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Ann Thorac Surg 2003;75:393-398
© 2003 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, Missouri, USA
* Address reprint requests to Dr Cooper, One Barnes-Jewish Hospital Plaza, Suite 3108 Queeny Tower, St. Louis, MO 63110, USA
e-mail: cooperjo{at}msnotes.wustl.edu
Presented at the Thirty–eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.
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Abstract |
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METHODS: Twelve human emphysematous lungs, removed at the time of lung transplantation, were placed in an airtight ventilation chamber with the bronchus attached to a tube traversing the chamber wall, and attached to a pneumotachometer. The chamber was evacuated to -10 cm H2O pressure for lung inflation. A forced expiratory maneuver was simulated by rapidly pressurizing the chamber to 20 cm H2O, while the expiratory volume was continuously recorded. A flexible bronchoscope was then inserted into the airway and a radiofrequency catheter (Broncus Technologies) was used to create a passage through the wall of three separate segmental bronchi into the adjacent lung parenchyma. An expandable stent, 1.5 cm in length and 3 mm in diameter, was then inserted through each passage. Expiratory volumes were then remeasured as above. In six experiments, two additional stents were then inserted and forced expiratory volumes again determined.
RESULTS: The forced expiratory volume in 1 second (FEV1) increased from 245 ± 107 mL at baseline to 447 ± 199 mL after placement of three bronchopulmonary stents (p < 0.001). With two additional stents, the FEV1 increased to 666 + 284 mL (p < 0.001).
CONCLUSIONS: Creation of extra-anatomic bronchopulmonary passages is a potential therapeutic option for emphysematous patients with marked hyperinflation and severe homogeneous pulmonary destruction.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsDiscussionReferences |
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The loss of lung tissue alters the physical properties of the lung, leading to a loss of lung elastic recoil and to progressive dynamic hyperinflation of the lungs. These changes result in an enlargement of the thorax, flattening of the diaphragm, increased work of breathing, increased dyspnea, and reduced exercise tolerance [2, 3]. The progressive loss of elastic recoil traps the patient in a state of hyperinflation in which forced effort cannot reduce the residual volume, since the force exerted to empty the lungs collapses the small airways and obstructs the outflow of gas. Progressive hyperinflation of the lungs and hyperexpansion of the chest wall also diminishes inspiratory capacity. To maintain adequate minute ventilation, the respiratory rate must increase, resulting in an increase in the work of breathing and in dyspnea.
It has been repeatedly demonstrated that collateral ventilation—the ability of gas to move from one part of the lung to another through nonanatomic pathways—is greatly increased in emphysema, because of the extensive breakdown of alveolar walls and lobular septae [4, 5]. We hypothesize that the increased collateral ventilation can be used to bypass collapsing and obstructed small airways. We postulate that creation of noncollapsing, extraanatomic stents connecting lung parenchyma to large airways can facilitate expiration and help alleviate some of the adverse consequences of dynamic hyperinflation. Experiments were undertaken in excised human emphysematous lungs to explore the feasibility of this concept.
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Material and methods |
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Before initiating the forced expiratory maneuvers, the lung was expanded by adjusting the lung chamber pressure to -10 cm of water. Measurement and recording of airway pressure, chamber pressure, and inspiratory and expiratory flow and volume over time was performed with an external data acquisition device connected to a laptop computer (RSS100HR Research Pneumotachygraph system, Hans Rudolph Inc). Once the lung was fully inflated to a chamber pressure of -10 cm of water pressure, any continuing inspiratory flow through the airway represented air leakage from the surface of the lung. The lung was considered to be suitable for the experiment only if rate of air leakage was less than or equal to 400 mL/min. If this could not be achieved, the lung was discarded.
After inflation of the lung to a steady-state condition, the forced expiratory maneuver was produced by sudden opening of the ball-valved port attaching the ventilating chamber to the pressurized reservoir. This raised the pressure in the ventilating chamber to +20 cm of water pressure in less than 0.4 seconds, after which the pressure in the chamber remained constant at +20 cm H2O. After data acquisition for 5 seconds, the valve connecting the pressure drum to the ventilating chamber was closed, the ventilating chamber again evacuated to -10 cm of water pressure, and the forced expiratory maneuver and measurements were repeated. Three measurements were obtained and the results were averaged.
We created the communications between the bronchial tree and adjacent lung parenchyma at the level of the segmental or subsegmental bronchi. A standard fiberoptic bronchoscope, 4.8 mm im external diameter (BF-20D Olympus American Inc, Melville, NY) was passed through the Plexiglas cylinder attached to the bronchus and advanced into the airway. A radiofrequency catheter (Broncus Technologies Inc, Mountain View, CA) was passed down the working channel of the bronchoscope and a small hole made through the bronchial wall into the adjacent lung. The probe was withdrawn and a balloon-expandable coronary stent, 3.0 mm in diameter and 15 mm in length, was inserted through the bronchial fenestration and expanded, with the proximal end of the stent barely projecting into the airway and the distal end of the stent in the lung parenchyma. The bronchoscope was then withdrawn and the pneumotachygraph reattached to the external end of the airway port. Figure 2 is a schematic drawing of the fenestration procedure and stent insertion.
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In the last six experiments, after the expiratory measurements had been obtained following placement of the three stents, the bronchoscope was reinserted, and two more fenestrations were made and two additional stents were placed to give a total of five stents. The forced expiratory measurements were then repeated.
The opportunity for studying a normal human lung occurred when a proposed bilateral lung transplant was converted to a single lung transplant, and the contralateral donor lung could not be used. That lung was taken to the laboratory and studied in the same fashion as the excised emphysematous lungs. After baseline determination of forced expiratory volume in the ventilation chamber, three fenestrations were made and coronary stents, 3.5 mm in diameter, were placed and expanded as for the emphysematous lungs. The measurements were then repeated.
The sites chosen for the bronchopulmonary stents generally included two in the upper lobe and one in the superior segment of the lower lobe, based on the general tendency of emphysematous destruction to be greatest in the upper lobes and in the superior segments of the lower lobes. When two additional stents were inserted, one was generally placed in a basal segment of the lower lobe and the other in a previously unused segment of the upper lobe. When a right lung was used, no stents were placed in the middle lobe.
A total of 12 human lungs were studied in this manner. For each forced expiratory maneuver, the expiratory flow rates were integrated electronically to produce expiratory volume for each of the first 5 seconds. The results of the three duplicate maneuvers were averaged for each experiment. Statistical analysis was calculated using one-way repeated measures analysis of variance test on ranks (SPSS Software, Chicago, IL). Statistical significance was assumed at a p value of less than 0.05.
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Results |
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Table 1 shows the total forced expired volume at the end of 1 second for the 12 lungs, at baseline, after placement of three stents, and in the last 6 lungs after two additional stents were placed.
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Comment |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsDiscussionReferences |
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The extensive collateral ventilation present in emphysematous lungs can be demonstrated at the time of lung volume reduction surgery. The portion of the lung to be removed (usually the upper lobe) remains distended after suspension of ventilation to that lung. Compression of the lung will not significantly deflate the lobe because of the collapse of the small airways. However a 1-mm puncture in the surface of the lung will lead to rapid collapse of the lobe because of the extensive collateral ventilation from other parts of the lobe to the lobule that has been punctured. This observation, along with previous studies confirming extensive collateral ventilation in emphysematous lungs, suggested that creation of new exit pathways for the trapped gas that is present in emphysema patients might help to relieve dynamic hyperinflation and formed the basis for these ex vivo experiments with human lungs. The results confirm that creation of several, relatively small, extraanatomic communications between pulmonary parenchyma and large airways (segmental bronchi) can markedly improve forced expiratory volume in human emphysematous lungs. On inspiration, the regular airways can open, allowing inspiration through normal channels. On expiration, the new passageways provide escape pathways to bypass the collapsed small airways. Clinically, one would anticipate that the improved expiratory flow would reduce dynamic hyperinflation with resulting improvement in respiratory mechanics, increase in exercise tolerance, and alleviation of dyspnea. The benefits resulting from decreasing dynamic hyperinflation in emphysematous patients has been clearly demonstrated in patients undergoing lung volume reduction surgery [8–10].
We embarked on this study in the hopes of developing a palliative treatment for patients with homogenous severe emphysema. Such individuals are not candidates for volume reduction surgery, and this homogenous severe pattern of destruction represents the most common contraindication to volume reduction surgery.
We were encouraged by the marked improvement in expiratory volumes achieved with the relatively minor intervention described in these experiments. We used all available lungs from patients undergoing lung transplantation for chronic obstructive pulmonary disease (except patients with 
1 antitrypsin deficiency) without regard to preoperative pulmonary function, degree of small airway disease, or radiologic pattern of emphysematous destruction. In addition, the sites used for creation of fistulae were not preselected by evaluation of current computed tomographic scans, which were not readily available for many of these transplant patients. In actual practice, candidate selection and interventional sites would be determined in part by the assessment of high-resolution computed tomographic scans of the chest.
A number of issues need to be addressed before this type of intervention can be applied clinically. The safety of the procedure must be established, especially the ability to insert bronchopulmonary stents without significant hemorrhage or production of a pneumothorax. We are working to develop the necessary technology to achieve this goal. Design of an appropriate stent to maintain patency for as long as possible will be another challenge. Patients who are candidates for this procedure need to be defined. At the outset, patients with severe homogenous emphysematous destruction who have exhausted all other available treatments would seem to be most appropriate for this type of intervention.
Surgical options in the treatment of emphysema include lung transplantation and lung volume reduction surgery, both of which have limited application. Medical therapy includes exercise rehabilitation to improve the efficiency of the respiratory muscles, and the use of bronchodilators and steroids to improve expiratory flow. An improvement of 15% or more in expiratory flow rates is considered to be therapeutically significant. In this context, the improved flow rates observed in these ex vivo emphysematous lungs after a relatively simple endoscopic intervention is encouraging and warrants further exploration.
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Acknowledgments |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsDiscussionReferences |
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Discussion |
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TopAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsDiscussionReferences |
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DR LAUSBERG: Thank you very much, Dr Wood. Yes, the stents that we used were conventional coronary stents, as I mentioned, 3 mm in diameter and 15 mm in length when fully expanded, and they were not covered; that is correct.
DR WOOD: And do you have any experience yet with what happens over any period of time with these?
DR LAUSBERG: Those are very preliminary data, and most of the data and most of the experience we have gained are ex vivo. However, there is some upcoming experience that shows that the stent design that we use is not ideal yet and there still needs to be a lot of work done.
DR WOOD: But the stents you are using are uncovered, so the air can come through the interstices of the stent as well?
DR LAUSBERG: That is correct.
DR WOOD: Thank you.
DR WALTER WEDER (Zurich, Switzerland): Congratulations on these exciting data. I have a question for you. You presented expiratory flow as average flow. Could you give us some information about interindividual results? Were there lungs studied that were emphysematous but did not respond, and if so, what is the explanation?
DR LAUSBERG: Actually, all the lungs we chose had not bullous emphysema and not 1 antitrypsin emphysema. So the population of lungs that we used was quite homogeneous. Of course there were some interindividual changes in the flows according to the degree of emphysema in the lungs and according to the sites where we placed the stents, but in general all the data that we gained were quite homogeneous.
DR DANIEL MILLER (Rochester, MN): I thought this was a very elegant study from a group that has been pioneers in the treatment of end-stage lung disease secondary to emphysema. My question is, did you try to do this without using a stent? I think that making multiple openings within terminal bronchioles may be a possible, but may close up without a stent over time. Did you explore that at all?
DR LAUSBERG: Thank you very much. Yes, we tried to only puncture the bronchial wall without a stent. The problem is that in this level of the segmental bronchi, this approach doesn’t work. You can really nicely observe through the bronchoscope that the holes close when you do the forced expiratory maneuver. They close down either by concentric closure or by the deeper line parenchyma being pressed against the hole. We haven’t shown the results yet, but the data are very similar to the baseline data.
DR STEVEN R. DEMEESTER (Los Angeles, CA): Fascinating work you are doing. I have a quick question. Did you dissect out the stents after you placed them, and was there any injury to surrounding vascular structures when you placed the stents in a blind fashion like that?
DR LAUSBERG: Thank you. Yes, sir, we did examine the stents, and so far we have not experienced any injury of the vessels or the visceral pleura. However, we have some preliminary experience in an in vivo model, and there is special technology being evolved right now that helps us prevent these major injuries, damaging vessels or the pleura.
DR JOSEPH LOCICERO (Chicago, IL): I want to congratulate this group. They have done outstanding work and continue to do so over the years. These results are quite spectacular. This is a wonderful adjunct to our knowledge in emphysema.
Back to Doug Wood’s question, these were uncovered stents. If you think about the size and length of these stents, if they were completely covered, the resistance would probably be too high to produce that same sort of result. Although you haven’t had time to figure out whether or not the results with the uncovered stents will change over time, have you tried covered stents and do they get the same results?
DR LAUSBERG: Yes, that is what we plan to do. Thank you.
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