Does Endobronchial Valve Treatment Improve Outcomes in Severe Emphysema Without Collateral Ventilation?

Andrew Shorr, MD, MPH


April 15, 2016

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This is Andy Shorr from the MedStar Washington Hospital Center, with a pulmonary critical care literature update.

I would like to discuss the STELVIO trial, which was published by Klooster and colleagues in the New England Journal of Medicine in December 2015.[1] The trial dealt with management approaches using endobronchial valves in patients with severe emphysema. Endobronchial valves have really been of interest as a way to accomplish lung volume reduction surgery without putting the patient through actual lung volume reduction surgery. The theory is that with the valve in place, you can fix the issues with severe emphysema, allow all of the benefits of lung volume reduction surgery that are theoretically possible, but without exposing the patient to a major surgery and its associated morbidity and potential mortality.

The STELVIO trial was a randomized controlled trial evaluating the Zephyr®valve [Pulmonx Corporation; Redwood City, California] in a group of patients with severe emphysema. Looking back at a prior trial, the Endobronchial Valve for Emphysema Palliation Trial (VENT),[2] the investigators realized that if participants had collateral flow across lobes and lung, putting in a valve was going to be pointless because there would be another way for there to be flow to that area of the lung you were trying to collapse. The 84 patients who they enrolled were different from in previous trials because they all had to have either complete fissures present on a high-resolution CT near the target area or nearly complete fissures present. The theory was that this would be a surrogate for eliminating patients with collateral flow, but that alone wasn't enough. They then required patients to undergo initial bronchoscopy as part of the trial where they actually assessed for the presence of collateral flow, using balloons to occlude airways and measure flow. If the patient still had no collateral flow, they could be enrolled in the trial; but if they did have collateral flow, they were no longer eligible. Of these 84 patients they enrolled initially, only 68 underwent randomization, mainly because they had to exclude people who did in fact have collateral flow.

The 68 patients who were randomized—34 to no valve and 34 to a valve—were a pretty severe group of patients in terms of their illness. Mean forced expiratory volume in 1 second (FEV1) was less than 30% predicted; mean 6-minute walks were in the 375 m range; quality-of-life scores were very low; and all were on maximum medical therapy. The patients underwent valve placement, and the primary endpoint was change in FEV1, forced vital capacity (FVC), and 6-minute walk distance at 6 months. They analyzed the data both in terms of the intention-to-treat population and per-protocol population (ie, the group of patients who had valves that lasted and made it to all of the follow-up visits). They also looked at issues related to quality of life.

When the trial was completed at 6 months, it was clear that the patients who were randomized to the valve group had better spirometry and better 6-minute walk distances. Mean FEV1, for example, went up by 140 mL, and again, if you are dealing with a group that is starting at less than 30% predicted FEV1, that is rather substantial. It certainly passes what we would consider the minimal clinically important difference in terms of effect size. Six-minute walk distances went up compared with the control arm by nearly 75 m. Again, this exceeds the minimal clinically important difference. Quality-of-life scores also substantially improved. You would think that overall this was good efficacy. Even when they looked at the per-protocol population and not just the intention-to-treat population, results were similar.

However, I think we have to look at some of the tradeoffs, and the authors are very explicit about this. By the end of the trial, 18% of patients developed a pneumothorax. Now, not all of these in the treatment arm required a chest tube, but they certainly required observation. In fact, all of these patients were hospitalized after the procedure and all of the pneumothoraces were identified within 1 day. Similarly, some of these patients had to have the valves removed because of complications, such as valve migration and failure of pneumonia to resolve, and one third of the 34 patients underwent repeat bronchoscopy. Some actually dropped out of the trial because the valves had to be removed.

Overall, from a physiologic perspective, this approach is clearly efficacious, and we have gotten much better at patient selection by addressing this issue of collateral flow. More importantly, this trial demonstrates that high-resolution CT alone is not adequate for identifying whether a patient has collateral flow or not. In this trial, 13 of 84 patients were found to have collateral flow even though their high-resolution CT suggested they wouldn't, so high-resolution CT isn't a perfect screening test. The benefits of this therapy were clear and it certainly avoided issues that you might see with lung volume reduction surgery, and there was no mention about a diffusing capacity [of the lungs] for carbon monoxide (DLCO) exclusion issue, which has certainly been a concern in the past for patients who are potential candidates for lung volume reduction surgery. Here, the tradeoff really is the other bronchoscopies that the patient may have to undergo and the risk for pneumothorax. This has been a consistent theme with the valves and is certainly a concern with these mechanical devices.

In the end, I think we are going to need much better data about patient selection and potential predictors of response to therapy. We are also going to need very careful cost-benefit analyses. Yes, I can improve your 6-minute walk. Yes, I can make you feel better. However, if 1 in 3 patients has to undergo a repeat bronchoscopy and everyone has to spend a day in the hospital, this is not without cost. All of these things need to be evaluated. Finally, no information was provided in this trial about COPD exacerbations, although the study was small and the follow-up was only 6 months, but this would have been interesting to understand.

I am not sure that this is ready for everybody, but certainly I think patient selection has to be clear. However, it is an exciting new option that is coming down the pipe for our patients with severe end-stage emphysema and who have no other options.

This is Andy Shorr from Washington, DC.


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