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Send to a FriendBronchoscopic alternatives to lung volume reduction surgery (LVRS) have been recently proposed; the airway bypass [1-3] and bronchoscopic lung volume reduction (BLVR) are certainly one step beyond current LVRS practice. In particular, BLVR with one–way valves has been attempted in the experimental laboratory [4] and in selected clinical settings [5-8]. The one–way valve allows air to be vented from the isolated lung segment during normal expiration and prevents air from refilling the lung during expiration. It has been postulated that the placement of these valves in the segmental bronchi could functionally isolate the airway that supplies the most hyperinflated parts of the emphysematous lungs, favoring deflation and even atelectasis, and thus mimicking LVRS in its contribution to alleviate symptoms.
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| Figure 1: First generation of endobronchial one–way valves. |
These valves are usually placed in a general operating room setting, with the patient intubated under intravenous anaesthesia (Propofol infusion) and spontaneous assisted ventilation. After the patient is intubated, the flexible
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| Figure 2: Delivery catheter for the first generation of endobronchial one–way valves. |
The first generation of EBV have been extensively employed in several prospective, nonrandomized, single center longitudinal pilot studies to evaluate safety and short term efficacy with promising results in a selected group of patients with heterogeneous end stage emphysema.
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| Figure 3: Zephyr (second generation) endobronchial one–way valve. |
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| Figure 4: Air flow resistance of the different types and sizes of airway valves. The parameter is compared to the flow of the first generation of valves of small size. The resistance is clearly lower for the large valves of the second generation. |
A flexible delivery catheter is used to place this second generation EBV valve into the targeted bronchial lumen. The catheter is constructed of a flexible stainless steel and polymer composite shaft. It has an actuation handle (Figure 5) on the proximal end and a retractable polymer housing for containing the compressed Zephyr EBV on the distal end (Figure 6). A bronchial diameter measurement gauge made of flexible polymer is attached to the proximal end of the distal housing (Figure 6). This measurement gauge allows the user to visually (bronchoscopically) measure the diameter of the bronchial lumen prior to device deployment to verify that the size of the valve is appropriate for the target lumen. The measurement device consists of two sets of flexible gauges. On the delivery catheter for the Zephyr EBV 4.0 the larger gauge spans a 7 mm diameter and the smaller gauge spans a 4 mm diameter, indicating the maximum and minimum treatable bronchial diameters for this size of device. On the delivery catheter for the Zephyr EBV 5.5, the two gauges are sized to span diameters of 8.5 mm and 5.5 mm. The EBV is compressed into the retractable distal housing by the operator using a specifically designed EBV loader system. The loaded catheter is advanced to the target location and the valve is deployed by actuating the deployment handle, which retracts the distal housing and releases the EBV. The delivery catheter is designed to be inserted through a 2.8 mm diameter working channel of a flexible bronchoscope. Thus, this new generation of valves can be placed under local anaesthesia since the deployment maneuver is much simpler.
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| Figure 5: Handle of the deployment system designed for the second generation of valves (Zephyr EBV). | Figure 6: Distal end of the deployment system for the Zephyr EBV (see text for description) |
After a series of animal experiments, more than 100 patients have been treated so far in pilot studies performed at several centers worldwide, with selection criteria similar to those for LVRS. The inclusion criteria in these pilot studies were similar to those for surgical lung volume reduction: heterogeneous emphysema, FEV1 less than 30%, CLCO higher than 20%, no pulmonary hypertension, no hypercapnia. Heterogeneous emphysema was chosen since this type of disease shows less collateral ventilation that the homogeneous one; thus, it should be easier to achieve volume reduction and even atelectasis. The first series of patients treated with a first generation type of EBV were reported by Snell and colleagues [6]. They demonstrated that that type of bronchoscopic prosthesis could be safely and reliably placed into the human bronchi; however, symptomatic improvement was observed only in 4 patients, with no major change in radiographic findings, lung function, or 6 minute walk distance at one month, although gas transfer improved from 7.47 ± 2.0 to 8.26 ± 2.6 ml/min/mmHg and nuclear upper lobe perfusion fell from 32 ± 10 to 27 ± 9 %. Toma and colleagues subsequently reported on 8 patients [5] undergoing unilateral volume reduction with a second generation of EBV. Five patients had emphysema judged too severe for volume reduction surgery and 3 refused the operation. After valve placement there was a 34% increase in FEV1 and 29% difference in DLCO; CT scans showed a substantial reduction in regional volume in four of the eight patients. The same group also reported that in a subgroup of patients in whom invasive measurements were performed, improvement in exercise capacity was associated with a reduction of lung compliance and isotime esophageal pressure–time product [9]. Other two series of patients treated with EBV have been reported [7, 8] with encouraging functional results. Along with the functional improvement there was also a subjective improvement benefit reported by most of the patients, even if a dyspnoea score was not available in all the series. Overall, all patients tolerated the treatment well. Between 3 and 5 valves were placed in the target lobe and most of them received unilateral treatment. It has been demonstrated that the procedure can be safely performed with encouraging short–term results. Up to now the data available for this technique are still extremely limited and the follow–up is too short to be compared with other therapies.
In our experience [8] with the first generation of EBV valves we have observed 1 contralateral and 2 bilateral pneumothorax out of 17 treatments (2 staged bilateral); this complication has been experienced also by other authors [7]. However, with the second generation of EBV valves (5 patients – unpublished data) we have not observed this complication any more. Three of our patients showed granulation tissue obstructing one or more of the valves; this complication occurred with the first generation valves 6 months after placement. One patient had pneumonia in the non treated lobe; this complication was easily managed with the administration of broad spectrum antibiotics. The functional improvement was statistically significant; in particular FEV1 markedly improved and the residual volume decreased: at 3 months more than 50% of the patients still show at least a 30% functional improvement; most of them required less supplemental oxygen and 7 out of 15 were able to stop it. We were not able to observe a complete atelectasis of the lobe where valves where implanted, even if it has been described by other authors; however, in most of the patients, the shape of the chest was redesigned. Exercise tolerance was also improved and remained stable after 3 months of follow up. Contralateral BLVR could be attempted to obtain a second functional improvement when pulmonary function tests start to deteriorate again, as it is done for LVRS. A contralateral BLVR was performed in two of our patients, but neither was required for functional reasons: both patients had pneumothorax on the contralateral side and valves were placed with the aim of stopping the air leak; this result was easily obtained, along with further functional improvement. With more experience, simultaneous bilateral insertion of the valves could be attempted. One of the advantages of the endobronchial lung volume reduction is that the procedure can be reversed and other treatments tried if necessary.
The short term results with BLVR are encouraging, but long term follow up is certainly required, as well as multicenter trials, to evaluate the therapeutic potential of this procedure.