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General Information

LAM Week

Pulmonary lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that affects predominantly women of childbearing age. LAM is very rare, affecting approximately 3-8 women per million. The mean age of diagnosis of LAM is 34-35 years, and patients registered with the LAM Foundation have a median survival of nearly 30 years after onset of symptoms. LAM can be classified as sporadic (S-LAM) or associated with tuberous sclerosis complex (TSC-LAM). Approximately 30% of women with TSC develop cystic changes in the lung consistent with LAM and the incidence increases with age.

LAM is characterized by the diffuse infiltration of atypical smooth muscle (‘LAM cells’) in the lung and lymphatics resulting in cystic destruction and remodeling of the lung parenchyma. It is currently thought that LAM cells are neoplastic (although very slowly proliferating) and arise in the uterus and adnexa as a result of mutations in the TS1 or TS2 genes. In patients with S-LAM, the genetic mutations occur in somatic cells whereas in patients with TSC-LAM, the mutations occur in germ cells and the condition is therefore heritable. Many of the clinical manifestations of LAM are the result of lymphatic obstruction by these LAM cells resulting in the collection of chylous fluid in the pleural (chylothorax) and peritoneal (chylous ascites) cavities and in fluid-filled lymphangiomyomas in the chest and abdomen. Benign tumors comprised of smooth muscle and fat, known as angiomyolipomas (AML), are present in kidneys of up to 50% of S-LAM patients.

Presenting symptoms may include dyspnea, cough, hemoptysis, chyloptysis, spontaneous pneumothorax, abdominal tumors, chylothorax, and/or chylous ascites. Definitive diagnosis often requires a lung biopsy (either transbronchial or surgical) for confirmation with immunohistochemical staining of LAM cells with the monoclonal antibody HMB-45. However, in the appropriate clinical setting, a diagnosis can be established based on high resolution chest CT scan demonstrating a characteristic diffuse distribution of cysts in both lungs in the presence of other diagnostic features of LAM such as renal AML, lymphangiomas, chylothorax, or chylous ascites.

Major advances have been made in constraining LAM cell growth using inhibitors of the mTOR pathway such as sirolimus and everolimus (‘rapalogues’). These drugs slow the disease progression by inhibiting growth of LAM cells thus stabilizing the decline in lung function. While there is no cure for LAM at this time, these mTOR inhibitors result in a marked improvement in symptoms in most patients. New treatments, either alone or in combination with mTOR inhibitors, are being developed and tested in preclinical models and clinical trials.

With our PAR partner, the LAM foundation, we will continue to provide resources for clinicians, researchers and patients and to support research pursuits in LAM.

Four Facts About LAM

  1. Lymphangioleiomyomatosis (LAM) is a progressive disease that predominantly affects women, especially during the prime of their lives.  Symptoms may include shortness of breath, collapsed lung, chest pain, cough, fatigue and in 40% of patients one or more benign kidney tumors called angiomyolipomas.

  2. Women with LAM may be misdiagnosed with asthma, emphysema, or bronchitis. The diagnosis of LAM can most often be made without surgical lung biopsy using a combination of high resolution CT imaging of the lungs and abdomen, clinical signs and symptoms, serum VEGF-D levels and sometimes transbronchial biopsy

  3. In May of 2015, the FDA approved Sirolimus as a proven therapy for LAM that can stabilize lung function and improve some measures of quality of life and functional performance. Lung transplant remains the option of last resort for patients with advanced disease.

  4. Median survival in patients with LAM has varied from 10 to 30 years. Most patients have dyspnea on exertion with daily activities by 10 years after symptom onset and many will require supplemental oxygen over that interval.