Emphysema is defined pathologically as the abnormal and permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of the alveolar wall (with no significant fibrosis). Emphysema may or may not occur in conjunction with chronic bronchitis. These two disease states have been grouped under the category of chronic obstructive pulmonary disease (COPD). This category alludes to the physiologic defect where there is permanent obstruction to the flow of air, which leads to the major symptom of shortness of breath seen in patients with COPD. In patients with Emphysema, this is further complicated by a gas exchange abnormality due to the disruption of the alveolar-capillary membrane interface.
WHY DO SOME PATIENTS WITH EMPHYSEMA BENEFIT FROM LUNG VOLUME REDUCTION?
The obstructive pathophysiology, along with the destruction in the alveolar walls, facilitates the trapping of air in the lung parenchyma. This happens predominantly in the areas of significant alveolar-capillary membrane destruction, as these areas do not allow for the exchange of air and oxygen. The oxygen that goes to these areas does not get transferred to the capillaries. When the patient exhales, a significant proportion of the air cannot travel outside of the lung parenchyma (due to the obstruction to flow that occurs during expiration in COPD). This leads to air trapping and dynamic hyperinflation, which causes a significant mechanical disadvantage for the thoracic cage. In simple terms, the thoracic cage remains over expanded throughout the respiratory cycle and the amount of thoracic and lung space available to allow new air to enter the lungs is reduced significantly. This causes the sensation of dyspnea and eventually leads to the retention of carbon dioxide as the patient walks a pathologic fine line between hyperventilation and hypoventilation. The latter leads to hypercapnic respiratory failure needing non-invasive positive pressure ventilation, the need for endotracheal intubation and mechanical ventilation, hence increasing the mortality rate of patients with emphysema. Therefore, removing those areas of non-functional lung parenchyma that facilitate air trapping would be theoretically beneficial.
Given the issue of dynamic hyperinflation with air trapping and its clinical consequences, numerous clinical trials have been already completed, with the most compelling trial being published in the New England Journal of Medicine back in 2003. In this trial known at the NETT trial (National Emphysema Treatment Trial), a randomized, multi-center model was used to compare lung volume reduction via surgical resection (LVRS) with maximal medical therapy. In this trial, the overall result was an increase in exercise capacity but no survival advantage. However, subgroup analysis of the extensive data from the 1218 randomized participants showed that patient with upper-lobe predominant emphysema that had a low exercise capacity preoperatively, had a significant survival advantage with a clinical and statistical significant reduction in mortality. In patients who are not surgical candidates, bronchoscopic placement of endobronchial valves is an exciting potential alternative option. Bronchoscopic lung volume reduction (BLVR) has the benefit of its superior safety profile when compared to surgery, which allows higher risk patients a chance of receiving the benefits from lung volume reduction.
One of the methods that is being actively studied is the use of an “umbrella-shaped” device known as the Spiration Valve System (Olympus, d.b.a. Spiration, Inc., Redmond, WA) to selectively treat the target emphysema lobe. This device is FDA approved for humanitarian use in patients with air leaks following lung surgery and is being investigatively studied to treat patients with emphysema. Central Florida Pulmonary Group (CFPG) is part of a clinical device trial, sponsored by Spiration, Inc., to evaluate the safety and effectiveness of the Spiration Valve System when placed in the airways of patients with severe emphysema. The EMPROVE study is a follow-up to the Spiration IBV Valve Trial. Although the IBV Valve Trial did technically achieve statistical significance for patient improvement, this was felt to be too modest to be clinically significant. However, substantial lessons were learned from this trial, and other trials in Europe, that have led to a significant study redesign. The result is the EMPROVE study. The EMPROVE clinical trial is a randomized study in which qualified candidates will be assigned to the treatment group or a control group in a ratio of 2:1. This means that there is a 66% chance of a study participant getting the valves and a 33% chance of being in the control group. Given that the valves have shown potential benefit in previous studies, a fair bias has been given towards the likelihood of getting the valves. It is also important to understand that although the valves are meant to be permanent, their design allows us to remove them with ease in the event of complications.
The procedure should be done under general anesthesia and under flexible bronchoscopy. Once the patient receives anesthesia, an endotracheal tube is placed. The bronchoscope is introduced through it, and advanced to the target lobe. The bronchoscope is advanced to the target lobe, any secretions are suctioned and using a balloon through the bronchoscope, the segmental airways are sized in order to select the adequate caliber valve for each segment. The goal is to occlude the target lobe completely. It has been shown that the greater the volume loss, the greater the potential benefits and the higher the chance they can be measured objectively. Typically 3 or more valves are needed to completely occlude a lobe. Using a special deployment catheter advanced through the bronchoscope, sequential deployment of valves is done. Expertise in the deployment of the valves is imperative given the higher difficulty when trying to deploy them to the upper lobes due to the acuteness of the angle, which leads to incomplete closure of the target bronchi. The bronchoscope is then removed completing the procedure. The procedure time typically ranges from 30-40 minutes. Potential complications that can occur in a small proportion of patients include: COPD exacerbations from stimulation of the airways, pneumothorax (from the pressure differential that may cause traction of blebs especially in those with pleural adhesions), and pneumonia due to inspissated mucus distal to the valves. The valves are usually left permanently in the patient. However, if needed, they are designed for safe bronchoscopic removal even months after deployment (given their low granulation tissue profile).
The EMPROVE study is a scientifically rigorous clinical trial that will likely be the final step to making endoscopic lung volume reduction a reality for patients with emphysema. Men and women who are over 40 years of age, who have severe emphysema and who are still able to walk may possibly be able participate in this investigational device trial. Subjects will be seen at Central Florida Pulmonary Group’s Department of Research for screening evaluations to confirm eligibility for the study. There will be no cost to subjects for the evaluations or study procedure. If you are a doctor who has a patient with severe emphysema or if you are a patient who may be interested in hearing more about this clinical trial, please contact Kathleen Summo at Central Florida Pulmonary Group Research Department by dialing 407-841-1100 Ext. 225 or email at firstname.lastname@example.org . If you wish to discuss the trial in more detail, please feel free to contact me at 407-841-1100 or email me at email@example.com .