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.
|Classification and external resources|
Lymphangioleiomyomatosis (LAM) is a rare lung disease that results in a proliferation of disorderly smooth muscle growth (leiomyoma) throughout the lungs, in the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways (leading to pulmonary cyst formation and pneumothorax) and lymphatics (leading to chylous pleural effusion). LAM occurs in a sporadic form, which predominantly affects females, usually of childbearing age; LAM also occurs in patients who have tuberous sclerosis.
Signs and symptoms
- shortness of breath on exertion
- hemoptysis, as a result of vascular congestion
- recurrent pneumothorax
- chylous pleural effusion and chylous ascites, as a result of lymphatic obstruction.
Symptoms are more likely in women, with average age at onset 34 years. Symptoms may precede radiographic abnormalities.
The proliferating smooth muscle that occurs in the type of LAM seen in patients with tuberous sclerosis (TSC-LAM) has been shown to represent clones of the smooth muscle in those patients' renal angiomyolipomas. Thus it is believed to represent metastases of this "benign" tumor. There is a female preponderance to TSC-LAM.
Investigations may include:
- Spirometry studies, which may include an increased FVC, with a decreased FEV1/FVC ratio.
- High-Resolution CT, which may demonstrate an interstitial pattern with cystic changes 
- Vascular endothelial growth factor D, which is typically elevated.
In patients with typical cystic changes on high resolution CT scanning serum levels of vascular endothelial growth factor-D greater than 800 pg/ml are considered to be diagnostic for LAM.
In some cases, the diagnosis of LAM can be made with confidence on clinical grounds (without biopsy) in patients with typical cystic changes on high resolution CT scanning of the lung and findings of tuberous sclerosis, angiomyolipoma or chylothorax
Serum VEGF-D concentration has been shown to be a biologically plausible and useful biomarker in lymphangioleiomyomatosis that correlates with disease severity and treatment response. 
On May 28, 2015, the U.S. Food and Drug Administration approved the drug Rapamune (sirolimus) to treat LAM. This is the first drug approved to treat the disease. Rapamune originally was approved to help prevent organ rejection in kidney transplant patients. Approximately 1,400 American women and an estimated 3,500 globally have been diagnosed with LAM and many more remain undiagnosed.
“This is a major step toward successful treatment of this disease,” said Dr. Frank McCormack, director of internal medicine at the University of Cincinnati Medical Center and chair of the Scientific Advisory Board for The LAM Foundation. “Women who had limited choices for treatment now have a drug proven to help LAM patients.”
Before the approval of Rapamune, LAM was treated with a number of therapies.
Anti-estrogen therapy. This may include use of tamoxifen or surgical removal of the ovaries. Other drugs may include progesterone or GnRH agonists. This therapy has been in use since the 1980s, and was developed in light of reports of LAM worsening during pregnancy. None of these therapies has been shown to be clearly efficacious, and all have undesirable side-effects. There is some evidence which shows that tamoxifen may actually cause worsening of LAM in some patients.
Sirolimus. Sirolimus is an antiproliferative and immunosuppressant interleukin-2 inhibitor that is used in some patients with LAM. Unlike anti-estrogen therapy, Sirolimus has statistically significant efficacy, improving quality of life in mild-to-moderately severe LAM patients.
Lung transplantation may be considered when pulmonary function has sufficiently deteriorated. Following lung transplant, LAM patients have Kaplan-Meier estimators (survival curves) similar to other lung transplant patients. Although LAM has been reported to recur in the transplanted lung , there have been no reported cases of graft failure or death due to recurrence. LAM-specific complications may occur secondary to transplantation, include pneumothorax secondary to a ruptured cyst, chylothorax, LAM recurrence, and abdominal complications.[which?] General transplant-related may include bacterial, viral and fungal lung infections, and rejection of the lung, including graft-versus-host disease and host-versus-graft disease.
A chylothorax should be managed conservatively. Surgical interventions may be pursued, including pleural abrasion, pleurodesis and pleurectomy, however these should be avoided in early stages of the disease, as intervention may impact on future lung transplantation.
10-year survival figures range from 49-79%, with LAM believed to be progressive, ultimately leading to respiratory failure. High reported survival may stem from improvements in diagnosis, allowing for earlier diagnosis of LAM at a less severe stage. Thus survival differences may not reflect changes in treatment, but rather earlier diagnosis. There are women who have survived LAM for more than 30 years, and continue to survive, according to The LAM Foundation..
LAM almost always affects women, with only a handful of cases reported in men. The first of these was in a man with tuberous sclerosis, reported in 2000 from the Mayo Clinic by a team led by Henry Tazelaar
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- The LAM Foundation (US)
- LAM Treatment Alliance
- LAM Action (UK)
- J-LAM (Japan)
- LAM Australasia Research Alliance (LARA)
- LAM Trust of New Zealand
- LAM Italia Non Profit of Italy