Abstract

Summary: Lymphangioleiomyomatosis (LAM) is a lung disease that strikes women in the prime of their lives. The disease is progressive and often fatal, and is caused by a proliferation of cysts that destroy healthy tissue. Complications of LAM include decreased lung function, spontaneous lung collapses, and pulmonary hypertension. For several years the only two treatment options were full-time supplemental oxygen and lung transplantation in end-stage illness. The LAM Foundation was established in 1995 to support patients and spearhead research into the illness. The New England Journal of Medicine (NEJM) recently recognized the achievements of The LAM Foundation in an editorial. In the same issue, NEJM also published results of the MILES Trial, which yielded the first oral drug treatment for LAM.
Keywords: Lymphangioleiomyomatosis, tuberous sclerosis complex, LAM Foundation, LAM Treatment Alliance, TSC, e-patients, support groups.
Citation: A breath of hope for lam patients: the relentless pursuit to defy the odds. J Participat Med. 2011 Jun 2; 3:e25.
Published: June 1, 2011.
Competing Interests: The author has received honoraria from Flince Research for participating in research projects related to Tuberous Sclerosis Complex. She is employed by Medscape, a subsidiary of WebMD Health, and is a past board member of the Tuberous Sclerosis Alliance.

What is Lymphangioleiomyomatosis (LAM)?

There are approximately 250,000 to 300,000 women worldwide who have LAM.[1] The hallmark of the disease is uncontrolled growth of cysts and smooth muscle tissue in the lung. These cysts secrete proteins that destroy the healthy tissue around the lung. This causes a progressive decline in lung function; often resulting in numerous lung collapses, pulmonary hypertension, and fluid buildup in the lung. Emphysema or asthma-like breathing issues are also common. The disease is progressive and terminal in nature, but is variable in its expression — some women decline rapidly, whereas others have a slower downhill course. This disease involves the same genes as tuberous sclerosis complex (TSC), resulting in 40 percent of women with TSC also having LAM.[2] However, more women have the sporadic form (non TSC-related) of the disease. It is not known exactly what factors trigger the sporadic form of LAM. Since this disease almost exclusively affects women, it is thought that estrogen plays some role in the illness. Many physicians recommend that women affected with LAM avoid high levels of estrogen to try and avert more rapid progression; especially since some women have been diagnosed following a lung collapse during pregnancy (when estrogen levels are at their highest).

The LAM Foundation: A Small, Yet Powerful, Voice

The New England Journal of Medicine (NEJM) recently published an editorial highlighting the achievements of the LAM Foundation since its founding in 1995.[3] The LAM Foundation is an invaluable support system to women with this diagnosis. The organization was founded by a woman who serves as an inspiration and mentor to all “Lammies.” NEJM also concurrently published the results of the MILES Trial (Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus)[4] which documented the first effective treatment of the disease.

A few weeks after this study was published, National Public Radio produced a program detailing how The LAM Foundation has supported their community and enabled women to take charge of their own care and help others.[5] The LAM Foundation has established 24 Clinics in the United States to provide expertise in LAM care and to help organize clinical trial participation. The clinics often collaborate with local clinicians to provide care for complex LAM-related issues in addition to collecting valuable data on the women they serve. The LAM Foundation also holds an annual patient and family conference (and a joint research conference) where researchers, patients, and other professionals lead sessions on how to live better and brainstorm ideas for fundraising and awareness efforts and learn about the latest treatments and research developments.

The organization relies heavily on “Lammies” to raise awareness. Patients willingly share their stories on talk shows, radio, and other media outlets. They distribute brochures to health professionals and provide information at health fairs. They also manage exhibit booths on behalf of The LAM Foundation at major medical conferences such as the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST) conference. LAM Foundation volunteers serve as patient liaisons and are assigned to every region in the country, spearheading local support groups, developing patient-led fundraisers, and holding regional informational gatherings.

Every member of The LAM Foundation Board of Directors has a loved one with LAM or suffers from LAM.

Advancing Rare Disease Research through Partnerships

For a rare disease that only a few years ago had no treatment option other than lung transplantation in the late stages, the recent results of the MILES Trial published in the New England Journal of Medicine (NEJM) was a significant moment.

Researchers have labored to discover better options against a disease that has limited options and a five to 10 year life expectancy after diagnosis — often with use of full-time supplemental oxygen; or lung transplantation after the ravages of LAM had eaten away the patient’s quality of life and her healthy lung tissue.

Only about 40% to 50% of those who receive treatment with sirolimus respond. But it is a good start and illustrates how researchers and patients can forge an alliance to find a viable treatment. Exchanges between researchers and LAM women have been vital to this process.

Frank McCormack, MD was the principal investigator for the treatment trial to test sirolimus as a viable treatment option. Many patients participating in Dr. McCormack’s studies traveled long distances — sacrificing work and personal time to participate. Since most of the trials were double-blinded, many women had the potential to receive placebo instead of actual drug. This is a courageous step as the temptation (especially for women in active progression) is greater to take the drug off-label.

Patients are currently participating in saliva analysis to assist with a GWAS (Genome-Wide Association) study that may lead to more breakthroughs in LAM’s genetic makeup and guide future research efforts. GWAS studies have yielded valuable insight into other diseases, so women have been actively collecting and remitting their samples.

Another LAM Patient, Amy Farber, PhD, a social scientist from Harvard, along with her husband, founded the LAM Treatment Alliance in 2005. Being in the medical community, Amy felt that she and her husband might have some success eliminating red tape in accessing tissue and engaging new groups of researchers to study the mTOR pathway (the prime pathway for both LAM and TSC). For the past six years, Dr. Farber has hosted a very successful LAM/TSC Seminar Series, which brings together researchers and patients to brainstorm new avenues in researching and treating both LAM and TSC.[6] She also founded LAMSight, a web portal for LAM Patients and Researchers, to share experiences about relevant and possibly overlooked symptoms of LAM on a global level.[7]

My Personal Journey With LAM: The Good, Bad, and Ugly

Many of the researchers involved in the NEJM study have become invaluable partners in my personal medical, advocacy, and research endeavors. Drs. Joel Moss, Angelo Taveira-DaSilva, and Frank McCormack have devoted countless hours of their professional careers to the study of LAM and an equal amount of their personal time helping women understand how to live with their illnesses. This trio served as mentors in my personal participatory medicine journey.

My diagnosis came over a year after my first encounter with a pneumothorax (lung collapse). An astute resident noted my existing TSC diagnosis and asked me if I knew about LAM. At that time, I had no clinical markings — but later, when symptoms developed, I learned of Dr. Moss’ protocol from other LAM patients with Tuberous Sclerosis Complex. I obtained a screening at the NIH and was diagnosed immediately by Dr. Taveira-DaSilva.[2] Many women are often misdiagnosed for years with asthma, emphysema, or other incorrect diagnoses before learning they have LAM.

I went through a scary medical situation in 2006. I had a tumor that affected only 2% of both LAM and TSC women. I had good access to medical resources, but I still felt helpless. I could only find one or two articles that mentioned this problem in passing (I was later told that there were at best only 50 cases documented at that time). I emailed Dr. Henske, who I hoped could shed some light on this diagnosis. She put my fears to rest since she had experience with this tumor. She guided my oncologist and me in gaining confirmation about the diagnosis and deciding the best way to address it.

I was shocked when I learned my diagnosis in 2003. I joined the LAM Listserv hosted by The LAM Foundation. Several women, who were successfully living with LAM at varying stages, provided sage wisdom and shared their experiences. This early support was vital because, when I was diagnosed, there was so much information that was out-dated and incorrect (if it could be found on the internet or in a medical book at all). Anyone who is diagnosed with a rare disease is often left to fend for themselves to find their own truth to deal with their situation in the face of a lot of conflicting information.

A few years ago, in the throes of a very serious illness caused by LAM and TSC, circumstances prevented me from enrolling in the MILES Trial, although I wanted badly to participate. So I decided to use the drug “off-label” under close monitoring by my nephrologist and pulmonologist. We all agreed this was the best option to try and prevent progression and additional surgeries from LAM and TSC complications (I had nine surgeries between 2003 and 2009). Because Dr. McCormack had been studying the drug and led several trials, my physicians reached out to him for guidance on dosage and monitoring standards. I am one of the fortunate 50% who has responded to the drug; so I have been directly helped by the LAM women who participated in these trials and I thank them for their sacrifices.

Before LAM Clinics were established, The LAM Foundation formed a physician referral list stockpiling information about doctors in local areas across the United States that were willing to treat LAM patients. When I recently moved, I was happy to see there was a LAM Clinic in Philadelphia (as well as a TSC Clinic), but I called The LAM Foundation to inquire who I could see locally. To my relief, I found a new pulmonologist who was open to collaborating with the LAM or TSC Clinic as well as my new local primary care doctor and nephrologist; so there were no gaps in my care.

As I settled into my diagnosis, I have tried to return the kindness shown to me by mentoring new patients as I was mentored. It wasn’t always pleasant; there’s a lot of ugliness with this disease. It has been worth it to be open with others in both the LAM and TSC communities.

I grew up in a rural area and did not have easy access to a teaching hospital or an academic center. Organizations like The LAM Foundation provide a lifeline to people like me who may have difficulty obtaining care for a rare illness. People can turn to an organization like this to find a knowledgeable practitioner or clinic within a reasonable distance.

The Future: Looking Brighter

As I look back, I see many women (who could have shrunken in fear) take charge of their illness and help blaze a trail to change the course of their disease.

I see an organization that started in a teacher’s basement become nationally respected by both the public and the provider community. I found a group of women who are actively engaged in funding treatment and research by starting letter-writing campaigns, holding special events, and raising money for travel grants for women to attend LAMposium when medical bills, disability, or other circumstances would make it financially impossible for them to attend.

We take care of each other — any time a woman has a transplant, becomes ill, or has a triumph or sorrow to share there is a community available for support. When one of us succumbs to the disease, we all celebrate that person’s life, but are motivated to fight harder.

Many women have started side businesses selling t-shirts, bracelets, and other products to raise additional money for research and for The LAM Foundation and its programs. In fact, the first online fundraiser held last year which was spearheaded by a woman with LAM raised over $100,000.

The accolades given to The LAM Foundation for their efforts in empowering their own community and others (through their collaborations) are well deserved; especially considering there are only 2000 patients in their registry.[5]

This brings hope to those facing chronic, terminal, and rare illnesses — the odds are great, but not insurmountable.

References

1. The Epidemiology of LAM. The LAM Foundation. Available at: http://www.thelamfoundation.org/medical-providers/the-epidemiology-of-lam. Accessed May 26, 2011. ↩
2. Seefeldt NM. Armchair advocacy for tuberous sclerosis complex: a patient’s perspective. J Participat Med. 2011 Jan 5; 3:e2. Available at: https://participatorymedicine.org/journal/perspective/narratives/2011/01/05/armchair-advocacy-for-tuberous-sclerosis-complex-a-patients-perspective/.Accessed April 10, 2011. ↩
3. Ingelfinger, JR, Drazen, JM. Patient organizations and research on rare diseases. N Engl J Med 2011; 364:1670-1671. Available at: http://www.nejm.org/doi/full/10.1056/NEJMe1102290. Accessed March 18, 2011. ↩
4. McCormack FX, Inoue, Y, Moss J, et al. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med 2011; 364:1595-1606. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1100391#t=article. Accessed March 18, 2011. ↩
5. Shute N. Web Communities Help Patients with Rare Diseases. National Public Radio. http://www.npr.org/2011/04/04/135106113/patients-with-rare-diseases-connect-online. Accessed April 4, 2011. ↩
6. LAM/TSC Seminar Series. LAM Treatment Alliance. Available at: http://lamtreatmentalliance.org/seminars.html. Accessed April 4, 2011. ↩
7. LAMSight. LAM Treatment Alliance. Available at: http://lamtreatmentalliance.org/lamsight.html . Accessed April 4, 2011. ↩

Acknowledgements

The author graciously thanks The LAM Foundation (especially for updating statistics), Sally Nagel, Susie Picart, Madeline Nolan, and other women of LAM for their guidance in developing this article.

Copyright: © 2011 Nicole M. Seefeldt. Published here under license by The Journal of Participatory Medicine. Copyright for this article is retained by the author, with first publication rights granted to the Journal of Participatory Medicine. All journal content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. By virtue of their appearance in this open-access journal, articles are free to use, with proper attribution, in educational and other non-commercial settings.