Effects of sirolimus in lymphangioleiomyomatosis patients on lung cysts and pulmonary function: long-term follow-up observational study

  • 146 Accesses



To determine whether sirolimus has beneficial effects on lymphangioleiomyomatosis (LAM) lung cysts in CT with long-term follow-up (FU) and to investigate whether CT is an appropriate imaging biomarker to monitor and evaluate LAM progression.


In this retrospective study, 73 female patients diagnosed with definite LAM between May 2001 and June 2018 were included. Among these, 39 (53.4%) were treated with sirolimus. Quantitative and qualitative CT scoring for lung cysts (CS) were performed and compared between time points (baseline vs. FU at starting sirolimus, baseline vs. last FU, and FU at starting sirolimus vs. last FU for patients treated with sirolimus; baseline vs. last FU for patients without sirolimus). The correlation between CS at each time point and pulmonary function tests (PFTs) at each time point in the patients treated with sirolimus was also investigated. The quantitative and qualitative analyses and PFT results were compared between time points.


In both quantitative and qualitative analyses, CS significantly increased from baseline to FU after starting sirolimus, and from baseline to last FU (all p < 0.05), whereas there was no significant difference between scores at the start of sirolimus vs. last in the patients treated with sirolimus. After sirolimus treatment, diffusing capacity for carbon monoxide (DLCO) was significantly increased. There were significant correlations between CS at each time point and PFT (correlation coefficient [r], − 0.383–0.935; all p < 0.001).


Patients with LAM benefited from sirolimus. CT could be a useful imaging biomarker for evaluating and monitoring lung cysts in LAM.

Key Points

• Qualitative analysis showed a total of 15.8% to 21.1% of patients had a reduced lung cyst volume after sirolimus treatment, and in quantitative analysis, there was no significant difference in lung cyst volume between CT at the start of sirolimus therapy and the last CT.

• Pulmonary function was also improved or maintained after sirolimus treatment.

• Chest CT could be a useful imaging biomarker for evaluating and monitoring lung cysts in patients with lymphangioleiomyomatosis.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 199

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2



Diffusing capacity of the lungs for carbon monoxide


European Respiratory Society


Forced expiratory flow 25–75%


Forced expiratory volume in 1 s


Ratio of FEV1 to FVC


Forced vital capacity




Mammalian target of rapamycin


Pulmonary function test


Residual volume


Total lung capacity


Tuberous sclerosis complex


  1. 1.

    Harknett EC, Chang WY, Byrnes S et al (2011) Use of variability in national and regional data to estimate the prevalence of lymphangioleiomyomatosis. QJM 104:971–979

  2. 2.

    Avila NA, Dwyer AJ, Moss J (2011) Imaging features of lymphangioleiomyomatosis: diagnostic pitfalls. AJR Am J Roentgenol 196:982–986

  3. 3.

    Kitaichi M, Nishimura K, Itoh H, Izumi T (1995) Pulmonary lymphangioleiomyomatosis: a report of 46 patients including a clinicopathologic study of prognostic factors. Am J Respir Crit Care Med 151:527–533

  4. 4.

    Taylor JR, Ryu J, Colby TV, Raffin TA (1990) Lymphangioleiomyomatosis. Clinical course in 32 patients. N Engl J Med 323:1254–1260

  5. 5.

    Sengupta S, Peterson TR, Sabatini DM (2010) Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 40:310–322

  6. 6.

    Juvet SC, McCormack FX, Kwiatkowski DJ, Downey GP (2007) Molecular pathogenesis of lymphangioleiomyomatosis: lessons learned from orphans. Am J Respir Cell Mol Biol 36:398–408

  7. 7.

    Johnson SR, Tattersfield AE (1999) Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment. Am J Respir Crit Care Med 160:628–633

  8. 8.

    Taveira-DaSilva AM, Stylianou MP, Hedin CJ, Hathaway O, Moss J (2004) Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone. Chest 126:1867–1874

  9. 9.

    Johnson SR, Whale CI, Hubbard RB, Lewis SA, Tattersfield AE (2004) Survival and disease progression in UK patients with lymphangioleiomyomatosis. Thorax 59:800–803

  10. 10.

    Argula RG, Kokosi M, Lo P et al (2016) A novel quantitative computed tomographic analysis suggests how sirolimus stabilizes progressive air trapping in lymphangioleiomyomatosis. Ann Am Thorac Soc 13:342–349

  11. 11.

    Bee J, Fuller S, Miller S, Johnson SR (2018) Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study. Thorax 73:369–375

  12. 12.

    Taveira-DaSilva AM, Julien-Williams P, Jones AM, Stylianou M, Moss J (2018) Rates of change in FEV1 and DLCO as potential indicators for mTOR inhibitor therapy in pre-menopausal lymphangioleiomyomatosis patients. Eur Respir J.

  13. 13.

    Zhan Y, Shen L, Xu W et al (2018) Functional improvements in patients with lymphangioleiomyomatosis after sirolimus: an observational study. Orphanet J Rare Dis 13:34

  14. 14.

    Johnson SR, Cordier JF, Lazor R et al (2010) European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J 35:14–26

  15. 15.

    Kim C, Lee SM, Choe J, Chae EJ, Do KH, Seo JB (2018) Volume doubling time of lung cancer detected in idiopathic interstitial pneumonia: comparison with that in chronic obstructive pulmonary disease. Eur Radiol 28:1402–1409

  16. 16.

    Yao J, Taveira-DaSilva AM, Colby TV, Moss J (2012) CT grading of lung disease in lymphangioleiomyomatosis. AJR Am J Roentgenol 199:787–793

  17. 17.

    Wanger J, Clausen JL, Coates A et al (2005) Standardisation of the measurement of lung volumes. Eur Respir J 26:511–522

  18. 18.

    Harari S, Cassandro R, Torre O (2017) The ATS/JRS guidelines on lymphangioleiomyomatosis: filling in the gaps. Am J Respir Crit Care Med.

  19. 19.

    Davies DM, Johnson SR, Tattersfield AE et al (2008) Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med 358:200–203

  20. 20.

    Bissler JJ, McCormack FX, Young LR et al (2008) Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358:140–151

  21. 21.

    McCormack FX, Inoue Y, Moss J et al (2011) Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med 364:1595–1606

  22. 22.

    Washko GR, Parraga G (2016) Imaging biomarkers in lymphangioleiomyomatosis clinical trials. A wolf in sheep’s clothing? Ann Am Thorac Soc 13:307–308

Download references

Author information

Correspondence to Kyung-Hyun Do.

Ethics declarations


The scientific guarantor of this publication is Kyung-Hyun Do.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was waived by the Institutional Review Board.

Ethical approval

Institutional Review Board approval was obtained.


• Retrospective

• Observational

• Performed at one institution

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Supplementary Table 1

(DOCX 18 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kim, C., Do, K., Cha, J. et al. Effects of sirolimus in lymphangioleiomyomatosis patients on lung cysts and pulmonary function: long-term follow-up observational study. Eur Radiol 30, 735–743 (2020) doi:10.1007/s00330-019-06412-4

Download citation


  • Multidetector computed tomography
  • Lymphangioleiomyomatosis
  • Respiratory function tests
  • Sirolimus
  • Tuberous sclerosis complex