New clinical practice guidelines pertaining to the diagnosis and treatment of a rare lung disease were recently published in the American Journal of Respiratory and Critical Care Medicine.

Lymphangioleiomyomatosis (LAM) is a systemic disease that affects an estimated 5 per million women, primarily those of child-bearing age. Neoplastic smooth muscle-like cells arise from an unknown source and infiltrate the lung, resulting in cystic changes.

Patients with LAM experience a decline in lung function at 2 to 4 times the normal rate, and are often plagued with repeated lung collapses. Most patients require supplemental oxygen within 10 years of the onset of symptoms.

The guidelines were written by a multidisciplinary committee of 27 scientists and clinicians who are a part of the American Thoracic Society (ATS) and the Japanese Respiratory Society (JRS).

The committee created 5 recommendations related to the diagnosis and treatment of LAM based on a systemic review of medical studies that were published through May 2015. The strength and quality of the recommendations and the evidence supporting them was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.

Based on evidence of varying quality, the committee made 5 key recommendations:
  • LAM patients with abnormal/declining lung function should be treated with sirolimus rather than observation, a strong recommendation based on moderate quality evidence.
  • Select LAM patients with problematic chylous effusions should be treated with sirolimus before invasive management, a conditional recommendation based on very low-quality evidence.
  • Not using doxycycline to treat LAM, a conditional recommendation based on low-quality evidence.
  • Not using hormonal treatment for LAM, a conditional recommendation also based on very low quality evidence.
  • Having vascular endothelial growth factor D testing for patients whose computed tomography scan shows cystic abnormalities characteristic of LAM, but who have no other confirmatory clinical or extrapulmonary radiologic features of LAM, in order to establish the diagnosis of LAM before considering a diagnostic lung biopsy. This is a strong recommendation based on moderate-quality evidence.
“The sirolimus and VEGF-D recommendations were based on moderate quality evidence, but overall the evidence base for LAM is limited,” said Francis X. McCormack, co-chairmen of the committee. “The literature search only uncovered 2 randomized, controlled trials. As the field evolves, recommendations regarding hormonal therapies and other interventions are likely to change.”

The study authors emphasized that the guidelines should be applied with consideration to context, as well as to special circumstances that affects individual patients.

“No 2 patients are alike,” said Joel Moss, MD, PhD, co-chairmen of the committee. “The guidelines cannot take into account all of the complexities that clinicians face when making treatment decisions for patients with a rare lung disease.”

In addition to the 5 recommendations, the guidelines also highlighted research opportunities that are related to each of the recommendations, including: dosing, agent selection, patient selection, and timing of initiation and duration of therapy of mTOR inhibitors – including sirolimus and everolimus – and whether their combined use or use as prophylactic therapies benefits the patients; and the role of serum VEGF-D as a prognostic biomarker to help guide treatment decisions, as well as the development of additional biomarkers that will reduce the need for surgical biopsy, facilitate clinical trials, and lead to personalized treatments.

“The LAM guidelines will need to be updated frequently because the pace of discovery in LAM continues to accelerate,” McCormack added.