基于经支气管镜肺减容术治疗慢性阻塞性肺疾病的临床研究进展

目的综述经支气管镜肺减容术（bronchoscopic lung volume reduction,BI,VR）治疗COPD的最新临床报道和研究进展,为COPD的临床治疗和研究思路提供更多的选择。方法对近20年来国内外发表的相关文献进行整理、分析和归纳。结果BI．VR是根据肺减容术（1ung volume reduction surgery,LVRS）原理,不需行开胸术,利用支气管镜完成肺减容的微创技术。目前常用的方法有支气管封堵法和支气管开窗法。其目的都是获得LVRS益处,而减少手术创伤、风险及长期的康复过程。结论BLVR是一种无须开胸、创伤性小的新治疗方法,在临床上大大降低了潜在的病死率和发病率,展现了巨大的临床应用前景。但由于目前还缺少大规模的随机对照临床试验结果,一些方法还处于动物实验阶段,缺乏临床研究,尚处于起步阶段。     

支气管镜新技术的评价

21世纪，人类医学进入微创时代，国内、外很多学科的微创技术都在飞速发展，呼吸微创介入诊疗技术也顺应时代发展不断完善，成为呼吸系统疾病诊疗的重要方法。近年来支气管镜下新的介入诊疗技术不断涌现，在众多的新技术方面：广受关注的诊断技术包括荧光支气管镜、经支气管镜超声引导下穿刺及经支气管镜电磁导航活检技术；治疗技术主要集中在慢性阻塞性肺疾病(COPD)与哮喘的治疗方面，包括支气管活瓣肺减容术、支气管壁开窗旁路通气肺减容术及支气管哮喘的热消融术。     

支气管镜新技术的评价

21世纪，人类医学进入微创时代，国内、外很多学科的微创技术都在飞速发展，呼吸微创介入诊疗技术也顺应时代发展不断完善，成为呼吸系统疾病诊疗的重要方法。近年来支气管镜下新的介入诊疗技术不断涌现，在众多的新技术方面：广受关注的诊断技术包括荧光支气管镜、经支气管镜超声引导下穿刺及经支气管镜电磁导航活检技术；治疗技术主要集中在慢性阻塞性肺疾病（COPD）与哮喘的治疗方面，包括支气管活瓣肺减容术、支气管壁开窗旁路通气肺减容术及支气管哮喘的热消融术。     

经支气管镜肺减容术微创治疗COPD及其相关并发症的现况及展望

【】肺部疾病是威胁人类健康的重要疾病。传统肺减容术在治疗COPD、COPD相关肺大疱及术后持续性肺漏气等具有一定的局限性。经支气管镜肺减容术微创治疗是肺部疾病的新型治疗方式,具有理想的疗效和较少的并发症,已在COPD及肺大疱治疗领域得到推广。同时,经支气管镜肺减容术可以有效预防持续性肺漏气的产生,而且,对于术后出现的经支气管镜肺减容术,经支气管镜肺减容术或存在有待开发的治疗潜力。本综述旨在介绍经支气管镜肺减容术在多种COPD相关病症的治疗效果及进展。     

活瓣肺减容术研究进展

COPD是临床常见的慢性气道炎症性疾病,具有较高的发病率和病死率.目前COPD 的药物治疗主要是以吸入支气管舒张剂为主,辅以吸人性糖皮质激素等,来达到减少急性加重和延缓肺功能下降的目的.近10多年来,内镜下肺减容术(endoscopichial lung volume reduction,ELVR)已经在晚期肺气肿患者的治疗上获得有益尝试,在经过严格选择的患者可以取得较好的临床效果.ELVR有不同的手段,主要包括气道旁路、活瓣肺减容术、热蒸汽肺减容术和肺减容线圈.这些方法在作用机制、临床效果、适应证、并发症和可逆性等方面均存在差异.目前临床应用最为广泛的是单向活瓣肺减容术,其主要适应证是叶间裂完整的异质性肺气肿患者.近10年在世界范围的推广应用,在该方法的适应证、禁忌证、并发症,术前和术后的评估等方面均取得了大量的临床资料,加深了对该方法的理解,有助于优化临床应用.本文就活瓣肺减容术的有关研究进展作一综述.     

外科干预治疗COPD

COPD（尤其是重度阻塞性肺气肿）的治疗是临床一大难题，对内科治疗不能奏效的终末期肺气肿患者施行肺移植术（LT）和肺减容术（LVRS）等外科干预治疗，是目前公认的能够缓解症状、延长患者生命的有效措施。     

经支气管镜肺减容术研究进展

肺减容术是治疗晚期肺气肿的选择之一,外科肺减容术由于其并发症、病死率及治疗费用等限制其发展.但促进了经支气管镜肺减容术的发展.目前包括经支气管镜旁路通气法肺减容术,经支气管镜生物学肺减容术,经支气管镜单向活瓣放置肺减容术,其微创、简便、痛苦及其并发症少等特点展现了其巨大的临床应用前景.     

支气管镜肺减容现状和展望

外科肺减容手术治疗重度肺气肿术后病死率较高，适应证少，不适宜临床推广。支气管镜肺减容术通过支气管镜下的技术操作，简便、安全，有望替代外科肺减容术治疗重度肺气肿。目前研究比较有效的方法有支气管腔内单向阀、生物胶、蒸汽消融和肺减容线圈。支气管镜肺减容术治疗重度肺气肿，可以明显改善气促指数、6 min步行距离及生活质量(SGRQ)评分等主观指标，但对于评价该项技术有效性的客观指标如肺功能指标及运动耐力仅有部分改善。采用该项技术安全性好，住院时间短，极少出现危及生命的严重并发症，可能出现的并发症包括慢性阻塞性肺疾病急性加重、肺炎和气胸。下一步需开展前瞻性的随机对照研究，证实支气管镜肺减容术的确切疗效。     

终末期COPD的治疗

肺气肿是一种严重威胁人类健康的慢性阻塞性肺疾病（COPD），临床表现为进行性呼吸困难，终末期肺气肿病人的5年生存率仅为25％左右。目前尚缺少治疗这一常见病和多发病的有效的内科手段，为探索治疗终末期肺气肿的有效手术方法，人们在过去的一个世纪中付出了艰苦的努力并取得了一些成绩，其中以肺移植术和肺减容术最为有效，本文就肺移植术和肺减容术对终末期肺气肿的治疗作一综述。     

慢性阻塞性肺病诊治进展——外科干预治疗COPD

COPD(尤其是重度阻塞性肺气肿 )的治疗是临床一大难题 ,对内科治疗不能奏效的终末期肺气肿患者施行肺移植术(L T)和肺减容术 (L VRS)等外科干预治疗 ,是目前公认的能够缓解症状、延长患者生命的有效措施。1　 L VRS1.1　历史　早在 2 0世纪 2 0年代部分学者即开始探索外科疗法治疗重度肺气肿。 Voelcker采用胸廓成形术使肺气肿患者水平走行的肋骨恢复正常倾斜位置 ,Reich等提出采用人工气腹法提高膈肌的位置 ,限制肺气肿肺的过度膨胀 ,此阶段可视为广义上肺减容术的雏形阶段。由于当时的医学水平和对肺气肿病理改变认识的限制 ,外科…     

Innovative approaches to lung volume reduction for emphysema

The 10 years of resurgent interest in lung volume reduction surgery (LVRS) and recent National Emphysema Treatment Trial findings for emphysema have stimulated a range of innovative alternative ideas aimed at improving outcomes and reducing complications associated with current LVRS techniques. Concepts being actively investigated at this time include surgical resection with compression/banding devices, endobronchial blockers, sealants, obstructing devices and valves, and bronchial bypass methods. These novel approaches are reaching the stage of clinical trials at this time. Theory, design issues, methods, potential advantages and limitations, and available results are presented. Extensive research in the near future will help to determine the potential clinical applicability of these new approaches to the treatment of emphysema symptoms.     

Bronchoscopic interventions for severe emphysema: Where are we now?

Patients with severe emphysema have limited treatment options and only derive a small benefit from optimal medical treatment. The only other therapy to have significant clinical beneficial effect in emphysema is LVRS but the perceived risk and invasiveness of surgery has fuelled bronchoscopic approaches to induce lung volume reduction. There are multiple bronchoscopic methods for achieving volume reduction in severe emphysema: EBV, airway bypass procedure, endobronchial coils, thermal (vapour) sclerosis and chemical sclerosis (sealants). Optimal patient selection is key to successful patient outcomes. This review discusses bronchoscopic approaches for emphysema treatment which has progressed through clinical trials to clinical practice.     

New and emerging minimally invasive techniques for lung volume reduction

Lung volume reduction surgery (LVRS) has been shown to improve pulmonary function, exercise capacity, quality of life, and survival in selected patients with heterogeneous emphysema. However, LVRS is a major surgical procedure with potential morbidity and mortality. Minimally invasive techniques are emerging to achieve lung volume reduction without open thoracotomy. Devices and techniques under study include one-way bronchial valves inserted via fiberoptic bronchoscopy to promote atelectasis in emphysematous lung, promotion of focal atelectasis and fibrosis by bronchoscopic injection of polymers into emphysematous regions of lung, bronchopulmonary fenestrations to enhance expiratory flow, and thoracoscopic plication or compression of emphysematous lung. The goal of all of these procedures is to replicate the benefit of LVRS without the trauma, risks, and extended recovery of open LVRS. Refinement and application of these techniques will allow patients with emphysema and their physicians and surgeons to choose from a number of viable options for lung volume reduction.     

Bronchoscopic lung volume reduction in severe emphysema

Lung volume reduction surgery (LVRS) produces physiological, symptomatic, and survival benefits in selected patients with advanced emphysema. Because it is associated with significant morbidity, mortality, and cost, nonsurgical alternatives for achieving volume reduction have been developed. Three bronchoscopic lung volume reduction (BLVR) approaches have shown promise and reached later-stage clinical trials. These include the following: (1) placement of endobronchial one-way valves designed to promote atelectasis by blocking inspiratory flow; (2) formation of airway bypass tracts using a radiofrequency catheter designed to facilitate emptying of damaged lung regions with long expiratory times; and (3) instillation of biological adhesives designed to collapse and remodel hyperinflated lung. The limited clinical data currently available suggest that all three techniques are reasonably safe. However, efficacy signals have been substantially smaller and less durable than those observed after LVRS. Studies to optimize patient selection, refine treatment strategies, characterize procedural safety, elucidate mechanisms of action, and characterize short- and longer-term effectiveness of these approaches are ongoing. Results will be available over the next few years and will determine whether BLVR represents a safe and effective alternative to LVRS.     

Endobronchial volume reduction: a myth or a marvel?

Recently, several techniques and devices have been suggested for achieving endobronchial volume reduction in patients with emphysema. The proposed devices include bronchial blockers, bronchial valves, glues, biomodulators, and stents for bronchial fenestration; all could be positioned only with flexible bronchoscopy. The current available evidence on safety and efficacy for these methods is based on animal studies and patient case series at best; therefore, all the results should be seen with caution. However, the preliminary work reviewed here suggests that most of the proposed techniques can work, and seem to be safer than surgical volume reduction. We do not yet have a proven, widely applicable endobronchial palliative treatment for severe emphysema, but we have a rapidly growing area of new research in interventional pneumology with preliminary results that challenge traditional medical thinking.     

Functional and morphological heterogeneity of emphysema and its implication for selection of patients for lung volume reduction surgery.

Lung volume reduction surgery (LVRS) in patients with advanced pulmonary emphysema aims to alleviate symptoms and enhance quality of life by improving respiratory mechanics. The theoretical concepts of the operation predict the greatest functional benefit in patients with marked hyperinflation, and with airflow obstruction due to loss of elastic recoil. Consistent observations in several centres, have confirmed these expectations. To achieve maximal reduction in lung volume at the least cost of functional tissue, resection is targeted to the lung zones with the most severe destruction by emphysema, leaving zones with relatively well-preserved tissue intact. Heterogeneity in emphysema distribution as assessed by visual scoring of the chest computed tomography scan according to a simple grading system has been shown to correlate with LVRS outcome variables. Therefore, evaluation of lung volume reduction surgery candidates has to include the functional and morphological characteristics of the emphysema as well as a general assessment of perioperative risk. However, the knowledge of potential predictive factors of lung volume reduction surgery outcome is so far based on retrospective analysis of highly selected patients. Therefore, many questions in respect of the selection of ideal candidates for this procedure remain unanswered at the present time.     

Surgery for chronic obstructive pulmonary disease: the place for lung volume reduction and transplantation

Lung volume reduction surgery and lung transplantation have been shown to improve lung function, exercise capacity, and quality of life in patients with advanced emphysema. Because the indications for both surgical procedures overlap, lung volume reduction surgery may be used as an alternative treatment or as a "bridge" to lung transplantation. In this article, we discuss patient selection, clinical outcome parameters, and the morbidity and mortality associated with each surgical procedure. We focus on the different preoperative predictors of good and poor outcomes after lung volume reduction surgery, the role of pulmonary rehabilitation, and the preferred surgical techniques for lung volume reduction surgery. An overview of the postoperative care of emphysema patients who undergo single-lung transplantation is also discussed.     

Short- and long-term functional results after lung volume reduction surgery for severe emphysema.

Lung volume reduction surgery (LVRS) has emerged as a surgical therapeutic intervention for advanced emphysema. Designed for the relief of dyspnoea, LVRS has been demonstrated to be efficacious in a subset of carefully selected patients. Short-term improvements in dyspnoea are accompanied by improvements in forced expiratory volume in one second ranging 13-96%. Lung volumes likewise improve, with lessening of trapped gas, residual volume, and total lung capacity. Improvements in functional status and quality-of-life measures parallel the improvements in dyspnoea and lung function. One preliminary study suggests that life expectancy after 3 yrs may be improved following LVRS. Many questions regarding lung volume reduction surgery in terms of operative technique, selection of patients, and outcome remain to be answered. Data are available which begin to address some of these issues. Bilateral procedures have greater short-term improvements than unilateral procedures, but the rate of loss of function following the surgery may also be greater. Stapled resection of lung tissue has been demonstrated to be superior to laser ablation. In a majority of reports, outcome is superior in patients with heterogeneous distribution of their emphysema, and patients with alpha1-proteinase inhibitor deficiency emphysema do less well than patients with smoker's emphysema.     

133Xenon ventilation scintigraphy applied to bronchoscopic lung volume reduction techniques for emphysema: relevance of interlobar collaterals

BACKGROUND: 133Xenon ventilation scintigraphy and (99m)Tc-MAA perfusion scintigraphy can be used to assess dynamic ventilation patterns in patients with severe emphysema. AIM: To describe the scintigraphic features of attempted bronchoscopic lung volume reduction (BLVR), exploring mechanisms that might explain the unexpected lack of postoperative atelectasis. METHODS: Five patients with heterogenous severe upper lobe emphysema were evaluated with 133Xenon ventilation and (99m)Tc-MAA perfusion scintigraphy, chest radiography, bronchoscopy and high resolution computed tomography before and up to 1 month after endoscopic placement of bronchial prostheses (BLVR). Ex vivo assessment of the lungs of two further patients with severe upper lobe emphysema was performed. RESULTS: No significant subsegmental or lobar collapse was evident on post-procedure chest radiography or high resolution computed tomography, despite bronchoscopic confirmation of adequate position and functioning of prostheses. 133Xenon ventilation scintigraphy confirms significantly decreased upper lobe wash-in (P < 0.023), unchanged lower lobe wash-in and significantly increased lower lobe wash-out rates (P < 0.005) after BLVR. Significant redistribution of perfusion to the lower lobes occurred after BLVR (P < 0.025). Ex vivo experiments on explanted emphysematous lungs demonstrated that these findings could best be explained by collateral interlobar ventilation, which was calculated in one specimen to be as high as 15% of total lower lobe ventilation. Peri-valvular leak is a much less likely possibility. CONCLUSION: 133Xenon ventilation scintigraphy indicated the presence of significant interlobar collateral ventilation in patients with severe emphysema that may have major relevance to these novel alternative techniques to lung volume reduction surgery. 133Xenon scintigraphy can be used in the evaluation of severe emphysema before and after novel therapeutic interventions.     

Lung volume reduction surgery in canine model of predominantly upper lobe emphysema: advantages of new surgical system

OBJECTIVE: Lung volume reduction surgery has been shown to be an effective treatment for selected patients with advanced emphysema. Nevertheless, prolonged air leaks are a significant complication that limits the utility of this procedure. This study evaluated the safety and effectiveness of a novel surgical system designed to minimize this complication. METHODS: In 14 dogs, severe upper lobe emphysema was produced by repeated bronchial instillations of papain administered over an approximate 6-month interval. Pulmonary function testing that included lung volumes and flows was performed at baseline, after emphysema, and at 1 month and 6 months after resection in the surgical group, while at comparable intervals in the nonsurgical group. Seven animals were randomly assigned to a surgical group to test a vacuum-assisted surgical system (VALR Surgical System; Spiration; Redmond, WA) that deploys a compression silicone sleeve over portions of the diseased tissue. The other seven dogs comprised the nonsurgical group. RESULTS: In both groups, emphysema increased total lung capacity (TLC) approximately 125% as compared to baseline. In the surgical group, no air leaks were observed after resection, and TLC significantly decreased at the 1-month and 6-month periods as compared with postemphysema measurements. At necropsy, histologic examination revealed fibrosis of the compressed lung contained within the sleeve and fibrotic encapsulation of the device. Two animals had evidence of localized infection. CONCLUSION: We successfully created a model of predominantly upper lobe emphysema. The vacuum-assisted surgical system provided safe and effective lung reduction without air leak complications and with sustained improvement in pulmonary function over 6 months.