【Abstract】 Objective To observe the plasma levels of adiponectin and interleukin-17 ( IL-17) in patients with chronic obstructive pulmonary disease ( COPD) at acute exacerbation or stable stage, and analyze their relationship. Methods Sixty male COPD patients with normal weight ( with BMI range of 18. 5-24. 9 kg/m2 ) were enrolled, including 30 patients with acute exacerbations of COPD ( AECOPD) and 30 patients with stable COPD. Twenty healthy nonsmoking male volunteers were included as controls. The plasma levels of adiponectin and IL-17 as well as lung function ( FEV1% pred and RV% pred) were measured in all subjects. Results The concentrations of adiponectin and IL-17 were significantly higher in the AECOPD patients than those of the patients with stable COPD and the contro1s ( P lt; 0. 001) . Theconcentrations of adiponectin and IL-17 were significantly higher in the patients with stable COPD than those of the controls ( P lt;0. 01) . Adiponectin was positively correlated with IL-17 in the AECOPD patients ( r =0. 822, P lt;0. 001) and in the patients with stable COPD ( r =0. 732, P lt;0. 001) . Adiponectin was positivelycorrelated with RV% pred in the AECOPD patients ( rs = 0. 764, P lt;0. 001) and in the patients with stable COPD ( rs =0. 967, P lt;0. 001) . There was no significant relationship between adiponectin and FEV1% pred ( P gt;0. 05) . Conclusions The plasma level of adiponectin in COPD patients is elevated which is relatedwith excessive inflation of lung. Adiponectin may be involved in the process of inflammation in COPD as a new pro-inflammatory cytokine.
Objective To study the effect of noninvasive positive pressure ventilation (NPPV) in chronic obstructive pulmonary disease (COPD) patients with hypercapnic coma secondary to respiratory failure.Methods COPD patients with or without coma secondary to respiratory failure were both treated by bi-level positive airway pressure (BiPAP) ventilation on base of routine therapy.There were 32 cases in coma group and 42 cases in non-coma group.Such parameters as arterial blood gas (ABG)，Glasgow coma scale (GCS)，time of NPPV therapy，achievement ratio，and adverse effects were investigated.Results 30 patients in the coma group were improved after NPPV treatment (26 cases recovered consciousness treated by BiPAP in 2 hours，3 cases recovered between 3~8 hours，1 case recovered after 24 hours).The parameters of ABG，the tidal volume and the minute ventilation volume were improved after BiPAP.The time of effective therapy was (9±4) days in the coma group and (7±3) days in the non-coma group with no significant difference (Pgt;0.05).The achievement ratio was similar in two groups (93.75% vs 97.62%，Pgt;0.05).But the incidence of gastrointestinal tympanites reached to a higher level in the coma group (80.5%) than the non-coma group (10.6%).Conclusion COPD patients with hypercapnic coma secondary to respiratory failure isn’t the absolute contraindication of NPPV treatment.
Objective To investigate the changes of pulmonary diffusing capacity and pulmonary capillary blood volume in stable COPD patients with mixed ventilation dysfunction, and explore the possible pathophysiological factors. Methods 159 stable COPD patients with mixed ventilation dysfunction were recruited in the study and 36 normal subjects were recruited as control. The Belgium medisoft box5500 was used to determine the pulmonary ventilation function, lung capacity, and pulmonary diffusing capacity. The measured parameters included forced vital capacity ( FVC) , forced expiratory volume in one second ( FEV1 ) ,maximal voluntary ventilation ( MVV) , vital capacity ( VC) , total lung capacity( TLC) , residual volume ( RV) , minute volume of alveolar ventilation ( VA ) , lung diffusing capacity for carbon monoxide ( DLCO) , pulmonary membrane diffusing capacity for carbon monoxide ( DMCO) , and pulmonary capillary blood volume ( Vc) . The above parameters were compared between the COPD patients and the normal subjects. The relationship was analyzed between DLCO% pred, DMCO% pred, Vc% pred and all the ventilation parameters. Results In stable COPD patients with mixed ventilation dysfunction, all parameters of pulmonary ventilation function, lung capacity, and pulmonary diffusing capacity were significantly different from the normal subjects ( Plt;0. 05 or Plt;0.01) . FVC, VC, VA, and DMCO of the COPD patients were about 66% of the calculated value or more. The average TLC%pred was a little higher than the normal. FEV1 , MVV, DLCO and Vc were abnormally lower which were between 36% ～44% . The average RV%pred was 188% of the predicted value. Obvious correlation could be detected between DLCO% pred, DMCO% pred, Vc%pred and FEV1%pred, FEV1/FVC, TLC% pred, RV%pred, RV/TLC and VA% pred etc.Conclusions In COPD patients with mixed ventilation dysfunction, the pulmonary blood capillary is damaged seriously which lead to a significant decrease of the capacity of pulmonary blood capillary, as well as seriously air distribution disturbance and ventilation/bloodstream mismatch. The Vc decline may develope before the impairment of pulmonary diffusing capacity which may contribute to the damaged of DLCO and DMCO.
Objective To investigate the effects of histone modification on the expression of chemokines in alveolar epithelial typeⅡ cells ( AECⅡ) in a rat model of chronic obstructive pulmonary disease ( COPD) . Methods 20 SD rats were randomly assigned to a normal control group and a COPD group. The rat model of COPD was established by cigarette smoking. Lung histological changes were observed by HE staining. AECⅡ cells were isolated and identified by alkaline phosphatase staining and electron microscopic. The mRNA expressions of monocyte chemoattractant protein ( MCP) -1, IL-8, and macrophage inflammatory protein ( MIP) -2αwere detected by real-time quantitative PCR. The expression of histone deacetylase ( HDAC) 2 was measured by western blot. Chromatin immunoprecipitation ( ChIP) was used todetect H3 and H4 acetylation, and H4K9 methylation in the promoter region of chemokine gene. Results Compared with the control group, the mRNA expressions of MCP-1, IL-8, and MIP-2αin the COPD group increased 4. 48,3. 14, and 2. 83 times, respectively. The expression of HDAC2 protein in the COPD group wassignificantly lower than in the control group ( 0. 25 ±0. 15 vs. 0. 66 ±0. 15, P lt; 0. 05) . The expression of HDAC2 had a negative correlation with the gene expressions of IL-8, MCP-1, and MIP-2α( r = - 0. 960,- 0. 914, - 0. 928, respectively, all P lt;0. 05) . The levels of H3 and H4 acetylation were higher, and H4K9 methylation level was lower in the promoter region of chemokine gene in the COPD group compared with the control group ( all P lt; 0. 05) . Conclusions MCP-1, IL-8, and MIP-2α participate and promote the lung inflammatory response in COPD. HDAC2-mediated histone modification may play an important role in COPD inflammation.
Objective To investigate the expression and significance of Fork head /winged helix protein 3 (Foxp3) , retinoic acid-related orphan receptorγt (RORγt) , and interleukin-17 (IL-17) in Guinea pigs with emphysema. Methods Smoking and active immunization with elastin were separately used in guinea pigs to establish emphysema model. Then the destruction of lung tissue was assayed by measurement of the average radius of alveolar. The expressions of Foxp3 , RORγt, and IL-17 in lung tissue of the guinea pigs were detected by immunohistochemical technique. The results were compared with the normal control group by the analysis of variance or kruskal-Wallis test. Spearman rank correlation was used to analyze the correlation between the ratio of Foxp3/RORγt and IL-17, also the correlation between Foxp3/RORγt and the average radius of alveolar. Results In the smoking group and the active immunization group, the average radius of alveolar were significantly longer than the control group (Plt;0.05) . And the expression of Foxp3/RORγt was significantly unbalanced, with the number of Foxp3-positive cells decreased and RORγt-positive cells increased (Plt;0.05) . Meanwhile the level of IL-17 was significantly increased compared with the control group ( Plt;0.05) . The difference between the smoking group and the active immunization group was not significant (Pgt;0.05) . The ratio of Foxp3/RORγt was negatively correlated with the level of IL-17 and the average radius of alveolar. Conclusions Active immunization with elastin can induce emphysema in guinea pigs. The Foxp3/RORγt expression was unbalanced in lung tissue of guinea pigs with emphysema.This imbalance may be an important mechanism attributed to the disordered expression of CD4+ Treg cells and Th17 cells, which may be involved in autoimmune regulation and development of chronic obstructive pulmonary disease.
Objective To analyze the influence of COPD on the structure and function of left ventricular. Methods Sixty-nine COPD patients ( mean age: 69. 0 ±7. 8 yrs) and forty healthy controls ( mean age: 67. 8 ±7. 6 yrs) were enrolled in this study. Both groups underwent Doppler echocardiography.Heart rate ( HR) were recorded. Left ventricular end-diastolic volume ( LVEDV) , left ventricular enddiastolic diameter ( LVEDD) , interventricular septum( IVS) , stroke volume ( SV) , and cardiac output ( CO)were measured. The changes of left ventricular were compared between the COPD patients and the healthy controls, and also between the COPD patients with or without chronic cor pulmonale. Results Compared with the healthy controls, movement range of IVS, LVEDD, LVEDV, and SV reduced significantly ( P lt;0. 05) , and HR raised significantly in the COPD patients ( P lt; 0. 05) . CO had no significant difference between two groups ( P gt;0. 05) . Sub-group analysis indicated that the thickness and movement range of IVSwere greater in the patients with cor pulmonale secondary to COPD than those without cor pulmonale ( P lt;0. 05) . Conclusions In COPD patients, left ventricular chamber size decreases, and left ventricular systolic function is impaired. Left ventricular function is impaired more severe in cor pulmonale secondary to COPD than COPD without cor pulmonale.
Objective To explore the effects of enteral tube feeding on moderate AECOPD patients who underwent noninvasive positive pressure ventilation ( NPPV) . Methods Sixty moderate AECOPD patients with NPPV admitted from January 2009 to April 2011 were recruited for the study. They were randomly divided into an enteral tube feeding group (n=30) received enteral tube feeding therapy, and an oral feeding group (n=30) received oral feeding therapy. Everyday nutrition intake and accumulative total nutrition intake in 7 days, plasma level of prealbumin and transferrin, success rate of weaning, duration of mechanical ventilation, length of ICU stay, rate of trachea cannula, and mortality rate in 28 days were compared between the two groups. Results Compared with the oral feeding group, the everyday nutrition intake and accumulative total nutrition intake in 7 days obviously increased (Plt;0.05) , while the plasma prealbumin [ ( 258.4 ±16.5) mg/L vs. (146.7±21.6) mg/L] and transferrin [ ( 2.8 ±0.6) g/L vs. ( 1.7 ±0.3) g/L] also increased significantly after 7 days in the enteral tube feeding group( Plt;0.05) . The success rate of weaning ( 83.3% vs. 70.0%) , the duration of mechanical ventilation [ 5. 6( 3. 2-8. 6) days vs. 8. 4( 4. 1-12. 3) days] , the length of ICU stay [ 9. 2( 7. 4-11. 8) days vs. 13. 6( 8.3-17. 2) days] , the rate of trachea cannula ( 16. 6% vs. 30. 0% ) , the mortality rate in 28 days ( 3. 3% vs. 10. 0% ) all had significant differences between the enteral tube feeding group and the oral feeding group. Conclusions For moderate AECOPD patients with NPPV, enteral tube feeding can obviously improve the condition of nutrition and increase the success rate of weaning, shorten the mechanical ventilation time and the mean stay in ICU, decrease the rate of trachea cannula and mortality rate in 28 days. Thus enteral tube feeding should be preferred for moderate AECOPD patients with NPPV.
Objective To investigate the clinical characteristics of acute myocardial infarction ( AMI) in elderly patients with acute exacerbation of chronic obstructive pulmonary disease ( AECOPD) .Methods Clinical data of 16 elderly patients with AECOPD and AMI from may 2007 to December 2009 were reviewed. Meanwhile, 128 elderly AECOPD patients without AMI were analyzed as control. Results Neither the AMI group nor the control group had typical precordial pain, conscious disturbance, andhypotension. Compared with the control group, the main symptoms of the AMI group were worsening of chest tightness and dyspnea( 16 /16 vs. 4/128, P lt;0. 01) ,most of which accompanying fever( 11/16 vs. 6/128, P lt;0. 05) and anorexia ( 10/16 vs. 23 /128, P lt; 0. 05) . The incidence of patches-like shadow on chest X-rayincreased ( 16 /16 vs. 62/128, P lt;0. 05) , PaO2 ( mm Hg) decreased ( 43. 72 ±3. 64 vs. 82. 26 ±11. 41, P lt;0. 001) , the red blood cell count ( ×1012 /L) increased ( 6. 43 ±0. 42 vs. 4. 11 ±1. 24, P lt; 0. 05) , the concentration of total cholesterol ( mmol /L) increased ( 6. 51 ±0. 84 vs. 3. 93 ±1. 14, P lt; 0. 05) , the needfor invasive mechanical ventilation increased ( 13/16 vs. 11 /128, P lt; 0. 05) , the days in hospital were prolonged ( 35 ±13 vs. 11 ±3, P lt; 0. 01) , the cost ( 1000 RMB) increased( 32 ±11 vs. 7. 6 ±2. 8, P lt;0. 01) , and the mortality also increased ( 2/16 vs. 3 /128, P lt;0. 01) . Conclusion AMI should be alerted in the case of sudden exacerbation of chest tightness and dyspnea in elderly patients with AECOPD.
Objective To investigate the therapeutic effects of tiotropium in the treatment of stable COPD ( chronic obstructive pulmonary disease) patients of group D. Methods Sixty-two subjects with stable COPD in group D classified by combined COPD assessment in GOLD 2011, were randomly divided into a treatment group ( n = 32) and a control group ( n = 30) . The treatment group was treated with tiotropium ( 18 μg, inhalation, once daily) plus salmeterol /fluticasone ( 50/500 μg, inhalation, twice a day)and the control group was treated only with salmeterol / fluticasone ( 50/500 μg, inhalation, twice a day) . The exercise tolerance, dyspnea score and lung function were measured before and 1, 8,24, and 48 weeks after the treatment respectively. Results 8, 24, 48 weeks after the treatment respectively, there were improvements of 6 minute walk test and the dyspnea score of medical research council scale( MRC) in both groups than before treatment, and which was better in the treatment group. Compared with baseline and the control group, significantly greater improvements in the FVC, FEV1 and FEV1% pred were seen in the treatment group at all time points. In the control group, FVC, FEV1 and FEV1% pred 1 and 8 weeks after treatment were higher than those before treatment, but there was no significant difference after treatment of 24 and 48 weeks.Conclusion Combination treatment with tiotropium and salmeterol / fluticasone inhalation results in greater therapeutic benefits than salmeterol / fluticasone inhalation alone in stable COPD patients of group D.
Objective To investigate the role of AKT/FOXOs /atrogin-1/MuRF1 signaling pathway in skeletal muscle atrophy in rats with chronic obstructive pulmonary diseases( COPD) .Methods Passive cigarette smoking was used to establish COPD model. The protein expression of atrogin-1, MuRF1, FOXO-1, phosohorylated-AKT and total AKT were measured by Western blot. The mRNA expression of atrogin-1, MuRF1 and FOXO-1 were measured by reverse transcription-polymerase chain reaction( RT-PCR) . Results Compared with the control group, the mRNA expressions of atrogin-1, MuRF1 and FOXO-1 significantly increased in extensor digitorum longus ( EDL) of the COPD group (Plt;0.05 ) . Meanwhile the protein expression of atrogin-1 and MuRF1 significantly increased in the COPD group(Plt;0.05) , while the protein expression of FOXO-1 was not significantly different between two groups(Pgt;0.05) . In addition, , the protein expression of phosohorylated-AKTand the ratio of phosohorylated-AKT to total AKT significantly increased in EDL of the COPD group(Plt;0.05) . Conclusion The mRNA and protein expression of AKT/FOXOs/ atrogin-1 /MuRF1 in skeletal muscle are significantly increased in COPD rats, suggesting that AKT/FOXOs/ atrogin-1 /MuRF1 signalling pathway plays a crucial role in skeletal muscle atrophy of COPD.