American Thoracic Society Clinical Practice Guidelines
The American Thoracic Society (ATS) and the Japanese Respiratory Society (JRS), in conjunction with an ad hoc guideline development committee of LAM experts, prepared the following guidelines for the treatment of lymphangioleiomyomatosis.
- To view the ATS/JRS 2016 LAM Clinical Practice Guidelines, Click here
- To view the ATS/JRS 2017 LAM Clinical Practice Guidelines, Click here
To download the infographic in English, click here
European Respiratory Society Treatment Guidelines
The European Respiratory Society, along with the ERS LAM Task Force, has put together the following guideline for the treatment of lymphangioleiomyomatosis.
- To view the ERS 2010 LAM diagnosis and management guidelines, click here.
- To view the French recommendations and diagnosis and management of lymphangioleiomyomatosis, click here.
The mainstay of LAM management involves therapies aimed at stabilizing or slowing the rate of progression of lung disease and handling other disease-related complications such as spontaneous pneumothorax, lymphatic manifestations such as chylous effusions, and renal angiomyolipomas.
mTOR Inhibitor Therapy
Long-term treatment with mechanistic target of the rapamycin (mTOR) inhibitors such as sirolimus is recommended for patients in the following scenarios: abnormal lung function (FEV1 < 70%), progressive lung function decline (FEV1 decline ≥90 ml/year), refractory chylous effusions, angiomyolipomas ≥4 cm, or other measures suggesting substantial disease burden (abnormal DLCO, air trapping or hyperinflation, radiological extent of cystic lung disease, or need for supplemental oxygen).
RAPAMUNE® (sirolimus) is the first drug to be approved by the FDA for the treatment of LAM. It is a highly specific inhibitor of the mTOR signaling pathway that is dysregulated in LAM cells. Treatment with the drug suppresses the growth of LAM cells. The efficacy of sirolimus was proven by the Multicenter International Safety and Efficacy of Sirolimus in LAM (MILES) trial. Click here to learn more. The MILES trial was a phase 3, double-blind, placebo-controlled randomized trial that showed that treatment with sirolimus can stabilize lung function decline, reduce serum VEGF-D levels, and improve some measures of quality of life in women with moderate to severe LAM. Treatment with sirolimus is suppressive rather than remission-inducing, and durable disease control requires long-term treatment with sirolimus. An ongoing trial is evaluating the role of pre-emptive treatment with sirolimus in patients with preserved lung .
Afinitor (everolimus) is also used in the treatment of LAM, although it is not FDA-approved for that purpose. Everolimus has been shown to be effective for the treatment of angiomyolipomas, subependymal giant cell astrocytomas, and epilepsy control in patients with tuberous sclerosis complex. It is a derivative of sirolimus and has very similar functions and side effects.
Supportive Oxygen may be needed as LAM progresses and administered to maintain arterial oxygen saturations of 90% or greater. Bronchodilators may benefit a subset of patients with LAM. About 20-25% of LAM patients have an asthma-like component that responds to bronchodilators.
Management of other LAM Manifestations
Spontaneous pneumothorax can occur in about two-thirds of patients with LAM during their lifetime and is the presenting manifestation that leads to the diagnosis of LAM in about 25% of patients with LAM. Pneumothorax in LAM has a very high (>70%) chance of recurrence if managed conservatively. The risk of recurrence can be reduced to ~30% by pleurodesis. As such, it is recommended that pleurodesis be performed following the initial episode of pneumothorax rather than waiting for a recurrence. VATS-guided mechanical abrasion is the preferred initial modality of pleurodesis, with sclerosant agents such as talc reserved for patients who experience recurrent pneumothorax despite pleurodesis. Prior pleurodesis is not a contraindication for future lung transplantation. Recent reports are suggesting a protective role of sirolimus in reducing the risk of future pneumothoraces. However, sirolimus reduces wound healing and may need to be withheld to allow proper closure of an active air leak.
Chylous effusions such as chylous ascites and chylothorax can happen in about 20% of patients with LAM. These tend to happen more frequently in patients with sporadic LAM compared with TSC-LAM. These effusions respond well to treatment with mTOR inhibitors, and treatment with sirolimus is the recommended first-line treatment for problematic chylous effusions rather than invasive procedures.
Renal angiomyolipomas (AMLs) can be seen in about one-third of patients with sporadic LAM and the majority (80-90%) of patients with TSC-LAM. The most serious complication from a renal AML is the risk of hemorrhage that might result in acute abdomen and shock. The risk of hemorrhage is increased in larger lesions (≥4 cm) and in patients with a large burden of vascular aneurysms within the AMLs. Treatment with mTOR inhibitors can shrink AMLs and should be considered for patients with large (>3-4 cm) or growing AMLs. Embolization can also be performed to reduce bleeding risk, especially in patients with large aneurysmal burden or in patients where renal AML would otherwise be the sole indication to treat with mTOR inhibitors. Surgical resection should be the last resort for the management of AMLs and should generally be undertaken with nephron-sparing approaches rather than a complete nephrectomy.
Referral for evaluation for lung transplantation should be considered when the FEV1 approaches 30% predicted. Patients may also be eligible based on other factors that profoundly affect the quality of life, such as disabling shortness of breath or problems maintaining oxygen saturation despite high supplemental oxygen delivery rates. Both single and bilateral lung transplantation have been performed for patients with LAM and both are suitable options. In general, women with LAM fare better than patients with other chronic lung diseases post-transplantation; the average post-transplant survival in women in LAM is about 12 years with one, five, and ten-year survival rates of 94%, 73%, and 55%, respectively.
Frequently Asked Questions from Patients and Families
How will LAM affect my family and reproductive planning? (Pregnancy, contraception)
LAM progression can be accelerated in the presence of exogenous estrogen and during pregnancy. Estrogen supplements and estrogen-containing birth control options should be stopped. Please see this guide for contraception options in patients with LAM. The role of anti-estrogen therapies such as progesterone, Gonadotrophin-releasing hormone (GnRH) antagonists, and oophorectomy, is not clear, and they are not routinely recommended for the treatment of LAM. Clinicians sometimes consider hormonal therapies in special situations, such as the progression of lung function decline despite sirolimus use and in patients who have recurrent pneumothoraces that are timed with the menstrual cycle.
The risk of pregnancy in LAM has not been rigorously studied. However, case reports and small series have suggested an increased risk of spontaneous pneumothoraces, growth and bleeding in AMLs, and accelerated lung function decline, in pregnant patients with LAM. Although women with LAM may have successful pregnancies, pregnancy may be more of a risk for those with poor lung function. The physician and patient should discuss the risks of pregnancy carefully and decisions should be made on an individual basis.
Sirolimus is an FDA Category C drug and the exact risks associated with use during pregnancy are unknown. Generally, most patients and physicians avoid the use of sirolimus during pregnancy. However, some published care reports and anecdotal observations suggest this might be an option for some pregnant patients. Like the overall pregnancy decision, the decision to use sirolimus during all or a part of pregnancy should be made by utilizing the principles of shared decision-making following careful discussion of the potential risks and benefits. Consultation and close collaboration with maternal fetal medicine specialists is also recommended to help with decision making.
Can I travel by plane if I have LAM?
Many LAM patients have been advised to avoid air travel because of the theoretical risk of lung cyst rupture associated with atmospheric pressure changes during flight. The risk of air travel related pneumothorax in women with LAM is approximately 1-2 episodes per 100 flights. This risk is low enough that in most LAM patients, air travel is considered safe. In advising individual patients with LAM about air travel, it is reasonable to consider additional factors, including a history of frequent or recent pneumothoraces, and the overall extent of cardiopulmonary impairment. Patients with poor cardiopulmonary reserve may tolerate even small pneumothoraces poorly. If patients have a newly diagnosed pneumothorax, complete resolution for at least two weeks prior to flying is recommended, based on expert opinion and limited available data. In any patient with unexplained chest pain, shortness of breath, or symptoms suggestive of a new pneumothorax, appropriate radiologic testing should be performed prior to air travel. Assessment for the need for supplemental oxygen during flight should be undertaken similar to patients with other pulmonary conditions.
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This content was created for general informational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.