Short-Term Goals, Long-Term Effects: Outcomes of the 2017 LAM Patient Benefit Conference

Posted on November 30, 2018   |   


How can we improve the lives of LAM patients in five years or less? This is the question scientists, clinicians, and patients themselves gathered to answer at the first-ever LAM Patient Benefit Conference.

Before the meeting began in November 2017, The LAM Foundation conducted surveys with patients and clinic directors to identify the mental and physical issues that were most important to them. The results determined the mission of the conference: to identify and fund proposals for new products or services that can best meet patients’ needs in the short term.

Several main topics were generated from patient and clinic director feedback. During the Patient Benefit Conference, participants and thought leaders focused on these topics in moderated workshops, generating potential solutions and grant proposals.

Among the many valuable ideas shared, the following proposals have received funding to move forward. Each was chosen for its potential to result in solutions that will positively impact the diagnosis, care, or quality of life of LAM patients by the year 2023.



Biomarkers and LAM

“Identification and validation of new biomarkers based on single-cell RNAseq data”

Why do I have this disease, and how will it develop? For LAM patients, this question is often asked, but not always answered. Understanding the origin and development of LAM is dependent on a greater understanding of how disease cells function, interact, and grow.

Anne Karina Theresia Perl, MS, PhD of Cincinnati Children’s Hospital has proposed new methods to identify and validate biomarkers in LAM. Biomarkers give us medical signs of disease presence and severity—and LAM has very few. Serum VEGF-D has shown value as a diagnostic biomarker, but there are other categories of biomarkers we have yet to develop. Prognostic biomarkers can help determine disease progression, and predictive biomarkers can estimate response to treatment.

To identify these biomarkers, Dr. Perl will utilize the powerful, state-of-the-art technology of single-cell RNA sequencing. This method helps us understand how individual cells function and interact with the other cells around them. Dr. Perl plans to use this approach to develop new LAM-specific biomarkers.

Single-cell RNA sequencing has changed the way we interpret disease. The more we understand a cell’s actions, the better we can identify and treat abnormal cell function. Dr. Perl aims to use this method to develop new treatments for LAM.

These approaches can go a long way in advancing research, but the results typically take a longer amount of time to directly benefit patients. But this study will take advantage of a rare opportunity—there are already multiple LAM samples in existence that can be used to identify biomarkers. This accelerated pace of discovery will lead to patient benefit in less than five years.

“Single-cell RNA sequencing for identifying differential responses to sirolimus therapy in LAM”

The MILES study showed that sirolimus can suppress lung function decline and improve symptoms in patients with LAM. But reaction to sirolimus therapy can also differ among patients—many are responsive to treatment, while others are resistant. What causes these reactions, and how can we predict them?

Jane Yu, PhD of the University of Cincinnati aims to answer these questions by enhancing our understanding of sirolimus therapy in LAM. In studying cell response to sirolimus exposure, we can discover why LAM cells evade the actions of sirolimus, leading to a more individualized approach to treatment.  

For all patients, sirolimus treatment must be continuous to sustain benefits—if drug exposure stops, lung function declines. This means that sirolimus works by inhibiting growth in LAM cells rather than killing them. And in some cases, cells can develop resistance or stop responding altogether. Why are these cells able to withstand treatment, while others cannot?

Dr. Yu and her team will use single-cell RNA sequencing techniques to identify the molecules that determine the behavior of sirolimus-resistant LAM cells. With these findings, they can develop new biomarkers to identify which patients may be resistant to sirolimus treatment. If sirolimus resistance is detected earlier, new treatment strategies can be implemented sooner, meaning less lung function decline for these patients.

These insights could aid in the ultimate goal of Dr. Yu’s laboratory—to develop new treatments that not only stop the growth of LAM cells, but eliminate them altogether.

“Impact of menstrual cycle related variation in lung function on disease progression in LAM”

We know that symptomatic LAM occurs almost exclusively in women. We know that symptoms can intensify with pregnancy. We know that premenopausal patients tend to decline faster than postmenopausal patients. From these observations, we believe that hormonal influences play a pathogenic role in LAM—but we do not know for sure.

Adam Gerard Cole, MD of the University of Cincinnati aims to find concrete answers to the questions surrounding estrogen and LAM. By studying fluctuations in lung function and pulmonary symptoms during the menstrual cycle, Dr. Cole can provide strong circumstantial evidence for the impact of hormones on disease progression.

Home spirometry methods will be used to measure changes in lung function over time. Patients will perform a daily spirometry test, record menstrual cycle dates, and keep track of ovulation. Researchers will then determine the variation in lung function for each patient throughout the course of the menstrual cycle. Trends in this data will demonstrate whether patients who experience menstrual variation in symptoms tend to decline faster than patients who do not.

If this difference is shown, menstrual cycle variation in home spirometry could become a new way to identify patients at risk for faster lung function decline, helping physicians decide when to initiate treatment. With a better understanding of estrogen and LAM, these treatments could someday include hormone-based therapy options. 



Imaging and LAM

“Worldwide standardization of cystic lung disease CT with implementation of ultra-low radiation”

For patients with LAM, CT scans are a necessary part of life with a cystic lung disease. Diagnosis and follow-up care depend on regular x-ray imaging. But the benefits of regular scans also come with a drawback—potential carcinogenic effects of continued radiation exposure.

Dr. Marcus Y. Chen, MD of the National Institutes of Health aims to reduce these risks as much as possible. His research focuses on standardizing CT imaging protocols so that no patient is exposed to more than the minimum amount of radiation.

When LAM patients go in for a scan, there is currently 150-fold variability in the amounts of radiation used. This means that scans can range anywhere from a single chest x-ray of 0.1 mSv all the way up to 15 mSv. Because there are no established protocols for chest scans in LAM, the amount of radiation exposure depends on the model of CT scanner used and the preferences of the local physician.

The basic principal of x-ray imaging is to use the lowest amount of exposure possible. But how low is the lowest? To establish new protocols, Dr. Chen and his research team are going to find out. They will begin by constructing a model of human lungs, complete with cystic abnormalities that are characteristic of LAM patients. These lungs, made of plastic yet medically realistic, will become an invaluable resource for the LAM community.

Individual clinic sites will be able to repeatedly scan the model lungs—something they could not safely do with a patient. Scanners will then be calibrated to the specific requirements of LAM lungs, reducing radiation exposure and optimizing image quality.

Less radiation means a lower risk of patients developing cancer. With these risks decreasing, physicians may decide to lessen the time between follow-up scans. The sooner changes in LAM lungs can be assessed, the earlier changes in therapeutic treatments can be made—leading to better care for all.

“Feasibility study of [11C]acetate PET as an indicator of early response to rapamycin in LAM patients”

Positron emission tomography (PET) scans allow doctors to check for diseases in the body. The scans can help evaluate organ and tissue functions, identify body changes at the cellular level, and detect early onset of disease. Because there are currently no imaging biomarkers for LAM, healthcare providers are unable to detect the disease using these scans. What would it mean for patients if they could?

Carmen Priolo, MD, PhD of Brigham and Women’s believes that the impact could be essential to improving care for LAM. Her research aims to test the potential for PET scans to detect whole-body tumor burden and metabolic activity in LAM patients.

PET scans use small amounts of radioactive materials called radiotracers to follow molecular activity in the body. [11C]acetate is a radiotracer that is commonly used to detect renal, pancreatic, and prostate tumors. Dr. Priolo hypothesizes that [11C]acetate could be used to follow the metabolic activity of lungs in patients with LAM.

In following the metabolic activity of kidney tumors, the study also aims to reveal a new imaging biomarker for LAM. This activity could help physicians predict how a patient may respond to rapamycin, allowing for more personalized dosages and lengths of treatment. As a low-radiation risk option for imaging in LAM, [11C]acetate PET scans show great promise for both patients and researchers.



Exercise and LAM

“Mobile health to increase patient accessibility to exercise and elucidate exercise & fatigue in LAM”

LAM patients are often instructed to stay as active as possible, but they aren’t often instructed on how to achieve this while dealing with the symptoms of chronic respiratory disease. For many, exercise intolerance and fatigue are everyday realities. How can patients be better equipped to overcome these barriers on their own terms?

Mary Beth Brown, PhD, PT of Indiana University has proposed a mobile health platform that empowers LAM patients to understand their optimum level of exercise and stick with a regular routine. The user-friendly, web-based platform—“LAmHealth”—will be the first to collect patient data related to exercise and fatigue in LAM.

An activity monitor worn on patients’ wrists integrates with a smartphone app to capture heart rate, physical activity, and sleep metrics. Patients also record data on blood oxygen saturation, pulmonary function, and supplemental oxygen use, along with symptoms of fatigue, emotional wellness, and sleep quality.

The data comes together in the mobile health platform to give us a better understanding of the factors that affect physical activity for LAM patients. Armed with this knowledge, we can provide evidence-based guidance for optimal exercise approach—meaning that no LAM patient will have to base their decisions on trial and error.

Still, the guesswork that comes with developing an unguided exercise routine isn’t the only barrier to consider. Traditional, medically-supervised programs require regular trips to pulmonary rehabilitation centers. When schedules are busy, wait lists are long, and transportation options are limited, it can be difficult for patients to participate in these programs.

Home-based rehabilitation, however, offers greater flexibility for patients to follow their own schedules and preferences. More control over where and when exercise occurs means less obstacles to accessing and maintaining care. When patients are given the means and the tools to take charge of their own exercise routines, they can make major improvements in their own health.



Due to their high importance to patients, the following grants will receive funding through The LAM Foundation with money raised from the LAM Patient Benefit Conference:

Supplemental Oxygen and LAM

The realities of LAM may mean that some patients use supplemental oxygen devices, but this doesn’t mean that they stop being active. So why is there a lack of supplemental oxygen therapies that fit an active lifestyle?

In the initial surveys from the LAM Patient Benefit Conference, women with LAM clearly expressed their frustration with the limitations of supplemental oxygen devices. Survey results showed that these devices were often inconsistent in quality and difficult to access.

One of the Patient Benefit Conference workshops focused on improving the quality and technology of supplemental oxygen therapy to address this patient need. Through discussion between both patients and clinicians, the group generated ideas for making supplemental oxygen devices easier to use, less burdensome, and more appropriate for living an active lifestyle.

The “EasyOX” is the resulting idea that won the most votes for the Patient Choice Award. This digitally-controlled device can remotely adjust oxygen flow, improving the function and mobility of an oxygen tank.

Funds have been reserved to support further research and product development for the “EasyOX” device. The LAM Foundation is pursuing academic programs in biodesign and technology in hopes of identifying a program that will adopt this project.


Mental Wellness and LAM

The physical manifestations of LAM are, by necessity, the primary focus of care. But for women coping with the everyday realities of this disease, the effects do not simply stop at the surface. How can we improve care for the whole person—inside and out?

Patients and clinicians thoughtfully addressed this sensitive and important need in a dedicated workshop. The discussion included topics of anxiety, fear, and depression. Patients expressed the stress and worry that comes with financial burden on their families. They also shared the challenges of dealing with the limitations in life with LAM.

In 2019, The LAM Foundation will develop a new webpage on to address these topics. Now, there will be a place for patients to access content and resources for mental health needs. Dr. Sian Cotton and Stacy Sims, experts in integrative medicine and mindfulness, will author this new content.

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