What Is LAM?

LAM, or lymphangioleiomyomatosis (lim-FAN-je-o-LI-o-MI-o-ma-TO-sis), is a rare lung disease. It mostly affects women in their mid-thirties and forties.

In LAM, abnormal, muscle-like cells begin to grow out of control in certain organs or tissues, especially the lungs, lymph nodes, and kidneys.

Over time, these LAM cells can grow throughout the lungs and destroy the normal lung tissue. As a result, air can’t move freely in and out of the lungs. In some cases, this means the lungs can’t supply the body’s other organs with enough oxygen.

Overview

There are two forms of LAM. Sporadic LAM occurs for unknown reasons. LAM also can occur in women who have a rare disease called tuberous sclerosis complex (TSC). Women who have TSC often have a milder form of LAM.

About 6 out of 10 women who have LAM develop pneumothorax (noo-mo-THOR-aks), or collapsed lung. In this condition, air leaks out of a lung and into the space between the lung and the chest wall (the pleural space).

This condition can cause pain and shortness of breath. Sometimes one lung will collapse over and over again. Pneumothorax is a serious condition that usually requires treatment and can sometimes be life threatening.

Normal Lungs and Lungs With LAM

Figure A shows the location of the lungs and airways in the body. The inset image shows a cross-section of a healthy lung. Figure B shows a view of the lungs with LAM and a collapsed lung (pneumothorax). The inset image shows a cross-section of a lung with LAM.

Many women who have LAM get tumors called angiomyolipomas (AN-je-o-my-o-li-PO-mas), or AMLs, in their kidneys. Women who have LAM also may develop:

• Growths in other organs, including the liver and brain
• Large tumors in their lymph nodes
• A buildup of fluid in their chests, abdomens, or pelvic areas

Outlook

LAM has no cure. The disease tends to worsen over time. How quickly the disease worsens varies from woman to woman. LAM may lead to death from respiratory failure. Lung transplant is a treatment option for women whose lungs have been damaged by LAM.

Not long ago, doctors thought women who had LAM wouldn't live more than 10 years following diagnosis. They now know that some women may survive for more than 20 years after diagnosis.

Doctors have learned a lot about LAM in recent years. They're now able to diagnose the condition earlier. Support services also are now available to help improve the quality of life for women who have LAM.

Researchers continue to explore and test new treatments for LAM.

What Causes LAM?

The cause of LAM and why it mainly affects women isn’t known. Recent studies show that sporadic LAM has some of the same traits as another rare disease called tuberous sclerosis complex (TSC). This has begun to provide some valuable clues about what causes LAM.

The common features of sporadic LAM and TSC are:

• Kidney growths. People who have TSC get growths in their kidneys. These growths are the same as the angiomyolipomas that many women who have LAM get in their kidneys.
• Lung cysts. About 1 out of every 3 women who has TSC gets cysts in her lungs. These cysts are the same as the ones that women who have sporadic LAM get in their lungs. When a woman who has TSC gets these cysts in her lungs, the lung disease is called TSC-associated LAM or TSC–LAM.

TSC is a genetic disease. A defect in one of two genes causes the disease. These genes are called TSC1 and TSC2. They normally make proteins that control cell growth and movement in the body. In people who have TSC, the genes are abnormal. The proteins that the genes make can’t control cell growth and movement.

Women who have LAM also have abnormal TSC1 and TSC2 genes. Researchers have found that these genes play a role in causing LAM. This finding is leading to new treatments for LAM.

Because LAM mostly affects women, the hormone estrogen also may play a role in causing LAM.

Who Is At Risk for LAM?

Except for rare cases, LAM only affects women. More than 70 percent of women who develop LAM are between the ages of 20 and 40 when they begin to have symptoms. However, LAM can occur in women as old as 80.

More than 800 women in the United States have been diagnosed with either sporadic LAM or TSC–LAM.

Many more women may have LAM and not know it. They may have been wrongly diagnosed with another, more common lung disease, such as emphysema (em-fi-SE-ma), asthma, or bronchitis (brong-KI-tis).

LAM affects about 3 out of every 10 women who have TSC. Thus, as many as 10,000 women in the United States who have TSC also may have undiagnosed LAM. Many of these women may have mild cases of LAM that don’t cause symptoms. Not everyone who has TSC and LAM has lung symptoms.

What Are the Signs and Symptoms of LAM?

The uncontrolled growth of LAM cells and their effect on nearby body tissues causes the signs and symptoms of LAM. The most common signs and symptoms are:

• Shortness of breath, especially during activity. At first, shortness of breath may occur only during high-energy activities. Over time, you may have trouble breathing even during simple activities, such as dressing and showering.
• Chest pain or aches. This pain may be worse when you breath in.
• Frequent cough. This may occur with bloody phlegm (a sticky fluid).
• Wheezing (a whistling sound when you breathe).

Other signs and symptoms of LAM include:

• Pneumothorax, or collapsed lung. This condition 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.
• Pleural effusions. This condition can occur if bodily fluids collect in the space between the lung and the chest wall. Often the fluid contains a milky substance called chyle. The excess fluid in the chest may cause shortness of breath because the lung has less room to expand.
• Blood in the urine. This sign may occur in women who have kidney tumors called angiomyolipomas.
• Enlarged lymph nodes. These usually occur in the abdomen or the chest. Very rarely, enlarged lymph nodes may occur in locations where they can be felt, such as the neck or under the arms.
• Abdominal swelling, sometimes with pain.
• Swelling in the legs, ankles, or feet.

Other diseases also can cause many of these signs and symptoms. It’s important to see your doctor and find out what’s causing these problems.

How Is LAM Diagnosed?

Methods for diagnosing LAM have improved. It's now possible to diagnose the disease at an early stage. LAM is diagnosed based on your signs and symptoms and the results from tests and procedures.

If you have LAM, you may need to see a pulmonologist. This is a doctor who specializes in lung diseases and conditions. These specialists usually are located at major medical centers.

Signs and Symptoms

Your doctor will ask about your signs and symptoms related to LAM. He or she may ask how long you’ve had them, and whether they’ve become worse over time.

Many of LAM’s signs and symptoms are the same as those of other diseases, such as asthma, emphysema, and bronchitis. It’s important for your doctor to rule out those conditions before making a final diagnosis.

Diagnostic Tests and Procedures

To diagnose LAM, you usually will have tests to show how well your lungs are working and what your lung tissue looks like.

These tests can show whether your lungs are getting enough oxygen to your blood. You also may need tests to check for complications of LAM.

Tests for Lung Function

Lung function tests. For lung function tests, you breathe through a mouthpiece into a machine called a spirometer (spi-ROM-e-ter). The spirometer measures the amount of air you breathe in and out.

Other lung function tests can show about how much air your lungs can hold and how well your lungs deliver oxygen to your blood.

Blood tests. Your doctor may take a blood sample from a vein in your arm to look at your blood cells and blood chemistry.

Pulse oximetry. For this test, a small sensor is attached to your fingertip. The sensor can give an estimate of how much oxygen is in your blood while you’re sitting still and while you’re walking.

Tests To Check for Complications or Detect LAM Cells

Chest x ray. A chest x ray takes pictures of your heart and lungs. It can show a collapsed lung or fluid in your chest. In the early stages of LAM, your chest x rays may look normal. As the disease gets worse, the x rays may show cysts in your lungs.

High-resolution CT (HRCT) scan. The most useful imaging test for diagnosing LAM is an HRCT scan. This test creates a computer-generated picture of your lungs. The picture shows more detail than the pictures from a chest x ray.

A HRCT scan can show cysts, shadows of cell clusters, excess fluid, a collapsed lung, and enlarged lymph nodes. It also can show how much normal lung tissue has been replaced by the LAM cysts.

HRCT scans of your abdomen and pelvis can show whether you have growths in your kidneys, other abdominal organs, or lymph nodes.

Procedures To Look for LAM Cells

The results from the above tests, along with information about your signs, symptoms, and medical history, are sometimes enough for your doctor to diagnose LAM.

However, if more information is needed, the most useful method involves looking at samples of your lung tissue for LAM cells.

You may want to see a doctor who specializes in LAM for this test. Several procedures can be used to get a sample of lung tissue.

Video-assisted thoracoscopy (tho-rah-KOS-ko-pe). In this procedure, also called VAT, your doctor inserts a small, lighted tube into little cuts made in your chest wall. This lets him or her look inside your chest and snip out a few small pieces of lung tissue.

This procedure is done in a hospital. The procedure isn’t major surgery, but it does require general anesthesia (that is, you’re temporarily put to sleep during the procedure).

Open lung biopsy. In this procedure, your doctor removes a few small pieces of lung tissue through a cut made in your chest wall between your ribs. An open lung biopsy is done in the hospital, while you’re temporarily put to sleep.

This procedure is rarely done anymore because the recovery time is much longer than the recovery time from VAT.

Transbronchial biopsy. In this procedure, your doctor inserts a long, narrow, flexible, lighted tube down your windpipe and into your lungs. He or she then snips out bits of lung tissue with a tiny device.

This procedure usually is done in a hospital. Your mouth and throat are numbed to prevent pain. You usually can go home right after the procedure.

The amount of tissue that’s removed is very small, so this test doesn’t always provide enough information.

Other biopsies. LAM also can be diagnosed using the results of other tissue biopsies, such as biopsies of lymph nodes or lymphatic tumors called lymphangiomyomas.

Other Tests

If you’re diagnosed with sporadic LAM, your doctor may advise you to have a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of your head. These tests can help screen for underlying tuberous sclerosis complex (TSC).

CT and MRI scans will reveal TSC in only a small fraction of people who are diagnosed initially with sporadic LAM.

Researchers are exploring other tests that may help diagnose LAM. These tests include blood tests for the LAM cells or a blood vessel growth factor called VEGF-D.

How Is LAM Treated?

Currently, no treatment is available to stop the growth of the cysts and cell clusters that occur in LAM.

An experimental medicine, rapamycin (sirolimus), shows promise in shrinking tumors in the kidneys of women who have LAM. Studies are under way to find out if this medicine improves lung function in women who have LAM.

Most treatments for LAM are aimed at easing symptoms and preventing complications. The main treatments are:

• Medicines to improve air flow in the lungs and reduce wheezing
• Oxygen therapy
• Procedures to remove fluid from the chest or abdomen and stop it from building up again
• Procedures to shrink angiomyolipomas (AMLs)
• Lung transplant
• Hormone therapy

Medicines

Medicines That Help You Breathe Better

Certain medicines can help open your lungs so that you can breathe better.

Bronchodilators are medicines that relax the muscles around the airways. This helps the airways open up, making it easier for you to breathe. About 1 out of 4 women who has LAM breathes better with the use of bronchodilators. Lung function tests can sometimes show whether these medicines are likely to help you.

Medicines That Prevent Bone Loss

Women who have LAM are at risk for a bone-weakening condition called osteoporosis (OS-te-o-po-RO-sis). This is in part because many LAM therapies block the estrogen action needed to keep bones strong.

To prevent osteoporosis, your doctor may measure your bone density. If you have lost bone density, your doctor may prescribe medicines that prevent bone loss. He or she also may prescribe calcium and vitamin D supplements.

Rapamycin

Rapamycin (sirolimus) is the first medicine to be tested as a treatment for slowing or stopping the growth of LAM cell clusters.

This medicine was originally developed to prevent the immune system from rejecting kidney transplants. However, studies show that rapamycin helps regulate the abnormal growth and movement of LAM cells.

A study on a small number of women who have LAM and/or TSC found that rapamycin shrank kidney tumors by 50 percent over 1 year. The medicine also seemed to improve lung function in some women who have LAM.

However, the study showed that the medicine had a number of side effects. Thus, more research is needed to see how well this medicine works in women who have LAM, and whether its risks outweigh its benefits.

Oxygen Therapy

If the level of oxygen in your blood is low, your doctor may suggest oxygen therapy. Oxygen usually is given through nasal prongs or a mask. At first, you may only need oxygen while exercising. It also may help to use it while sleeping. Over time, you may need full-time oxygen therapy.

A standard exercise stress test or a 6-minute walk test can show whether you need oxygen while exercising. A 6-minute walk test measures the distance you can walk in 6 minutes. An exercise stress test measures how well your lungs and heart work while you walk on a treadmill or pedal a stationary bike.

You also may need a blood test to show what your oxygen level is and how much oxygen you need.

Procedures To Remove Air or Fluid From the Chest or Abdomen

Several procedures help remove air or fluid from your chest and abdomen. These procedures also help prevent air or fluid from building up again.

Removing fluid from your chest or abdomen may help relieve discomfort and shortness of breath. The procedure to remove fluid from the chest is called thoracentesis (THOR-a-sen-TE-sis). The procedure to remove fluid from the abdomen is called paracentesis (PAR-a-sen-TE-sis).

Your doctor often can remove the fluid with a needle and syringe. If large amounts of fluid build up in your chest, your doctor may have to insert a tube into your chest to remove the fluid.

Removing air from your chest may relieve shortness of breath and chest pain caused by a collapsed lung. Your doctor usually can remove the air with a tube. The tube is inserted into your chest between your side ribs. Often, the tube is attached to a suction device. If this procedure doesn't work, or if your lungs collapse often, you may need surgery.

If fluid and air often leak into your chest, your doctor may inject a chemical at the site of the leakage. The chemical fuses your lung and chest wall together. This removes the space for leakage.

Your doctor may do this procedure at your bedside in the hospital. You will be given medicine to prevent pain. The procedure also may be done in an operating room using video-assisted thoracoscopy. In this case, you will temporarily be put to sleep for the procedure.

Procedures To Remove or Shrink Angiomyolipomas

AMLs often don’t cause symptoms, but sometimes they can cause ongoing pain or bleeding. If this happens, you may need surgery to remove some of the tumors.

If bleeding isn’t too severe, a radiologist can often block the blood vessels feeding the AMLs. This may cause them to shrink.

Lung Transplant

A lung transplant improves lung function and quality of life in patients who have advanced LAM.

Lung transplants have a high risk of complications. These include infections and rejection of the transplanted lung by the body.

Studies suggest that more than three-quarters of women with LAM who receive a lung transplant survive for at least 3 years.

In a few cases, doctors have found LAM cells in the newly transplanted lungs and other parts of the body. However, LAM cells don’t seem to stop the transplanted lung from working.

Hormone Therapy

Estrogen is thought to play a role in causing LAM. Thus, your doctor may want to treat you with a hormone therapy that limits the effects of estrogen on your body.

Hormone therapy can be taken as a pill or with regular shots. Some doctors also suggest surgery to remove the ovaries. This causes menopause and greatly reduces estrogen levels in the body.

Unfortunately, at this time, there’s no clear evidence that this type of treatment is effective for LAM.

Living With LAM

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, it may be harder for you to be active. You also may need oxygen therapy full time.

Ongoing Care

Getting ongoing medical care is important. You may need to see a pulmonologist. This is a doctor who specializes in treating lung diseases and conditions. These specialists usually are located at major medical centers.

Take steps to care for your lungs. Get a flu shot every year and a pneumonia shot every 5 years.

Lifestyle Changes

Take good care of your health. This means following the same healthy lifestyle that’s recommended for all Americans. Follow a healthy eating plan, get as much physical activity as you can, and get plenty of rest. If you smoke, try to quit. Talk to your doctor about programs and products that can help you quit smoking.

You also should check with your doctor before traveling by air or traveling to areas where medical attention isn’t readily available. Also, talk to your doctor before traveling to places where the amount of oxygen in the air is low.

Pregnancy and Birth Control

If your lung function is normal, pregnancy may be an option. However, hormones during pregnancy might worsen your LAM. Therefore, you should discuss a possible pregnancy with both a pulmonologist who specializes in LAM and your obstetrician.

Most doctors don’t recommend birth control pills containing estrogen to women who have LAM. Talk to your doctor about birth control options.

Support Groups

You may find it helpful to join a LAM support group. Information about patient support groups is available from the National Heart, Lung, and Blood Institute (NHLBI) Health Information Center at 301–592–8573 or the National Institutes of Health/NHLBI Pulmonary-Critical Care Branch at
1–877–NIH–LUNG (1–877–644–5864), extension 3.

Key Points

• LAM, or lymphangioleiomyomatosis, is a rare lung disease. It mostly affects women in their mid-thirties and forties.
• In LAM, abnormal, muscle-like cells begin to grow out of control in certain organs or tissues, especially the lungs, lymph nodes, and kidneys.
• Over time, these LAM cells can grow throughout the lungs and destroy the normal lung tissue. As a result, air can’t move freely in and out of the lungs. In some cases, this means the lungs can’t supply the body’s other organs with enough oxygen.
• LAM also can lead to pneumothorax (collapsed lung), angiomyolipomas (AMLs), growths in certain organs, large tumors in the lymph nodes, and a buildup of fluid in the chest, abdomen, or pelvic area.
• There are two forms of LAM. Sporadic LAM occurs for unknown reasons. LAM also can occur in women who have a rare disease called tuberous sclerosis complex (TSC). Women who have TSC often have a milder form of LAM.
• The cause of LAM and why it mainly affects women isn’t known. Sporadic LAM has some of the same traits as TSC. The abnormal genes that cause TSC also play a role in causing LAM.
• Except for rare cases, LAM only affects women. More than 70 percent of women who develop LAM are between the ages of 20 and 40 when they begin to have symptoms. LAM affects about 3 out of every 10 women who have TSC.
• The uncontrolled growth of LAM cells and their effect on nearby body tissues causes the signs and symptoms of LAM. The most common signs and symptoms are shortness of breath, especially during activity; chest pain or aches; frequent cough; and wheezing.
• Methods for diagnosing LAM have improved. It’s now possible to diagnose the disease at an early stage. LAM is diagnosed based on your signs and symptoms and the results from tests and procedures.
• Currently, no treatment is available to stop the growth of the cysts and cell clusters that LAM causes. Most treatments for LAM are aimed at easing symptoms and preventing complications. Treatments include medicines, oxygen therapy, procedures to remove fluid from the chest or abdomen, procedures to remove AMLs, lung transplant, and hormone therapy.
• An experimental medicine, rapamycin (sirolimus), shows promise in shrinking tumors in the kidneys of women who have LAM. Studies are under way to find out whether this medicine improves lung function in women who have LAM.
• In the early stages of LAM, you usually can do your normal daily activities. In the later stages of LAM, it may be harder for you to be active. You also may need oxygen therapy full time. If you have LAM, you can take steps to care for yourself. Get ongoing medical care. Following a healthy lifestyle, including a healthy eating plan.
• Researchers continue to look for the causes of LAM and for better treatments.

Links to Other Information About LAM

Non-NHLBI Resources

• Lung Diseases (MedlinePlus)
• Tuberous Sclerosis Complex (MedlinePlus)
• Tuberous Sclerosis Fact Sheet (National Institute of Neurological Disorders and Stroke)

Clinical Trials

• Current Research (ClinicalTrials.gov)
• Patient Recruitment for Studies Conducted by NHLBI, NIH