144 Chinese）.Results The frequency of-1195AA homozygote was significantly higher than the controls in Chinese COPD （adjusted OR=2.43,95% CI 1.14-4.19）,Japanese COPD （adjusted OR=-2.25,95% Cl 1.06-4.76） and combined COPD groups （adjusted OR=2.26,95% CI 1.34-3.99）.There was no difference in COX-2-765G〉C polymorphism between COPD and control groups in either Japanese or Chinese,while more Chinese individuals carried the-765C allele than Japanese in both groups （15.3% vs.2.9% in COPD,18.8% vs.5.5% in control）.Chinese individuals with the haplotype-765G：-1195A were at higher risk for COPD （adjusted OR=1.93,95% CI 1.05-3.55）.Conclusions The COX-2-1195AA genotype is associated with increased risk for COPD in both Japanese and Chinese individuals.Although COX-2-765G〉C polymorphism was not associated with COPD in either ethnic group,the-765C allele frequency was higher in Chinese than Japanese and haplotype-765G-1195A may confer susceptibility to COPD in Chinese.

Association of chronic obstructive pulmonary disease with type 2 diabetes mellitus

Chronic obstructive pulmonary disease （COPD） is a complex disorder, characterized by an irreversible airflow limitation during breathing. This may lead to various extrapulmoanry comorbidities, such as cardiovascular disease, osteoporosis, and diabetes mellitus （DM）. Type 2 （T2DM） accounts for a large proportion of DM, and is also showing a rising prevalence in developed and developing countries. In addition to the known factors for T2DM, several studies have demonstrated that COPD is also an important risk factor for T2DM. In this study, we aimed to determine the prevalence of COPD in patients with T2DM, and to analyze the clinical characteristics of COPD accompanied by T2DM.

Association between restrictive pulmonary disease and type 2 diabetes in Koreans:A cross-sectional study

BACKGROUND Diabetes is a progressive disease that increases glucose levels in the blood.While studies have shown that patients with pulmonary disease(both obstructive and restrictive pulmonary disease)have a higher prevalence of type 2 diabetes mellitus(T2DM),there have been more studies on restrictive patterns than chronic obstructive pulmonary disease.AIM To assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans.METHODS For our analysis,we used data from the Korea National Health and Nutrition Examination Survey.A total of 2830 subjects were included in this study.Spirometry results were categorized into three patterns:Normal,restrictive pulmonary disease(RPD),and obstructive pulmonary disease(OPD).RESULTS The factors used as diabetic indicators(i.e.homeostatic model assessment of insulin resistance,homeostatic model assessment of beta-cell function,glycated hemoglobin,and fasting insulin)were among the highest in RPD but not in OPD.Based on multivariate logistic regression analysis,subjects with RPD were found with an increased odds ratio[OR:1.907,95%confidence interval(CI):1.110-3.277]for T2DM compared with subjects with normal pulmonary function,whereas in patients with OPD,the OR had not increased.Model 4,which adjusted for the variables that could affect diabetes and pulmonary disease,showed a significant increase in the T2DM OR to RPD(OR:2.025,95%CI:1.264-3.244).On the other hand,no statistically significant difference was shown in OPD(OR:0.982,95%CI:0.634-1.519).CONCLUSION RPD,not OPD,is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.

CCR1 and CCR5 expression on inflammatory cells is related to cigarette smoking and chronic obstructive pulmonary disease severity

Background Chronic obstructive pulmonary disease （COPD） is a progressive disease associated with a cellular inflammatory response mostly concerned with cigarette smoking. Chemokine receptors CCRI/5 play an important role in the inflammatory cells recruitment in the lung of COPD patients. The aim of this study was to determine the impact of cigarette smoking on the expression of CCRI/5 on inflammatory cells in induced sputum, and the relationship between the receptors expression and COPD severity. Methods Differential cells in induced sputum were counted and the optical densities of CCR1 and CCR5 on inflammatory cells in induced sputum from COPD patients （n=29）, healthy smokers （n=11）, and nonsmokers （n=6） were measured using immunocytochemistry. Concentrations of CCL3, the ligand of CCRI/5, in supernatant of induced sputum were detected by enzyme-linked immunosorbent assay. Results The expressions of CCR1 and CCR5 on inflammatory cells in healthy smokers were significantly higher than those in nonsmokers, and the expression of CCR1 in patients with COPD was significantly increased when compared with nonsmokers but not healthy smokers. The expressions of CCR1 and CCR5 on inflammatory cells in severe and very severe COPD patients were higher compared with mild and moderate COPD patients. CCL3 level was positively correlated with the total cell counts in induced sputum and smoking history, and negatively correlated with percentage of predicted FEV1. Conclusions Cigarette smoking could increase the expression of CCR1 on the inflammatory cells. Both CCR1 and CCR5 expressions on the inflammatory cells in induced sputum could be associated with COPD severity.

Effect of Tanreqing Injection(痰热清注射液)on Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Chinese Medicine Syndrome of Retention of Phlegm and Heat in Fei(肺)

Objective：To explore the effect of Tanreqing Injection（痰热清注射液,TRQI） on the treatment of acute exacerbation of chronic obstructive pulmonary disease（AECOPD） with Chinese medicine syndrome of retention of phlegm and heat in Fei（痰热阻肺证,RPHF）.Methods：In a prospective randomized controlled clinical trial,90 patients with AECOPD of RPHF syndrome were randomly assigned to 3 groups,TRQI and controls A and B,each with 30 cases.The TRQI group was administered with the intravenous injections of 20 mL TRQI once a day and conventional Western medicine treatment.Control group A was administered with the intravenous injection of 15 mg ambroxol hydrochloride twice a day and conventional Western medicine treatment,and control group B was administered with conventional Western medicine treatment only.The treatments were administered for 10 days.Chinese medical symptoms and signs were scored,and plasma concentrations of interleukin（IL）-8 and neutrophil elastase（NE） were recorded.Results：（1） The Chinese medical symptoms （cough,sputum amount,expectoration,dyspnea and fever） and signs（tongue and pulse） improved significantly in the TRQI group（P〈0.05 or P〈0.01）,and improvements in cough,sputum amount and expectoration were better in the TRQI group than control group B（P〈0.05）;there was no significant difference between the TRQI group and control group A（P〉0.05）.The sign of tongue was also improved significantly in the TRQI group （P〈0.05）.（2） The overall effects in the TRQI group and control group A were significantly better than in control group B（P〈0.05）,with no significant differences between the TRQI group and control group A（P〉0.05）.There was no significant difference in the total effective rate among the three groups（P〉0.05）.（3） After treatment, the plasma concentrations of IL-8 and NE decreased in the TRQI group and control group A（P〈0.05）,and the concentration of IL-8 in control group B decreased（P〈0.05）.The difference in IL-8 was greater in the TRQI group than in control group A and B before and after treatment,and the change in NE was greater in control group A than in the TRQI group and control group B,but there was no statistical significance among the three groups with regards to the change in IL-8 or NE（P〉0.05）.Conclusion：TRQI could improved the Chinese medical signs and symptoms in the patients with AECOPD,possibly because of the decreasing plasma levels of IL-8 and NE which could improve response to airway inflammation and mucus hypersecretion.

Effects of leukotriene receptor antagonist on chronic obstractive pulmonary disease induced pulmonary hypertension

Objectives To assess the hemodynamic, oxygen-dynamic and ventilative effects of Zafirlukast in chronic obstructive pulmonary disease (COPD) induced chronic cor pulmonale at acute exacerbation stage and the mechanisms of Zafirlukast efficacy.Methods Eleven cases of chronic cor pulmonale at acute exacerbation were examinted using Swan-Ganz catheter and peripheral intra-artery catheter. The hemodynamic, oxygen-dynamic parameters and respiratory rate, plasma endothelium-1 (ET-1) level, and urea leukotriene E4 (LTE4) level were measured before and at the 1st, 3rd, 5th, 7th, 9th, 12th hour after taking 40 mg Zafirlukast orally. Artarial and mixed venous blood gas analyses were done correspondingly.Results The average pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRI) were lowered at the 3rd hour after taking Zafirlukast by 23% and 36.5%, respectively. They returned to the baseline around 12th hour. Respiratory rate decreased significantly within the 3rd-7th hour after taking Zafirlukast. LTE4 and ET-1 levels lowered at the 3rd hour and showed a positive correlation with change of mPAP. Conclusions Zafirlukast can reduce mPAP, pulmonary vascular resistance (PVR) and does not affect the ambulatory blood pressure monitoring (ABPM) and oxygenation in cases of chronic cor pulmonale at acute exacerbation stage. Zafirlukast may play a role as an alternative to decrease PAP in COPD patients.

Richness of sputum microbiome in acute exacerbations of eosinophilic chronic obstructive pulmonary disease

Background:The eosinophilic chronic obstructive pulmonary disease(COPD)is known to be more sensitive to corticosteroid.The sputum microbiome has been shown to affect COPD prognosis,but its role in acute exacerbations of eosinophilic COPD is unclear.This study aimed to investigate the dynamic changes of the airway microbiome in patients with acute exacerbations of eosinophilic COPD.Methods:Fifty-seven patients with acute exacerbations of COPD from the First Affiliated Hospital of Guangxi Medical University between June 2017 and June 2018 were divided into two groups.Patients with eosinophils≥300 cells/mL in the peripheral venous blood were assigned to the eosinophilic group(Eos)and the rest to the non-eosinophilic group(Noneos).All patients received similar treatment including inhaled budesonide according to the guidelines.The induced sputum microbiome was analyzed on the 1st and 7th day of treatment using the 16S ribosomal RNA(rRNA)method.The levels of interleukin(IL)-6 and IL-8 were measured in the plasma and the sensitivity to corticosteroids was determined in isolated peripheral blood mononuclear cells.Quantitative data were compared between the two groups using the independent samples t test or Mann-Whitney U test.Categorical data were evaluated using Chi-squared test or Fisher’s exact test.Results:Twenty-six patients were classified into Eos group and 31 patients were classified into Noneos group.Prior to treatment,the alpha diversity(Shannon index)(2.65±0.63 vs.2.56±0.54,t=0.328,P=0.747)and the structure of the sputum microbiome were similar in the Eos group and the Noneos group.After 7 days of treatment,alpha diversity increased in both groups,while the microbiome richness(Ace index)was significantly lower in the Eos group(561.87±109.13 vs.767.88±148.48,t=-3.535,P=0.002).At the same time,IL-6(12.09±2.85 pg/mL vs.15.54±2.45 pg/mL,t=-4.913,P<0.001)and IL-8(63.64±21.69 pg/mL vs.78.97±17.13 pg/mL,t=-2.981,P=0.004)decreased more significantly in the Eos group,and the percentages of inhibition of IL-8 at dexamethasone concentrations 10-8 to 10-6 mol/L were significantly higher in the Eos group than those in the Noneos group(all P<0.05).Conclusions:The induced sputum microbiome richness decreased more significantly following treatment in the Eos patients compared to the Noneos patients.The lower plasma inflammatory factor levels and the higher percentage of inhibition of IL-8 might be due to higher corticosteroid sensitivity in Eos patients.

Achieving therapeutic benefits of inhaled corticosteroids/beta2 agonist in chronic obstructive airway disease

Asthma and chronic obstructive pulmonary disease t（COPD） are the two commonest causes of adultairflow obstruction. The fundamental dltterences anti similarities between the pathological mechanisms of asthma and COPD are well recognized.^1 Both asthma and COPD involve inflammation of airway, but the pattern and distribution of inflammation markedly differ between typical patients with asthma and COPD. Chronic lung disease is now the most important long-term pulmonary complication in daily practice, and is associated with prolonged hospitalization and long-term pulmonary and clinical problems.^2