阻塞性睡眠呼吸暂停患者的心脏早期损伤

目的：评估尚无心血管症状的单纯阻塞性睡眠呼吸暂停（OSA）造成的心脏早期损害。方法：将随机纳入的92例OSA患者依照呼吸暂停低通气指数（AHI）分为轻、中、重三组（轻度25例,中度30例,中度36例）,另取正常健康者25例作为正常对照组,分析血清中脑钠肽N末端前体（NT-proBNP）、心脏型脂肪酸结合蛋白（h-FABP）及超声心动参数的变化状况来评估OSA患者的早期心脏损伤。随机选取中、重度30例（重度20例,中度10例） OSA患者予以持续正压通气（CPAP）治疗一个月,比较治疗前、后NT-proBNP、h-FABP及超声心动参数的变化。结果：与对照组比较,OSA各亚组患者的h-FABP和NT-proBNP水平均显著升高（P<0.01）,并与AHI呈正相关;OSA各组患者的Em/Am值和中、重度OSA组的E/A值均明显降低（P<0.01）;Em/Am值各组之间差异有统计学意义（P<0.01）;与治疗前对比,CPAP治疗后患者血清中的h-FABP和NT-proBNP水平均显著降低（P<0.01）,Em/Am值和E/A值均明显增加（P<0.01）。结论：OSA患者早期心脏损伤以左室舒张功能损伤和心肌早期微损伤为主,CPAP治疗可显著改善OSA患者的早期心脏损伤。     

双水平气道正压通气对88例重叠综合征患者的临床疗效

目的:探讨双水平气道正压通气(Bi PAP)治疗重叠综合征(OS)患者的临床疗效。方法:选取2012年7月-2014年2月本院收治的88例诊断为重叠综合征的患者,随机分成实验组与对照组,对照组43例,给予常规药物治疗;实验组45例,在常规药物治疗的基础上辅以双水平气道正压通气治疗,对两组治疗前后的监测结果进行比较分析。结果:治疗后,实验组患者在不同时间点上p H和Pa O2高于对照组,Pa CO2、呼吸暂停指数(AHI)、睡眠紊乱指数、最长呼吸暂停时间以及病死率和不良反应发生率均低于对照组,差异均有统计学意义(均P0.05)。结论:采用Bi PAP治疗OS患者,能够有效降低患者病死率、减少不良反应发生率,并改善患者呼吸情况,提高睡眠质量。     

Effects of continuous positive airway pressure on plasma fibrinogen levels in obstructive sleep apnea patients: a systemic review and meta-analysis

Objective: Fibrinogen has been implicated to play a role in the pathophysiology of obstructive sleep apnea (OSA). Many studies have evaluated the effect of continuous positive airway pressure (CPAP) on plasma fibrinogen levels in OSA patients. However, results from different reports were not consistent. To assess the effect of CPAP treatment on plasma fibrinogen levels of patients with OSA, a meta-analysis was performed.Methods: A systematic search of Pubmed, Embase, Cochrane, Wanfang Database and Chinese National Knowledge Infrastructure was performed. Data were extracted, and then weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using a random-effects model.Results: Twenty-two studies involving 859 patients were included in this meta-analysis. Combined data showed that plasma fibrinogen concentrations decreased after CPAP therapy (WMD = −0.38 g/l, 95% CI [−0.54 to −0.22 g/l], P<0.001). In the subgroup analyses by therapy duration, plasma fibrinogen concentrations declined significantly in the long-term (≥1 month) CPAP therapy subgroup (WMD = −0.33 g/l, 95% CI [−0.49 to −0.16 g/l], P<0.001) but not in the short-term (<1 month) CPAP therapy subgroup (WMD = −0.84 g/l, 95% CI [−1.70 to 0.03 g/l], P=0.058). Moreover, in patients with long-term CPAP therapy duration, plasma fibrinogen levels decreased with good CPAP compliance (≥4 h/night) (WMD = −0.37 g/l, 95% CI [−0.55 to −0.19 g/l], P<0.001) but not with poor CPAP compliance (<4 h/night) (WMD = 0.12 g/l, 95% CI [−0.09 to 0.33 g/l], P=0.247).Conclusion: Long-term CPAP treatment with good compliance can reduce the plasma fibrinogen levels in patients with OSA.     

Stem/progenitor cells and obstructive sleep apnea syndrome-new insights for clinical applications

Obstructive sleep apnea syndrome(OSAS) is a widespread disorder, characterized by recurrent upper airway obstruction during sleep, mostly as a result of complete or partial pharyngeal obstruction. Due to the occurrence of frequent and regular hypoxic events, patients with OSAS are at increased risk of cardiovascular disease, stroke, metabolic disorders, occupational errors, motor vehicle accidents and even death. Thus, OSAS has severe consequences and represents a significant economic burden. However, some of the consequences, as well as their costs can be reduced with appropriate detection and treatment. In this context, the recent advances that were made in stem cell biology knowledge and stem cell- based technologies hold a great promise for various medical conditions, including respiratory diseases. However, the investigation of the role of stem cells in OSAS is still recent and rather limited, requiring further studies, both in animal models and humans. The goal of this review is to summarize the current state of knowledge regarding both lung resident as well as circulating stem/progenitor cells and discuss existing controversies in the field in order to identify future research directions for clinical applications in OSAS. Also, the paper highlights the requisite for inter-institutional, multi-disciplinary research collaborations in order to achieve breakthrough results in the field.     

夏季老年慢性阻塞性肺疾病患者口咽菌群分析

分析夏季老年慢性阻塞性肺疾病（COPD）患者与健康人群的口咽菌群构成,旨在确定老年COPD患者与健康人群上呼吸道菌群间的差异。

选择2018年6—8月沈阳市沈阳医学院附属第二医院COPD患者29例和健康体检者25例,采集口咽拭子进行细菌16S rRNA高通量测序。通过菌群多样性分析、物种组成和物种差异分析,比较老年COPD患者与健康人群口咽部微生物的异同。

老年COPD患者口咽中菌群丰富度显著高于健康人群,物种多样性低于健康人群。在门水平上,老年COPD患者口咽菌群中拟杆菌门相对丰度降低,放线菌门相对丰度显著增高;在属水平上,老年COPD患者口咽菌群中罗氏菌属、放线菌属和劳特罗普氏菌属丰度均显著高于健康人群,奈瑟菌属和普雷沃菌属相对丰度降低,差异均具有统计学意义（P＜0.05）。

老年COPD患者口咽部正常菌群组成发生变化,机会致病菌如罗氏菌属、劳特罗普氏菌属比例增加,提示夏季老年COPD患者口咽菌群失调。

     

血浆N端脑钠肽前体与COPD合并慢性肺源性心脏病患者肺动脉压的相关性分析

目的探讨血浆N端脑钠肽前体与COPD合并慢性肺源性心脏病患者肺动脉压的相关性。方法将我院收治的94例COPD稳定期患者,根据心脏彩超检查明确合并慢性肺心病患者分为观察组46例,单纯COPD患者分为对照组48例,采用化学发光法测定两组患者血浆NT-proBNP水平,心脏彩超检查两组患者右心室前壁厚度、右心室舒张末期内径、左室射血分数、主肺动脉宽度、肺动脉压,并进行比较。结果与对照组比较,观察组血浆NT-proBNP水平明显升高(P0.05),右心室前壁厚度、右心室舒张末期内径、主肺动脉宽度、肺动脉压明显升高(P0.05)。血浆NT-proBNP水平与肺动脉压成明显正相关(r=-0.284,P0.01)。结论 COPD合并慢性肺心病患者血浆NT-proBNP水平升高,有助于评估肺动脉高压的严重程度。     

双水平气道正压通气联合舒利迭对COPD合并呼吸衰竭患者呼吸衰竭症状、免疫功能及生活质量的影响

目的:探讨双水平气道正压通气(Bi-PAP)联合舒利迭对慢性阻塞性肺疾病(COPD)合并Ⅱ型呼吸衰竭患者呼吸衰竭症状、免疫功能以及生活质量的影响。方法:按照随机数字表法将2012年6月至2016年12月间我院收治的157例COPD合并Ⅱ型呼吸衰竭患者分为观察组(n=79)和对照组(n=78),对照组患者在平喘、解痉、化痰、抗感染等常规治疗同时联合Bi-PAP治疗,观察组患者在对照组治疗方案的基础上给予舒利迭治疗。比较两组患者治疗前后呼吸衰竭症状、免疫功能以及生活质量改善情况。结果:观察组治疗后有效率为89.87%(71/79),显著高于对照组的73.08%(57/78)(P0.05)。治疗后两组患者的呼吸、心率、动脉二氧化碳分压较治疗前降低,动脉氧分压较治疗前升高,且观察组患者呼吸、心率、动脉二氧化碳分压低于对照组,动脉氧分压高于对照组(均P0.05)。治疗后两组患者血清免疫球蛋白M(IgM)、免疫球蛋白G(IgG)以及免疫球蛋白A(IgA)水平均较治疗前明显升高,且观察组患者治疗后的IgM、IgA、IgG水平高于对照组(均P0.05)。随着时间的推移,两组患者治疗后的圣·乔治医院呼吸问卷(SGRQ)评分逐渐降低,且观察组治疗后3个月、6个月的SGRQ评分均低于对照组(均P0.05)。结论:Bi-PAP联合舒利迭能明显改善COPD合并Ⅱ型呼吸衰竭患者呼吸衰竭症状,提高机体免疫力和患者的生活质量,临床推广应用价值高。     

慢性阻塞性肺病继发曲霉菌感染96例临床分析

目的探讨慢性阻塞性肺病（COPD）继发呼吸系统曲霉菌感染的临床特点及防治对策。方法分析浙江大学附属第一医院2007年6月至2008年6月收治的96例COPD痰培养曲霉菌阳性患者的临床表现、治疗方法及治疗结果。结果96例COPD痰培养曲霉菌阳性患者经治疗后,9例死亡,87例好转,其中45例未用抗真菌药物治疗,38例应用氟康唑针治疗,13例加用伏立康唑针治疗。结论近年来COPD患者痰培养曲霉菌阳性呈持续增多趋势,感染因素为长期反复住院、老年、抗生素及激素的不合理应用、医源性侵袭性操作,早期诊断,早期治疗及合理预防用药是减少呼吸系统曲霉菌感染发生的关键。     

慢性阻塞性肺疾病患者肠道微生物组成及基因功能分析

探讨慢性阻塞性肺疾病（COPD）患者肠道微生物组成、丰度及差异基因功能变化。

收集我院呼吸科10例确诊COPD患者（COPD组）和10例对照受试者（对照组）粪便样品进行宏基因组高通量测序分析。

PCA分析组间比较发现2组研究对象粪便样品微生物群落差异大,具有可比性。物种组成分析显示：对照组粪便样品中高度富集的菌科主要包括毛螺菌科、理研菌科、韦荣球菌科、优杆菌科、臭杆菌科、氨基酸球菌科、乳杆菌科等,属层面富集的主要包括罗斯菌属、胃瘤球菌属、小杆菌属、真杆菌属、拟杆菌属、粪球菌属、双歧杆菌属等;COPD组粪便样品富集菌群主要包括紫单胞菌科、Selenomonadaceae、巨单胞菌属和韦荣球菌属。物种多样性分析与对照组相比,COPD组多样性更低,差异有统计学意义（W = 87,P = 0.0039）。物种相关性网络图分析显示与其他门类菌群相比,拟杆菌门、厚壁菌门、变形菌门与其他物种的关联性最强（size = 52.07、18.87、14.01）。组间差异基因进行GO功能显著性富集分析,差异基因均富集在如细胞学过程、刺激应答、生物学黏附及调节、代谢过程及信号通路等。KEGG功能显著性富集分析显示差异基因主要富集途径包括代谢途径、次生代谢物合成、淀粉和蔗糖的合成、抗生素的合成等。

COPD患者肠道内存在菌群及基因功能失调。

     

Airway wall thickness is increased in COPD patients with bronchodilator responsiveness

Rationale

Bronchodilator responsiveness (BDR) is a common but variable phenomenon in COPD. The CT characteristics of airway dimensions that differentiate COPD subjects with BDR from those without BDR have not been well described. We aimed to assess airway dimensions in COPD subjects with and without BDR.

Methods

We analyzed subjects with GOLD 1–4 disease in the COPDGene® study who had CT airway analysis. We divided patients into two groups: BDR + (post bronchodilator ΔFEV₁ ≥ 10%) and BDR-(post bronchodilator ΔFEV₁ < 10%). The mean wall area percent (WA%) of six segmental bronchi in each subject was quantified using VIDA. Using 3D SLICER, airway wall thickness was also expressed as the square root wall area of an airway of 10 mm (Pi10) and 15 mm (Pi15) diameter. %Emphysema and %gas trapping were also calculated.

Results

2355 subjects in the BDR-group and 1306 in the BDR + group formed our analysis. The BDR + group had a greater Pi10, Pi15, and mean segmental WA% compared to the BDR-group. In multivariate logistic regression using gender, race, current smoking, history of asthma, %emphysema, %gas trapping, %predicted FEV₁, and %predicted FVC, airway wall measures remained independent predictors of BDR. Using a threshold change in FEV₁ ≥ 15% and FEV₁ ≥ 12% and 200 mL to divide patients into groups, the results were similar.

Conclusion

BDR in COPD is independently associated with CT evidence of airway pathology. This study provides us with greater evidence of changes in lung structure that correlate with physiologic manifestations of airflow obstruction in COPD.     

慢性阻塞性肺疾病合并糖尿病患者口腔菌群及肠道菌群的研究

探讨慢性阻塞性肺疾病(COPD)合并糖尿病患者与糖尿病患者口腔菌群及肠道菌群的差异。

选取2019年5月到2020年5月于我院就诊的COPD合并糖尿病患者与仅患糖尿病的患者各30例。检测两组患者的各项身体指标以及生化指标。采集两组患者牙体颊/舌面液体, 提取细菌基因组DNA, 采用荧光定量PCR鉴定常见口腔细菌。采用贴纸收集粪便样本, 并用选择性琼脂培养基培养菌群, 结果以每毫升粪便的菌落形成单位(CFU)表示。通过BBL Crystal^TM鉴定系统对分离出的细菌进行鉴定。采用Elisa试剂盒测量粪便中Zonulin的水平(ng/mL)。

COPD合并糖尿病患者体质量指数[(29.54±2.16)kg/m²]较高, 血糖水平也较高, 但与糖尿病组比较差异无统计学意义(均P＞0.05)。COPD合并糖尿病患者CRP水平升高(P＜0.05), 其他各项指标两组间差异无统计学意义(均P＞0.05)。30例COPD合并糖尿病患者链球菌检出率为60.0%, 奈瑟菌检出率为30.0%, 放线菌检出率为66.7%, 韦荣球菌检出率为40.0%, 牙龈卟啉单胞菌的检出率为70.0%。30例糖尿病患者链球菌检出率为40.0%, 奈瑟菌检出率为56.7%, 放线菌检出率为36.7%, 韦荣球菌检出率为73.3%, 牙龈卟啉单胞菌的检出率为46.7%。Zonulin与炎症和真菌数量之间存在显著正相关。

COPD合并糖尿病患者肠道真菌数量、肠屏障功能与全身性炎症之间存在密切联系。

     

舒利迭联合无创正压通气治疗COPD合并呼吸衰竭的临床疗效观察

目的:分析舒利迭联合无创正压通气治疗慢性阻塞性肺疾病(COPD)合并Ⅱ型呼吸衰竭的临床疗效。方法:选取于我院诊治的COPD合并Ⅱ型呼吸衰竭患者120例,随机均分为观察组和对照组。所有患者均予以常规、对症和支持治疗,在此基础上对照组予以无创正压通气(NIPPV)治疗,观察组在对照组的基础上加用舒利迭治疗。分析和比较两组患者治疗前后的动脉血气、炎性因子水平、肺功能和CAPS评分。结果:与治疗前相比,两组患者治疗后的pH、PaO_2、SaO_2水平均明显升高,PaCO_2明显降低,血清IL-33、TNF-α、sICAM-1水平均明显降低,FVC、PEFR、FEV1%、FEV1/FVC水平均明显升高,CAPS评分明显下降,且观察组的上述指标变化均较对照组更为明显(P0.05)。结论:舒利迭联合NIPPV能够较单用NIPPV更有效降低COPD合并Ⅱ型呼吸衰竭患者炎性因子水平,改善血气和肺功能。     

慢性阻塞性肺疾病合并糖尿病患者肺部真菌感染病原学及易感因素分析

目的探讨慢性阻塞性肺疾病(COPD)合并糖尿病患者肺部真菌感染的病原学及易感因素。方法对58例COPD合并糖尿病肺部真菌感染患者进行病原学及预后分析,并与无糖尿病的COPD真菌感染患者76例进行比较。结果 2组患者病原菌均以白色念珠菌占首位,研究组真菌发病率高于对照组,预后较对照组更差。抗生素、年龄、糖皮质激素和营养状态等因素对2组患者真菌感染的影响差异无统计学意义。结论白色念珠菌仍是COPD患者肺部真菌感染的主要致病菌。糖尿病增加COPD患者感染真菌的风险,并且加重病情,影响预后。     

丹参川芎嗪注射液联合NIPPV治疗COPD合并呼吸衰竭的临床疗效

目的:探讨丹参川芎嗪注射液联合无创正压通气(NIPPV)治疗慢性阻塞性肺病COPD合并呼吸衰竭的临床疗效。方法:选择2015年1月至2016年12月在我院进行治疗的COPD合并呼吸衰竭患者70例,随机分为两组,每组35例。对照组患者采用NIPPV治疗,观察组在此基础上给予丹参川芎嗪注射液静脉滴注。比较两组患者治疗期间的动脉血气分数、肺功能指标,评价两组患者治疗前后的病情状况以及阻塞性肺病及支气管哮喘生理状况。结果:治疗后3 d以及10 d,观察组动脉血氧分压(PaO_2)、一秒用力呼气容积(FEV1)、用力肺活量(FVC)以及FEV1/FVC均显著高于对照组(P0.05),观察组动脉二氧化碳分压(PaCO_2)显著低于对照组(P0.05),而两组间动脉血氧饱和度(SaO_2)、pH比较差异无统计学意义(P0.05)。治疗后,观察组的急性生理性与慢性健康状况(APACHEⅡ)以及慢性阻塞性肺疾病和支气管哮喘生理(CAPS)评分均显著低于对照组(P0.05)。结论:丹参川芎嗪注射液辅助NIPPV有利于COPD合并呼吸衰竭患者肺功能的恢复,改善患者血气指标和预后。     

慢性阻塞性肺疾病并念珠菌性口炎患者病原学及危险因素分析

目的 探讨入院慢性阻塞性肺疾病(COPD)并念珠菌性口炎患者的病原学特征以及相关危险因素.方法 采用病例研究,对2007年4月1日至2011年1月31日入院的82例COPD并念珠菌性口炎患者和82例无念珠菌性口炎COPD患者进行匹配,应用SPSS 17.0统计软件行条件logistic回归模型分析COPD患者念珠菌性口炎发生的危险因素.结果 (1)从念珠菌性口炎患者假膜培养共分离出念珠菌83株,以白念珠菌(90.4％)为最多,其次为光滑念珠菌(3.6％)、克柔念珠菌(2.4％)、热带念珠菌(2.4％)、近平滑念珠菌(1.2％);(2)统计学分析结果显示全身应用、吸入糖皮质激素是入院患者口腔念珠菌感染的独立危险因素.结论 白色念珠菌是COPD患者口腔部念珠菌感染的主要病原菌,规范使用全身糖皮质激素、正确吸入糖皮质激素是预防COPD患者口腔念珠菌感染的关键.     

The role of uPAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease

Background

Epithelial-mesenchymal transition (EMT) plays a crucial role in small airway fibrosis of patients with chronic obstructive pulmonary disease (COPD). Increasing evidence suggests that the urokinase plasminogen activator receptor (uPAR) is involved in the pathogenesis of COPD. Increased uPAR expression has been implicated in the promotion of EMT in numerous cancers; however the role of uPAR in EMT in small airway epithelial cells of patients with COPD remains unclear. In this study, we investigated the degree of EMT and uPAR expression in lung epithelium of COPD patients, and verified the effect of uPAR on cigarette smoke extract (CSE)-induced EMT in vitro.

Methods

The expression of EMT biomarkers and uPAR was assessed in lung epithelium specimens from non-smokers (n = 25), smokers (n = 25) and non-smokers with COPD (n = 10) and smokers with COPD (n = 18). The role of uPAR on CSE-induced EMT in human small airway epithelial cells (HSAEpiCs) was assessed by silencing uPAR expression in vitro.

Results

Markers of active EMT and uPAR expression were significantly increased in the small airway epithelium of patients with COPD compared with controls. We also observed a significant correlation between uPAR and vimentin expression in the small airway epithelium. In vitro, CSE-induced EMT in HSAEpiCs was associated with high expression of uPAR, and targeted silencing of uPAR using shRNA inhibited CSE-induced EMT. Finally, we demonstrate that the PI3K/Akt signaling pathway is required for uPAR-mediated EMT in HSAEpiCs.

Conclusions

A uPAR-dependent signaling pathway is required for CSE-induced EMT, which contributes to small airway fibrosis in COPD. We propose that increased uPAR expression in the small airway epithelium of patients with COPD participates in an active EMT process.     

Use of a mandibular advancement device in patients with congestive heart failure and sleep apnoea

Objective: To evaluate the practical use of the mandibular advancement device (MAD) for treatment of sleep apnoea (SA) in patients with congestive heart failure (CHF) over 1 year. Subjects: Twenty‐five patients aged 66 ± 8 years (mean ± SD) met the inclusion criteria and were included in the study. Design: In a prospective, clinical trial, the apnoea‐hypopnoea index (AHI), a measure of SA, was determined with a portable device. Failure to enter treatment and compliance, adverse events and signs and symptoms of temporomandibular disorders (TMD) were examined before intervention and 4–6 weeks, 6 months, and 1 year after intervention. Results: Six patients had removable dentures of whom four had complete dentures. Before treatment, eight patients reported minor symptoms of TMD. The AHI fell from 19.3 ± 12.1 to 11.8 ± 9.5 (p = 0.004) with use of the device. In most patients, use of the MAD had no severe effects on the signs and symptoms of TMD. Adverse events such as pain in the temporomandibular joints, soreness in the teeth, and tiredness in the jaws were reported by 10 patients. Dental complications were observed in two patients. Sixty‐four per cent of the patients were still using the MAD at the 1‐year follow‐up. Conclusions: Both the general and oral health of CHF patients were important in treatment with a MAD. The MAD therapy had no severe effect on the masticatory system and edentulous patients could be treated.