Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosisReport as inadecuate

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Respiratory Research

, 12:66

First Online: 01 December 2011Received: 20 July 2010Accepted: 21 May 2011


BackgroundLymphangioleiomyomatosis LAM is a rare lung disease characterised by progressive airflow obstruction. No effective medical treatment is available but therapy with sirolimus has shown some promise. The aim of this observational study was to evaluate sirolimus in progressive LAM.

MethodsSirolimus trough level 5 - 10 ng-ml was administered to ten female patients 42.4 ± 11.9 years with documented progression. Serial pulmonary function tests and six-minute-walk-distance 6-MWD assessments were performed.

ResultsThe mean loss of FEV1 was -2.30 ± 0.52 ml-day before therapy and a significant mean gain of FEV1 of 1.19 ± 0.26 ml-day was detected during treatment p = 0.001. Mean FEV1 and FVC at baseline were 1.12 ± 0.15 l 36.1 ± 4.5%pred. and 2.47 ± 0.25 l 69.2 ± 6.5%pred., respectively. At three and six months during follow-up a significant increase of FEV1 and FVC was demonstrated 3 months ΔFEV1: 220 ± 82 ml, p = 0.024; 6 months ΔFEV1: 345 ± 58 ml, p = 0.001; 3 months ΔFVC: 360 ± 141 ml, p = 0.031; 6 months ΔFVC: 488 ± 138 ml, p = 0.006. Sirolimus was discontinued in 3 patients because of serious recurrent lower respiratory tract infection or sirolimus-induced pneumonitis. No deaths and no pneumothoraces occurred during therapy.

ConclusionsOur data suggest that sirolimus might be considered as a therapeutic option in rapidly declining LAM patients. However, sirolimus administration may be associated with severe respiratory adverse events requiring treatment cessation in some patients. Moreover, discontinuation of sirolimus is mandatory prior to lung transplantation.

Abbreviation listDLCOsingle breath diffusing capacity for carbon monoxide

FVCForced Vital Capacity

FEV1forced expiratory volume in 1 second


mTORmammalian target of rapamycin

6-MWDdistance covered in 6 minutes

PFTPulmonary function tests

SEMstandard error of the mean

TSCtuberous sclerosis complex.

Electronic supplementary materialThe online version of this article doi:10.1186-1465-9921-12-66 contains supplementary material, which is available to authorized users.

Claus Neurohr, Anna L Hoffmann contributed equally to this work.

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Author: Claus Neurohr - Anna L Hoffmann - Patrick Huppmann - Vivian A Herrera - Franziska Ihle - Stefan Leuschner - Werner von Wu


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