June 2026 Research Update

This month's treatment-focused studies added reassurance that some commonly used approaches in LAM line up with patient-centered outcomes, but they did so in different ways. In a long-running clinic cohort, sirolimus (an mTOR-targeting medicine) was linked with stable lung function and clearer improvement in lymphatic and kidney-related LAM problems. In a separate evidence review, structured non-drug exercise programs most consistently improved how far people could walk, while changes in breathing tests and quality of life were mixed or not statistically clear. [1] [2]

In 71 adults treated with sirolimus at one center, lung function stayed generally stable over about 5 years, with a small early rise in the breathing test measure FEV1 at 12 months. Measures outside the lungs also moved in a clearer direction: chylous effusions (a type of lymph fluid leakage) resolved by 12 months in affected patients, and imaging showed angiomyolipoma and lymphangioleiomyoma volumes decreased in those with paired scans. Side effects were mostly mild, and about 6% permanently stopped sirolimus. [1]

Across 5 studies of non-pharmacological approaches (such as pulmonary rehabilitation, aerobic and strength training, yoga, and telemonitored exercise), the combined results pointed most strongly to improved exercise capacity. When a case report was excluded, structured exercise increased 6-minute walk distance by about 37 meters, while changes in FEV1 and quality of life were not statistically significant in the pooled analysis. No serious adverse events were reported in these programs, although mild short-term symptoms like breathlessness or muscle soreness were described. [2]

For patients, this month strengthened the idea that different parts of living with LAM can respond differently depending on what is being measured. The sirolimus cohort suggests that in routine care, people may see stability in lung function alongside more noticeable improvement in lymphatic complications and LAM-related tumors in the kidneys or abdomen, though this was not a randomized comparison. The exercise review suggests that supervised, structured activity can improve day-to-day physical capacity (walking distance), but it is still uncertain whether it reliably improves breathing tests or quality of life scores across studies. These results add to understanding now, while also showing where stronger studies would help clarify who benefits most and which outcomes change the most. [1] [2]

This month's observational studies did not test new treatments, but they made the bigger picture of LAM in healthcare systems clearer. One registry showed how often LAM appeared among several rare lung diseases and described common complications at diagnosis. Another nationwide pneumothorax dataset explained why women can have a different age pattern for collapsed lung, with a subgroup in reproductive years linked to LAM and catamenial pneumothorax. [3] [4]

In a Korean multicenter registry of 304 people with rare interstitial lung diseases, LAM was one of the most frequent diagnoses, making up 28.3% of cases. Pneumothorax at the time of diagnosis was reported in 11.6% of people with LAM, and treatment patterns reflected current practice, with sirolimus used in 53.5% of LAM cases in this registry. This kind of dataset helps patients understand how often certain complications occur at the start of diagnosis and how care patterns vary by condition. [3]

In a Japanese inpatient dataset of 1,747 spontaneous pneumothorax cases, women showed a trimodal age pattern, and the second peak was mainly explained by LAM and catamenial pneumothorax. The study also reported that after age 35, women were more likely to have secondary (underlying-disease-related) pneumothorax compared with primary pneumothorax, while this shift happened later in men. This helps explain why the reasons for a collapsed lung can differ by sex and age, and why LAM may be part of the evaluation in certain groups. [4]

For patients and caregivers, these datasets mainly add context rather than changing what an individual person should expect. They show that pneumothorax is a recognized part of how LAM can first come to attention, but the reported frequency at diagnosis varies by disease group and setting. They also clarify that in large pneumothorax populations, LAM contributes to a distinctive age pattern among women, which supports ongoing research attention to earlier recognition and accurate labeling of pneumothorax type. What remains uncertain from these studies is how these population patterns translate to any single person's risk over time, because they describe groups rather than predicting individual outcomes. [3] [4]

This month's diagnostic studies reinforced a practical point: no single test result should be read in isolation when cystic lung diseases can resemble each other. A pathology series suggested a tissue marker called GPNMB could help confirm LAM on biopsy when traditional stains are weak or negative. At the same time, a case report described a person with an elevated VEGF-D blood level who ultimately had Birt-Hogg-Dube syndrome, showing that a result that "looks like LAM" can sometimes occur in other conditions. [5] [6]

In 40 biopsy cases that included 17 LAM samples and several non-LAM mimics, GPNMB staining was present in all LAM cases, often in more than 75% of the LAM cells. GPNMB appeared to perform better than some traditional melanocytic markers that were sometimes absent or minimal in LAM, and it performed similarly to cathepsin K. The study also noted pitfalls, because GPNMB can highlight alveolar macrophages and was positive in metastatic dermatofibromas, so results still need careful interpretation. [5]

A separate single-patient report described a 32-year-old woman with diffuse cystic lung disease whose VEGF-D was 839 pg/mL, a level that initially supported LAM. After re-review of the CT pattern and genetic testing, she was found to have a pathogenic FLCN variant consistent with Birt-Hogg-Dube syndrome, and surgical biopsy showed no features of LAM. The case highlights that VEGF-D elevation can sometimes occur outside LAM and that multiple pieces of evidence may be needed to settle a diagnosis. [6]

For patients, this section mainly affects understanding of diagnosis rather than treatment. These studies suggest that when diagnosis is uncertain, tissue-based markers like GPNMB may make biopsy interpretation clearer in some situations, but they are not perfect and can be confusing in certain rare look-alike tumors. The VEGF-D case report is a reminder that blood tests can occasionally be misleading, so imaging patterns and genetic testing can matter a great deal when the diagnosis sits between LAM and other cystic lung diseases. What remains uncertain is how often false-positive VEGF-D results happen, because a single case cannot estimate frequency. [5] [6]

This month added several pieces to the picture of LAM as more than a single cell type growing in the lung. Studies using human tissue and lab models described multiple LAM-like cell states, nearby fibroblasts that may help shape the lung environment, and immune and signaling pathways that might influence how LAM cells persist. These are early research findings, but they help explain why LAM can look different across people and why blood markers and pathways beyond mTOR may matter in future research. [7] [8] [9] [10]

A multiomics atlas built from human LAM tissue reported three LAM subtypes (CORE1, CORE2, CORE3) and two LAM-associated fibroblast states that appear to organize around the LAM cell cluster in a spatial pattern. CORE1 was described as a canonical, mTORC1-hyperactive smooth muscle-like state, while CORE2 looked more fibroblast-like with strong extracellular matrix remodeling. This kind of map does not test a therapy, but it gives a more detailed blueprint of which cell neighborhoods might be driving scarring-like changes or supporting LAM cells in the lung. [7]

Another study focused on glucocorticoid receptor signaling, a pathway activated by steroid hormones like cortisol. In LAM and angiomyolipoma cell models, activating this receptor increased a slow-cycling state and increased the cells' ability to form colonies, while blocking the receptor reduced these effects. In patient cohorts, ACTH and cortisol levels were higher in LAM than in controls, and ACTH levels were linked with more advanced imaging stage in one prospective cohort, suggesting a possible hormone-related signal worth further study. [8]

Two additional preclinical studies pointed to other pathways that could be relevant to future biomarkers or drug targets. One lab study using primary LAM/TSC cells reported that blocking CXCR2 reduced cellular senescence signals and reduced senescence spreading to lung fibroblasts, with IL-8 carried in small extracellular vesicles as a possible driver. A separate single-cell study in a TSC mouse tumor model, with validation in LAM patient lesions and serum, described a neural crest-like tumor cell signature and reported that blood markers such as SPP1 and KRT18 were elevated in some LAM patients, while LCN2 was decreased in nearly all, alongside distinct increases in VEGF-D. [9] [10]

For patients, these studies are mainly about building the next generation of understanding, tests, and possible treatment ideas rather than changing care now. They suggest that LAM tissue may contain multiple LAM cell states and supportive neighboring cells, which could help explain differences in disease behavior across people and point to future targets beyond the mTOR pathway. They also raise specific, testable ideas about hormone signaling (ACTH and cortisol patterns) and inflammatory aging-like changes (IL-8 and CXCR2) that might someday connect to biomarkers or new therapies if confirmed in larger human studies. What remains uncertain is which of these signals reliably predicts symptoms or progression, because much of the evidence is from lab work or small cohorts. [7] [8] [9] [10]

This month's case reports showed two very different real-world situations: long-term living with TSC-LAM under ongoing treatment, and a situation where early testing pointed toward LAM but later evidence changed the diagnosis. Together, they underline that LAM care can involve multiple organs and long follow-up, and that reaching the right diagnosis may take more than one step. Because they describe single individuals, these reports are best read as examples rather than typical outcomes. [11] [6]

In a 36-year-old woman with tuberous sclerosis complex-associated LAM and recurrent pneumothoraces, sirolimus dosing guided by blood levels was reported alongside stable disease over 3 years. The report noted no progression of lung cysts on imaging, a decrease in right kidney angiomyolipoma volume, and improvement in 6-minute walk distance from 367 m to 497 m, with no drug-related adverse events described. Cascade genetic testing found the same pathogenic variant in her daughter, illustrating how LAM linked to TSC can involve family-based genetic evaluation. [11]

The second case involved a 32-year-old woman with diffuse cystic lung disease whose initial VEGF-D value suggested LAM, but later CT pattern review and FLCN genetic testing supported Birt-Hogg-Dube syndrome, and biopsy showed no LAM features. The report described a final diagnosis change after combining blood testing, imaging interpretation, and genetics. It adds a concrete example of how LAM and other cystic lung diseases can overlap in early workups. [6]

For patients, these individual stories highlight two practical realities: LAM can be a multi-organ condition needing coordinated monitoring over years, and some tests can point in the wrong direction when cystic lung diseases look similar. The TSC-LAM report may matter now as an example of long-term stability being possible in a treated individual and of how genetic findings can lead to family testing, but it cannot predict what will happen for others. The diagnostic reversal case may matter now by illustrating why a diagnosis sometimes changes as more information is gathered, and why confirmatory steps like genetics or biopsy can be important when results do not fully match. [11] [6]