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 meet the NETT study inclusion criteria, have the characteristics just described and are not surgical candidates because of comorbidities, 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. The mortality with intrabronchial valves is 1% (vs 5% with LVRS). The hospital length of stay ranges from 1-4 days (vs 7-10 days with LVRS). There are different endoscopic modalities available for lung volume reduction, but by far most of the data comes from the endobronchial valve trials both with a duckbill (Zephyr Valve, PulmonX, Neuchatel, Switzerland) and the Umbrella-shaped valves (Olympus, Spiration, Inc., Redmond, WA). Only the latter is available in the United States and has attained FDA approval for compassionate use in patients with bronchopleural fistulas . Data from the endobronchial valves has shown significant improvement in dyspnea (reported in up to 85% of the subjects that undergo valve placement), as well as clinically significant improvement in health related quality of life. Static measures of pulmonary function such as that seen on pulmonary function testing following valve placement seem to only change significantly on those patient’s who achieve complete lobar collapse, have complete fissures and have favorable Fessler-Permutt multivariate mechanics. The improvements in shortness of breath and hence on quality of life in patients with no improvement in pulmonary function testing are likely explained by the already proposed theory of diversion of air to less diseased areas. By occluding diseased airways with the endobronchial valves, the increased airflow resistance forces air to relatively less emphysematous parts of the lung resulting in less air trapping. This results in less shortness of breath and would explain why even patients with only minimal lung volume reduction after placement of the valves still benefit from this procedure.
The procedure should be done under general anesthesia and under flexible bronchoscopy. All the trials have shown that suboptimal valve deployments and increased procedural times happen in those cases done under conscious sedation for obvious reasons. Once the patient receives anesthesia, a laryngeal mask airway (LMA) or an endotracheal tube is placed. The bronchoscope is introduced through either one, and advanced to the target upper lobe. At this point there is controversy on doing unilateral vs bilateral procedures (given conflicting data in the valve trials when single vs double upper lobes were done). The current consensus for the Intrabronchial valve is to do a single lobe as there may be less side effects (but this is only a theoretical consideration). 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 upper lobe completely. It has been shown that the greater the volume loss, the greater the benefits and the higher the chance they can be measured objectively. Typically 3 valves are needed to completely occlude either upper 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 ranges from 30-45 minutes (with most patients leaving the same day). However, the published length of stay ranges from 1-4 days. 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).
Lung volume reduction surgery (LVRS) produces symptomatic, physiological and a survival benefit in selected patients. BLVR has the potential benefit of its marked superior safety profile when compared to surgery, which allows higher risk patients a chance of receiving the benefits from lung volume reduction. Patients who are not surgical candidates for LVRS because of comorbidities, may one day benefit from BLVR. Patients must be on maximal medical therapy prior to being considered for bronchoscopic lung volume reduction. Evaluation by an interventional pulmonologist proficient at BLVR is warranted given that patient selection and the perfect placement of valves is key to the success of this newer treatment option for patients with emphysema.
By Jorge Guerrero, MD, FCCP
Jorge Guerrero, MD, graduated from Universidad Javeriana School of Medicine in 2002. He then completed an Internal Medicine Internship and Residency at Tufts University School of Medicine (Carney Hospital) in Boston, Massachusetts. Next he went on to complete an Adult Tracheobronchomalacia Novel Clinical Research in the Division of Interventional Pulmonology at Harvard Medical School in Boston, Massachusetts. He also completed a Pulmonary Disease and Critical Care Fellowship at Georgetown University School of Medicine in Washington, D.C. He then completed his Fellowship in the Division of Interventional Pulmonology at Harvard Medical School (Beth Israel Deaconess Medical Center) in Boston, Massachusetts. Since August 2012, he has been a member of Central Florida Pulmonary Group in Altamonte Springs.
Dr. Guerrero may be contacted at 407-841-1100 or by visiting www.cfpulmonary.com .