Objective To investigate the relationship of pulmonary surfactant protein D( SP-D) with chronic obstructive pulmonary disease ( COPD) by measuring SP-D level in serum and lung tissue of rats with COPD.Methods The rat COPD model was established by passive smoking as well as intratracheal instillation of lipopolysaccharide ( LPS) . Thirty male SD rats were randomly divided into a control group, a LPS group, and a COPD group( n =10 in each group) . The pathologic changes of lung tissue and airway were observed under light microscope by HE staining. Emphysema changes were evaluated by mean linear intercept ( MLI) of lung and mean alveolar number ( MAN) . The level of SP-D in serum was measured by enzymelinked immunosorbent assay ( ELISA) . The expression of SP-D in lung tissue was detected by Western-blot and immunohistochemistry.Results The MLI obviously increased, and MAN obviously decreased in the COPD group compared with the control group ( Plt;0.05) . There was no significant difference in the MLI and MAN between the LPS group and the control group ( Pgt;0.05) . The serum SP-D level was ( 49.59 ±2.81) ng/mL and ( 53.21±4.17) ng/mL in the LPS group and the COPD group, which was significantly higher than that in the control group [ ( 42.14±2.52) ng/mL] ( Plt;0.05) . The expression of SP-D in lung tissue was 0.56±0.01 and 0.63±0.01 in the LPS group and the COPD group, which was also obviously ber than that in the control group ( 0.39 ±0.01) ( Plt;0.05) .Meanwhile the SP-D levels in serumand lung tissue were higher in the COPD group than those in the LPS group ( Plt;0.05) . The levels of SP-D between serum and lung tissue were positively correlated in all three groups ( r=0.93, 0.94 and 0.93, respectively, Plt;0.01) .Conclusion Both the SP-D level in serum and in lung tissue increase significantly in COPD rats and correlate well each other, which suggests that SP-D may serve as a biomarker of COPD.
随着近年来对慢性阻塞性肺疾病( COPD) 的深入研究，人们逐渐揭示了其发病机制中的众多关键环节，据此开发了新型的药物和治疗手段。大量国际多中心临床研究已证明COPD 是一个可防可治的疾病，正确的治疗能够改善患者的症状，提高生活质量，乃至延缓疾病的进程。为更好地防治COPD，全球学者共同推出了《慢性阻塞性肺疾病全球倡议 ( GOLD) 》以指导广大医师规范、合理地诊断、治疗和预防COPD。然而， 在我国由于多方面的原因，COPD 的防治工作面临如下的难题。
Objective To explore the role of macrophage-stimulating protein ( MSP) and receptor tyrosine kinase RON in the airway inflammation of chronic obstructive pulmonary disease( COPD) , and investigate its possible mechanism. Methods The rat COPDmodel was established by exposing the rats to cigarette smoke daily for three months. Rat alveolar macrophages ( AMs) were isolated in vivo and cultured,and then challenged with different concentrations of MSP for 24 hours. The concentrations of MSP in broncho-alveolar lavage fluid ( BALF) and serum, and the levels of IL-1β, TNF-α, IL-8, and IL-10 in the supernatants were measured by ELISA. The expression of RONmRNA in lung tissue was assessed by reverse transcription-polymerase chain reaction. The levels of RON protein in the lung tissue and AMs cultured in vitro were observed by immunohistochemistry. The activity of superoxide dismutase ( SOD) and malondialdehyde ( MDA) content in the culture solution were measured with chromatometry method. Results Compared with the control group, the concentrations of MSP in serum and BALF of the COPD rats were significantly higher ( P lt;0. 01) . The levels of RONmRNA and RON protein in the COPD rats were also upregulated significantly ( P lt; 0. 01) . MSP evoked the AMs isolated from the normal and COPD rats to generate more content of MDA and caused a reduction in activity of SOD. In addition, MSP stimulated TNF-α, IL-8, IL-1βand IL-10 release fromAMs of the normal and COPD rats dose-dependently. The levels of TNF-α, IL-8, and IL-1βwere higher, while the level of IL-10 and the SOD activity were lower in AMs of the COPD group than those of the control group in the same dose of MSP ( P lt;0. 01) . The more significant increase in the levels of TNF-α, IL-8, IL-1β, and the more notable decrease in the activity of SOD was found in the COPD group compared with the control group. But the degree of increasing MDA and IL-10 in the AMs of the COPD group was lower than that in the control group. Linear correlation analysis showed that the MSP concentration and the RON protein level in the COPD rats were positively associated with the total cellcounts and AM counts in BALF, and were related to the indexes for pulmonary emphysema. Conclusions There is a close correlation between the MSP and receptor tyrosine kinase RON with the airway inflammation of COPD. The mechanism might be that MSP promote the macrophages release inflammatory factors and increase the production of oxygen free radicals.
Objective To determine if supervised hospital-based exercise can maintain the benefits of functional exercise ability and quality of life gained from a pulmonary rehabilitation program in COPD.Methods A prospective and randomized study was carried out. Following completion of an eight-week pulmonary rehabilitation program in hospital, 43 COPD patients were recruited and randomized into either a supervised group ( supervised, every 10 days, hospital-based exercise, 22 cases ) or a control group ( unsupervised home exercise,21 cases) and followed for 12 months. Measurements were taken at baseline and 12 months later. Exercise measurements include six-minute walk test( 6MWT) and pulmonary function test. Quality of life was measured using the Chronic Respiratory Questionnaire ( CRQ) . Results After 12 months of different exercise program,6MWT in the supervised group was significantly longer than that in the unsupervised group[ ( 532. 0 ±168. 4) m vs ( 485. 0 ±151. 6) m, P lt; 0. 05] . There was no significant difference in pulmonary function between the two groups. The quality of life of the supervised group was higher than that of the unsupervised group( 114. 6 ±20. 8 vs 105. 6 ±21. 7, P lt;0. 05) . Conclusions After the completion of pulmonary rehabilitation program, a supervised, every 10 days, hospital-based following exercise program can maintain better functional exercise capacity and quality of life compared to home exercise in COPD patients.
Objective To evaluate the efficacy and safety of glucocorticoids (GC) monotherapy and GC combined with tacrolimus (TAC) therapy in patients with anti-synthetase syndrome-associated interstitial lung disease (ASS-ILD). Methods Through retrospective analysis and propensity score matching (PSM) analysis, the 2-year progression-free survival (PFS) and related side effects of ASS-ILD patients in TAC+GC group and GC monotherapy group were compared. Predictors associated with PFS were analyzed with COX. Results The 2-year PFS rate of TAC+GC group was better than that of GC group [P=0.0163; hazard ratio (HR) 0.347]; Univariate and multivariate analysis of the COX regression model for 2-year PFS in the two groups suggested that creatine kinase level (P=0.0019, HR 1.002) and initial treatment selection [(TAC+GC) vs. GC, P=0.0197, HR 0.207] were independent predictors of PFS; PSM analysis showed that the 2-year PFS rate of TAC+GC group (54.5%) was higher than that of GC group (18.2%) (P=0.0157, HR 0.275). In terms of adverse effect, there was no significant increase in GC+TAC group compared with GC group. Conclusion Compared with GC monotherapy, initial TAC+GC treatment significantly prolonged PFS in ASS-ILD patients and did not increase the incidence of drug-related complications.
目的 观察噻托溴铵治疗慢性阻塞性肺疾病急性加重期（AECOPD）临床疗效与安全性。 方法 选取 2010 年 1 月－2011年12月入院的69例AECOPD 患者随机分为试验组（A组，n=36）和对照组（B组，n=33），A组在B组常规治疗的基础上吸入噻托溴铵。治疗起始及结束分别观察两组肺功能指标、慢性阻塞性肺疾病评估测试（CAT）评分、血气分析、6分钟步行距离、住院时间及药物不良反应。 结果 两组均显示出一定的临床效果，A组治疗后肺功能指标、CAT评分、血气分析、6分钟步行距离均优于B组，差异均具有统计学意义（P＜0.05）。A组住院时间短于B组（P＜0.05），且无严重不良反应。 结论 AECOPD患者在常规治疗同时吸入噻托溴铵，疗效显著且临床安全性较高。
Objective The risk factors of noninvasive positive pressure ventilation (NPPV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with failure of respiratory failure were identified by meta-analysis, so as to provide a basis for early clinical prevention and treatment failure and early intervention. Methods PubMed, The Cochrane Library, EMbase, China National Knowledge Infrastructure, Wanfang, VIP and CBM Data were searched to collect studies about risk factors about failure of noninvasive positive pressure ventilation in AECOPD and respiratory failure published from January 2000 to January 2021. Two researchers independently conducted literature screening, literature data extraction and quality assessment. Meta-analysis was performed on the final literature obtained using RevMan 5.3 software. Results Totally 19 studies involving 3418 patients were recruited. The statistically significant risk factors included Acute Physiology and Chronic Health Evaluation (APACHEⅡ) score, pre-treatment PCO2, pre-treatment pH, Glasgow Coma Scale (GCS), respiratory rate (RR) before treatment, body mass index (BMI), age, C-reactive protein (CRP), renal insufficiency, sputum disturbance, aspiration of vomit. Conclusions High APACHE-Ⅱ score, high PCO2 before treatment, low pH value before treatment, low GCS score, high RR before treatment, low BMI, advanced age, low albumin, high CRP, renal insufficiency, sputum disturbance, and vomit aspiration were the risk factors for failure of respiratory failure in patients with COPD treated by NIPPV. Failure of non-invasive positive pressure ventilation in COPD patients with respiratory failure is affected by a variety of risk factors, and early identification and control of risk factors is particularly important to reduce the rate of treatment failure.
Objective To explore the regulation of peroxisome proliferator-activated receptor γ coactivator 1α( PGC-1α) and NF-E2-related factor 2( Nrf2) on expression of γ-glutamylcysteine synthetase ( γ-GCS) , and their roles in chronic obstructive pulmonary disease( COPD) . Methods Twenty-four SD rats were randomly divided into a COPD group and a normal control group. COPD model was established by intratracheal instillation of lipopolysaccharide ( LPS) and daily exposure to cigarette smog in the COPD group. The lung function was measured and the pathological changes were observed. The protein and mRNA expressions of PGC-1α, Nrf2, and γ-GCS in lung tissue were measured by immunohistochemistry, Western blot, in site hybridization ( ISH) , and reverse transcription-polymerase chain reaction ( RT-PCR ) ,respectively. Results In the COPD group, the pulmonary function ( FEV0. 3, FEV0. 3 /FVC, PEF) damage and lung pathological changes were conformed as morphological characteristics of COPD. The mRNA of PGC-1α and Nrf2 expressed in lung tissues of two group rats in the region consistent with γ-GCS mRNA. The protein and mRNA expressions of PGC-1αand γ-GCS were markedly increased in the COPD group( all P lt;0. 05) ,and the protein expression of Nrf2 was obviously up-regulated ( P lt; 0. 01) , while Nrf2 mRNA had no significant difference between the two groups( P gt;0. 05 ) . Linear correlation analysis showed that the level ofPGC-1αprotein was positively correlated with the levels of Nrf2 protein and mRNA ( r = 0. 775, 0. 515, all P lt; 0. 01) , and the levels of PGC-1αand Nrf2 protein were positively correlated with the levels of γ-GCS protein ( r = 0. 531, 0. 575, all P lt; 0. 01) and mRNA ( r = 0. 616, 0. 634, all P lt; 0. 01) . Conclusions PGC-1α, which may serve as a co-activator of Nrf2, can up-regulate the expression of γ-GCS gene cooperatively with Nrf2 through a common pathway, which might involve in the oxidative and antioxidative mechanism in the pathogenesis of COPD.