Summary of Lymphangioleiomyomatosis (LAM)

ICD-10 code for LAM is J84.81.

Lymphangioleiomyomatosis, better known as LAM, is a rare, cystic lung disease associated with mutations in tuberous sclerosis genes, renal angiomyolipomas, lymphatic spread and remarkable female gender restriction. The clinical course of LAM is characterized by progressive dyspnea on exertion, recurrent pneumothorax, and chylous fluid collections. Lung function declines at approximately 2-3 fold times rate of normal subjects, based on an annual drop in forced expiratory volume in one second (FEV1) of 75-120 cc in various reported series.

The diagnosis of pulmonary LAM can be made on high resolution CT scan with a reasonable degree (>80%) of certainty by expert radiologists, but generally requires a lung biopsy in cases where tuberous sclerosis complex, angiomyolipomas or chylous effusions are absent. Measurement of serum vascular endothelial growth Factor D has been considered to be supportive for the diagnosis if available.

Currently available treatment strategies for LAM are based on antagonism of estrogen action, and are empiric and unproven. A trial of bronchodilators is warranted in LAM patients with reversible airflow obstruction on pulmonary function testing. Pleurodesis should be performed with the initial pneumothorax in each hemithorax because the rate of ipsilateral recurrence is over 70%. Angiomyolipomas that exceed 4 cm in size are more likely to bleed and should be evaluated for embolization. Air travel is safe in most patients with LAM. Lung transplantation is an important option for women with LAM, and can be safely performed by experienced surgeons despite prior unilateral or bilateral pleurodesis in most patients. From the recent publications, sirolimus may be considered as a trial on an individual basis in progressive patients with possible benefit, after careful evaluation of risk/benefit ratio in an experienced centre.

There have been great strides in the basic science of LAM in the past fifteen years, due in large part to a confluence of scientific discoveries from the tuberous sclerosis and signaling biology fields, and remarkably effective, grass roots patient advocacy. Multicenter LAM clinical trials based on several well-defined molecular targets are currently underway or have just finished in the United States, Europe, Canada, and Japan. To read more about them click below:

MILES Trial (US, Canada, Japan)
TSC Multicenter Clinical Trial (US)

The Future - LAM Clinical Trials

LAM and TSC researchers have identified a wealth of potential molecular targets and experimental therapies that may be appropriate for testing in clinical trials. These include mTOR inhibitors (e.g., sirolimus, everolimus), Rheb inhibitors (e.g., farnesyltransferase inhibitors and statins), selective estrogen antagonists (e.g., fispemifene), tyrosine kinase inhibitors (e.g., imatinibmesylate), metalloproteinase inhibitors (e.g., doxycycline), angiogenesis inhibitors (e.g., bevacizumab), and lymphangiogenesis inhibitors (e.g., anti-VEGF-D antibody). Many of these drugs are FDA approved or in development for other indications. In the absence of a known effective treatment, participation in clinical trials should be encouraged. Widespread off label use of candidate therapies like those above will deprive patients of the opportunity to find an effective treatment, and condemn LAM to the same fate as dozens of other pulmonary diseases where the prospects for controlled trials have passed us by.

The LAM Foundation's Role

The LAM Foundation is committed to supporting the development of effective treatments for LAM. The Foundation has committed the majority of the $13 million raised to date to support 75 peer-reviewed research projects for the study of lymphangioleiomyomatosis (LAM), many of which have provided the scientific basis for current and future trials. Annual LAM scientific meetings organized and sponsored by The LAM Foundation have become the primary forum for presentation of landmark LAM research and scientific exchange. The National Heart, Lung, and Blood Institute has shown tremendous support for LAM by investing more than $20 million to support LAM conferences, a national registry of LAM patients and a LAM protocol that evaluates LAM patients. The stage is set. LAM is poised for great advances!