Michela Bezzi

Multicentre European study for the treatment of advanced emphysema with bronchial valves

This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis. Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n=37) or without (n=36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥4-point improvement in St George’s Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography. At 3 months, there were eight (24%) positive responders in the treated group versus none (0%) in the control group (p=0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean±sd -7.3±9.0%) to the non-treated lobes (6.7±14.5%), with minimal change in the control group (p<0.05). Mean SGRQ total score improved in both groups (treatment: -4.3±16.2; control: -3.6±10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups. Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.

A randomised trial of lung sealant versus medical therapy for advanced emphysema

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events. Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility. Emphysematous lung sealant therapy is highly efficacious in some patients, but benefits bring significant risks http://ow.ly/JJ2vg

Central airways remodeling in COPD patients

Background The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD) patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM) area and the extracellular matrix (ECM) protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion These findings indicate that airway remodeling also affects the large airways in COPD patients who have greater deposition of ECM proteins in the subepithelial layer and a larger smooth muscle area than control smoker subjects. These changes may contribute to chronic airflow obstruction in COPD patients.

Additive effect on pulmonary function and disability of intensive pulmonary rehabilitation following bronchoscopy lung volume reduction (BLVR) for severe emphysema

BACKGROUND Pulmonary rehabilitation (PR) is mandatory before bronchoscopy lung volume reduction (BLVR); there is scant information about its efficacy post-BLVR. We retrospectively evaluated pulmonary function (PF) and disability in patients pre/post-BLVR and its additive effect on an intensive PR program post-BLVR vs matched non-BLVR controls. We analyzed changes within BLVR patients according to presence or not of atelectasis. METHODS We compared PF and exercise tolerance (6-min walk test, 6MWT) in 39 BLVR patients (FEV1% pred. 28.9 ± 1.5; RV% pred. 236.1 ± 7.7) pre-/post-BLVR, and vs. 32 controls (FEV1% pred. 32.7 ± 1.5; RV % pred. 217.8 ± 8.3) before and after PR. RESULTS BLVR patients showed a greater improvement than controls in PF (difference between groups: 3.8 for FEV1% pred., p = 0.043; -20.5 for RV % pred., p = 0.02) and 6MWT response rate (12/39 vs. 1/39 subjects, p = 0.003). Both groups further improved significantly 6MWT after PR without a significant difference between groups. Atelectasis after BLVR mainly accounted for the improvement in FEV1% pred, RV% pred. and 6MWT compared to both BLVR without atelectasis and controls. CONCLUSION BLVR improves PF (particularly RV) and exercise tolerance, patients with lobar exclusion being the best improvers. PR following BLVR yields a further improvement in exercise tolerance in both (atelectasis and non-atelectasis) subgroups.

Reopening the Airway: Fast Methods

Central airway obstruction can occur secondary to a number of lung primary or secondary malignancy and benign processes presenting as vegetation, infiltration, or compression. Approximately 30% of lung cancer patients develop central airway obstruction. The technique of endobronchial coagulation and disobstruction plays a pivotal role in all these situations, since conventional treatment with chemo- and radiotherapy is often performed with unsatisfactory results with regard to the endobronchial component of the tumor. Palliative airway treatments are essential to permit ventilation and control hemorrhage and to improve quality and length of life. Rigid bronchoscopy has proven to be an excellent tool to provide airway access for these therapies: the degree of obstruction and severity of symptoms, the nature of the disease, and the patient’s overall prognosis and quality of life impact the choice of intervention. The number and scope of therapeutic options have increased dramatically; they can be divided into “slow methods” such as photodynamic therapy, cryotherapy, and brachytherapy or fast methods: laser, argon plasma coagulation, and electrocautery. Laser therapy more often integrates rigid bronchoscopic resection; this procedure is worldwide known as laser-assisted mechanical resection (LAMR) and represents the safest and more effective way to obtain all potential effects of laser in bronchoscopy.

Complications related to endoscopic lung volume reduction for emphysema with endobronchial valves: results of a multicenter study

Background Despite bronchoscopic lung volume reduction (BLVR) with valves is a minimally invasive treatment for emphysema, it can associate with some complications. We aimed at evaluating the rate and type of complications related to valve treatment and their impact on clinical outcomes. Methods It is a retrospective multicenter study including all consecutive patients with severe heterogeneous emphysema undergoing BLVR with endobronchial valve treatment and developed any complications related to this procedure. The type of complication, the time of onset, the treatment required and the out-come were evaluated. Response to treatment was assessed according to the minimal clinically important difference (MCID) as follows: an improvement of ≥15% in forced expiratory volume in one second (FEV1); of -8% in residual volume (RV); of ≥26 m in 6-minnute walking distance (6MWD); and of ≥4 points on the St. Georges Respiratory Questionnaire (SGRQ). Target lobe volume reduction (TLVR) ≥350 mL was considered significant. Results One hundred and seven out of 423 (25.3%) treated patients had complications related to valve treatment including pneumothorax (17.3%); pneumonia (1.7%), chronic obstructive pulmonary disease (COPD) exacerbation (0.9%), respiratory failure (1.4%), valve migration (2.1%), and hemoptysis (1.9%). In all cases complications resolved with appropriate treatment including removal of valves in 21/107 cases (19.6%). Patients with TLVR ≥350 mL (n=64) vs. those <350 mL (n=43) had a statistically significant higher improvement in FEV1 (19.0%±3.9% vs. 3.0%±0.9%; P=0.0003); in RV (-10.0%±4.8% vs. -4.0%±2.9%; P=0.002); in 6MWD (33.0±19.0 vs. 12.0±6.3 metres; P=0.001); and in SGRQ (-15.0±2.9 vs. -8.0±3.5 points; P=0.01). Only patients with TLVR ≥350 mL met or exceeded the MCID cut-off criteria for FEV1 (19.0%±3.9%), RV (-10.0%±4.8%), 6MWT (33.0±19.0 metres), and SGQR (-15.0±2.9 points). Five patients (1.2%) died during follow-up for causes not related to valves treatment neither to any of the complications described. Conclusions Valve treatment is a safe and reversible procedure. The presence of complications seems not to have a significant impact on clinical outcome in patients with lobar atelectasis. Due to poor clinical conditions and possible complications, BLVR should be performed in high volume centers with a multidisciplinary approach.

Endoscopic treatment with endobronchial valves of Persistent Air Leak (PAL)

Introduction: Persistent air leak is defined as prolonged (>5 days) need for a chest drain after pneumothorax, chest trauma or lung resection (28% to 60%). Standard treatment consists in maintaining the chest tube with or without suction. Pleurodesis, pleural decortication or surgical resection are further options. PAL occurrence extends the average hospital stay and increases costs. Aims and objectives: We evaluated safety and efficacy of endoscopic treatment of PAL with endobronchial valves. Methods: We reviewed the files of all patients treated for PAL during 6 years in 2 Italian Interventional Pulmonology Center. Results: Since September 2011 25 patients underwent endoscopic treatment of PAL due to: lung resection (9, 7 cancer), pneumothorax (11, 6 spontaneous-5 iatrogenic) or pleural empyema (5). Treatment was performed 17.5±10 days after chest tube insertion through flexible (92%) or rigid bronchoscopy (2 pt). Air leaks were located at a segmental (11pt) or lobar (12 pt) level using an Olympus balloon; in 2 patients 2 adjacent lobes were excluded. We used Zephyr Endo Bronchial Valves (6 pt) or Olympus Spiration Valve System (17 pt) or both (2 pt). Bronchoscopies lasted 28.6±11.5 minutes, air leak resolved immediately in 23 pt out of 25 (92%). No severe complications were described and pneumothorax never recurred. Conclusions: This retrospective study suggests that bronchoscopic treatment of PAL with bronchial valves is a minimally invasive procedure, effective and safe, regardless of its cause. Future prospective studies should focus of cost/effectiveness compared to conventional treatment.

Patient selection and efficacy of valve bronchoscopic lung volume reduction (BLVR) in emphysema

BLVR has been proposed as an alternative to lung volume reduction surgery in patients with severe emphysema (TomaTP et al Lancet 2003; 361:931-3). There is agreement that for bronchial valves to work, fissure integrity is needed as it is associated with lobar volumetric changes which predicts efficacy of BLVR (VenutaF et al Ann Thorac Surg 2005;79:411-416). Two methods are available to evaluate fissure integrity: HRCT with direct observation of fissures and Chartis to directly assess the absence of collateral ventilation as the functional result of fissure integrity. We evaluated the response of 11 consecutive patients (FEV1 0,80L±0,25; RV 5,05L±1.3) with severe heterogeneous emphysema and complete fissure based on Chartis and CT scan analysis. Patients had valves (Olympus SVS) placed in the most diseased lobe with complete fissure (Chartis). Fissure completeness was also evaluated through quantitative CT (SeleCT by VIDA, Olympus). Lung function (FEV1, RV) showed significant improvement at 6 months. Follow up CT at 3 months showed significant volume reduction in the target lobe and a 62% responder rate as defined as ≥ 350ml volume reduction

Transanastomotic endobronchial migration of a pericardial flap.

A 36-year-old woman underwent left main bronchus sleeve resection for a typical carcinoid. The bronchial anastomosis was reinforced with a bovine pericardial flap fixed by fibrin glue. Six months after the surgery the patient presented with acute dyspnea. Flexible bronchoscopy disclosed an endoluminal migration of the pericardial flap through the anastomotic dehiscence and a cicatricial stenosis of the left upper bronchus. The migrated flap was successfully removed and the stenosis segment of the bronchus was dilated using a rigid bronchoscope. Two months after complete recovery from the bronchial dehiscence, the patient developed an anastomotic cicatricial stenosis, which was effectively treated by laser photoresection and mechanical dilatation. Eight months after the last procedure the patient remains symptom free.