Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Lymphangioleiomyomatosis: a rare disease update

  Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease characterized by the abnormal growth of smooth-muscle-like LAM cells. These cells can infiltrate the lungs, lymphatic system, and kidneys, gradually damaging lung structure and reducing airflow. The condition primarily affects women, most often during the reproductive years.

  LAM may occur sporadically or alongside tuberous sclerosis complex (TSC), a genetic disorder caused by changes in the TSC1 or TSC2 genes. Although improved imaging and biomarker testing have made diagnosis more reliable, many patients still experience delays because early symptoms resemble asthma, chronic obstructive pulmonary disease, or recurrent chest infections.

  Current care combines accurate diagnosis, pulmonary monitoring, management of complications, and targeted therapy. Advances in understanding the mammalian target of rapamycin (mTOR) pathway have also changed the outlook for people with declining lung function.

  Understanding the disease process

  LAM cells display abnormal activation of the mTOR signaling pathway, which regulates cell growth and metabolism. In the lungs, these cells form around airways, blood vessels, and lymphatic channels. Progressive tissue destruction produces multiple thin-walled cysts, a characteristic finding on high-resolution computed tomography (HRCT).

  As cysts expand and rupture, patients may develop airflow obstruction, reduced gas transfer, and spontaneous pneumothorax. Lymphatic involvement can lead to chylous pleural effusion, chylous ascites, or enlarged abdominal lymphatic structures. Angiomyolipomas, benign tumors containing blood vessels, muscle, and fat, are frequently found in the kidneys and may bleed if they become large.

  The clinical course varies considerably. Some individuals remain stable for many years, while others experience a steady decline in forced expiratory volume in one second (FEV1). TSC-associated LAM may be accompanied by seizures, skin lesions, renal angiomyolipomas, and other manifestations of tuberous sclerosis.

  Recognizing symptoms and risk factors

  Breathlessness during exertion is a common initial complaint. Other symptoms include chronic cough, chest discomfort, fatigue, wheezing, and reduced exercise tolerance. A pneumothorax may be the first clear sign, particularly in a younger woman without a history of smoking or significant respiratory disease.

  Hormonal influences are clinically important because LAM cells often express estrogen and progesterone receptors. Symptoms or lung decline may become more apparent during pregnancy or with exogenous estrogen exposure. Hormonal contraception, fertility treatment, and menopausal therapy therefore require individualized discussion with a respiratory specialist and gynecologist.

  A detailed history should include previous pneumothoraces, kidney lesions, pregnancy-related changes, TSC features, and family history. Pulmonary function testing, oxygen assessment, and exercise evaluation help establish a baseline and identify changes that may require treatment.

  Confirming the diagnosis

  HRCT is central to evaluation. The typical pattern consists of numerous, diffuse, round, thin-walled cysts distributed throughout both lungs. However, similar appearances can occur in conditions such as Birt-Hogg-Dubé syndrome, pulmonary Langerhans cell histiocytosis, and certain forms of emphysema.

  A serum vascular endothelial growth factor-D (VEGF-D) level can support a diagnosis when it is substantially elevated, particularly in a patient with characteristic HRCT findings. A normal result does not exclude LAM. TSC assessment, abdominal imaging, and renal evaluation are also important because extrapulmonary findings can strengthen diagnostic confidence.

  Lung biopsy is not always necessary. When imaging, clinical features, VEGF-D, and TSC evaluation do not provide a clear answer, transbronchial or surgical biopsy may be considered. Pathologists typically use markers such as HMB-45 and smooth muscle actin to identify LAM cells.

  Clinical feature	Why it matters	Common evaluation
  Diffuse lung cysts	Suggests LAM or another cystic lung disease	HRCT and pulmonary function tests
  Elevated VEGF-D	Supports a noninvasive diagnosis in the right context	Serum biomarker testing
  Recurrent pneumothorax	Indicates fragile cystic lung tissue	Chest imaging and pleural assessment
  Renal angiomyolipoma	May cause bleeding and suggest TSC-associated disease	Abdominal MRI or CT
  Chylous effusion	Reflects lymphatic involvement	Pleural fluid analysis and imaging

  Targeted therapy and monitoring

  Sirolimus, an mTOR inhibitor, is the principal disease-modifying treatment for patients with abnormal or declining lung function, symptomatic chylous complications, or selected large angiomyolipomas. Clinical studies have shown that it can stabilize lung function and improve several disease-related outcomes while treatment continues.

  Therapy requires careful monitoring of drug levels, blood counts, kidney function, lipids, blood pressure, and adverse effects. Mouth ulcers, diarrhea, acne, menstrual changes, infections, and ovarian cysts may occur. Stopping treatment can be followed by renewed disease activity, so decisions about duration should be made through shared planning.

  Not every patient needs immediate medication. Those with preserved lung function and minimal symptoms may be followed with periodic spirometry, diffusion capacity testing, oxygen measurements, and symptom review. A fall in FEV1, worsening breathlessness, recurrent complications, or progressive angiomyolipoma growth may change the treatment approach.

  Managing complications and daily health

  Pneumothorax carries a high risk of recurrence in LAM. Early referral to a thoracic team is important, and pleurodesis is often considered after the first episode rather than waiting for repeated events. This can affect future transplant surgery, so the choice of pleural procedure should be discussed with specialists familiar with LAM.

  Renal angiomyolipomas should be monitored for size, aneurysm formation, and bleeding risk. Embolization or mTOR therapy may be used for lesions requiring intervention. Chylous effusions may require dietary modification, drainage, treatment of the underlying lymphatic problem, or systemic therapy.

  Patients benefit from vaccinations, smoking avoidance, pulmonary rehabilitation, resistance and aerobic exercise adapted to capacity, and prompt treatment of respiratory infections. Oxygen therapy may improve quality of life and exercise tolerance when chronic hypoxemia is present.

  Practical priorities for long-term care

  A coordinated plan helps patients manage a condition that affects the lungs, kidneys, lymphatic system, reproductive decisions, and emotional wellbeing.

  • Arrange regular pulmonary function testing and compare results over time rather than relying on symptoms alone.
  • Review estrogen-containing medicines, pregnancy plans, and fertility treatment with the appropriate specialists.
  • Assess renal angiomyolipomas and other TSC-related features through periodic imaging.
  • Seek urgent care for sudden chest pain, severe breathlessness, faintness, or coughing blood.
  • Connect with a rare lung disease center or patient organization for education and psychosocial support.

  Care should also account for work, travel, exercise, and access to emergency services. Air travel may require assessment after a recent pneumothorax or when oxygen levels are low. A written emergency plan can help patients and local clinicians respond quickly to sudden respiratory symptoms.

  Research directions and specialist collaboration

  Research continues to examine biomarkers that predict progression, treatments that target LAM cell survival, and approaches that may reduce the need for lifelong mTOR inhibition. Better understanding of TSC1 and TSC2 biology could support more individualized treatment, while registries and international collaborations are improving knowledge of long-term outcomes.

  Education remains valuable because LAM is uncommon and expertise is unevenly distributed. The detailed congress program offers a useful example of how respiratory medicine meetings bring together clinical updates, specialist perspectives, and research discussions relevant to rare pulmonary disorders.

  Patients and clinicians should treat LAM as a condition requiring structured follow-up rather than isolated visits. Early recognition, careful surveillance, timely treatment of complications, and access to multidisciplinary expertise can preserve function and support a fuller quality of life. Use these principles to prompt referral to a specialist respiratory team and to build an individualized monitoring plan.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)