Therapeutic Strategies for LAM

Management of pneumothrox in LAM
Perspectives on pneumothorx in patients with LAM

While there is currently no cure for LAM, research has led to major progress in understanding and diagnosing LAM, including the identification of the genetic basis of the disease and a blood test that may assist with the diagnosis ( VEGF-D).  These research efforts have prompted subsequent studies, including the first large-scale controlled clinical trial for women with LAM, which was  supported by the National Institutes of Health and The LAM Foundation.

The Multicenter International LAM Efficacy of Sirolimus (MILES) Trial tested sirolimus (rapamycin), which showed this medication to stabilize lung function and improve quality of life in patients with moderate to severe LAM.  Learn more about this study.

In early stages of the disease, most patients can go about their daily activities, but as the disease progresses, patients may require  supplemental oxygen and lung transplantation.  Whether long-term treatment with sirolimus may prevent this gradual deterioration is not known at the present time and will vary from patient to pateent- this sentence should go with  the previous paragraph.  Other management options are listed below.:

Sirolimus (rapamycin)

Sirolimus blocks mammalian target of rapamycin (mTOR) signaling pathway that is dysregulated in LAM cells and lead to their proliferation.  The use of sirolimus therapy may be considered in patients with moderate to severe LAM or those with progressive disease (See above MILES trial).

Hormone Therapy

Because LAM is thought to be hormone dependent, treatment strategies aimed at blocking estrogen are used, although there is no definitive study showing that these strategies are effective.  Estrogen-containing contraceptives or hormone replacement should be discontinued.  For patients with progressive decline in lung function, progestin therapies (both oral and intramuscular) or gonadotropin releasing hormone (GnRH) agonists may be considered.

Progestins

Doses of oral progestin that are sufficient to suppress serum estrogen production (e.g., Agestyn) are suggested over the use of larger doses of intramuscular progesterone  (e.g., Depo-Provera). Progestins can cause fluid retention and mood swings.

GnRH Agonists

GnRH agonists (e.g. Lupron) have been used in patients with LAM, but benefits are unproven and induction of early menopause is distressing and morbid in young women.

Oophorectomy

Oophorectomy is no longer recommended in LAM patients. The procedure is invasive without clear evidence of efficacy.

Pregnancy

Patients should be advised that pregnancy has been reported to result in exacerbations of LAM and pneumothorax. However, the risk of pregnancy in LAM has not been rigorously studied.  Physicians and patients should discuss the risks of pregnancy carefully and decisions should be made on an individual basis.

Oxygen Therapy

Oxygen therapy may become necessary as the disease progresses,lung function becomes severely impaired, and hypoxemia is limiting.  Based on extrapolation from the COPD populations, the use of oxygen may prolong life in hypoxic patients with LAM.  Oxygen should be administered to maintain arterial oxygen saturations of 88-89% percent or greater with rest, exercise and sleep.  Oxygen Supplementation will enhance exercise ability and distance and provide a more restful sleep.  It can also help stabilize pulmonary hypertension.  Newer and lighter weight oxygen systems allow for easier and more long distance travel.

Pleurodesis

More than 65 percent of patients with LAM develop pneumothorax and the average number of pneumothoraces per LAM patient is 3.5. The use of a pleurodesis procedure is recommended on the first pneumothorax, given the more than 70 percent chance of recurrence. Chemical pleurodesis (preferably with talc), mechanical abrasion, talc poudrage and pleurectomy have all been effective in patients with LAM.  

Chyle does not cause pleural inflammation or fibrosis, and small chylous effusions (chylothorax) most often require no intervention once the diagnosis is made.  Shortness of breath may mandate drainage with a tube or catheter, and in some cases this may need to be repeated.  Pleural effusion may be required to prevent nutritional and lymphocyte deficiencies that can result from repeated removal of fluid or persistent drainage. Dietary maneuvers (low fat intake), pleurodesis and thoracic duct ligation have been used in the management of recurrent chylothorax.

Management of Renal Angiomyolipomas

Although most renal angiomyolipomas are asymptomatic, larger tumors (>4cm) may cause pain and bleeding. Transcatheter embolization therapy is usually preferred in the management of symptomatic renal angiomyolipomas. Renal-sparing surgical resection of tumors is another option.