Sustained effects of sirolimus on lung function and cystic lung lesions in
lymphangioleiomyomatosis
#MMPMID25329516
Yao J
; Taveira-DaSilva AM
; Jones AM
; Julien-Williams P
; Stylianou M
; Moss J
Am J Respir Crit Care Med
2014[Dec]; 190
(11
): 1273-82
PMID25329516
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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.
|Adult
[MESH]
|Antibiotics, Antineoplastic/administration & dosage/adverse effects/therapeutic
use
[MESH]
free
free
free
