Ramsey R. Hachem, M.D.
Washington University School of Medicine

Barnes-Jewish Hospital

Division of Pulmonary and Critical Care 
 

Photopheresis for Lung Transplant Rejection

          Lung transplantation is the ultimate treatment for patients with end-stage lung disease.  Indeed, transplantation improves the quality of life and survival for most patients.  However, the long-term outcomes after transplantation remain disappointing, and the average survival is approximately 5 years.  Unfortunately, this has not improved substantially over the past 10 years.  Chronic rejection, or bronchiolitis obliterans syndrome (BOS), has clearly emerged as the primary obstacle to better long-term outcomes and is the leading cause of death beyond the first year after transplantation.  In fact, the average survival after the diagnosis of chronic rejection is 3 years.  Chronic rejection scars the small airways in the lungs, narrowing their lumens.  While there is a great number of small airways in the lungs and these have a very large total cross-sectional area, each airway contributes little resistance to airflow and a large number may be damaged before symptoms appear.  BOS initially presents as a decrement in lung function that may occur in the absence of symptoms.  However, as the rejection progresses, patients typically develop symptoms such as cough and breathlessness.   

          The management of BOS varies from center to center, but the mainstay of treatment is intensifying the immunosuppressive regimen.  The maintenance immunosuppressive regimen is usually optimized; tacrolimus is substituted for cyclosporine and/or mycophenolate mofetil or sirolimus is substituted for azathioprine.  Additionally, azyitromycin, an antibiotic that is frequently used for upper respiratory tract infections, has some immunomodulatory effects beyond its antibacterial properties and is often used as an adjunctive treatment for BOS.  In some cases, when the decrement in lung function is small or slowly progressive, these adjustments are sufficient to stabilize lung function.  However, in cases where the decrement in lung function is larger or more rapid, more intensive treatments are necessary.  At our program, a 5 to 7 day course of an anti-lymphocyte globulin preparation is usually the next step.  The results of this treatment have been variable; some patients have a good response and their lung function stabilizes.  Unfortunately, others don't respond and have a relentless decline in lung function.  Over the past several years, we have used photopheresis as a salvage, or second-line therapy for progressive BOS at our program. 

          Photopheresis was initially introduced in the 1980s as a treatment for cutaneous T-cell lymphoma and is currently FDA approved for this indication.  Because of photopheresis' effects on lymphocytes, the primary immune cells responsible for rejection, it was soon introduced as a potential therapy in organ transplantation.  Blood is withdrawn from the patient and the immune cells are separated from red blood cells and plasma, which are then returned to the patient's circulation.  The immune cells remain in the photopheresis machine where they are treated with methoxsalen, a photosensitizing agent, and irradiated with ultraviolet light.  Upon irradiation with ultraviolet light, methoxsalen disrupts the immune cells' DNA.  This arrests their ability to proliferate and results in apoptosis, or programmed cell death.  These immune cells are then returned to the patient's blood stream where they are phagocytosed, or eaten, by specialized cells.  This results in a state of better graft tolerance.  Exactly how this happens and the specific biologic events that lead to this remain unclear.  One explanation is that the introduction of apoptotic immune cells into the blood stream results in the expansion of regulatory lymphocytes.  These are key cells of the immune system that control or dampen the immune response thereby limiting collateral damage.  As such, they are considered immunosuppressive immune cells.  In fact, recent studies suggest that the number of circulating regulatory lymphocytes is decreased in chronic rejection.  So, expanding their numbers would be advantageous in the setting of rejection.

          Unfortunately, there have been very few clinical studies examining the efficacy of photopheresis for lung transplant rejection.  However, there are case series that have demonstrated an important benefit.  Our program's experience with photopheresis has been consistently positive.  We recently reported the results of our experience with photopheresis for BOS.  All patients in this series had progressive BOS despite treatment with anti-lymphocyte globulin.  Overall, the decline in lung function was significantly slower after the initiation of photopheresis than beforehand.  In addition, 25% of patients had an improvement in lung function over the 6 months period after photopheresis was initiated.  The most common serious complication of treatment was catheter-related bloodstream infection although some patients don't need an indwelling venous catheter.  In general, the treatments were tolerated well; approximately 15% of patients had a complication during therapy.  However, Medicare does not currently cover photopheresis for lung rejection, and this has limited the access to photopheresis for many patients and has limited its use at many centers.  A formal request for Medicare coverage is being prepared and a decision will likely be made in the next 6 to 12 months. 

Christmas Party EQUALS Success!!

By: Amanda Helderle

            The weather outside was truly frightful, but I can say it was delightful inside Chris' Pancake & Dining on December 12th for Second Wind's Annual Christmas Party. Hors d'oeuvres of cheese, fruit and toasted ravioli began promptly at 2:15pm with almost everyone who reserved a spot in attendance. The party carried on with a social hour until 3:30pm. Dinner began at 4:00 pm; Co-Chair Marian Frentzel choose a delicious dinner of which included a choice of Chicken Marsala, Broiled Filet of Grouper or Spaghetti and Meatballs. After our orders were taken, our waitress informed us that the oven was out of order and that there would be no baked potatoes. What a let-down!! However, we prevailed with mashed potatoes and red potatoes instead. The meal was excellent! To complete a wonderful meal, we had cake provided by Barbara and Richard Rhyner - Thank you Barb and Richard! We finished the party with a drawing for some very great prizes. Thank you to all who donated items for the party.  Our big winner for the day was Edan, Marian Frentzel's grandson with multiple wins! Congratulations Edan Clow!  What a wonderful afternoon of visiting and sharing stories with one another. On a gloomy note, Jan and Larry Kwasigroh were in an automobile accident in Springfield, Illinois on their way to St Louis. Neither Jan nor Larry were injured, but the car they were driving was damaged. They were stuck on the highway for four hours unable to make it to the party. We missed you guys!  Wishing you all a very healthy, happy new year!  Be Well.  

A Year in Photos

By: Gary Brandenburger 

It's been a busy year and a great one at that for Second Wind! I've added photos to our Flickr library to remember the Picnic, Run Walk and Christmas party: http://www.flickr.com/photos/secondwindstl_pix/ I'll be adding more from 2010 as time goes by.

Thanks to Richard Rhyner for his help in photographing these three special events! Got favorites of your own to share? Just email your photos to: secondwindstl_pix@yahoo.com

I wish each of our members and their families Love, Joy, Peace and Wellness
in this New Year!
Gary

 

Treasurer's Report 

By Peter Nicastro

Second Wind began December with $164,359.66 in assets.  During the month, we received $2,730.20.  Because of your generosity, Second Wind provided $4,159.30 in assistance during December to six recipients.  Payments were for gasoline, medication and co-pays, cellular phone service, rent and groceries.  We had other expenses of $792.89.  At the end of the year, our balance was $162,137.67.

The breakdown of our balance at the end of the year is as follows:

Every organization, including Second Wind, is well served by a reserve, which is sometimes called an endowment, to meet emergency expenses, continue programs through lean times, and provide a foundation for future growth, just as we as individuals and families should keep an emergency fund for ourselves..  Through the careful management of my predecessors as treasurer, Betty Wallace and Linda Nottestad, and past and present members of your Boards of Directors, each Lung Walk has produced a modest profit that was set aside for the future at the most attractive terms that could be found, in keeping with the Board's conservative philosophy of protecting our asset's principal.

Dues are directed to the operating fund, which pays for the costs of running the association, including this newsletter.  Honoraria, memorials, and non-designated donations are directed to the assistance fund, where they provide the assistance to patients and families which is disclosed to you.

 Pre-Paid Dues Renewals
Gary Brandenburger, Ronald & Carol Schwartz, Connie Winks, Joe & Sharon Pemberton, Peter & Ellen Nicastro, Hank & Mary Gross, Jerry & Margaret Sims, Fred & Sharon Kelsay, Carolyn Vanhoose.  Please remember that dues are due at the beginning of each calendar year.

Honoraria
Sarah Mensing & Erica Ogelsby in honor of Michael Randolph
 

Memorials
John & Judith Ludwig, Carolyn Reed, and Ned Gutierrez in memory of Adam Durant
Randall & Mame Nowlin in memory of Mary Ann Barker William & Nancy Morse and Angela Hartman in memory of Raymond Hartman

Other Donations
Andrew & Candace Westgard, Carol Harney, Randall & Mame Nowlin, Adam & Katie Lange, David & Kimberly Smoot, Neil & Leann Banwart, Barbara Deitrich, Rick & Sandy Patterson, Marianna Musick, Jason & Sarah Anderson, Shari Farthing, Mitch & Kristine Krueger, Mary Matychowiak, Linda McCulla, Barbara & Thomas Huber, Denise & Emmett Reidner, David & Brenda Varner, Wayne & Susan Glenn, Ronald & Carol Schwartz, Peter & Ellen Nicastro; Hank & Mary Gross

January 2011 Transplant Anniversaries

By Jan and Larry Kwasigroh 

Turning a page to a new year in my calendar always brings fresh plans for how my intentions in my daily existence will play out.  Eager to lose weight, save more money, say "I love you" more, sleep more, read more...the list goes on and on, ever eager to finally be perfect in my endeavors.  Well, I might be able to pick up on a couple of those aforementioned but perfect is not on my horizon.  When I asked some transplant folks what their 2011 resolutions would be many replied that they wanted to honor their donor and donor family by being the best possible sanctuary.  The following started their new year with a fresh breath of life and we say many Happy New Years to you all!

16  years              Bob Augustine

13  years              Robin Davis

13  years              Holly Hahn-Baker

11  years              Linda Britton

11  years              Connie Winks

10  years              Dianne Seymour

10  years              Linda Toy

 9  years               Todd Goldstein

 9  years               Don Orrick

 8  years               William Ash

 7  years               Peter Martin

 6  years               Carolyn Van Hoose

 5  years               Emory Bock

 5  years              Melvin Odell Woods

 4  years               Judge Morris

 4  years               Tammy Penrod

 3  years               Ray Henrich

 2  years               Larry Smith

Calendar

FEBRUARY 13: Second Sunday Social at Chris' Pancake and dining 2:00 P.M.