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Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

Neurohr C, Hoffmann AL, Huppmann P, Herrera VA, Ihle F, Leuschner S, von Wulffen W, Meis T, Baezner C, Leuchte H, Baumgartner R, Zimmermann G, Behr J - Respir. Res. (2011)

Bottom Line: No effective medical treatment is available but therapy with sirolimus has shown some promise.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Int, Medicine I, Division of Pulmonary Diseases, Klinikum Grosshadern, Ludwig-Maximilians University, Comprehensive Pneumology Center, Marchioninistrasse 15, 81377 Munich, Germany. claus.neurohr@med.uni-muenchen.de

ABSTRACT

Background: Lymphangioleiomyomatosis (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.

Methods: Sirolimus (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.

Results: The 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.

Conclusions: Our 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.

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Related in: MedlinePlus

Changes of FEV1 before and during sirolimus therapy. Serial individual values of FEV1 (forced expiratory volume in 1 second) before and during sirolimus therapy in ten patients.
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Figure 3: Changes of FEV1 before and during sirolimus therapy. Serial individual values of FEV1 (forced expiratory volume in 1 second) before and during sirolimus therapy in ten patients.

Mentions: Figure 1 depicts the individual mean rate of change of FEV1 before and after initiation of therapy and figure 2, and 3 demonstrates the individual course of FEV1 with and without sirolimus. The overall mean loss of FEV1 amounted to -2.30 ± 0.52 ml/day before therapy. During the treatment with sirolimus, patients demonstrated a significant mean FEV1 gain of 1.19 ± 0.26 ml/day (p = 0.001). However, further analysis revealed no significant positive or negative correlation between the rate of change of FEV1 before and during sirolimus therapy or baseline FEV1 and relative increase of FEV1 after initiation of sirolimus, respectively (p > 0.05 each).


Is sirolimus a therapeutic option for patients with progressive pulmonary lymphangioleiomyomatosis?

Neurohr C, Hoffmann AL, Huppmann P, Herrera VA, Ihle F, Leuschner S, von Wulffen W, Meis T, Baezner C, Leuchte H, Baumgartner R, Zimmermann G, Behr J - Respir. Res. (2011)

Changes of FEV1 before and during sirolimus therapy. Serial individual values of FEV1 (forced expiratory volume in 1 second) before and during sirolimus therapy in ten patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3116484&req=5

Figure 3: Changes of FEV1 before and during sirolimus therapy. Serial individual values of FEV1 (forced expiratory volume in 1 second) before and during sirolimus therapy in ten patients.
Mentions: Figure 1 depicts the individual mean rate of change of FEV1 before and after initiation of therapy and figure 2, and 3 demonstrates the individual course of FEV1 with and without sirolimus. The overall mean loss of FEV1 amounted to -2.30 ± 0.52 ml/day before therapy. During the treatment with sirolimus, patients demonstrated a significant mean FEV1 gain of 1.19 ± 0.26 ml/day (p = 0.001). However, further analysis revealed no significant positive or negative correlation between the rate of change of FEV1 before and during sirolimus therapy or baseline FEV1 and relative increase of FEV1 after initiation of sirolimus, respectively (p > 0.05 each).

Bottom Line: No effective medical treatment is available but therapy with sirolimus has shown some promise.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Int, Medicine I, Division of Pulmonary Diseases, Klinikum Grosshadern, Ludwig-Maximilians University, Comprehensive Pneumology Center, Marchioninistrasse 15, 81377 Munich, Germany. claus.neurohr@med.uni-muenchen.de

ABSTRACT

Background: Lymphangioleiomyomatosis (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.

Methods: Sirolimus (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.

Results: The 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.

Conclusions: Our 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.

Show MeSH
Related in: MedlinePlus