21^st Century Therapies for COPD
Richard Casaburi, Ph.D.,M.D. 
President, PERF

VI. Lung Volume Reduction Surgery

      The concept sounds awfully strange.  Lung Volume Reduction Surgery (LVRS) proposes that removing 20-40% of the volume of each lung in patients with pulmonary emphysema will result in improved lung function.  Strange indeed, when we consider that a primary problem of patients with emphysema is that there is too little functioning lung tissue.

      The procedure was pioneered by Dr. Otto Brantigan, a Baltimore surgeon who, by trial and error, established this procedure in the 1950’s.  He noticed that emphysema tends to affect some portions of the lung more severely.  Often, the upper portions of the lung become relatively more “Swiss cheese-y”, composed mostly of large non-functional airspaces.  This has two results; first the overall volume of the lung increases, forcing the chest wall out and the diaphragm down – an inefficient configuration.  Second, the more normal portions of the lung (usually the lower lung) become relatively compressed.  This means that the airways are not held open (especially during expiration) by the elastic fibers surrounding the airways.  This impedes flow of air out of the lung – the airways tend to collapse.

      Cutting out “Swiss-cheese-y” portions of the lung decreases overall lung volume without removing much functioning lung.  The decreased lung volume increases the efficiency of the chest wall and diaphragm.  It also tends to “tighten” the elastic network holding open the airways so that airflow during expiration is improved.

      Although Brantigan reported that his patients usually felt better after the operation, the procedure was not without problems.  Principal among these was the fact that once the lungs of patients with emphysema are cut, they tend to leak!  Prolonged air leaks caused Dr. Brantigan to abandon his procedure by about 1960.

      It was more than 30 years before LVRS was revived.  During this period, the theoretical basis for LVRS was given support when Dr. Tom Petty in 1986 showed that emphysema results in a decrease in the number of elastic attachments to the airways. The fewer the attachments, the smaller the airways became.  This established loss of “radial traction” as an important mechanism in airflow limitation in emphysema.

      Dr. Joel Cooper, an innovative St. Louis surgeon, revived the LVRS technique. Modern techniques of removing lung portions utilize a line of staples to close the wound. Cooper found that reinforcing the staple line with a self-sealing material (pig pericardium) greatly reduced air leaks.  His 1995 publication of his results in 60 patients created a frenzy of interest.  He reported an average increase in FEV₁ (the primary measure of airflow obstruction) from 0.77 to 1.4 liters – an 82% increase!  This near-miraculous improvement resulted in intense interest from thousands of desperate patients.  Other centers quickly began to offer the procedure to fill the demand.

      Problems arose, though, in the months following the publication following Dr. Cooper’s initial report.  Results reported by other centers were often not nearly as good. Three likely factors were inferior surgical skill and experience, less intensive pre- and post-operative care and failure to adhere to the rigorous selection criteria that Cooper had established.  Further, Federal bureaucrats made some simple calculations and realized that, based on the huge numbers of COPD patients who would likely request this procedure, the costs to the Medicare system would be several billions of dollars per year.  As a result, in early 1996 it was announced that Federal funding would be withheld until the procedure was demonstrated to be safe and effective.

      What followed was a brief tug of war.  On one side were (mostly) pulmonary physicians who felt that the only way to prove effectiveness was a long-term randomized controlled trial.  “Controlled” means that half of the patients participating would not be allowed surgery (receiving “best medical care”, instead).  “Randomized” means that individual participants would have no choice as to whether they were in the group receiving surgery.  On the other side were (mostly) chest surgeons who felt that the value of the surgery had already been adequately demonstrated and questioned whether it was ethical to deny half the study participants an effective therapy.

      In the end, the proponents of a large scale trial won.  In January of 1998 recruitment began for a trial at 17 centers around the US.  Named the National Emphysema Treatment Trial (NETT), the goal is to recruit 2500 patients, randomize them to surgery or medical management and then follow them for up to 5 years.  Participants will have their care paid for through Medicare, but there are appreciable sacrifices.  Participants are required to undergo a rigorous pulmonary rehabilitation program (even if they have already completed one previously) and they must undergo a large number of testing procedures for the purposes of the study.  There are reports that recruitment for this study is lagging behind projections, meaning that we will have to wait even longer to definitively decide whether the procedure is safe and effective.

      In the meantime, for patients who wish to consider undergoing LVRS, there are generally two options.  First, volunteer to participate in the NETT study and accept the 50:50 chance that you will receive surgery.  Second, there are a number of good surgeons who are performing this procedure for “self pay” patients, at a cost that I believe is in the range of $100,000.

      A key thing to realize is that most patients with COPD are not candidates for LVRS. The majority of COPD patients have airway obstruction principally on the basis of airways disease, in other words they have bronchitis.  This variety of COPD will not be helped by LVRS. Only patients with predominant alveolar destruction, in other words, emphysema, are candidates.  Moreover, it seems likely that the emphysema must be uneven in its distribution – so there are “target” areas of bad lung for the surgeon to go after.  It is becoming clear that some target areas are better than others.  Patients with emphysema based on α₁-antitrypsin deficiency tend to have target areas near the diaphragm.  These resections have proven less successful than resections near the top of the lungs (typically seen in smoker’s emphysema).  Finally, the severity of the disease needs to be “just right” – not too mild and not too severe.  Those with only moderate disease should be able to have a good quality of life with less-dramatic therapy, bronchodilators and rehabilitation, for example.  Also, those with only moderate disease are unlikely to have “target areas” of destroyed lung for the surgeon to attack. On the other hand, those with very severe disease are often poor candidates.  People with poor functional status are unlikely to tolerate the rigors of surgery.  Further, those with severe CO₂ retention and with pulmonary hypertension are though to be poor candidates (though this has not been conclusively proven).

      Still interested?  A recent analysis of published studies (encompassing about 1,000 patients’ experience) tells us what to expect, in the short-term, after undergoing LVRS.  Hospital stay averages 15 days.  The chances of dying during, or shortly after, surgery is about 4%.  FEV₁ increases from an average of 0.7 liters to about 1 liter (about 43%).  Exercise tolerance also increases, documented by an average increase in the distance walked in 6 minutes of about 40%.

      A few very important issues need to be resolved before a prospective patient can make a fully informed decision.  The NETT study should provide these answers.

1. How long do the benefits last?  This is really the $64,000 question.  There are clear signs that, following LVRS, the decline in lung function is faster than before LVRS.  If lung function declined to pre-surgery levels in, say, one year, we would likely judge the surgery to be not worth the risk and expense.  If, on the other hand, benefits last 7 or 10 years, the procedure would be an unequivocal success.  The true answer appears to lie somewhere in between.  A recent small study demonstrated that, 4 years after surgery, 25% of the patients retained appreciable improvements over pre-surgery lung function.
   

2. Is survival improved?  Again, no clear answer.  A recent indirect analysis indicated that a modest survival benefit might be obtained by those undergoing LVRS.
   

3. Does the need for supplemental oxygen decrease?  Many of us were surprised by early reports showing that the majority of oxygen dependent patients no longer required oxygen (or required it only during exercise) after LVRS.  What is now clear is that, for the majority of patients, this is only a temporary reprieve; within two years or so the majority will need supplemental oxygen again.

     It is my educated guess that, eventually, LVRS will be proven to be an effective palliative measure for a select group of patients.  The search for a cure for COPD goes on!

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