Lymphangioleiomyomatosis Patient Research Priorities Survey (LAM-PREP): Developing a Patient-Centered Research Agenda.

We used a mixed-methods approach consisting of focus groups and a quantitative survey to collect the perspectives of patients with LAM and caregivers regarding their health needs and research priorities ( Fig 1 ), following the Standards for Reporting Qualitative Research. 20 The executive oversight committee conducted an environmental scan to identify knowledge from prior and related assessments, and formulated the study purpose, primary research questions, and study methodology. The research team included individuals with diverse expertise and relationships to LAM. The principal investigator (M. K. H.) is a laboratory scientist and public health researcher with extensive experience in LAM research but no personal diagnosis of LAM. Our team members included LAM pulmonologists (G. P. D. and N. G.), a nonprofit executive (S. E. S.), laboratory scientists investigating LAM pathogenesis (M. K. H. and V. P. K.), and individuals living with LAM (A. D. S., E. J. P., L. M. H., and S. R. D.). Figure 1 Stages of LAM-PREP. Illustration of the LAM-PREP design, delivery, and implementation. LAM-PREP = LAM Patient Research Priorities Survey. Stages of LAM-PREP. Illustration of the LAM-PREP design, delivery, and implementation. LAM-PREP = LAM Patient Research Priorities Survey. Focus groups were selected as the primary qualitative data collection method because they facilitate interactive discussion and idea generation among participants with shared experiences. We conducted 3 in-person focus groups in June, September, and October 2023 during the joint regional TSC Alliance and TLF conferences. These sessions included registered meeting attendees—patients with LAM and caregivers (defined as family members [eg, spouses or parents] and friends). To reduce barriers to participation for patients who are unable to travel, 2 focus groups were conducted virtually via Zoom in November 2023 and were attended by patients only. Each focus group lasted 75 to 90 minutes and was facilitated by a moderator (M. K. H.). One observer (S. E. S.) recorded field notes during the in-person sessions. All 5 sessions were audio-recorded and transcribed using the native Zoom function. Informed consent and permission to be audio-recorded were obtained from all participants. The study was reviewed and approved by the Institutional Review Board of New York Medical College (Protocol No. 20301). Patients with LAM and caregivers were eligible to participate if they were > 18 years of age and able to give informed consent. Participants were selected through an email-based invitation to take part in a focus group, administered by TLF. Each focus group began with the moderator’s introduction, explanation of the study objectives, and reassurance regarding the confidentiality of information gathered during the session. All attendees were asked to complete a demographic questionnaire, introduce themselves, and state the reasons for participating in the focus groups. Prompt questions were designed to engage flexibly with the focus group participants regarding the health and research needs in LAM: (1) What is your most frustrating challenge as you navigate the treatment and management of LAM?; (2) Can you tell us about one health need for which you have not found a suitable clinical solution?; (3) What do you wish will be different/true for women who are diagnosed 10 years from now?; and (4) What research project would you fund if you could distribute research funding raised by TLF? The focus group script and questionnaire are included in e-Appendix 1 . Demographic data and participant characteristics were analyzed and tabulated using Stata SE version 17 (StataCorp LLC). The audio and transcripts were reviewed by 1 author, who generated a list of verbatim answers of the focus group participants. Answers were grouped into thematic categories and subcategories. The grouping of answers into categories was reviewed by an additional author. We observed thematic saturation with focus group responses. Using inductive analysis, 2 thematic groups emerged from the data: comments relating to unmet health and quality of life needs, and comments regarding the participants’ research priorities. The research priorities spanned the range of basic, translational, and clinical science. Nonresponsive comments regarding the reasons for participation in the focus groups and the participants’ thoughts about TLF were grouped separately. The survey was designed by the executive oversight committee using the results of the focus group analysis to formulate priorities to be ranked, and the survey was pilot tested by 3 members of the TLF’s staff (which included 1 patient). The survey began with a demographic questionnaire for all participants, which contained specific questions for patients with LAM, family and friends, LAM scientists, and LAM clinicians ( e-Appendix 1 ). Patients with LAM, family, and friends were then asked to rank the following: urgent unmet LAM health needs, priorities in quality of life and LAM management, and areas of research they feel should be given priority. Clinicians were asked to rank health needs of patients with LAM they encounter the most, health needs for patients with LAM for which they do not have an adequate solution, priorities in patient quality of life and LAM management, and areas of research that should be given priority. Scientists were asked to rank priorities that address quality of life and LAM disease management, and areas of research in order of priority. The survey was created in SurveyMonkey ( SurveyMonkey.com ) and distributed via email and social media channels. The survey was open from March 6, 2024, to May 31, 2024. Stata SE version 17 was used for all quantitative data analysis. Patient health needs and research priorities were categorized as high priority if ranked among the top 3 by respondents.

The 5 focus groups of phase 1 involved 88 participants, including 67 patients and 21 caregivers. All patients were female, as expected, whereas 14 caregivers (66.7%) who attended the in-person focus groups were male. The sociodemographic characteristics of the participants are reported in e-Table 1 . Among the participants who were patients with LAM, most (n = 53, 79.1%) had sporadic LAM, with a mean age of diagnosis of 40 years. Approximately two-thirds of the patients (n = 41, 62.7%) had at least moderate lung function impairment (FEV 1 or diffusing capacity of the lungs for carbon monoxide < 70%), 26 (38.8%) required supplemental oxygen, and 53 (79.1%) reported taking mTOR inhibitors ( Table 1 ). Table 1 LAM Disease Characteristics of Focus Group Participants (n = 67) Characteristic Value Disease type  TSC-LAM 12 (17.9)  Sporadic LAM 53 (79.1)  Unsure/do not know 2 (3.0) Menopausal status  Premenopausal 24 (35.8)  Postmenopausal 37 (55.2)  Perimenopausal 2 (3.0)  Unsure/do not know 4 (6.0) LAM disease severity  Mild: lung function (FEV 1 ) > 70% 18 (26.9)  Moderate: lung function (FEV 1 or D lco ) between 50% and 70% 26 (38.8)  Severe: lung function (FEV 1 or D lco ) < 50% 16 (23.9)  Unsure/do not know 7 (10.5) Use of mTOR inhibitor  No 13 (19.4)  Yes 53 (79.1)  Unsure/do not know 1 (1.5) Use of supplemental oxygen  No 39 (58.2)  Yes 26 (38.8)  Unsure/do not know 2 (3.0) Age of LAM diagnosis, y 40.1 [10.4] Age of symptom onset, y 35.0 [9.4] Data are presented as No. (%) or mean [SD]. Dlco = diffusing capacity of the lungs for carbon monoxide; LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin; TSC = tuberous sclerosis complex. LAM Disease Characteristics of Focus Group Participants (n = 67) Data are presented as No. (%) or mean [SD]. Dlco = diffusing capacity of the lungs for carbon monoxide; LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin; TSC = tuberous sclerosis complex. In discussing their health challenges, the participants noted several categories of health needs and quality of life priorities ( Table 2 ). Participants expressed concerns centered around difficulties in managing air travel, especially when needing supplemental oxygen, and noted a desire for better portable high-flow oxygen delivery devices. Participants voiced a need for improved assessment of sleep quality, effects of LAM on sexual health and intimate partner relationships, and balancing energy levels during daily activities and work. Patients and caregivers expressed frustration in the lack of knowledge about the implications of their symptoms on disease progression, and suboptimal management of common and rare LAM manifestations (eg, pneumothoraces, chylous effusions), and insufficient access to comprehensive LAM care, and in particular, noted the lack of awareness about LAM among clinical care providers. Furthermore, the participants noted a desire to meaningfully integrate complementary and holistic wellness into LAM care, receiving guidance for safe exercise, identifying and mitigating the causes of chronic fatigue experienced by many patients with LAM, and investigating the effect of diet both in disease progression and symptomatic management. The topic of childbearing and family planning was especially poignant to patients with LAM and their loved ones, specifically, the lack of research into the effects of pregnancy on LAM and the effect of fertility treatments and related interventions on disease progression. Managing the financial realities of living with LAM was also discussed (eg, cost of diagnostic tests and treatment, challenges of insurance coverage limits and restrictions). Table 2 Health Needs of Patients With LAM and Research Priorities Category Representative Patient/Caregiver Quotes LAM health needs and quality of life priorities  Travel, including by air “Guidance on is it safe to fly,” “Understanding oxygen needs for altitude,” “Risk for lung collapse at high altitude or during travel,” “Guidance regarding what to do during travel health emergency”  Sexual and women's health “Low sex drive, extreme dryness,” “Coughing up blood during orgasm—how is it triggered and what causes it?,” “Are common gyn issues like cystic ovaries, endometriosis, a result of LAM?”  Work/life balance and LAM “How to take care of yourself and plan the day,” “How to balance energy,” “Going back to work after diagnosis”  Impact of LAM on relationships “LAM comes between us, different than other chronic diseases because LAM patient who is otherwise healthy,” “Understanding disease as partner, being aware of any signs of progression,” “The effect on spouses who deal with side effects of LAM treatments,” “Managing emotions and relationships with progressive lung disease”  Understanding and interpreting LAM symptoms “Chest pain: is it anxiety or something more serious?,” “Panicking when there are any lung or breathing symptoms, fearing pneumothorax,” “Are migraines related to LAM?,” “Lung pains are scary,” “What symptoms mean for disease progression?”  Access to comprehensive LAM care and integrative wellness “Frustrating to put together a care team,” “Need for collaborative conversations between doctors,” “Integrating care with other diseases being treated for,” “Finding, connecting, accessing specialists for newly diagnosed”  Awareness of LAM among physicians and other health care providers “More awareness among primary care physicians about LAM,” “Lack of awareness from health care providers in general,” “Having to be own advocate for treatment, especially for other conditions”  Financial concerns “Having the care team under same insurance,” “Lifetime limit for pulmonary rehab,” “Financial stressors may exacerbate disease,” “Cost of medications, tests, and treatment”  Supplemental oxygen “Hate heavy and unfriendly oxygen equipment,” “Impacts mobility,” “Needs longer lasting oxygen”  Effects of LAM on sleep “Need sleep studies,” “Chronic lung diseases alter sleep, need for better understanding of this relationship with LAM,” “Effect of supplemental oxygen and sleep”  Mental health “Managing the emotional impact of disease,” “Dealing with fear when newly diagnosed,” “Having a disease while looking healthy”  Childbearing/Family Planning “Impact of fertility treatments, what is safe with LAM?,” “What does stopping sirolimus for pregnancy mean in terms of progression?,” “How do IVF hormonal treatments affect progression?”  Safe exercise “How to be best active?,” “Want to exercise safely and be active without worrying,” “How to exercise to your limit?,” “Being active with LAM”  Lung transplantation “Make lung transplants more successful,” “Improve lung transplants, better outcomes post-transplant,” “Does LAM come back after lung transplant?,” “Fear of transplant”  Impact of diet “Dietary effects, and benefits or harms of nutritional inputs,” “Can diet contribute to disease?,” “Can any kinds of diet help for symptoms of LAM?”  Chronic fatigue “What are the causes of fatigue?,” “Not being able to do things I should be able to do at my age,” “Extreme fatigue, finding cause” Research priority areas  Role of hormones in LAM disease and treatment “Effect of LAM and sirolimus/Rapamune on regular menstrual cycles and PMS/PMDD,” “Does sirolimus slow down menopause?,” “Does progesterone IUD stabilize disease progression?,” “Better understanding about the need for hysterectomies and oophorectomies”  Effect on other organs “Effect of LAM and oxygen on circulation on muscle tone,” “Urinary incontinence, leaking urine even without prior childbirth,” “Understanding what non-pulmonary symptoms should also be treated”  Disease onset and progression “What to expect about disease progression for newly diagnosed,” “How does aging affect LAM progression?,” “Understanding disease progression and how it will affect the rest of my life, effects on life expectancy, possibility of future lung transplant,” “Learn about progression for someone relatively young and active”  Lung regeneration “Repairing lung tissue, repairing existing lung damage,” “New lung tissue to replace cysts,” “Repair at the cellular level”  Lymphatic system and the immune system “Are lymphedemas caused by LAM?,” “Is my immune system compromised by LAM?,” “Does rapamycin affect immune function?”  Identifying the origin of LAM cells “What is causing LAM and what are the markers associated with it?,” “Why LAM cells migrate to lungs and kidneys?”  LAM genetics and heredity “Is LAM hereditary?,” “Understanding how women can pass LAM on to children,” “How to prevent LAM in women with TSC?,” “Worrying if and/or when daughter with TSC will get LAM”  Lung function testing “Need additional metrics of progression in addition to FEV 1 and D lco ,” “Better indicators of lung function in addition to x-rays and PFTs”  Diagnosis “Early detection for people at risk,” “Need better and less invasive diagnostics,” “Lack of new diagnostic tools,” “Need better biomarkers and algorithms for diagnosis”  Management of mTOR inhibitors “Will taking sirolimus sooner slow down disease progression?,” “Need other options to mitigate side effects,” “Sirolimus is incompatible with surgery,” “Frustrating side effects from sirolimus, and interactions with other medications,” “Effects of sirolimus on pregnancy and fetus”  Finding new treatments and a cure “Need more medication options alternatives to sirolimus for those who have side effects or decline rapidly,” “Repurposing other drugs,” “Solutions to treat LAM instead of just maintaining it,” “Need new targets besides mTOR” Patient motivations for participation  Research contribution “To talk about future research,” “Know the importance of clinical research and studies, and how much benefit it is to us patients,” “Yay new research,” “Being able to help future research,” “Want to be part of the solution,” “I understand the importance of research,” “Excited to have input”  Disease knowledge “Understanding symptoms,” “To learn more about disease,” “Find out what's happening in the field,” “Find out about advances in research because there is only so much one can find online”  Community support “Happy to be here and connect,” “Community support,” “To learn more, see ‘Lammies’ and meet new ones,” “Like being around other women with LAM,” “To see friends and make new ones,” “To meet a community,” “Meet other patients,” “Want to be a part of this group because I’d love to work on patient advocacy,” “To support people and to learn what I can, be an advocate for others” Dlco = diffusing capacity of the lungs for carbon monoxide; IUD = intrauterine device; IVF = in vitro fertilization; LAM = lymphangioleiomyomatosis; PFT = pulmonary function test; PMDD = premenstrual dysphoric disorder; PMS = premenstrual syndrome; TSC = tuberous sclerosis complex; Health Needs of Patients With LAM and Research Priorities Dlco = diffusing capacity of the lungs for carbon monoxide; IUD = intrauterine device; IVF = in vitro fertilization; LAM = lymphangioleiomyomatosis; PFT = pulmonary function test; PMDD = premenstrual dysphoric disorder; PMS = premenstrual syndrome; TSC = tuberous sclerosis complex; The participants discussed LAM-related health needs that could be addressed through basic, translational, and clinical research projects ( Table 2 ). The focus group participants described many areas of unmet health needs that could be prioritized in future studies (eg, need for more accurate diagnostic biomarkers, ways to prevent the development of LAM in young women with TSC, improved understanding of the genetic and molecular pathogenesis of LAM). The participants expressed a sense of urgency when discussing the lack of research regarding potential hormonal interventions in the management of LAM, alone and in combination with mTOR inhibitors, and determining the safety of sirolimus use during pregnancy; these topics were consistently identified as areas of major unmet need. Other areas identified by the participants included advances in lung transplantation, lung regeneration, and improved understanding of lymphatics biology and the role of the immune system in LAM. The participants expressed many ideas for projects investigating the initiation, timing, and dosing of sirolimus in disease management. Finally, it was universally agreed that finding novel treatments and a cure for LAM should be the foremost priority of the research community. The participants volunteered their reasons for joining the focus groups, which are summarized in an additional category in Table 2 . These opening comments, while serving as an icebreaker, revealed 3 main reasons for participating in a focus group. Participants expressed excitement about shaping the direction of future LAM research and providing input into the process. Participants also viewed the focus group as an opportunity to learn more about LAM. Overall, they valued the opportunity to meet and engage with other members of the LAM community in a supportive environment. The phase 2 survey was sent to 5,417 recipients, including 3,064 patients, 432 relatives and friends, and 1,921 clinicians and scientists. We received 756 responses (overall response rate, 14%), including 624 patients (20.4% response rate), 61 relatives or friends, 37 clinicians, 27 scientists, and 7 individuals who identified as other ( e-Table 2 ). As shown in e-Table 3 , a total of 32 clinicians and 22 scientists completed the survey in its entirety and their data were included in the analysis. There was a balanced sex distribution in both groups, and most respondents were from the United States with a wide range of clinical experience ( e-Table 3 ). Most clinicians were pulmonologists, and the scientists’ research programs spanned the range of basic, translational, and clinical. As shown in e-Table 4 , a total of 575 patients and 55 caregivers completed the survey in its entirety and their data were included in the analysis. Among patient respondents, the median patient age group was 45 to 54 years. As shown in Table 3 , most patients (n = 399, 69.4%) had sporadic LAM, about one-third (n = 173, 30%) were on supplemental oxygen, and over one-half (n = 305, 53%) were on sirolimus. The disease characteristics of survey respondents were reflective of the general LAM population, in contrast to the focus groups that tended to be skewed toward participants with more severe disease ( e-Table 1 ). Table 3 LAM Disease Characteristics of Survey Respondents (n = 575) Characteristic Value Disease type  TSC-LAM 76 (13.2)  Sporadic LAM 399 (69.4)  Unsure/do not know 100 (17.4) Menopausal status  Premenopausal 167 (29.0)  Perimenopausal 64 (11.1)  Postmenopausal 270 (47.0)  Unsure/do not know 74 (12.9) LAM disease severity  Mild: lung function (FEV 1 ) > 70% 242 (42.1)  Moderate: lung function (FEV 1 or D lco ) between 50% and 70% 151 (26.3)  Severe: lung function (FEV 1 or D lco ) < 50% 102 (17.7)  Posttransplant 18 (3.1)  Do not know 62 (10.8) Use of mTOR inhibitor  No 270 (47.0)  Yes 305 (53.0) Use of supplemental oxygen  No 402 (69.9)  Yes 173 (30.1) Age of LAM diagnosis, y 35.1 [13.5] Age of symptom onset, y 25.0 [12.7] Data are presented as No. (%) or mean [SD]. Dlco = diffusing capacity of the lungs for carbon monoxide; LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin; TSC = tuberous sclerosis complex. LAM Disease Characteristics of Survey Respondents (n = 575) Data are presented as No. (%) or mean [SD]. Dlco = diffusing capacity of the lungs for carbon monoxide; LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin; TSC = tuberous sclerosis complex. We next asked a set of survey questions which were phrased somewhat differently to each set of participants. These questions are summarized in Table 4 . The participants were asked to order the answers in order of priority, and we analyzed the answers that were placed in the top 3. Table 4 Survey Questions Question 1: LAM health needs Travel, including by air Sexual and women’s health Work/life balance and LAM Impact of LAM on relationships Understanding and interpreting LAM symptoms Access to comprehensive LAM care and integrative wellness Awareness of LAM among physicians and other health care providers Financial concerns (eg, health insurance, cost of drugs, supplemental oxygen, tests) Other Question 2: top priorities in quality of life and managing LAM Supplemental oxygen Effects of LAM on sleep Mental health Childbearing/family planning Safe exercise Lung transplantation Impact of diet Chronic fatigue Other Question 3: rank the areas of research you feel should be given priority Role of hormones in LAM disease and treatment Studying how having LAM may affect other organs (ie, heart, skeletal muscle, kidney) Disease onset and progression Lung regeneration Lymphatic system and the immune system Identifying the origin of LAM cells in the body Understanding LAM genetics and heredity Lung function testing Diagnosis Management of mTOR inhibitors such as sirolimus (eg, initiating treatment, dosing, long-term effects) Finding new treatments and a cure Other LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin. Survey Questions LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin. This question aimed to prioritize unmet health needs and was posed only to clinicians, patients, and caregivers, but not to scientists, who may not have direct experience with the clinical aspects of LAM. The question was posed in 2 different ways to the clinicians to discern any nuance between the health needs of patients with LAM they encounter most frequently vs the health needs of patients with LAM for which they lack adequate clinical solutions. As illustrated in Figure 2 , notable differences emerged between stakeholder groups. Patients and caregivers prioritized access to comprehensive LAM care and integrative wellness, understanding and interpreting LAM symptoms, and awareness of LAM among physicians and other health care providers ( Fig 2 A). In contrast, clinicians highlighted understanding and interpreting LAM symptoms as the health need of patients with LAM they encounter most frequently, whereas identifying sexual and women’s health was the area most lacking adequate clinical solutions ( Fig 2 B). Figure 2 A, B, Top LAM health needs. A, Ranked health needs of most concern to patients and caregivers. B, Clinician-ranked priorities for LAM health need encountered the most, and LAM health needs without an adequate solution. LAM = lymphangioleiomyomatosis. A, B, Top LAM health needs. A, Ranked health needs of most concern to patients and caregivers. B, Clinician-ranked priorities for LAM health need encountered the most, and LAM health needs without an adequate solution. LAM = lymphangioleiomyomatosis. Similar to question 1, this question was also restricted to clinicians, patients, and caregivers. Again, we observed some differences in priorities: patients and caregivers ranked mental health, effects of LAM on sleep, supplemental oxygen, and chronic fatigue as their top priorities, whereas clinicians ranked supplemental oxygen and childbearing and family planning higher ( Fig 3 ). Figure 3 Top LAM quality of life and disease management needs. Ranked priorities for patients, caregivers, and clinicians. LAM = lymphangioleiomyomatosis. Top LAM quality of life and disease management needs. Ranked priorities for patients, caregivers, and clinicians. LAM = lymphangioleiomyomatosis. This question, pertaining to prioritizing the LAM research directions, was asked of all survey respondents—clinicians, scientists, and patients. Overall, there was broad agreement between the different groups of respondents with finding new treatments and a cure being the top research priority, with some divergence between clinicians and patients in other aspects ( Fig 4 ). Figure 4 A, B, Top LAM research priorities. A, Ranked research priorities of patients and caregivers. B, Clinician and scientist ranked research priorities. LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin. A, B, Top LAM research priorities. A, Ranked research priorities of patients and caregivers. B, Clinician and scientist ranked research priorities. LAM = lymphangioleiomyomatosis; mTOR = mechanistic target of rapamycin.

To our knowledge, LAM-PREP is the most rigorous and systematic study to date of health needs and research priorities of patients with LAM and professionals. We observed a high degree of alignment between patient-ranked priorities, the priorities of their loved ones, and the priorities of clinical providers and scientific researchers. Our study underscores the value of engaging patients in developing research agendas to better reflect the lived experiences and real-world challenges faced by those affected by LAM and to enable the research and clinical communities to focus on the areas of highest priority to patients with LAM. Previous work to identify patient priorities in LAM conducted in Europe resulted in a list of 10 priorities based on a survey that generated 572 responses, of which 87% were patients with LAM. 18 A postsurvey workshop consisting of various stakeholders was then held where top priorities were discussed. In contrast, the current LAM-PREP used a different research design: ideas regarding health needs and research priorities of patients with LAM and caregivers were obtained first in focus groups, followed by a community-wide quantitative survey to rank these priorities. The focus groups were conducted in-person across 3 geographically distinct regions of the United States followed by 2 virtual sessions, allowing for participation of diverse participants. The observed discrepancies between patients’ priorities vs clinicians’ priorities highlight a need for increased awareness among health care providers about the systemic manifestations of LAM and the unique perspectives and needs of patients with LAM. LAM significantly impacts the quality of life through multiple mechanisms that extend beyond direct physical symptoms. Shortness of breath and chronic fatigue limit physical activity, whereas the progressive nature of the disease can lead to increased disability affecting personal and professional lives. Additionally, ongoing medical requirements create financial burdens and health care access challenges. These issues underscore the patient-articulated desire for integrating complementary wellness approaches into LAM care and suggest that a more holistic approach to treatment could be beneficial. In addition, patients’ emphasis on quality-of-life issues indicates that future efforts should prioritize improving the comprehensive care for patients with LAM. Moreover, clinical projects should focus not only on clinical outcomes but also on improving the day-to-day experiences of patients with LAM. Our results suggest that patient education and support programs may help patients with LAM better understand their disease, manage their symptoms, and navigate the health care system. Patient support groups and counseling services could also be made more accessible and can be stratified by age group and disease stage, and by health needs that arise within specific life stages (eg, childbearing concerns, perimenopause-related support, mental health support across the lifespan). The identified research priorities reveal important gaps in current knowledge and clinical approaches. The emphasis on finding new treatments beyond mTOR inhibitors suggests that current therapeutic options fall short of patient expectations. Similarly, the focus on hormonal factors reflects the gender-specific nature of the disease and underscores a critically underexplored aspect of LAM biology. The prioritization of quality-of-life concerns by patients highlights the need for research that addresses not only disease mechanisms but also the lived experience of those with LAM. The strengths of our study include the sample size and the diversity of the respondents, which includes all major stakeholders in LAM. Several limitations should be considered when interpreting our findings. First, selection bias may exist because respondents were predominantly those engaged with TLF community activities and comfortable sharing opinions. Second, the study relied on self-reported information, introducing potential recall bias. Third, the survey format may have favored participants with internet access, digital literacy, and English fluency. Fourth, the participant sample demonstrated high educational attainment (undergraduate degree or higher: focus groups, 80%; survey, 66%), potentially limiting generalizability to the broader LAM population. Finally, the research team acknowledged potential biases stemming from their professional roles and relationships to the LAM community. To mitigate this, the focus group moderator used open-ended questions and avoided leading participants, and team members explicitly discussed their assumptions before data collection.

None declared.

The LAM-PREP study represents a significant step in developing a patient-centered research agenda for LAM, emphasizing the importance of addressing both clinical and quality of life issues. The approach used in LAM-PREP could serve as a model for developing patient-centered research agendas for other rare diseases, particularly those predominantly affecting women. The alignment between stakeholder priorities regarding comprehensive care models and treatment innovation represents complex and evolving needs of the LAM community working in concert toward improved outcomes and, ultimately, a cure.

This study was supported by the 10.13039/100005963 LAM Foundation [Grant LAM0161S05 to M. K. H.]. No part of the research presented has been funded by tobacco industry sources.