2015 American Thoracic Society Annual Meeting Highlights: Approaches to Lung Volume Reduction Surgery (LVRS) for Emphysema and Heterogeneity of COPD
National Emphysema Foundation President, Laurence G. Nair also attended another session at the American Thoracic Society’s annual meeting, titled “Approaches to Lung Volume Reduction Surgery (LVRS) for Emphysema,” which highlighted the strides that lung volume reduction techniques have made since introduced about 20 years ago.
The "less is better" approach notes the "large" lungs that patients with COPD have contribute to shortness of breath in several ways. Among them is overstretching of the muscles of the chest wall and diaphragm due to oversized lungs weaken the force with which they can move air in and out of the body, increasing the work of breathing. In addition, hyper-inflated areas of lung themselves often have less functional lung tissue (referred to as bullae or blebs) and in fact, these areas can even compress neighboring normal tissue, rendering them unable to perform their duties as well. For these reasons, there is a thought that removing these overinflated, non-functional areas, which are not contributing and even are damaging to proper lung function, could be helpful. The session went on to explain that there are two ways to accomplish this. One is lung volume reduction surgery and the other is placement of one-way valves or coils into bronchial tubes that lead to these areas and essentially close them off from air so they could not inflate. These types of interventions could take place during a bronchoscopy. Bronchoscopic placement is attractive because it is a much less extensive procedure than surgical removal and when effective, and is functionally sufficient for the patient. However, who it will work on and where to place the valve or coil are topics still under discussion. It often is not successful or results in only mild improvement.
Nair reported that “a group in attendance from Columbia University, who are proponents of surgical lung reduction, brought up some interesting points.” They explained that with surgery, you can remove more damaged tissue and be more accurate as to what areas to take out. They also explained that the landmark study on LVRS was undertaken more than 20 years ago and that they feel the surgery is more refined now.” 20 years ago “the procedure was much more extensive and required a large incision. Now it can be done thorascopically (with several small incisions) so the surgery is much better tolerated than before.” The Columbia group felt surgery was the much more effective option and when successful has a track record of lasting improvement, whereas bronchoscopic lung reduction does not. Nair observed that most people in the room, though impressed by Columbia's track record, were not convinced surgery has proven to be safe enough to be thought of as the clear cut first option at this time. However, the spirited discussion is sure to spur some insightful ideas for future research in this interesting but still "not yet ready for prime time" area of treatment.
Dr. Laurence G. Nair was also in attendance at a session that highlighted the “heterogeneity” of chronic obstructive pulmonary disease (COPD). The moderators explained that it has been known for a long time that COPD patients can differ in several ways, among them, physical characteristics, pathophysiologic changes and the areas of the lung that are most diseased. The classic COPD profiles include the “blue bloaters” who are generally are more rotund, have lower oxygen in their blood, and produce abundant phlegm on a daily basis. This type of description is of someone who has "chronic bronchitis". Then there is the “pink puffer”, who generally has a normal oxygen level but is thinner and has a more hyper-inflated chest wall. They are the classic “emphysema" patient. Another type of COPD patient is more "wheezy" and has a sprirometry test that shows they are very responsive when tested for bronchodilator medication. This is very similar to those diagnosed with asthma. These types of patients are considered "overlap patients", meaning they have characteristics that “overlap” both COPD and asthma.
Data was presented from The COPD gene study, a National Institutes of Health-funded study conducted between 2008 and 2011. The study collected an array of information from about 10,000 smokers in an effort to find out why some smokers develop COPD and some do not, as well try to see if new more intricate classification schemes can be found to better identify different types of COPD. This was done by analyzing a more robust set of data including clinical variables, genetic analysis and evaluation of CT scans to view anatomic changes in each study participant. There is a "treasure trove" of data available to be mined at the genetic and cellular level to try to find new unique subtypes within the umbrella of COPD, Now scientists have the ability to identify clusters or groups with distinct profiles. Whereas, “pink puffer/blue bloater” identifiers differ by only a few basic variables, current analysis can cull through innumerable variables and find patterns that are more clinically unique, allowing for the creation of tailored or personalized therapies for individual patients. Additionally, Nair noted that this type of information could also help identify “people who more susceptible to develop rapid progression of COPD earlier than by current means. It may also allow a physician to match a given individual within a specific disease profile to the best medical treatment for them as opposed the current trial and error approach to find which medication regimen works best for someone.
Another interesting topic discussed during this session was the work done in the area of micro CT scans. A symposium lead by Dr. J.A. Hogg, a prominent pulmonary pathologist working out of Vancouver, cited findings that correlate micro CT scans with direct microscopic analysis of COPD excised lungs he did several decades ago. Dr. J.A. Hogg noted was that in the direct specimens, the loss of a part of airways called the ‘terminal bronchioles’ is the earliest finding of damage to the lungs that occurs in COPD. This finding, which can be seen on a micro CT scan occurs before evidence of COPD can be detected by traditional CT scan.” Therefore, these initial phases of COPD are "silent" and cannot be identified by today's most commonly used techniques. New technologies, such as the micro CT scan, offer the hope of finding COPD in its earliest stages. With more rapid detection of COPD, hopefully, will come earlier intervention to arrest the progression of emphysema in its tracks.
The American Thoracic Society (ATS) held its annual meeting in Denver, Colorado on May 15-20 this year, where chronic obstructive pulmonary disease (COPD) was a topic that many physicians decided to head to the Rockies to discuss. The conference brings together clinicians, researchers and other allied health care professionals from throughout the world in one place to take a look at the current state of the art care in pulmonary, sleep and critical care medicine as well as the future to see what could be the next breakthrough. During the conference, innovative research and study results were presented, each of which help provide clues and pieces of the puzzle as to the cause, effects and treatment of COPD.
A popular symposium is always the “Year in Review", where thought leaders present what they consider important papers published during the previous year. In the COPD part of the lecture R. Graham Barr, MD, DrPH, from Columbia University, reviewed an article on “Withdrawal of Inhaled Glucocorticoids and Exacerbations in COPD” from the New England Journal of Medicine (NEJM). The findings indicated that in the group of people that were studied, withdrawing the inhaled steroid from long acting b2 agonist and long acting antimuscarinics did not shorten the time to an exacerbation. In other words, the addition of the anti inflammatory effect that inhaled steroid provides, did not provide "protective" effect on getting an acute deterioration of symptoms. However, in favor of steroids was that the results did showed those who were not on inhaled steroids had worse quality of life scores and lower FEV1. So the benefit from inhaled steroids was mixed.
In attendance at the conference was National Emphysema Foundation President, Laurence G. Nair, who provided his thoughts on this topic, stating, “the goal of pharmacotherapy is to take as much medicine as needed, but not more. Unnecessary medications increases the chance of side effects, unwanted drug interactions and is costly. However, many of our current go-to COPD medications (Advair, Symbicort, Dulera, etc.) already incorporate inhaled steroids in them. So, though from a pharmacology standpoint, removing inhaled steroids means you are taking one less medication, from a practical standpoint, it would not make you feel like you pared down your medication regimen. It would simply feel like you just replace one inhaler (a combination product) with another inhaler (a single agent without the steroid).”
A second study reviewed was “Simvistatin for the Prevention of Exacerbations in Moderate to Severe COPD" looked at the question did simvastatin have a role in preventing COPD exacerbations? This study was felt to be a well designed since it was a large multicenter, prospective, randomized trial. Why this topic was even considered was because it has been postulated that statin medication has some anti-inflammatory effect and some of the damage of COPD is imparted from inflammation. Nair stated that “this would be an interesting finding if it were true that statins actually had some protective effect on the lungs in addition to its known beneficial effect on the cardiovascular system, especially since these were two of the most important medical problems prevalent in our society." In fact, those who conducted the study actually terminated it early because there was no signal that there was any difference made by taking or not taking Simvistatin. No benefit was seen whatsoever.
Sreedhar Nair, MD, FACP, FCCP, Founder and President of The National Emphysema Foundation (NEF), died on March 3, 2014, after bravely suffering from a long battle with heart disease. For the past 43 years, Dr. Nair has been the driving force behind the NEF and he has worked tirelessly to advance the efforts and the mission of the Foundation. Under his leadership, the NEF has played a pivotal role in increasing public awareness of emphysema by supporting educational, advocacy and research initiatives, and, through these efforts, in improving the quality of life for countless patients with emphysema and their caregivers.
Born in India, Dr. Nair came to the United States in 1951 for his medical residency and fellowship training at the New York Medical College, Metropolitan Hospital. He then served as an Eli Lilly Research Fellow and was a co-discoverer of Cycloserine, an anti-tuberculosis drug, which is still used today for drug-resistant tuberculosis. Of the era when pulmonary medicine was in its infancy, Dr. Nair was one of the first physicians to be board-certified in pulmonary medicine and was among the group of pioneering physicians who developed the field of critical care medicine. He began clinical practice in the late 1950s, quickly established a reputation as an astute and respected diagnostician, and over the course of a 40-year career would treat thousands of patients and help advance the practice of pulmonary and critical care medicine on a national and international level.
A man of ideas, his professional career was marked by a series of "firsts" and professional practice at the vanguard of pulmonary and critical care medicine. At Norwalk Hospital in Connecticut, he led the development of its Critical Care Unit and under his leadership, the Pulmonary Section of Norwalk Hospital flourished with the creation of several of its modern facilities, including the Hyperbaric Center, the Hinds Pulmonary Function Lab, the Sleep Center, and the Hinds Research Center. He also created the Pulmonary and Critical Care Fellowship programs at Norwalk Hospital and started one of the nations’ first schools of respiratory therapy. At Yale University, he helped establish the Boehringer Ingelheim Endowed Chair in Pulmonary Medicine. On a national and international level, Dr. Nair helped create and was a past Chairman of the International Society for Computers in Critical Care and Pulmonary Medicine. He was a consultant to the World Health Organization for many years and helped to improve the health of people in emerging nations through the use of improved technologies. He also organized and served on many national and international panels on the most pressing issues in pulmonary medicine and health policy. He was the editor of five books and published over 70 articles in peer-reviewed medical journals. Over the course of his career, Dr. Nair received many awards, including the Humanitarian Award of the American Lung Association, the William Tracey Award of the Norwalk Hospital, and the World Lung Health Award of the American Thoracic Society.
Yet among all these accomplishments, Dr. Nair's singular impact was no greater than in his visionary founding of the National Emphysema Foundation. In the early 1970s, emphysema was a disease not well known to the public, nor was there any national program to combat it. Concerned for the millions of patients suffering from this illness, Dr. Nair set about to establish a national organization to focus attention on this devastating disease with an aim of improving the lives of patients, their families and caregivers. With great persistence and effort, and assisted by the Beulah Hinds Foundation, Dr. Nair founded the National Emphysema Foundation in 1971.
Dr. Nair left an indelible mark on the National Emphysema Foundation. We will miss him greatly, but we at the Foundation are dedicated to continuing the work he championed in support of patients with emphysema and carrying out his vision for years to come.
Medical Conference Notes
These were some of the developments that were presented at an American College of Chest Physicians meeting that will be interesting to follow over the coming years.
A meeting of note at the ACCP conference was on smoking cessation. This was led by pulmonologists Dr. Jill Ohar and Dr. Stephen Rennard as well as a psychiatrist, Dr. John Hughes. They discussed the pitfalls of this difficult task. Smoking cessation is a 2 step process: physiologic withdrawal and then control of behavior afterwards. Dr. Hughes discussed a few things people can do to help control behavior. These include the following: Identify high risk situations and avoid them. Identify specific cues and triggers that may
There was a lecture on modern and novel therapies for COPD. For instance, part of a lecture discussed “regrowing” lungs. This requires two things: stem cells and growth factors. There are cells in the bronchial tubes called Clara cells. They would provide the stem cells. Growth factors can be obtained from any type of tissue. The politically charged debate about embryonic stem cells does not apply here. Growing lung tissue is a process requiring adult not embryonic stem cells. Perhaps someday these cells will repair and replace injured cells in the respiratory system. Don’t hold your breath yet though (pun intended).
Laurence G. Nair, MD
Pulmonary and Critical Care Medicine
Medical Conference Notes
At a recent conference of the American College of Chest Physicians held in Canada some of the topics discussed there were relevant to COPD. With regard to the venue, one might ask why hold an “American” chest physician meeting outside the United States? First, the ACCP meeting is an international meeting where people from all over the world come to exchange information about the latest clinical aspects of respiratory illness. Canada, itself, has a rich history of outstanding contributors to the understanding of
From a COPD standpoint a main theme at the conference was “inflammation”. I’m sure many of you have been told at one point that part of an acute medical problem you are suffering from is due to inflammation. It seems every illness has its own degree of inflammation associated with it. Sometimes I wonder if we take for granted that non physicians understand what “inflammation” means. Inflammation is a response produced by your body to an insult or irritation. Among possible inciting factors are infection, allergy or body injury from things such as trauma, burns or exposure to noxious stimuli (such as cigarette smoke). Another category is autoimmune disease where the body reacts against itself. In all of these situations the body mobilizes its defense mechanisms to fight something that is perceived as foreign or has the potential to harm normal tissue. It is most often a beneficial limited reaction in which the noxious stimulus is contained and eradicated at which times the inflammatory system shuts off. Fever is an example of an anti-inflammatory reaction; that is why anti inflammatories are taken to bring the temperature down. However, there are times when the inflammatory reaction becomes over vigilant and does not turn off. At these times there is no imminent threat, yet the inflammatory process continues. It is kind of a “friendly fire” situation. At this point inflammation is damaging the body instead of protecting it. Inflammation can be acute and fulminant or chronic but progressive. An extreme example of acute inflammation is when one goes into “shock.” In this situation not only is the original insult causing a problem, the inflammatory reaction is so exuberant it is actually worsening the situation. An example of chronic inflammation is rheumatoid arthritis which is chronic inflammation of the joints. It is now known that inflammation in the airways is what drives asthma.
In COPD the lung also affected by the inflammation which is provoked by a variety of stimuli, but most commonly of course, cigarette smoke. In Emphysema, chronic inflammation drives slow but relentless tissue injury. Inflammation is a very complex and elaborate network with many different cell types interacting with each other to produce a harmful result. Hopefully, the clinical application of this information will be that eventually, there will be drugs made that will affect specific parts of the inflammatory cascade within the lungs and attenuate its damage.
There continues to be interesting trends in the epidemiology of COPD. As has been noted many times, the number of newly diagnosed cases of COPD is growing rapidly. COPD is a disease frequently diagnosed in the 5th and 6th decades of life. This fact, coupled with the fact that the number of people who comprise this group is growing, makes this a very important demographic to follow. In the year 2002, 1 out of 10 people over 60 years old had COPD. In the not to distant future, 1 in 5 will have some degree of emphysema. COPD carries a very high burden in older people. Twenty-seven percent of the general population smoke, and of those, 15% have COPD. However, in the older range the percentage of people who smoke and have COPD is higher. In addition, the degree that COPD affects women is changing. For instance, in the year 2003, the number of women who died of COPD exceeded that of males. Females now have a higher rate of COPD than men in the 20 to 44 age range. This may be in part due to for a given rate of cigarette exposure, the decline if lung function in women is larger than that of males.
Laurence G. Nair, MD
Pulmonary and Critical Care Medicine