【摘要翻译】 一 氧化氮合酶( NOS) -2( NOS-2) 的诱导和一氧化氮产物增加是过敏性气道疾病的共同特征。严重哮喘与气道S-亚硝基硫醇减少相关。S-亚硝基硫醇是NO的生化产物, 可通过促炎症转录因子NF-κB 的S-亚硝基化抑制炎症反应。因此, 重建气道S-亚硝基硫醇对治疗可能有益。我们对此假设在以卵清蛋白诱导的过敏性炎症大鼠模型中进行验证。未使用或使用卵清蛋白致敏的动物均在卵清蛋白激发前于气管内灌注S-亚硝基谷胱甘肽( GSNO;50 μl, 10 mM) , 并在48 h 以后进行分析。GSNO 给药增加了肺组织S-亚硝基硫醇水平。与对照组比, GSNO 降低了卵清蛋白致敏动物NF-κB 的活性, 但对支气管肺泡灌洗细胞总数、分类计数及杯状细胞化生标记物均无显著影响。GSNO给药也改变了HIF-1 的活性, 导致未致敏大鼠HIF-1 活化,但抑制卵清蛋白致敏大鼠的HIF-1 活性。我们使用NOS-2基因敲除小鼠来评价内源性一氧化氮合成酶-2 在调节NF-κB和( 或) HIF-1 活性及气道过敏性炎症的作用。尽管在NOS-2 基因敲除小鼠中卵清蛋白诱导的NF-κB 活力轻度增高, 这与支气管肺泡灌洗中性粒细胞轻度增加有关, 其他的过敏性炎症指标和HIF-1 活性在NOS-2 基因敲除及野生型小鼠之间却无明显相差。总体来说, 我们的研究表明GSNO灌注能抑制气道过敏性炎症中NF-κB 活性, 但是并不能显著地影响大部分炎症及杯状细胞化生指标, 这样可能因为对其他信号通道( 比如HIF-1) 的影响而限制了它的治疗价值。【述评】 GSNO 是近年哮喘治疗研究的热点。既往的研究发现GSNO 在哮喘治疗中有一定前景。本研究却发现GSNO 气管内滴注虽能抑制过敏性气道炎症中NF-κB 活性,但并不能显著抑制气道炎症反应及杯状细胞化生这两个哮喘关键病理改变, 可能与GSNO 同时影响了HIF-1 等其他信号通路有关。该研究表明GSNO 对哮喘气道炎症治疗效果有限, 同时表明哮喘气道炎症调控机制较为复杂, 治疗药物的设计需考虑多种信号通路对哮喘气道炎症的影响。
Objective To identify the short ( lt;30 days) and intermediate ( 30 days to 6 months) benefits and risks of tracheobronchial stents in patients with malignant airway stenosis. Methods 55 cases with malignant airway disease who underwent tracheobronchial stents placement from January 2006 to May 2008 were followed up for 6 months. The efficacy rate, complication rate, reintervention rate, and survival were analyzed. Results There were 61 self-expanding metal stents placed in 55 patients with malignant disease, with no intraoperative mortality. The immediate efficacy rate was 100% , the short-term( lt;30 days) efficacy rate was 94. 5% , and the survival rate in 6 months was 32. 7% . The complications included tumor ingrowth, excessive granulation tissue, stent migration, and restenosis. A total of 14 cases of complicationswere observed, in which two occurred during the short-term period ( lt; 30 days ) and the remaining complications occurred after 30 days. Conclusions Tracheobronchial stents can improve symptoms immediately for the patients with unresectable malignant central airway obstruction with fairly safety. The benefit of airway stents is particularly seen in the short-termperiod and the complications occur mainly after 30 days.
Objective To investigate the expression of stromal cell derived factor-1 ( SDF-1) and the effects of budesonide suspension for inhalation ( Pulmicort Respules) in mice with asthma. Methods Thirty Kunming female mice were randomly divided into three groups, ie. a control group, an asthma group, and a pulmicort treatment group. The asthma group and the pulmicort treatment group were sensitized with ovalbumin ( OVA) by a combination of intraperitoneal injection and repeated OVA intranasal challenges to establish mouse asthma model. The pulmicort treatment group received 100μL pulmicort by intranasal administration before OVA challenge. The immunohistochemistry was used to estimate the expression of SDF-1 in lung tissues. HE staining and Wright-Giemsa staining method were used to assess inflammatory infiltration in the airway and bronchoalveolar lavage fluid ( BALF) respectively. Results The expression of SDF-1 in the asthma group increased significantly compared with the control group ( 0.48 ±0.03 vs. 0.21 ± 0.02, Plt;0.05) , and significantly decreased after the intervention with pulmicort ( 0.29 ±0.01 vs. 0.48 ± 0.03, Plt; 0.05 ) . Compared with control group, the infiltration of inflammatory cells in airway was significantly enhanced in the asthma group, and attenuated in the pulmicort treatment group. The total number of inflammatory cells and eosinophil, lymphocyte, neutrophil counts in BALF increased significantly in the asthma group compared with the control group, and decreased significantly after pulmicort intervention. Conclusion SDF-1 may play an important role in the recruitment of inflammatory cells in asthmatic airway and pulmicort may relieve airway inflammation by decreasing the expression of SDF-1.
Objective To study the clinical feasibility of invasive mechanical ventilation with bilevel positive airway pressure（BiPAP） non-invasive ventilator in the stable patients needing prolonged mechanical ventilation.Methods Eleven patients with respiratory failure admitted in intensive care unit（ICU）of our department，who needed prolonged mechanical ventilation，between Jun 2004 and Nov 2007 were enrolled in the study and followed until death or Jan 2008.The arterial blood gas analysis data，length of stay(LOS)，LOS after changing to BiPAP non-invasive ventilator（Synchrony，Harmony，RESPIRONICS，VPAP III ST-A，RESMED），survival time after discharge(or fulfilled the discharge standards) were reviewed retrospectively.Results The settings of inspiratory pressure，expiratory pressure and respiratory rate of non-invasive ventilation were 21.3 (16-26) cm H2O，4 cm H2O，and 16 min-1，respectively.The LOS (or up to the discharge standard) was (91.5±50.2) days.The LOS (or up to the discharge standard) after changing to BiPAP ventilator was (23.5±12.2) days.The mean survival time after discharge (or up to the discharge standard) was (353.1±296.5) days.Four patients were still alive up to the end of the study.The arterial pH，PaCO2，PaO2，and SaO2 were not significant different before and after changing to BiPAP ventilator.Conclusion The mechanical ventilation with BiPAP non-invasive ventilator via tracheotomy tube is an alternative choice for stable patients needing prolonged mechanical ventilation.
Objective To systematically assess the effectiveness of traditional Chinese medicines (TCM) in treating upper airway cough syndrome (UACS) or postnasal drip syndrome (PNDS). Methods Such databases as MEDLINE (1950 to 2011), PubMed (1996 to 2011), VIP (1989 to 2011), WanFang Data (1998 to 2011), CNKI (1979 to 2011) and CBM (1978 to 2011) were searched for collecting the randomized controlled trials (RCT) or quasi-RCTs about TCM treating UACS/PNDS. The trials were screened according to the inclusive and exclusive criteria, and then after the quality assessment and data extraction were conducted, the statistical analysis was conducted by using RevMan 5.0 software. Results A total of 10 RCTs and quasi-RCTs in Chinese were identified. The results of analysis showed that: a) The integrated Chinese and western medicine was superior to western medicine alone, either for adults and children with UACS, or for adults with PNDS. However the effectiveness had to be further assessed due to lack of high-quality literatures; b) TCM alone was probably more effective than western medicine alone for adults with PNDS, but not for adults and children with UACS. No obvious adverse reaction related to TCM was reported. Conclusion The recent research outcomes show that the integrated Chinese and western medicine is superior to western medicine alone, either for adults and children with UACS, or for adults with PNDS, but no definite evidence is found to support the superiority of TCM in treating UACS/PNDS. More high-quality RCTs with large scale need to be conducted in future to verify this conclusion due to the overall low methodological quality and significantly different intervention of the included trials.
目的：评价电子气管镜直视下置入镍钛合金支架治疗气道狭窄的疗效及安全性。方法：对我院3年来由各种原因引起的气管或支气管狭窄的21例患者行电子气管镜直视下经鼻置入国产镍钛合金支架术，观察置入支架前后症状、狭窄段气道直径变化、动脉血气变化情况及其并发症。结果：21例患者术后呼吸困难均明显改善，气道内径扩张及动脉血氧分压改善较术前均有统计学意义，未发生严重并发症。结论：电子气管镜直视下置入气道支架准确、迅速、安全，操作较方便，有助于延长患者的生存时间和提高生活质量，为进一步治疗创造条件。
Objective To evaluate the efficacy and safety of local triamcinolone combined with conventional interventional therapy in the treatment of benign airway stenosis. Methods PubMed, Cochrane Library, EMbase, Web of science, wanfang, VIP and China National Knowledge Infrastructure were searched by computer between the establishment of the database and August, 2019, and all literatures on the local treatment of benign airway stenosis using triamcinolone combined with conventional interventional therapy were searched. According to inclusion and exclusion criteria, 2 researchers screened the literatures and performed the data extraction and methodological quality evaluation. Meta-analysis was performed with Revman5.2 and Stata software. Results In total, nine randomized controlled trials were included in this meta-analysis, including 449 patients with airway stenosis. The total result showed that in the comparison of short-term efficacy, there were no statistically significant differences in breathability score (SMD=–0.16, 95%CI –0.45 - 0.13, P=0.27), airway diameter (SMD=0.14, 95%CI –0.13 - 0.41, P=0.30), and cross-sectional stenosis rate (SMD=–0.01, 95%CI –0.36 - 0.34, P=0.96) between the treatment group and the control group. In the comparison of long-term efficacy, the breathability score (SMD=–2.53, 95%CI –3.78 - –1.28, P<0.05), airway diameter (SMD=1.31, 95%CI 0.83 - 1.78, P<0.05), cross-sectional stenosis rate (SMD=2.58, 95%CI: 2.11~3.08, P<0.05), and FEV1(SMD=0.42, 95%CI 0.13 - 0.70, P=0.004) of patients in the treatment group were all better than those in the control group. But in terms of adverse reactions, the incidence of bleeding in the airway between two groups was similar (RR=2.00, 95%CI 0.88 - 4.52, P=0.10), other adverse reactions such as blood glucose and plasma cortisol levels were mild, which can be relieved symptomatically. Conclusion Current evidence suggests that topical triamcinolone combined with conventional interventional therapy for benign airway stenosis has a better long-term clinical efficacy with fewer adverse reactions and better overall patient tolerance, which has clinical application value
ObjectiveTo evaluate the clinical efficacy of balloon bronchoplasty and metallic stents in lung transplant-related central airway stenosis.MethodsData of lung transplant recipients with central airway stenosis who underwent therapeutic bronchoscopic interventions between January 2011 and June 2019 at our institution were reviewed. The clinical follow-up included dyspnea index, forced expiratory Forced expiratory volume in one second (FEV1), six-minute walk distance (6MWD), and the rate of bronchoscopic dilation.ResultsThirty-four lung transplant recipients with airway stenosis were included in our study. All these patients were treated by balloon bronchoplasty through flexural bronchoscopy, and 7 additionally needed temporary metal stent implantation for 28 to 67 days in order to palliate recurrent central airway stenosis. The percentages of immediate efficacy were 86% (180/209) and 100% (7/7), respectively. After serial balloon dilatation, the recipients with central airway stenosis had significantly lower dyspnea index (3.24±0.55 vs. 1.91±0.62, P<0.01), higher FEV1 ［(1.43±0.21)L vs. (1.72±0.27)L, P<0.01］ and longer 6MWD ［(317.3±61.7)m vs. (372.9±52.6)m, P<0.01］. Six recipients with central airway stenosis received 33 interventions in 6 months before stent implantation and 10 interventions in 6 months after stent extraction.ConclusionsLung transplant recipients with central airway stenosis have a good respond to balloon bronchoplasty and stent placement. Airway stenosis after lung transplantation can be successfully managed with bronchoscopic dilatation and temporary stent placement.
Objective To investigate the role of endogenous Hydrogen Sulfide ( H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking. Methods Male SD rats were randomly divided into a control group ( breathing fresh air) and a passive smoking group [ cigarette smoking( CS) passively] , with 18 rats in each group. Six rats in each group were randomly intraperitoneally injected with normal saline, sodium hydrosulfide ( NaHS) or propargylglycine ( PPG, an irreversible inhibitor of cystathionine- γ-lyase) . The animals were divided into six subgroups, ie. Con group, NaHS group, and PPG group, CS group, CS+ NaHS group, and CS + PPG group. After 4 months, lung histological change and airway tension were measured. The H2S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay. The expression of cystathionine-γ-lyase ( CSE) was measured by western blot. Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group( P lt;0. 05) ; the H2 S levels of plasma were significantly higher in CS group, NaHS group and CS + NaHS group, and much lower in PPG group ( P lt; 0. 05, respectively) . Compared with CS group, the H2S levels of plasma were significantly higher in CS + NaHS group, and much lower in CS + PPG group( P lt; 0. 05, respectively) . The H2S level of lung tissue in each group had no significant difference ( P gt; 0. 05) . Compared with Con group,score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to ACh and KCl was significant augmented in CS group. Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS +NaHS group( P lt;0. 05) , and vise versa in CS + PPG group( P lt; 0. 01) . Conclusion H2S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airwayinflammation and airway responsiveness.