Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis

Am J Respir Crit Care Med. 2014 Dec 1;190(11):1273-82. doi: 10.1164/rccm.201405-0918OC.

Abstract

Rationale: Sirolimus therapy stabilizes lung function and reduces the size of chylous effusions and lymphangioleiomyomas in patients with lymphangioleiomyomatosis.

Objectives: To determine whether sirolimus has beneficial effects on lung function, cystic areas, and adjacent lung parenchyma; whether these effects are sustained; and whether sirolimus is well tolerated by patients.

Methods: Lung function decline over time, lung volume occupied by cysts (cyst score), and lung tissue texture in the vicinity of the cysts were quantified with a computer-aided diagnosis system in 38 patients. Then we compared cyst scores from the last study on sirolimus with studies done on sirolimus therapy. In 12 patients, we evaluated rates of change in lung function and cyst scores off and on sirolimus.

Measurements and main results: Sirolimus reduced yearly declines in FEV1 (-2.3 ± 0.1 vs. 1.0 ± 0.3% predicted; P < 0.001) and diffusing capacity of carbon monoxide (-2.6 ± 0.1 vs. 0.9 ± 0.2% predicted; P < 0.001). Cyst scores 1.2 ± 0.8 years (30.5 ± 11.9%) and 2.5 ± 2 years (29.7 ± 12.1%) after initiating sirolimus were not significantly different from pretreatment values (28.4 ± 12.5%). In 12 patients followed for 5 years, a significant reduction in rates of yearly decline in FEV1 (-1.4 ± 0.2 vs. 0.3 ± 0.4% predicted; P = 0.025) was observed. Analyses of 104 computed tomography scans showed a nonsignificant (P = 0.23) reduction in yearly rates of change of cyst scores (1.8 ± 0.2 vs. 0.3 ± 0.3%; P = 0.23) and lung texture features. Despite adverse events, most patients were able to continue sirolimus therapy.

Conclusions: Sirolimus therapy slowed down lung function decline and increase in cystic lesions. Most patients were able to tolerate sirolimus therapy.

Keywords: LAM; lung cystic destruction; sirolimus.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects
  • Antibiotics, Antineoplastic / therapeutic use
  • Cysts / drug therapy
  • Disease Progression
  • Forced Expiratory Volume / drug effects
  • Humans
  • Lung / diagnostic imaging
  • Lung / drug effects*
  • Lung / pathology
  • Lung / physiopathology
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Lymphangioleiomyomatosis / drug therapy*
  • Lymphangioleiomyomatosis / pathology
  • Lymphangioleiomyomatosis / physiopathology
  • Quality of Life
  • Respiratory Function Tests
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Sirolimus / therapeutic use*
  • Time Factors
  • Tomography, X-Ray Computed

Substances

  • Antibiotics, Antineoplastic
  • Sirolimus