Types - LAM
The two types of LAM are tuberous sclerosis complex-LAM (TSC-LAM) and sporadic LAM.
TSC-LAM occurs in some people who have a rare tuberous sclerosis complex (TSC). This type of LAM is more common than sporadic LAM.disease called
Sporadic LAM occurs in people who do not have TSC. This type of LAM is not hereditary, meaning you cannot pass it on to your children.
Causes - LAM
LAM is caused by signs, symptoms, and complications of LAM.in the Tuberous sclerosis complex (TSC) 1 or TSC2 genes. Mutations in these can also lead to tuberous sclerosis complex (TSC). Abnormal TSC genes make proteins that cannot regulate cell growth and the movement of cells in the body. As a result, abnormal cells that behave like muscle cells appear and grow uncontrollably in certain organs or tissues, such as the lungs, kidney, and . The abnormal location and growth of these cells cause the
Researchers also believe that theestrogen plays a role, because the condition affects mostly women of childbearing age. The condition also worsens in a pattern that matches up with the menstrual cycle, during pregnancy, and after use of medicines such as birth control that contain estrogen. After menopause, LAM has also been known to stop progressing in severity.
- Treatment will discuss the latest clinical recommendations about not using hormone therapy to treat LAM.
Risk Factors - LAM
You may have an increased risk for LAM because of your age or sex.
LAM is more common in women of childbearing age, but it can occur after menopause.
LAM is a rare disease that affects mostly women. Women who have TSC have an increased risk of developing TSC-LAM.
Screening and Prevention - LAM
Currently, there are no screening methods to determine who will develop sporadic LAM. Your doctor may recommend screening or genetic tests before you get pregnant if you have TSC or TSC-LAM. If you have TSC, your doctor may also recommend strategies that may slow down the development of LAM.
Tests to screen for TSC-LAM
If you have TSC-LAM, your doctor may recommend genetic counseling before you get pregnant to help you understand the risk of passing TSC and LAM on to your children.
There are no current ways to prevent LAM. If you have TSC, your doctor may recommend that you not smoke or take medicines with hormones such as estrogen. This may help slow down the development of LAM.
Signs, Symptoms, and Complications - LAM
The uncontrolled growth of LAM cells and their effect on nearby body tissues causes the signs, symptoms, and complications of LAM.often start between the ages of 20 and 40. Usually, TSC-LAM is milder than sporadic LAM and may not cause symptoms affecting the lungs. If left untreated, LAM can cause serious and life-threatening complications.
Signs and symptoms
The most common signs and symptoms are:
- Chest pain or aches that may worsen when you breathe in
- Frequent cough that may occur with bloody phlegm
- Lymph nodes that are larger than normal. These usually occur in the abdomen or the chest. Very rarely, larger than normal lymph nodes may occur in locations where they can be felt, or palpated, such as the neck or under the arms.
- or collapsed lung. This potentially life-threatening condition can be a sign as well as a complication of LAM. Pneumothorax occurs when air leaks out of the lung and into the space between the lung and chest wall, an area called the pleural space. In LAM, a pneumothorax can occur if lung cysts rupture through the lining of a lung. Air that collects in the space between the lung and chest wall must be removed to reinflate the lung.
- Shortness of breath that at first may occur only during high-energy activities but over time may happen after simple activities such as dressing and showering
- Wheezing or a whistling sound when you breathe
Complications of LAM can be serious and life threatening. Possible complications include the following:
- Kidney or other . Many women who have LAM get tumors in their kidneys. Women who have LAM may also develop large tumors in the lymph nodes or in other organs such as the liver.
- Pleural effusions. This condition can occur if bodily fluids collect in the pleural space between the lung and the chest wall. The fluid may contain a milky substance called chylothorax. The excess fluid in the chest may cause shortness of breath because the lung has less room to expand.
- Swelling or fluid buildup in the body. This can happen in the abdomen, pelvic area, legs, ankles or feet. Pain may also occur with the swelling.
Diagnosis - LAM
LAM is diagnosed based on your medical history and the results from diagnostic tests and procedures, including blood tests, imaging tests, or aof your lung tissue. To help diagnose your condition, you may want to see a pulmonologist, a doctor who specializes in lung diseases and conditions, who has experience providing care to people who have LAM.
Your doctor will ask you about your medical history to see whether you have signs and symptoms. Your doctor may ask how long you have had symptoms and whether your symptoms have become worse over time.
Diagnostic tests and procedures
Your doctor may order blood tests, breathing tests, and imaging tests to measure how your lung tissue is working, and whether you have LAM. These tests can also show whether your lungs are delivering enough to your blood. Your doctor may also have you undergo other diagnostic tests, such as a lung biopsy, if other tests are inconclusive.
- Chest X-ray. In the early stages of LAM, your chest X-rays may look normal. As the disease gets worse, the X-rays may be used to detect cysts in your lungs and monitor any changes over time. Your doctor may use a chest X-ray to look for complications of LAM, such as a collapsed lung or fluid in your chest.
- High-resolution (CT) scan to provide detailed pictures of your lungs and detect lung cysts, excess fluid, a collapsed lung, or lymph nodes that are larger than normal. The test can also show damage to the lungs. High-resolution CT scans of your abdomen and pelvis can show whether you have tumors in your kidneys, other organs in your abdomen, or your lymph nodes.
- Pulmonary function tests to show how well your lungs are working and measure the amount of air you breathe in and out.
- Blood test for vascular endothelial growth factor D (VEGF-D) to look for increased VEGF-D levels in your blood. VEGF-D can be involved in the spread of tumors by stimulating the growth of new blood vessels. VEGF-D levels of 800 pg/mL (picograms per milliliter) or more may suggest a diagnosis of LAM.
- Biopsy of the lungs to check for LAM cells. There are several types of lung biopsy. Open lung biopsy involves making a cut in your chest wall between your ribs. With transbronchial biopsy, your doctor will insert a long tube down your windpipe and into your lungs. Your doctor also can diagnose LAM using the results from biopsies of other tissues such as from the lymph nodes. Video-assisted thoracoscopic surgery (VATS) is often done in lieu of a more invasive open lung surgery that requires a large chest incision, or after transbronchial biopsy that may not definitively diagnose LAM. This surgery does require general anesthesia to make you sleep. Your doctor will insert a small, lighted tube into little cuts made in your chest wall.
Tests for other medical conditions
Your doctor may need to order other diagnostic tests to determine whether you have TSC or to rule out another condition.
- CT scans or magnetic resonance imaging (MRI) scans of your head to help your doctor determine whether you have TSC. People who have TSC often have tumors in the brain and other parts of the body.
- Genetic testing to identify mutations in your TSC1 and TSC2 genes can help your doctor confirm that you have LAM and not another lung disease.
- Thoracentesis to collect fluid samples from the lining of your lungs. If your chest imaging tests show that you have pleural effusions, your doctor may order a pleural fluid analysis. For this test, a fluid sample is taken from the pleural space, which is a thin space between the two layers of tissue that line the lungs and chest cavity. The fluid is studied for a milky substance called a chylothorax.
Treatment - LAM
Your doctor may prescribe sirolimus to treat your symptoms or bronchodilators to help open up your airways.
- mTOR inhibitors, such as sirolimus, to help regulate the abnormal growth and movement of LAM cells. Sirolimus stabilizes lung function and improves quality of life, shrinks abnormal kidney and lymph node growths, and reduces abnormal fluid in the lungs. Sirolimus may cause side effects such as diarrhea, nausea, acne, high blood cholesterol, swelling of your mouth and lips, and fluid buildup in your legs. Sirolimus may also affect the function of your ovaries, liver, and kidneys and increase your risk of infections. If you have LAM, talk with your doctor about the benefits and risks of sirolimus, and whether it is an option for you.
- Bronchodilators to relax the muscles around the airways if you are having trouble breathing or are wheezing. These medicines help the airways open up, making it easier for you to breathe.
The following medicines or procedures are not recommended to treat LAM:
- Doxycycline did not show a clinical benefit when used to treat LAM.
- Hormone therapies including certain medicines—progestins, gonadotropin-releasing hormone (GnRH) agonists, and selective estrogen receptor modulators (SERMs) such as tamoxifen—or surgical procedures such as removing one or both ovaries. While these therapies had previously been used to treat LAM, newer analyses suggest that they may not benefit all people who have LAM. If you are taking any of these hormone medicines or are considering a surgical procedure to remove your ovaries, talk to your doctor.
Living With will discuss medicines your doctor may prescribe to help prevent complications such as osteoporosis.
Your doctor may recommend oxygen therapy to increase the amount of oxygen your lungs receive and deliver to your blood. At first, you may need oxygen only while exercising. It may also help to use it while sleeping. Eventually, you may need full-time oxygen therapy.
Some patients who have severe lung damage due to advanced LAM may be eligible for a lung transplant. While lung transplants can improve lung function and quality of life for eligible patients, they have a high risk of complications, including infections and rejection of the transplanted lung by the body.
- Research for Your Health will discuss how we are using current research and advancing research to treat people who have LAM.
- Participate in NHLBI Clinical Trials will discuss our open and enrolling clinical studies that are investigating treatments for LAM.
- Living With will discuss what your doctor may recommend including life-long lifestyle changes and medical care to prevent your condition from getting worse or causing complications.
Living With - LAM
If you have been diagnosed with LAM, it is important to follow your treatment plan and receive regular follow-up care. Your doctor will monitor your condition to see whether it is stable or getting worse and causing serious complications. Also, your doctor may recommend other medical care, including vaccines, lifestyle changes, and pregnancy and birth control planning.
The outlook for women who have LAM is much better today than it was in the past. Advances in diagnosis and treatment allow many women who have LAM to live longer with fewer complications.
Receive routine follow-up care
Your doctor may recommend vaccines to prevent lung infections, lifestyle changes to improve your overall health and avoid some complications, tests or medicines to care for your bones, and pregnancy and birth control options.
- Follow your treatment plan. It is important that you follow your doctor’s instructions for your treatment. It may take several months for you to respond to treatment. If you stop taking your medicines your symptoms may return or get worse.
- Get regular vaccinations for lung health. To help prevent additional problems with your lungs, talk with your doctor about getting a pneumococcal pneumonia vaccine and a yearly influenza or flu shot.
Monitor your condition
If you have LAM, it is important for you to have routine follow-up care so your doctor can monitor your condition. In the early stages of LAM, you usually can do your normal daily activities. These may include attending school, going to work, and doing common physical activities such as walking up stairs. In the later stages of LAM, you may find it harder to be active and you may need oxygen therapy.
Serious and possibly life-threatening complications can occur if you have LAM. Women who have LAM may develop pneumothorax. LAM may cause death from respiratory failure. Read more about possible signs, symptoms, and complications of LAM.
Take care of your mental health
Living with LAM may cause fear, anxiety, depression, and stress. Your doctor can evaluate how your condition is affecting your activity level and mental health. To improve your quality of life, your doctor may recommend steps you can take.
- Getting counseling, particularly cognitive behavioral therapy.
- Joining a patient support group, which may help you adjust to living with LAM. You can see how other patients manage similar symptoms and their condition. Talk with your doctor about local support groups or check with an area medical center.
- Seeking support from family and friends can help relieve stress and anxiety. Let your loved ones know how you feel and what they can do to help you.
- Taking medicines or other treatments. Your doctor may recommend medicines, such as antidepressants, or other treatments that can improve your quality of life.
Adopt healthy lifestyle changes
If you have LAM, it is important that you take good care of your health. Your doctor may recommend that you adopt the following healthy lifestyle changes.
- Healthy eating to improve overall health.
- Being physically active. Physical activity improves bone mineral density, muscle strength, flexibility, and posture. Before starting any exercise program, ask your doctor about what level of physical activity is right for you.
- Quitting smoking. If you smoke, quit. Also, try to avoid other lung irritants, such as dust, chemicals, and secondhand smoke. Visit Smoking and Your Heart and the National Heart, Lung, and Blood Institute's Your Guide to a Healthy Heart. For free help quitting smoking, you may call the National Cancer Institute's Smoking Quitline at 1-877-44U-QUIT (1-877-448-7848).
Your doctor may recommend these lifestyle changes as part of a larger pulmonary rehabilitation program that your doctors oversee.
Prevent or treat complications over your lifetime
Your doctor may recommend taking the following steps to prevent complications from LAM.
- Avoid air travel if you have symptoms of a collapsed lung. This includes sudden shortness of breath or chest pain. Talk to your doctor before traveling to places where the amount of oxygen in the air is low.
- Avoid scuba diving, which may increase your risk of complications.
- Care for your bones. Some women who have LAM may be at risk for . Your doctor may order tests to measure your bone density. If you have lost bone density, your doctor may prescribe medicines or calcium and vitamin D supplements to prevent more bone loss.
Your doctor may recommend procedures to treat the following complications of LAM:
- Pleural effusion. Your doctor may recommend removal of fluid from your chest, called thoracentesis, or abdomen, called paracentesis. This may help relieve discomfort and shortness of breath. Your doctor often can remove the fluid with a needle and syringe. If large amounts of fluid buildup in your chest, your doctor may have to insert a tube into your chest to remove the fluid.
- Pneumothorax. Removing air from your chest may relieve shortness of breath and chest pain caused by a pneumothorax. Removal of air in an abnormal location in your chest usually is done with a tube. The tube is inserted into your chest between your ribs. Often, the tube is attached to a suction device. If this procedure does not work, or if your lungs repeatedly collapse, you may need surgery to prevent a pneumothorax or to assist re-expansion of your lung.
- Kidney tumors. Kidney tumors, or angiomyolipomas, often do not cause symptoms, but sometimes they can cause ongoing pain or bleeding. If this happens, you may need surgery to remove some of them. If bleeding is not too severe, a radiologist often can block the blood vessels feeding the kidney tumors. This may cause them to shrink.
Pregnancy and birth control planning
Because hormone changes during pregnancy can worsen LAM, it is important to talk to your pulmonologist and obstetrician, a doctor that specializes in pregnancy and childbirth, before you get pregnant.
Most doctors do not recommend birth control pills containing estrogen to women who have LAM because estrogen is thought to contribute to or worsen LAM. If you have LAM, talk to your doctors about birth control options.
Return to Treatment to review possible treatment options for your LAM.
Research for Your Health
Improving health with current research
Learn about some of the ways the NHLBI continues to translate current research into improved health for people who have LAM. Research on this topic is part of NHLBI’s broader commitment to advancing lung disease scientific discovery.
- Pioneering the Discovery of Treatments for LAM. In 2011, the NIH-funded Multicenter International LAM Efficacy of Sirolimus (MILES) trial published key findings that showed sirolimus to be a safe and effective treatment for LAM. This ground-breaking discovery helped establish guidelines for treating LAM, and has helped improve the quality of life of women who have LAM. We continue to investigate new treatment options for LAM. Read Sirolimus Therapy Alleviates Symptoms of Lung Disease LAM and Bronchodilators combined with sirolimus lead to more stable lung function for more information.
- Monitoring the Quality of Life of Women Who Have LAM. We have supported research to better understand the complications of LAM and to determine the effects that these complications have on quality of life. NHLBI-funded studies have examined the use of various assessment tools to monitor the development of complications. Our studies have shown that women who have LAM often experience frustration and worry over worsening symptoms. This research has helped doctors address the emotional health of women living with LAM.
- Improving LAM Diagnosis. LAM can be difficult to diagnose because its symptoms can closely resemble those of other respiratory diseases. We have supported research to increase the number of techniques available to diagnose LAM. This research includes the use of transbronchial lung biopsy to collect lung tissue samples and computer software to analyze lung CT scans.
- Trans-NIH funding of the Rare Lung Diseases Consortium (RLDC). The NHLBI co-funds some RLDC activities with NIH’s National Center for Advancing Translational Sciences. Through funding the RLDC, the NHLBI is supporting new clinical trials for LAM.
Learn about some of the research contributions we have made over the years that have improved clinical care for people who have LAM.
- NHLBI Working Group on LAM. In 1995, the NHLBI organized a working group on LAM to determine what was needed to help find the cause and possible treatments for LAM. A critical recommendation from this group was to create a national LAM registry to store tissue and other biological specimens from LAM patients as a way to support basic and clinical research.
- NHLBI support for the LAM Registry and National Disease Research Interchange. In 1997, the NHLBI co-funded this national registry to obtain clinical data and blood and tissue samples from LAM patients. In 2007, management of the data and materials form this registry were transferred to the National Disease Research Interchange (NDRI). The NHLBI helps fund NDRI activities, which include the collection and distribution of fresh LAM lung tissue to qualified researchers.
- Understanding the causes of LAM. We have funded research to explore further the role of the TSC1 and TSC2 genes in causing LAM. We have also supported workshops to discuss the role of female hormones and the Study links heart failure biomarker to two rare tumor-causing diseases and Scientists Seek to Understand Lymphatic System’s Impact on Other Organ Systems for more information. in the development of LAM. Read
- Advancing the Understanding of Lung Development. The NHLBI-funded Molecular Atlas of Lung Development Program (LungMAP) is integrating many datasets to build a molecular map of the developing lung in both humans and mice. The program is helping advance lung research, in part through its web-based data resource, called BREATH, which allows users to access LungMAP data and findings. LungMAP has data that examines the TSC1 and TSC2 genes, which are linked to the development of LAM.
Advancing research for improved health
In support of our mission, we are committed to advancing LAM research in part through the following ways.
- We perform research. Our Division of Intramural Research, which includes investigators from the Pulmonary Branch, and its Laboratory of Translational Research, performs research on LAM.
- We fund research. The research we fund today will help improve our future health. Our Division of Lung Diseases, which includes the Lung Biology and Disease Branch, oversees much of the research on LAM we fund, helping us to understand and manage rare lung diseases such as LAM. Search the NIH RePORTer to learn about research the NHLBI is funding on LAM.
- We stimulate high-impact research. The NHLBI Strategic Vision highlights ways we may support research over the next decade.
Learn about other exciting research areas the NHLBI is exploring about LAM.
- Biomarkers to predict which LAM patients will respond to sirolimus treatment. Researchers from the NHLBI-funded MILES trial are trying to see whether VEGF-D can be a biomarker for LAM severity and help doctors predict which patients will respond well to sirolimus treatment. Early findings suggest that patients who show decreased VEGF-D levels over the course of sirolimus treatment are more likely to have improved lung function than patients whose VEGF-D levels are unaffected by sirolimus treatment.
- Exploring the molecular role of estrogen and progesterone in LAM to find new treatments. Because LAM primarily affects women, estrogen may play a role in this condition. NHLBI-funded research has discovered that estrogen activates signaling pathways in people who have LAM. We support research to determine whether these pathways are possible targets for new therapies for LAM. We also support research to discover the role of progesterone, another female hormone, in the development of LAM.
- Improving our understanding of the genes that control LAM development. We fund research to explore the ways in which mutations in the TSC1 and TSC2 genes can lead to the abnormal cell growth that causes LAM. This includes identifying other genes that work together with TSC1 and TSC2, and studying mice that develop symptoms of LAM.
- Using changes in the to help diagnose and treat LAM. LAM is often not diagnosed early because its symptoms can closely resemble the symptoms of several other respiratory diseases. This delay in diagnosing LAM can lead to delayed treatment and worsening symptoms and complications. We support research to explore whether LAM causes changes in a woman’s immune system that can be used for early diagnosis and as targets for treatment.
Participate in NHLBI Clinical Trials
We lead or sponsor many studies on LAM. See if you or someone you know is eligible to participate in ourand .
Trials at the NIH Clinical Center
Monitoring sirolimus dosages to treat LAM
Albuterol in patients who have LAM
Genetic causes of lung damage in patients who have LAM
To learn more about clinical trials at the NIH Clinical Center or to talk to someone about a study that might fit your needs, call the Office of Patient Recruitment 800-411-1222.
Are you an adult woman who would like to help develop methods to prevent the worsening of LAM?
Are you an adult woman willing to help improve treatments for LAM?
Are you an adult woman diagnosed with LAM who wants to support future studies of a new treatment?
After reading our LAM Health Topic, you may be interested in additional information found in the following resources.
Related Health Topics
- Lymphangioleiomyomatosis (National Library of Medicine [NLM], Genetics Home Reference)
- Lymphangioleiomyomatosis (LAM) (American Lung Association)
- Pneumococcal Vaccination (Centers for Disease Control and Prevention [CDC])
- Seasonal Influenza (Flu) Vaccination and Preventable Disease (CDC)
- Tuberous sclerosis (NLM, MedlinePlus)
- Tuberous Sclerosis Fact Sheet (National Institute of Neurological Disorders and Stroke)