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Ann Thorac Surg 1997;63:312-319
© 1997 The Society of Thoracic Surgeons
Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri
I was sent a humorous greeting card by one of our lung transplant recipients some time ago. On the cover it shows one of life's couch potatoes complaining about her lot in life, with the text, "Life is so hard." On the inside the text reads "It's breathe, breathe, breathe all the time." Well, considering who is on the cover of the card, it is rather humorous. However, there are many for whom its not funny. I am referring to patients suffering from end-stage lung disease, tethered to an oxygen tank, whose life is centered around a wheelchair, for whom each breath is a struggle. It has been exciting that in the last 10 to 12 years there are some new surgical procedures that have brought hope and relief to this group of patients. Today I would like to review with you the evolution of surgical procedures for chronic obstructive pulmonary disease.
The anatomic changes associated with emphysema were described two centuries ago. Even earlier, veterinary descriptions of the lungs, in what was termed "broken winded" horses, depicted the changes of emphysema.
In a text by Baillie in 1793, there is included a description of emphysematous lungs at autopsy. He noted that "in opening into the chest it is not unusual to find that the lungs do not collapse but that they fill up the cavity completely on each side of the heart. When examined their cells appear full of air so that there is seen upon the surface a prodigious number of small white vesicles" [1]. In his accompanying atlas, Baillie illustrated his autopsy findings. This particular drawing (Fig 1
) is of the lungs of Dr Samuel Johnson, whose autopsy was performed by Dr Baillie.
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He noted that at autopsy "the lungs seem as if confined in their cavity, and when exposed instead of collapsing as usual, they rise in some degree and project beyond the borders of the thorax." He noted that on percussion, "the whole chest yields a very distinct sound, and instead of its natural compressed shape it exhibits an almost round or globular outline, swelling out both before and behind. This conformation of the chest is sufficiently remarkable to have enabled me sometimes to announce the existence of emphysema from simple inspection."
Although the pathologic changes associated with emphysema were described 200 years ago, the pathophysiology of chronic obstructive pulmonary disease was poorly understood until the latter half of this century. This lack of understanding, however, did not prevent the trial of numerous operations directed at the consequences of emphysema.
Thus Freund, in 1906, observing the fixed state of the thorax, which was capable of very little respiratory movement, proposed costochondrectomy. To improve movement of the chest wall, Freund did a costochondrectomy of the upper ribs on one side, and sometimes on both sides. Others, focusing on the distention of the chest, proposed thoracoplasty to reduce the size of the chest.
Noting the depressed, flattened configuration of the diaphragm, physicians made attempts to restore it to a more normal position. These attempts included the use of abdominal belts, as proposed by Gordon in 1934 [3], phrenic crush as proposed by Allison in 1947 [4], and the use of pneumoperitoneum as proposed by Gaensler in 1950 [5]. Actually the abdominal belts and the pneumoperitoneum did improve pulmonary function, but both proved to be rather cumbersome and impractical means of achieving a rather modest improvement.
From autopsy findings showing diminished vascularity in emphysematous lungs, Crenshaw and Rowles [6], in 1952, proposed pleural abrasion to create systemic-to-pulmonary collateral blood flow in the hopes of improving lung function.
Osler Abbott, made famous by the Abbott Award of this Society, in fact proposed denervation of the lung. There were a whole series of denervation experiments and clinical applications. In an article he published in 1953 [7], he described pulmonary plexectomy, pulmonary artery, periarterial sympathectomy, upper dorsal sympathectomy, and a partial resection of lung. This was followed by one of the most unphysiologic, controversial, and infamous operations in all of surgical history: glomectomy, the excision of the carotid body for both asthma and emphysema. The initial report by Nakayama [8] in 1961 contained almost 4,000 cases done in Japan. A subsequent publication by Dr Richard Overholt [9] included more than 800 cases. It should be noted that subjectively more than 80% of the patients felt they had benefited from this procedure, which we now know has no physiologic basis. It took several randomized, double-blinded studies in which half of the patients underwent a sham operation and half the glomectomy before the procedure was finally proved worthless.
In a 1972 review article in The New England Journal of Medicine [10], Dr Eugene Laforet humorously summarized his perception of the various surgical procedures that had been proposed over the years for treating emphysema. "Thus," he noted, "resection of costal cartilages was proposed in an era when chronic obstructive lung disease was thought to be secondary to a skeletal deformity, and when incidentally chest-wall surgery was in its flower. The results were grim.
"Undaunted and starting with a new set of premises surgeons were soon advocating such procedures as thoracoplasty and phrenic nerve interruption, each calculated to reduce the volume of the over-distended lung. The alleged benefits of these maneuvers were frequently lost on patients whose worsened dyspnea left them little energy to debate with their surgeon."
Regarding excision of the carotid body, Laforet observed that "unfortunately, for its integrity, it is readily accessible to the scalpel and may even be attacked under local anesthesia. The benefits of its unilateral surgical removal (glomectomy) in [chronic obstructive lung disease] have been extolled with much vigor but little objectivity, although a tortured physiology is often invoked for support."
Laforet concluded his article with the observation that "probably the best surgical solution for the patient with crippling and potentially lethal chronic obstructive lung disease would be to start from scratch with a new set of lungs." Indeed, the eminent pulmonary physiologist David Bates in a previous editorial [11] had reflected that "any physician who has had the sad task of caring for a patient suffering from advanced pulmonary emphysema must on occasion have wished that human lung transplantation could offer some hope to these unfortunate patients."
But it was not for lack of interest, or hard work, that efforts to develop successful lung transplantation had not yet borne fruit. The famous Russian physiologist Demicoff began experimenting in the 1940s with lobar transplantation in dogs. You will remember that he is the person who did heart-lung transplantations without cardiopulmonary bypass 10 years before Gibbons' first successful use of the heart-lung bypass machine in 1953. He did a series of substituting anastomoses and inserted a new heart and set of lungs in a dog and removed the old ones without using bypass. He is best known, of course, for sewing a second head on a dog and having them both barking and eating for several days until the dog died.
Henri Metras [12], in 1950, reported to the French Academy his pioneering experiments with lung transplantation in dogs, including use of an atrial cuff for the venous anastomosis and direct revascularization of the bronchial artery.
But it was Drs James Hardy and Watts Webb who, after many years of laboratory investigation, performed the world's first human lung transplantation at the University of Mississippi in 1963. Although their patient died after 18 days, this event stimulated interest in lung transplantation throughout the world. Unfortunately, the time was not right, and although a number of attempts at human lung transplantation were made throughout the 1960s and early 1970s, interest waned considerably because of universal failure.
In 1978, one of those unsuccessful transplantations was performed by my colleagues and myself at the University of Toronto under the direction of my partner, Dr Bill Nelems. My role was primarily to supervise the use of the extracorporeal membrane oxygenator support system, which had been developed for use in patients with severe respiratory failure. Although the transplant procedure was successful, and the patient was subsequently weaned from both the membrane oxygenator and the respirator, he died 3 weeks later of bronchial disruption. His death prompted a review of the world experience, which indicated that virtually all patients surviving 2 weeks or more after lung transplantation had died because of, or in association with, complications of the bronchial anastomosis. We decided not to embark on any more lung transplantations, and it was not until a couple of years later that I became interested in investigating the causes and potential solutions for the airway complications occurring after lung transplantation. With the help of a number of colleagues and research fellows from around the world, we did a series of animal experiments looking at factors affecting bronchial healing. We concluded that the bronchial disruption was not primarily an immunologic event, as had been thought, because it occurred when you reimplanted a lung just as much as when you transplanted a lung. We found that the high doses of prednisone then being used for immunosuppression were clearly prejudicial to the anastomotic healing and that cyclosporine, which was just then becoming available, could be substituted without adverse effect on wound healing. We also found that an omental wrap around the bronchial anastomosis restored blood supply to the severed bronchial circulation within 2 to 3 days and protected the anastomosis from disruption or from bronchovascular fistula if it failed to heal properly. We then began a cautious clinical approach to lung transplantation again in 1983.
One major remaining issue was in whom do you perform transplantation? By that time the score was 0 successes for 44 attempts. A deathbed rescue attempt in a patient on a ventilator with multisystem failure is clearly not the environment that is likely to produce success. We decided to choose pulmonary fibrosis, a condition that can be indolent, but once the patients go on oxygen and show arterial desaturation with mild exercise, I can assure you they do not have a year to live. By selecting such a patient, we could try transplantation in a patient who was not yet hospital bound or ventilator dependent yet whose life expectancy was severely limited, justifying the enormous risks involved.
Our first attempt was in a 58-year-old man with severe pulmonary fibrosis and a rapidly deteriorating clinical course. The procedure was successful, and for the next 6 years he continued to work regularly. Sadly, he died 6
years afterward of renal failure. But thereafter, no one ever had to go through a lung transplantation again without seeing, or at least knowing of, someone who had success. Our first patient was a wonderfully brave pioneer.
We thought that pulmonary fibrosis was ideal for single-lung transplantation, because the extensive scarring and loss of compliance in the native lung would help ensure that both blood flow and ventilation were preferentially directed to the transplanted lung. It had been observed, in several unsuccessful single-lung transplantations for emphysema, that the native, overly compliant emphysematous lung received much of the ventilation and then became further distended while the transplanted lung received most of the blood flow, thus creating a ventilation-perfusion mismatch.
In the hopes of applying lung transplantation to patients with severe emphysema, and also to septic lung conditions such as cystic fibrosis, we sought ways of replacing both lungs. Initially we employed the combined heart-lung transplantation developed at Stanford but quickly realized that it should not be necessary to replace a patient's heart to transplant two lungs. It did not make sense to replace a heart in someone who did not need a new heart.
On the basis of further laboratory and autopsy studies, under the direction of my colleague, Dr Alec Patterson, the first version of a double-lung transplantation was developed and successfully applied. It included the use of a tracheal anastomosis, an atrial anastomosis, and anastomosis of the main pulmonary artery-sort of a heart-lung hold the heart. In fact, 9 years ago this month a woman with severe emphysema underwent the first successful application of this procedure. In 2 weeks she will be enjoying her ninth anniversary and continues to do quite nicely. In fact, the first 3 patients who underwent this operation will all be celebrating their ninth anniversaries in the next few months.
In spite of concerns that single-lung transplantation for emphysema was thought to be physiologically unsound, a group under the direction of Dr Andreasen in Paris performed a couple of successful single lung transplantations for emphysema. They were kind enough to send us the information and the postoperative roentgenograms, and their report was encouraging. In retrospect it seems probable that the reason patients were getting into trouble after a single-lung transplantation for emphysema was related to injury to the transplanted lung, such as reperfusion injury or poor donor selection or early rejection, so that the lung became less compliant, which would foster overexpansion of the native lung. But the group in Paris demonstrated you could get away with it. And so we began a series of single-lung transplantations in older patients with emphysema who at the time we did not consider candidates for the bilateral procedure. Figure 2 is the roentgenogram of the first patient with emphysema to undergo a single-lung transplantation in our program. Figure 2A is the preoperative film before left lung transplantation, which was done in 1989, and Figure 2B shows the postoperative result. There is some shift of the mediastinum, but the functional result was excellent.
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The first patient to undergo the procedure was a patient with emphysema due to 
1-antitrypsin deficiency. You just take out one lung and replace it while the other lung carries the patient. Then you go to the other side of the table and replace the second lung. This has now become the standard method of replacing both lungs for cystic fibrosis patients, for about half the emphysema transplantations and for a number of other conditions.
Figure 3 is a brief summary of the first 259 single and bilateral sequential transplantations that were done since 1988 in St. Louis. There is a 94.5% hospital survival rate. The first 3 years of the survival curve are what I call the ecstasy part of the agony and the ecstasy curve. The agony comes later when chronic rejection sets in, the major limiting step to all organ transplants. Thus, we have a 75% three-year survival but only a 53% five-year survival, very similar to what is achieved with other major organ transplants. If you look at just those patients who had emphysema, the survival is about 5% better all along, with a survival rate of about 80% at 3 years.
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They pointed out that in the great majority of emphysema patients there is diffuse involvement of the lungs and surgery has little to offer. In fact, that was the generally accepted viewpoint. The rationale was to get rid of the space-occupying bullae when there was clear-cut evidence of compression of relatively normal underlying lung, so that "normal" lung could reexpand and resume functioning.
There was one person, however, who had a somewhat different approach. That person was Otto Brantigan, Professor of Surgery and Surgical Anatomy at the University of Maryland, who wrote an article in 1959 with his colleagues titled, "A Surgical Approach to Pulmonary Emphysema" [14]. He noted, as had others, that the thorax in the emphysematous patient is more or less fixed in a state of full inspiration and the hemidiaphragms are lowered or depressed. He proposed that by resection of functionally useless areas of the emphysematous lung could be reduced in volume, improving respiratory mechanics and the outward pull on the lung, which he thought would help keep the small airways open.
He emphasized that it is an operation directed at restoration of a physiologic principle. It is not concerned with the removal of pathologic tissue, because all of the lung is affected to one degree or another by the emphysematous process, and if you remove all of the pathology you will not have anything left.
Brantigan used several techniques to reef up, or excise, the most abnormal portions of the lung. He thought that ideally both lungs should be operated on at the same time but because of the risks proposed staged bilateral procedures 3 months apart.
Brantigan combined the operation with radical hilar stripping, which was then in vogue. He observed that his patients felt and functioned better after the operation and in a subsequent publication indicated that the benefit in many patients lasted 5 years or more.
Because there was an operative mortality of 16%, and no attempt was made to objectively document the benefit, Brantigan's procedure did not gain acceptance and came in for much criticism. Gaensler and associates [15] noted that "although the idea of restoring lung tension and a more negative intrathoracic pressure is attractive, it is difficult to believe that a disease characterized by extensive loss of lung parenchyma can be effectively treated by further resection of lung." In fact, it is a rather odd notion to take people who cannot breathe to the operating room to remove more of their lung.
Well, I was not aware of Otto Brantigan's work until about 8 years ago when someone brought it to my attention, and I confess, it sounded a little odd to me as well. However, observations made in the course of our lung transplant program for emphysema give some credence to Brantigan's hypothesis.
Figure 4 is a chest roentgenogram of a woman with severe emphysema who subsequently underwent bilateral lung transplantation. Note the marked distention of the chest with bulging of the lower rib cage-the so-called thoracic waist-the depression and flattening of the hemidiaphragms, and the upward slope of the posterior ribs with broad posterior interspaces. It looks as if someone took a tire pump and inflated this woman's chest. In the early days of lung transplantation we wondered what type of donor lungs might be found for such a recipient. We were concerned that a normal lung would rattle around in the large chest, predisposing to air leaks, effusions, and empyema. We thought we might need to use the largest male donor for the smallest female recipient. It turns out that our concerns were groundless. Figure 5 shows this same woman several hours later after undergoing sequential bilateral lung transplantation. Note the more normal position of the hemidiaphragms and the reduced distention of the chest. This repeated observation that the chronically distended emphysematous chest could promptly resume a more normal configuration once the distending lungs were removed gave some credence to Brantigan's observations, namely, that downsizing the lung might improve respiratory mechanics. This same phenomenon was also seen after unilateral transplantation for emphysema. We noted that similar changes after single-lung transplantation for emphysema allowed the mediastinum to shift toward the transplant side, decompressing the opposite chest. This in turn improved the position of the diaphragm and chest wall on the side of the remaining, native lung. I believe that is one of the reasons these patients have done so well.
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And so these observations prompted us to look at volume reduction surgery. Candidates for the procedure are patients who are severely dyspneic, who have a distended thorax, and who have what I call "target" areas, namely, some regions with severe destruction where the lung is functionless but is taking up a lot of space. By removing those portions you can improve the function of the rest of the lung by two mechanisms: (1) improved chest wall and diaphragmatic position, which improves mechanics, and (2) redistribution of ventilation, which improves gas exchange.
The type of situation most favorable for this procedure is the so-called centriacinar or centrilobular emphysema, where the upper lobe and the superior segment of the lower lobe are most involved, while the middle lobe, lingular, and basal segments are less involved. This pattern of disease is often the case, however, and we are highly selective. We take only 20% of the patients referred. We have chosen to do a bilateral procedure using the median sternotomy approach to achieve the maximum benefit with the least morbidity and greatest operative flexibility. With this approach there is no trauma to any of the chest wall muscles or intercostal nerves, and excellent access to both pleural spaces is provided throughout the procedure.
Approximately 30% of the total lung volume is removed on either side, concentrating mainly on the upper lobes except in patients with the 1-antitrypsin deficiency form of emphysema, whose disease is centered in the lower lobes.
Persistent air leaks have always been a major problem after excision of emphysematous lung tissue, and this procedure was no exception. We recognized that the air leaks were not coming through the staple lines, but from the puncture of the lung by the most proximal row of staples, which tend to tear through as the lung is reinflated. We found that by applying strips of bovine pericardium to the stapler before its application, so as to buttress the staple lines, we could virtually eliminate this source of air leaks.
Ventilation to one lung is suspended and over several minutes the persistent blood flow causes absorption atelectasis in the better parts of the lung, which have preserved blood supply. The most destroyed parts of the lung have little if any blood supply and remain markedly distended.
Half or more of the upper lobe is excised, using a continuous buttressed staple line (Fig 6). The initial line of excision begins on the medial aspect of the right upper lobe near the horizontal fissure. This is followed by successive applications of the stapler producing an inverted U-shaped line of excision, which is carried toward the apex and down the posterolateral aspect of the right upper lobe. Half or more of the bulk of the right upper lobe is removed, but because the remaining lung is folded in by the staple line, the right upper lobe is reduced in volume by about two-thirds. In some cases, when the upper lobe is totally destroyed and the fissures are complete, a lobectomy rather than wedge excision may be performed. This has been done in approximately 10% of the cases. At the end of the excision, inflation of the lung under water usually reveals no air leak whatsoever. The same procedure is then repeated on the opposite side.
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The type of patient undergoing this operation is depicted in this summary of our first 100 patients (Table 1). All patients must enroll in a 6- to 8-week supervised pulmonary exercise rehabilitation program before operation to improve stamina and reduce as much as possible the operative risk. The preoperative data I will show during this presentation refer to the data obtained after completion of the rehabilitation program and optimization of medical management. The average preoperative forced expiratory volume in 1 second was somewhat less than 700 mL, or 24% of predicted, with more than 40% of patients having a first-second vital capacity of less than 500 mL. Ninety percent of patients require supplemental oxygen at some time during their daily routine, with more than half of the patients requiring continuous administration of oxygen. Although we try to reduce or eliminate oral steroids as much as possible, half of the patients remained on daily doses of oral prednisone at the time of the operation. Many of these are patients who cannot take a shower, who cannot walk stairs, who spend up to an hour and a half getting dressed, and for whom going out of the house is a real chore. Twenty-four percent use a wheelchair on a regular basis.
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Thus, although the patient comes to you because of distressing, subjective symptoms, perceived improvement in these symptoms is not enough to scientifically confirm the value of a procedure. That was shown, as previously noted, in the case of glomectomy, after which more than 80% of the patients recorded subjective improvement in symptoms. Remembering Santayana's dictum that "those who cannot remember the past are condemned to repeat it," we have tried to avoid this pitfall by making as many objective as well as subjective measurements as possible. These include spirometry, lung volumes, blood gases, exercise tolerance, two standard forms for evaluating dyspnea, and two quality of life instruments, namely, the Nottingham Health Profile and the Medical Outcomes Survey Short Form-36.
Follow-up is complete on all patients but 1, with more than 90% of the follow-up measurements being made in our own laboratory. I believe this is an extremely important point, because incomplete follow-up in this group of patients inevitably will give an overly favorable view of the results. Those patients not returning for follow-up are most likely to be the ones who are dead, disabled, disappointed, or disaffected.
When measured at 6 months, the average improvement in the forced expiratory volume in 1 second has been 400 mL, an increase of about 55% above baseline. The forced vital capacity has improved by 32% or 600 mL, and the residual volume has declined by almost 2 L. The oxygen tension rises an average of 10 mm Hg on room air, and the carbon dioxide tension normalizes.
As a result many of the patients are able to discontinue the use of supplemental oxygen. Whereas 90% of the patients required oxygen with maximum exertion beforehand, at 6 months only 33% of these patients require supplemental oxygen with maximum exertion, even though their level of exercise is much higher. Of the patients who required continuous oxygen before the operation, 85% are able to eliminate the use of continuous oxygen administration, but many require oxygen during periods of exercise.
During the preoperative preparation, the distance covered in a 6-minute walk test improved significantly but then it plateaued in spite of continued exercise training before operation. However, because the patients could walk faster, their need for oxygen increased. After the operation there was a further increase in the 6-minute walk, but in spite of the increased oxygen consumption associated with a higher exercise level, the need for supplemental oxygen decreased markedly. At 6 months after the procedure, we found that 82% of the patients taking prednisone before the operation had now discontinued their prednisone on the recommendation of their pulmonary physician.
The two standard measurements of dyspnea sh ional reaction/mental health, sleep, sex life, problems at work, looking after the home, and interest/hobbies/holidays. Of the 86 patients evaluable at 6 months, 80% consider their health much better than before the operation, 15% somewhat better, 2% about the same, and 2% worse.
Clearly one can not undertake this type of operation in this group of patients without anticipating a significant mortality rate. It is a tribute to our experienced, dedicated, and hard-working team of residents, nurses, chest physiotherapists, chest physicians, and others that to date mortality figures have been lower than anticipated, with a 30-day mortality of 2.5% and a late mortality that brings the overall 90-day mortality rate up to 4%. I believe that our experience in managing more than 300 lung transplant recipients in the past 8 years has been important in achieving these results.
For the 120 patients operated on to date, the mean follow-up time is about 1 year, and the total number of deaths due to all causes-postoperative and late mortality from any cause such as stroke, heart attack, and others-has been 5%.
It is a reflection of the skill of our anesthesia colleagues that to date all of the patients, except 1, have been extubated at the end of the procedure and sent to our specialized thoracic surgical unit rather than to the intensive care unit.
The postoperative care of these patients has been complicated, resulting in an average stay of 14 days and a median stay of 11 days. However, for the last 40 patients, because of some modifications in technique and postoperative care, the mean hospital stay has been reduced to 10 days, and half the patients go home within 8 days.
In conclusion, I started off by noting that throughout this century there have been many attempts to relieve dyspnea in emphysema patients by a variety of surgical procedures. All of these procedures really have been discarded into the wastebasket of history. The only procedures that have stood the test of time are the excision of giant bullae and lung transplantation. Whether or not the lung volume reduction procedure will be added to those two remains to be seen. We are pleased with the results to date. Our 1-year follow-up analysis of 31 patients shows that the benefits have been maintained for at least that period of time, but ultimately the judgment will rest on the balance between what is achieved in terms of reduced symptoms, improved longevity, and quality of life versus the morbidity, the mortality, and the cost of the procedure. Ultimately, the value of this procedure will be determined by long-term follow-up. As noted by my mentor, Ronald Belsey, "The follow-up clinics are the shoals upon which founder many attractive theories in surgery."
Footnotes
Presented at the Forty-second Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 9–11, 1995.
Address reprint requests to Dr Cooper, Division of Cardiothoracic Surgery, Washington University School of Medicine, 3108 Queeny Tower, One Barnes Hospital Plaza, St. Louis, MO 63110.
References
This article has been cited by other articles:
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  R. A. Wise and M. B. Drummond The Role of NETT in Emphysema Research Proceedings of the ATS, May 1, 2008; 5(4): 385 - 392. [Abstract] [Full Text] [PDF]
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 F. Venuta, E. A. Rendina, T. De Giacomo, and G. F. Coloni Bronchoscopic lung volume reduction MMCTS, December 17, 2007; 2007(1217): 2121. [Abstract] [Full Text] [PDF]
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 F. Venuta, E. A. Rendina, T. De Giacomo, M. Anile, D. Diso, C. Andreetti, F. Pugliese, and G. F. Coloni Bronchoscopic procedures for emphysema treatment Eur. J. Cardiothorac. Surg., March 1, 2006; 29(3): 281 - 287. [Abstract] [Full Text] [PDF]
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 B F Meyers and G A Patterson Chronic obstructive pulmonary disease * 10: Bullectomy, lung volume reduction surgery, and transplantation for patients with chronic obstructive pulmonary disease Thorax, July 1, 2003; 58(7): 634 - 638. [Abstract] [Full Text] [PDF]
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 R. L. Berger, B. R. Celli, A. L. Meneghetti, P. H. Bagley, C. D. Wright, E. P. Ingenito, A. Gray, and G. L. Snider Limitations of randomized clinical trials for evaluating emerging operations: the case of lung volume reduction surgery Ann. Thorac. Surg., August 1, 2001; 72(2): 649 - 657. [Abstract] [Full Text] [PDF]
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J. C. Baldwin, C. C. Miller III, R. A. Prince, and R. Espada Chest radiograph heterogeneity predicts functional improvement with volume reduction surgery Ann. Thorac. Surg., October 1, 2000; 70(4): 1208 - 1211. [Abstract] [Full Text] [PDF]
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J. Young, A. Fry-Smith, and C. Hyde Lung volume reduction surgery (LVRS) for chronic obstructive pulmonary disease (COPD) with underlying severe emphysema Thorax, September 1, 1999; 54(9): 779 - 789. [Abstract] [Full Text]
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