WHAT IS PULMONARY LYMPHANGIOLEIOMYOMATOSIS (LAM)?

Lymphangioleiomyomatosis (LAM) is a rare lung disease that was first described in the medical literature by von Stossel in 1937. The disease is characterized by an unusual type of muscle cell that invades the tissue of the lungs, including the airways, and blood and lymph vessels.

Over time, these muscle cells form into bundles and grow into the walls of the airways, and blood and lymph vessels, causing them to become obstructed.

Although these cells are not considered cancerous, they act somewhat like cancer cells in that they grow uncontrollably throughout the lung. Over time, the muscle cells block the flow of air, blood, and lymph to and from the lungs, preventing the lungs from providing oxygen to the rest of the body.

Kidney tumors that are often asymptomatic may also be found in patients with LAM.

Lymphangioleiomyomatosis is pronounced lim - fan' je - o - li' o - mi' o - ma - to' sis. Lymph and angio refer to the lymph and blood vessels. Leiomyomatosis refers to the formation of the bundles of the unusual muscle cells.

The cause of LAM is not known.

HOW COMMON IS LAM?

LAM affects almost exclusively women of childbearing age, although several cases have been reported in which the disease was thought to have developed after menopause. The international literature also includes reports of a few cases in men.
The precise number of people who have LAM is not known. It has been estimated that there may be up to several hundred women in the United States with the disease.

It also has been suggested that LAM has become more common during the past 5 to 10 years, although it may be that doctors are doing a better job of diagnosing it.

WHAT ARE THE SYMPTOMS OF LYMPHANGIOLEIOMYOMATOSIS?

A common symptom of LAM is shortness of breath (dyspnea) with physical activity. In the early stages of disease, the person with LAM may experience shortness of breath only during strenuous exercise, but as the disease advances, there may be shortness of breath even at rest.

Another common symptom is chest pain, and occasionally patients cough up small amounts of blood.

The symptoms associated with LAM are caused by the excessive growth of the muscle cells around the airways, and blood and lymph vessels. The excess muscle cells can block the airways, trapping air in the smallest air compartments in the lung (alveoli) and causing the person with LAM to have difficulty moving air out of the lungs.

This results in a breakdown of the lung tissue and the formation of small cysts (air-filled cavities).

Cysts near or on the surface of the lung (blebs) can rupture and, as air leaks from the lung into the chest cavity (pneumothorax), the lung or a part of the lung can collapse, causing pain. If the amount of air that leaks out is small, the lung may seal over the space and re-expand itself.

If air continues to leak into the chest cavity, however, it may be necessary to re-expand the collapsed portion of the lung by removing the air that has leaked into the chest cavity. This is an in-patient procedure, done using a tube inserted through the chest wall into the chest cavity.

The excessive muscle growth may also block blood vessels in the lung, causing them to become distended with blood and even to rupture. This can result in the patient coughing up blood-stained sputum or blood (hemoptysis).

Obstruction of the lymphatic vessels by the excess muscle growth can lead to leakage of fluid into the chest cavity (pleural effusion). The fluid may be straw-colored (lymph), or fat-containing, milky white (chyle), or pinkish-red if it contains blood.

A physician can remove some of this fluid with a needle and syringe to determine its composition and origin. If large amounts of this fluid accumulate in the chest cavity, it may have to be removed through a tube surgically inserted into the chest.

It is estimated that 30 to 50 percent of LAM patients will develop leakage of air into the chest cavity (pneumothorax), and up to 80 percent will have leakage of fluid into the chest cavity (pleural effusions). Coughing up blood-stained sputum or blood (hemoptysis) occurs less frequently.

WHAT IS THE COURSE OF LYMPHANGIOLEIOMYOMATOSIS?

LAM is generally progressive, leading to increasingly impaired lung function. The rate of development can vary considerably among patients. As the disease advances, there is more extensive growth of muscle cells throughout the lung and repeated leakage of fluid into the chest cavity (pleural effusions).

As an increasing number of cysts are formed, the lung takes on a honeycomb appearance. The survival time following the diagnosis of LAM is uncertain. It has been reported to be less than 10 years, but new reports show patients living more than 20 years after diagnosis. The reason for the apparently increased survival time is unknown.

HOW IS LYMPHANGIOLEIOMYOMATOSIS DIAGNOSED?

The diagnosis of LAM can be difficult because many of the early symptoms are similar to those of other lung diseases, such as asthma, emphysema, or bronchitis. Often the person with LAM first goes to the physician complaining of chest pain and shortness of breath that was caused by a pneumothorax.

Some patients first consult their physician because of shortness of breath upon exertion.

There are a number of tests the physician can do to confirm or rule out the existence of LAM.

Chest X-ray: This is a simple procedure that provides a picture of the lungs and other tissue in the chest. The chest x-ray is used to diagnose a pneumothorax or the presence of fluid in the chest cavity (pleural effusion).

Pulmonary Function Tests: The patient breathes through a mouthpiece into a machine (spirometer) that measures the volume of air in the lungs, the movement of air into and out of the lungs, and the movement of oxygen from the lungs into the blood.

Blood Tests: The patient's blood is analyzed to determine whether the lungs are providing an adequate supply of oxygen to the blood.

Computed Tomography (CT): CT is the most definitive imaging test for diagnosing LAM. The patient lies inside a long, cylindrical structure, and x-ray beams pass through the body from different angles, producing multiple images. A computer combines all of these images and provides a 3-dimensional picture of the inside of the lungs and chest. This is called a CT scan. On a CT scan, the presence of thin-walled cysts spread relatively uniformly throughout the lungs usually means LAM.

Lung Biopsy: Although it is sometimes possible to diagnose LAM based on the above tests, the most definitive test for the diagnosis of LAM is an open lung biopsy. In this procedure, a few small pieces of lung tissue are removed through an incision made in the chest wall between the ribs.

Another procedure, thoracoscopy, is also being used in some patients to obtain lung tissue. In this procedure, tiny incisions are made in the chest wall, and a small lighted tube (endoscope) is inserted so that the interior of the lung can be viewed, and small pieces of tissue are removed.

Both procedures must be done in the hospital under general anesthesia. Another technique, called transbronchial biopsy, may also be used to obtain a small amount of lung tissue. A long, narrow, flexible, lighted tube (bronchoscope) is inserted down the windpipe (trachea), and into the lungs. Bits of lung tissue are sampled, using a tiny forceps. This procedure is usually done in a hospital on an outpatient basis under local anesthesia. It is less reliable than an open lung biopsy because the amount of tissue that can be sampled is sometimes inadequate for diagnostic studies.

After the lung tissue is removed, it is examined in a pathology laboratory for the presence of the abnormal muscle cells and cystic changes characteristic of LAM.

HOW IS LAM TREATED?

Because LAM affects almost exclusively women of childbearing age, physicians have thought that the hormone estrogen might be involved in the abnormal muscle cell growth that characterizes the disease, just as it is in the growth of smooth muscle in the uterus in a woman's childbearing years.

Although there is no evidence that there is a relationship between estrogen and LAM, the treatment of LAM has focused on reducing the production or effects of estrogen.

Two treatments used are administration of medroxy-progesterone, a drug containing the hormone progesterone, or removal of the ovaries (oophorectomy). The response to treatment has been highly individual, and no therapy has been found to be effective for all LAM patients.

Oxygen therapy may be necessary if the disease continues to worsen and lung function is impaired.

For LAM patients with severe disease, lung transplantation is an established therapy. One year survival following transplant is approximately 70 percent, and 3-year survival is approximately 50 percent.

WHAT IS THE EFFECT OF LAM ON THE PATIENT'S LIFESTYLE?

In the early stages of the disease, most patients can go about their daily activities, including attending school, going to work, and performing common physical activities, such as walking up a hill. In more advanced stages, the patient may have very limited ability to move around and may require oxygen full-time.

Patients with LAM should follow the same healthy lifestyle recommended for the general population, including eating a healthy diet, getting as much exercise as they can, as well as plenty of rest, and, of course, not smoking.

Traveling to remote areas where medical attention is not readily available or to high altitudes where the blebs can expand and rupture should be considered carefully before undertaken.

In patients with normal lung function, there is probably no increased risk associated with pregnancy. However, in patients with compromised lung function, pregnancy is not advised.

There do not appear to be complications associated with oral contraceptives, but this issue should be discussed with the patient's pulmonologist and gynecologist.