Long-term outcomes from bronchoscopic lung volume reduction using a bronchial prosthesis

Background and objective: We evaluated long‐term safety and lung function outcomes in a cohort of patients with severe upper‐zone heterogeneous emphysema who underwent bronchoscopic lung volume reduction (BLVR) performed with the Emphasys one‐way valve. Methods: A retrospective cohort study was undertaken to assess long‐term outcomes in 23 consecutive patients who underwent upper lobe BLVR between July 2001 and November 2003 as part of a first‐in‐humans study. Long‐term follow up (>12 months) was available in 16/23 patients (median duration of follow up 64 months (range 15–90 months)). Both unilateral (n = 4) and bilateral (n = 12) BLVR procedures were performed with a mean of 6 (range 3–11) valves being inserted. Changes in pulmonary function tests were assessed longitudinally following the procedure. Results: 13/16 and 11/16 patients showed post‐procedure improvements in FEV₁ and DL_CO, respectively. However, early improvements in pulmonary function were not sustained with only 6/16 patients still showing improved lung function at the end of follow up. There were no significant improvements in other indices of pulmonary function. Three patients, in the absence of clinical benefit, proceeded to lung transplantation at 15, 16 and 44 months post BLVR. Four patients died during the course of the study at 27, 29, 39 and 50 months post procedure. Conclusions: BLVR with the Emphasys one‐way valve has an acceptable safety profile and in select patients may achieve long‐term sustained improvements in pulmonary function.     

经支气管镜肺减容术的研究及其临床应用

经支气管镜肺减容术（ bronchoscopic lung volume reduction,BLVR） 是在不开胸的情况下达到肺减容的目的，以减少肺减容术后并发症，为终末期COPD患者的治疗提供新的方法。与外科肺减容术比较BLVR的创伤小、费用低、术后恢复时间短、并发症少，且可以调整置入活瓣的位置或取出。基于以上优点，严重肺气肿不能耐受手术的患者可以接受BLVR。笔者结合文献介绍BLVR的国内外研究和临床应用现状。     

经支气管镜肺减容术的实验研究

目的 评价自主研制单向活瓣栓子治疗羊重度肺气肿的有效性及安全性.方法 采用与北京普益盛济科技有限公司合作研制的单向活瓣栓子,在解放军总医院动物实验中心进行动物实验.选择12～18个月龄健康雄性山羊12只,在支气管镜直视下向靶肺段置入自主研制的单向活瓣栓子,每只羊平均置入3枚,观察并记录实验动物的耐受性,分别于术后2、4、8和12周进行动脉血气测定和胸部CT扫描,观察栓子附近支气管组织及远端肺组织标本的病理变化.采用SPSS 13.0统计软件进行数据分析,各时间点血气分析结果比较采用组间t检验.结果 36枚栓子全部经支气管镜顺利置入.所有实验羊在观察期内的耐受性良好,置人栓子共脱落3枚.胸部CT示33枚栓子中有15枚(45%)栓子远端肺组织可见不同程度的萎缩或膨胀不全.组织病理学示肺泡腔缩小、塌陷,肺间质内可见淋巴细胞和单核细胞浸润,伴有少许纤维组织增生.结论 该单向活瓣柃子的性能稳定,栓子町经支气管镜活检通道直视下一次性置入,定位准确,组织相容性好,动物的耐受程度良好,可达到一定的肺减容效果,改良后有望用于重度肺气肿的临床治疗.     

Biological lung volume reduction: a new bronchoscopic therapy for advanced emphysema

BACKGROUND: Biological lung volume reduction (BLVR) using biological reagents to remodel and shrink damaged regions of lung has previously been accomplished in sheep with experimental pulmonary emphysema. This report summarizes the initial clinical experience including a 3-month follow-up using this technique in humans. METHODS: An open-label phase 1 trial designed to evaluate the safety of BLVR in patients with advanced heterogeneous emphysema enrolled six patients. Of these, three patients received unilateral treatment at two pulmonary subsegments (group 1) and three patients received unilateral treatment at four pulmonary subsegments (group 2). The incidence of adverse events and changes in pulmonary function test results, symptoms, and exercise capacity were evaluated. RESULTS: The mean (+/- SD) age of the six men enrolled in the study was 66 +/- 5.7 years (age range, 57 to 73 years). BLVR was well tolerated in both treatment groups and was not associated with any serious complications. All patients were discharged from the hospital on posttreatment day 1. Although the primary purpose of the study was to examine safety, improvements were observed in mean vital capacity (+7.2 +/- 9.5%; range, -2% to + 19%), mean residual volume (RV) [-7.8 +/- 8.5%; range, + 1% to -22%], mean RV/total lung capacity ratio (-6.6 +/- 4.7%; range, -1% to -15%), mean 6-min walk distance (+14.5 +/- 18.5%; range, 0 to + 51%), and in mean dyspnea score. On average, group 2 patients experienced greater benefit from BLVR than group 1 patients, suggesting a dose-response pattern. CONCLUSIONS: Preliminary results indicate that BLVR can be safe and may produce benefits in appropriately selected patients with advanced heterogeneous emphysema.     

支气管镜肺减容术治疗肺气肿的研究进展

除了传统内科疗法和外科肺减容术,近几年来人们又设想通过支气管镜减少肺容积从而达到治疗肺气肿的目的。方法有：①用液体冲洗出肺表面活性物质或注入生物相容性的黏合剂以促进气肿肺的不张;②用阻塞装置阻塞气肿肺段的气道,气肿肺内气体吸收造成肺不张;③在气肿肺的肺段置入单向活瓣以造成远端肺的不张。气管内放置单向活瓣被众多研究认为是上述方法中最有前途的治疗肺气肿的介入疗法,但其远期疗效还需观察。     

Methodological aspects of bronchoscopic lung volume reduction with a proprietary system

Bronchoscopic lung volume reduction (BLVR) is emerging as a new technique to palliate symptoms in patients with severe emphysema. Several devices and techniques are being developed to occlude airways resulting in collapse and reduced lung volume. Here we present in detail the methodological aspects of one such interventional bronchoscopic approach.     

Respiratory impedance following bronchoscopic or surgical lung volume reduction for emphysema

BACKGROUND: Bronchoscopic methods for achieving lung volume reduction (BLVR) are presently undergoing clinical trials, and will soon be clinically available. Understanding the differential effects of surgical volume reduction therapy (LVRS) and BLVR on lung and chest wall physiology will assist physicians in selecting an optimal approach for patients. OBJECTIVES: Determine whether LVRS adversely affects lung or chest wall physiology at 3-month follow-up relative to BLVR in an experimental model of sheep emphysema. METHODS: Twelve mixed-breed sheep were treated with papain to produce experimental emphysema, and were divided into control, LVRS, and BLVR treatment groups. Lung and chest wall impedance was measured at 0, 5, and 10 cm H2O positive end-expiratory pressure at baseline and 3-month follow-up. RESULTS: Emphysema was associated with increased airway resistance, decreased lung tissue resistance and elastance, and increased chest wall tissue resistance. Following treatment, equivalent increases in lung elastance occurred in the LVRS and BLVR groups compared to controls. LVRS did not adversely affect chest wall impedance despite causing extensive pleural scarring. CONCLUSIONS: (1) Experimental emphysema following prolonged papain exposure progresses after cessation of treatment. (2) BLVR and LVRS produced equivalent lung and chest wall impedance responses at 3-month follow-up. (3) LVRS did not adversely affect chest wall impedance despite being associated with extensive pleural scarring.     

内科肺减容术在慢性阻塞性肺疾病最新研究进展

阻塞性呼吸道疾病是多种疾病组成的,但它们都可因炎症导致气道狭窄,从而导致呼吸做功增加.由于其患病人数多,病死率高,严重影响患者的劳动能力和生活质量.不同群体的哮喘、慢性支气管炎和肺气肿最佳治疗策略应该是多方面的,如高危肺气肿患者应包括药物学和非药物方法以及手术治疗.回顾当前支气管镜介入水平,近十年其发展目标是更好地控制哮喘症状和缓解由于不适合肺减容手术的肺气肿患者症状,由此可见,新型支气管镜技术针对气道阻塞性疾病治疗有很大帮助.     

Clinical outcomes and quantitative CT analysis after bronchoscopic lung volume reduction using valves for advanced emphysema

BackgroundBronchoscopic lung volume reduction (BLVR) using Zephyr endobronchial valve (EBV) and intrabronchial valve (IBV) has been shown to improve lung function and exercise capacity in severe emphysema. However, changes in airway structures and whether these are related to the clinical improvements remain unclear.MethodsA retrospective study was performed on patients treated with BLVR. We compared changes in 2nd-, 3rd-, and 4th-generation bronchial structures after therapy, including wall thickness (WT), percentage of wall thickness (WT%), intraluminal area (LA), wall area (WA), and WA%. Responder and non-responder subgroup analysis according to minimum clinically important difference (MCID) which was defined as an improvement of 15% in forced expiratory volume in 1 s (FEV₁) and 26 m in 6 min walk distance (6MWD) was conducted.ResultsOf the 19 patients, 11 were treated with EBV and 8 with IBV. In ipsilateral non-target lobes, WT% decreased significantly in 3rd-generation bronchi at 1 month, 3, and 6 months, as well as their WA% at 1 month and 6 months. Non-responders, who were unable to achieve MCID, showed no consistent bronchial wall changes. And their LA of 3rd-generation bronchi decreased especially at 1 month. After BLVR, the target lobe volume decreased significantly until 12 months of follow-up. The volume of ipsilateral lobes could increase correspondingly and achieve the best improvements at 6 months. The contralateral lung volume showed slight amelioration but there was no statistical significance.ConclusionsBoth airway structures and lung volumes showed changes after BLVR. The 3rd- and 4th-bronchial walls tend to be thinner, which were consistent with clinical improvements. Further studies are needed to prove this conclusion and find detect potential mechanics.     

Long-term follow-up after bronchoscopic lung volume reduction in patients with emphysema

Bronchoscopic lung volume reduction (BLVR) is a novel emphysema therapy. We evaluated long-term outcome in patients with heterogeneous emphysema undergoing BLVR with one-way valves. 40 patients undergoing unilateral BLVR entered our study. Pre-operative mean forced expiratory volume in 1 s (FEV(1)) was 0.88 L · s(-1) (23%), total lung capacity was 7.45 L (121%), intrathoracic gas volume was 6 L (174%), residual volume (RV) was 5.2 L (232%), and the 6-min walk test (6MWT) was 286 m. All patients required supplemental oxygen; the Medical Research Council (MRC) dyspnoea score was 3.9. High-resolution computed tomography (HRCT) results were reviewed to assess the presence of interlobar fissures. 33 patients had a follow-up of >12 months (median 32 months). 37.5% of the patients had visible interlobar fissures. 40% of the patients died during follow-up. Three patients were transplanted and one underwent lung volume reduction surgery. Supplemental oxygen, FEV(1), RV, 6MWT and MRC score showed a statistically significant improvement (p ≤ 0.0001, p = 0.004, p = 0.03, p = 0.003 and p<0.0001, respectively). Patients with visible fissures had a functional advantage. BLVR is feasible and safe. Long-term sustained improvements can be achieved. HRCT-visible interlobar fissures are a favourable prognostic factor.     

CT肺功能成像对经支气管镜肺减容术术前筛选靶肺的价值

目的 应用CT肺功能成像检查同时行肺通气灌注核素扫描检查,评价CT肺功能成像检查对经支气管镜肺减容术患者术前筛选靶肺的价值.方法 纳入2011年3月至2012年3月北京天坛医院呼吸科门诊和住院的31例慢性支气管炎患者,均行肺功能、肺部高分辨率CT及肺通气灌注核素扫描检查,依据肺功能检查结果分为2组.正常组9例,男6例,女3例,年龄45 ～ 67岁,平均(55 ±9)岁;阻塞性功能障碍肺气肿组22例,男16例,女6例,年龄32～77岁,平均(55±12)岁.比较肺部高分辨率CT视觉评分、CT肺功能成像参数与肺功能结果之间的相关性,各肺叶的平均CT值和像素指数与通气血流比值各数据之间相关性,探讨CT肺功能成像技术对于确定拟行经支气管镜肺减容术患者的区域性无功能靶区的价值.结果 肺部高分辨率CT评分结果与RV/TLC、FEV1/FVC分级结果比较差异有统计学意义(x2=13.22和13.21,均P＜0.01),提示肺气肿的CT视觉评分与肺功能所示肺气肿严重程度分级不一致;而CT肺功能成像结果与RV/TLC、FEV1/FVC分级结果比较差异无统计学意义(x2 =3.110和2.891,均P＞0.01),提示像素指数-910 HU的CT肺功能成像与肺功能所示肺气肿严重程度分级一致性较好(r=0.262 ～0.470,均P＜0.01),各肺叶的平均CT值和像素指数与通气血流比值相关性较好(r=-0.382 ～0.698,均P＜0.01).结论 CT肺功能成像结果客观,操作简单,与肺功能评估结果和肺通气灌注扫描结果间相关性好,可作为经支气管镜肺减容术术前筛选靶肺的方法之一.     

支气管镜肺减容术之旁路通气法治疗肺气肿的研究进展

本文对支气管镜肺减容术尤其是旁路通气法治疗肺气肿研究成果和最新进展等进行综述.     

A pilot study of expiratory flow limitation and lung volume reduction surgery

STUDY OBJECTIVES: To examine the relationships between changes in expiratory flow limitation (FL) during anesthesia and postoperative responses to lung volume reduction surgery (LVRS). DESIGN: Prospective consecutive case comparison. SETTING: University medical center. PATIENTS: Eight patients with severe emphysema. INTERVENTIONS: General anesthesia with muscle paralysis and thoracic epidural analgesia were provided for LVRS via median sternotomy. MEASUREMENTS: FEV(1), functional residual capacity (FRC), and total lung capacity (TLC) were measured preoperatively and 3 months postoperatively. Tidal volume (VT) flow/volume (F/V) curves were obtained with a Pitot-type spirometer. VT, expiratory flow rate at 0. 25 x VT (V'VT,25% ), and peak expiratory flow rate (V'VT,MAX) were obtained from VT F/V curves to derive V'VT,25%/V'VT,MAX ratio as a measure of FL. RESULTS: Closed chest VT F/V curves during anesthesia pre-LVRS showed four patients with FL (group A) whose V'VT,25%/V'VT, MAX ratio was 0.38 +/- 0.06 (mean +/- SD) and four patients without FL (group B) whose V'VT,25%/V'VT,MAX ratio was 0.82 +/- 0.06 (p = 0. 0001). Closed chest post-LVRS V'VT,25%/V'VT,MAX ratio during anesthesia increased by 0.48 +/- 0.08 in group A, compared with a 0. 19 +/- 0.16 reduction in group B (p = 0.0001). Preoperative FEV(1) was 0.57 +/- 0.10 L for group A vs 0.82 +/- 0.13 L for group B (p = 0.02). Postoperative FEV(1) increased by 67 +/- 40% for group A (p = 0.03) vs 29 +/- 21% for group B (not significant). FRC decreased by 33 +/- 3% for group A vs 17 +/- 5% for group B (p = 0.0007), and FRC/TLC decreased by 0.14 +/- 0.05 for group A vs 0.01 +/- 0.07 for group B (p = 0.026). Post-LVRS V'VT,25%/V'VT,MAX ratio change during anesthesia correlated with postoperative reduction in FRC (r(2) = 0. 89, p = 0.0004) and FRC/TLC (r(2) = 0.52, p = 0.045). CONCLUSION: Post-LVRS change in V'VT,25%/V'VT,MAX ratio during anesthesia showed a linear relationship with 3-month postoperative improvement in dynamic hyperinflation. Thus, V'VT,25%/V'VT,MAX ratio may help provide valuable insights into the interactions between chest wall recoil, dynamic hyperinflation, and VT flow rates in patients with severe COPD and LVRS.     

Chartis系统辅助经支气管镜肺减容术治疗重度慢性阻塞性肺疾病合并肺气肿1例临床观察

目的介绍Chartis系统辅助的经支气管镜肺减容术(BLVR)的方法及提高对其认识。方法对2011-05-05中国医科大学附属第一医院收治的1例重度慢性阻塞性肺疾病(COPD)合并肺气肿患者行Chartis系统辅助的BLVR治疗的诊治过程及短期疗效。结果与治疗前比较,患者Chartis系统辅助的BLVR术后3个月的肺功能和圣乔治呼吸问卷(SGRQ)各指标得到了改善,6MWT中SpO2min略有提高,且出现SpO2min时的步行距离有所提高。术后第4天出现1枚气道瓣膜脱出,经重新植入后恢复良好。结论 Chartis系统辅助的BLVR安全、有效,并发症少。     

Severe bullous emphysema and hypercapnia successfully treated by bronchoscopic lung volume reduction

Patients with severe COPD may develop hypercapnic respiratory failure requiring mechanical ventilation and are at risk of becoming ventilator-dependent. We describe a patient with uncontrollable hypercapnic respiratory failure on mechanical ventilation whose respiratory condition and life were improved after bronchoscopic lung volume reduction. Further discussion of the possibility of bronchoscopic lung volume reduction in patients who require mechanical ventilation due to hypercapnic respiratory failure is warranted.     

Resection of bronchial carcinoma combined with lung volume reduction

Lung volume reduction (LVRO) combined with simultaneous resection of bronchial carcinoma ignores the well known principles of functional operability. In case of 6 patients with LVRO and resection of the lung because of a non-small-cell lung cancer (NSCLC) stage I (4 x), stage II (1 x) and stage IIIa (1 x) located in the emphysematous lung parenchyma lobectomy was done four times and extraanatomical resection twice. Because of a gangrene the resection of middle lobe was necessary in case of one patient. There were no other perioperative complications. 6 months after the operation 5 patients noticed decreased dyspnea. The survival rate after 2 years was 66 %, after 3 years 34 %. 1 patient is still alive after 56 months. Cause of death was in every case progress of tumour. Due to the principles of oncologic surgery lung resection will be functional tolerated if the cancer is located in the area of bullous lung destruction; in singular cases lung resection will improve the cardiorespiratory status at least temporary. In case of extraanatomic or segmental resections there is a low rate of morbidity and lethality but a high incidence of recurrence of carcinoma. The short- and medium- term functional results seem to be encouraging. Limiting factor for carrying out extensive resections is the tumour infiltration of non emphysematous lung parenchyma. There is no doubt that simultaneous resection will be reserved for a group of highly selected patients.