Key LAM Publications

McCarthy, Cormac, Nishant Gupta, Simon R Johnson, Jane J Yu, and Francis X McCormack. “Lymphangioleiomyomatosis: Pathogenesis, Clinical Features, Diagnosis, and Management.” The LancetRespiratory Medicine 9, no. 11 (2021): 1313–27. https://doi.org/10.1016/s2213-2600(21)00228-9. Published Online August 27, 2021, https://doi.org/10.1016/ S2213-2600(21)00228-9 

Eight LAM Articles That Led to An Effective Treatment

  1. Identification of the genes that cause tuberous sclerosis
    European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993 Dec 31;75(7):1305-15. PubMed PMID: 8269512.
  2. van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S,Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JB, Ward S, Green AJ, Yates JR, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997 Aug 8;277(5327):805-8. PubMed PMID: 9242607.
  3. Discovery of the function of LAM genes
    Ito N, Rubin GM. gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell. 1999 Feb 19;96(4):529-39. Erratum in: Cell 2001 May 4;105(3):415. PubMed PMID: 10052455.
  4. Discovery that tuberous sclerosis mutations cause LAM
    Smolarek TA, Wessner LL, McCormack FX, Mylet JC, Menon AG, Henske EP. Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13 loss of heterozygosity in angiomyolipomas and lymph nodes from women with lymphangiomyomatosis. Am J Hum Genet. 1998 Apr;62(4):810-5. PubMed PMID: 9529362; PubMed Central PMCID: PMC1377043.
  5. Carsillo T, Astrinidis A, Henske EP. Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci U S A. 2000 May 23;97(11):6085-90. PubMed PMID: 10823953; PubMed Central PMCID: PMC18562.
  6. Discovery that mTOR is activated in LAM tissues
    Goncharova EA, Goncharov DA, Eszterhas A, Hunter DS, Glassberg MK, Yeung RS, Walker CL, Noonan D, Kwiatkowski DJ, Chou MM, Panettieri RA Jr, Krymskaya VP.Tuberin regulates p70 S6 kinase activation and ribosomal protein S6phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM). J Biol Chem. 2002 Aug 23;277(34):30958-67. Epub2002 Jun 3. PubMed PMID: 12045200.
  7. Demonstration that mTOR inhibitors have promise in tuberous sclerosis models.
    Kenerson H, Dundon TA, Yeung RS. Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res. 2005 Jan;57(1):67-75. Epub 2004 Nov 19. PubMed PMID: 15557109.
  8. Identification of sirolimus as an effective therapy for LAM
    McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L,Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16. PubMed PMID: 21410393; PubMed Central PMCID: PMC3118601.

Articles That Are Most Important for LAM Patients

  1. Sirolimus is an effective treatment that slows lung function decline
    McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF,Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L,Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16. PubMed PMID: 21410393; PubMed Central PMCID: PMC3118601.
  2. Everolimus appears to be an effective treatment too
    Goldberg HJ, Harari S, Cottin V, Rosas IO, Peters E, Biswal S, Cheng Y, Khindri S, Kovarik JM, Ma S, McCormack FX, Henske EP. Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study. Eur Respir J. 2015 Sep;46(3):783-94. doi: 10.1183/09031936.00210714. Epub 2015 Jun 25. PubMed PMID: 26113676.
  3. Lower dose sirolimus may work as well as higher doses
    Ando K, Kurihara M, Kataoka H, Ueyama M, Togo S, Sato T, Doi T, Iwakami S, Takahashi K, Seyama K, Mikami M. Efficacy and safety of low dose sirolimus for treatment of lymphangioleiomyomatosis. Respir Investig. 2013 Sep;51(3):175-83. doi: 10.1016/j.resinv.2013.03.002. Epub 2013 May 30. PubMed PMID: 23978644.
  4. Doxycycline does not appear to work for LAM
    Chang WY, Cane JL, Kumaran M, Lewis S, Tattersfield AE, Johnson SR. A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis. Eur Respir J. 2014 Apr;43(4):1114-23. doi: 10.1183/09031936.00167413. Epub 2013 Dec 5. PubMed PMID: 24311763.
  5. Sirolimus is an effective treatment for chylous effusions and lymph node involvement.
    Taveira-DaSilva AM, Hathaway O, Stylianou M, Moss J. Changes in lung function and chylous effusions in patients with lymphangioleiomyomatosis treated with sirolimus. Ann Intern Med. 2011 Jun 21;154(12):797-805, W-292-3. doi: 10.7326/0003-4819-154-12-201106210-00007. PubMed PMID: 21690594; PubMed Central PMCID: PMC3176735.
  6. Treatment with sirolimus over long time frame is safe and provides durable benefit
    Bee J, fuller S, Miller S, Johnson SR. Lung function response and side effects to rapamycin for lymphangioleiomyomatosis: a prospective national cohort study. Thorax. 2018 Apr;73(4):369-375. 6 a) Taveira-DaSilva AM, Jones AM, Julen-Williams P, et al. Long-Term Effect of Sirolimus on Serum Vascular Endothelial Growth Factor D Levels in Patients With Lymphangioleiomyomatosis. Chest. 2018 Jan;153(1):124-132. 6 b)Hu S, Wu X, Xu W, et al. Long-term efficacy and safety of sirolimus therapy in patients with lymphangioleiomyomatosis. Orphanet J Rare Dis. 2019 Aug 20;14(1):206.
  7. Treatment with sirolimus helps women with LAM live longer
    Xu W, Yang C, Cheng C, et al. Determinants of Progression and Mortality in Lymphangioleiomyomatosis. Chest. 2023; Feb 18;S0012-3692(23)00272-6.
  8. Treatment with sirolimus might also reduce the risk of pneumothoracesCheng C, Xu W, Wang Y, et al. Sirolimus reduces the risk of pneumothorax recurrence in patients with lymphangioleiomyomatosis: a historical prospective self-controlled study. Orphanet J Rare Dis. 2022 Jul 8;17(1):257. 8 a)Cortinas N, Liu J, Kopras E, et al. Impact of Age, Menopause, and Sirolimus on Spontaneous Pneumothoraces in Lymphangioleiomyomatosis. Chest. 2022 Dec;162(6):1324-1327.
  9. Pulmonary rehabilitation might help improve shortness of breath and quality of life in women with LAM.
    Araujo MS, Baldi BG, Freitas C, et al. Pulmonary rehabilitation in lymphangioleiomyomatosis: a controlled clinical trial. Eur Respir J. 2016 May;47(5):1452-60
  10. VEGF-D is a diagnostic blood test that can substitute for lung biopsy in some patients
    Young LR, Vandyke R, Gulleman PM, Inoue Y, Brown KK, Schmidt LS, Linehan WM,Hajjar F, Kinder BW, Trapnell BC, Bissler JJ, Franz DN, McCormack FX. Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases. Chest. 2010 Sep;138(3):674-81. doi:10.1378/chest.10-0573. Epub 2010 Apr 9. PubMed PMID: 20382711; PubMed CentralPMCID: PMC2940071. 9 a) Young LR, Inoue Y, McCormack FX. Diagnostic potential of serum VEGF-D for lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10;358(2):199-200. doi: 10.1056/NEJMc0707517. PubMed PMID: 18184970; PubMed Central PMCID: PMC3804557
  11. VEGF-D is a blood test that can help with decisions about whether treatment will be effective
    Young L, Lee HS, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF,Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Downey GP, Swigris JJ, Taveira-DaSilva AM, Krischer JP, Trapnell BC, McCormack FX; MILES Trial Group. Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus(MILES) trial. Lancet Respir Med. 2013 Aug;1(6):445-52. PubMed PMID: 24159565; PubMed Central PMCID: PMC3804556. 11 a) Gupta N, Lee HS, Young LR, Strange C, Moss J, Singer LG, Nakata K, Barker AF, Chapman JT, Brantly MF, Stocks JM, Brown KK, Lynch JP, Goldberg HJ, Downey GP, Taveira-DaSilva AM, Krischer JP, Setchell K, Trapnell BC, Inoue Y, McCormack FX, for the NIH Rare Lung Diseases Consortium. Analysis of the MILES Cohort Reveals Determinants of Disease Progression and Treatment Response in LAM. Eur Respir J. 2019;53: 1802066. PubMed PMID: 30846465
  12. The average survival in women with LAM is greater than 25 years from the time to diagnosis and not 8-10 years.
    Gupta N, Lee HS, Ryu JH, Taveira-DaSilva AM, Beck GJ, Lee JC, McCarthy K, Finlay G, Brown K, Ruoss S, Avila NA, Moss J, McCormack FX. The NHLBI LAM Registry: Prognostic physiological and radiological biomarkers emerge from a 15-year prospective longitudinal analysis. CHEST. 2019;155:288-296. PubMed PMID: 29940164. 12 a) Oprescu N, McCormack FX, Byrnes S, Kinder B. Clinical predictors of mortality and cause of death in lymphangioleiomyomatosis: a population-based registry. Lung. 2013 Feb;191(1):35-42.
  13. Menopausal status and baseline lung function are important variables that can help predict the future course in LAM.
    Gupta N, Lee HS, Ryu JH, Taveira-DaSilva AM, Beck GJ, Lee JC, McCarthy K, Finlay G, Brown K, Ruoss S, Avila NA, Moss J, McCormack FX. The NHLBI LAM Registry: Prognostic physiological and radiological biomarkers emerge from a 15-year prospective longitudinal analysis. CHEST. 2019;155:288-296. PubMed PMID: 29940164. 13 a) Palipana A et al, Gecili E, Song S et al. Predicting Individualized Lung Disease Progression in Treatment-Naïve Patients With Lymphangioleiomyomatosis. CHEST. 2023 Jan 4;S0012-3692(23)00006-5.
  14. Air travel is safe in LAM
    Pollock-BarZiv S, Cohen MM, Downey GP, Johnson SR, Sullivan E, McCormack FX. Air travel in women with lymphangioleiomyomatosis. Thorax. 2007 Feb;62(2):176-80. Epub 2006 Oct 13. PubMed PMID: 17040934; PubMed Central PMCID: PMC2111263. 1: Taveira-DaSilva AM, Burstein D. 14 a)Hathaway OM, Fontana JR, Gochuico BR, Avila NA, Moss J. Pneumothorax after air travel in lymphangioleiomyomatosis, idiopathic pulmonary fibrosis, and sarcoidosis. Chest. 2009 Sep;136(3):665-70. doi: 10.1378/chest.08-3034. Epub 2009 Mar 24. PubMed PMID: 19318672; PubMed Central PMCID: PMC2775992.
  15. Lung transplantation is an effective option for end stage LAM with outcomes that are better than other lung diseases
    Khawar MU, Yazdani D, Zhu Z, Jandarov R, Dilling DF, and Gupta N. Clinical outcomes and survival following lung transplantation in patients with lymphangioleiomyomatosis. J Heart Lung Transplant. 2019;38:949-955. PubMed PMID: 31303421
  16. Clinical practice guidelines exist to guide proper diagnosis and management of patients with LAM
    Johnson SR, Cordier JF, Lazor R et al. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis. Eur Respir J. 2010 Jan;35(1):14-26 16 a) McCormack FX, Gupta N, Finlay GR, et al. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: LAM Diagnosis and Management. Am J Respir Crit Care Med. 2016 Sep 15;194(6):748-61. PMID:27628078. 16 b) Gupta N, Finlay GA, Kotloff RM, et al. Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline. Am J respir Crit Care Med. 2017 Nov 15;196(10):1337-1348.
  17. Understanding the priorities for women diagnosed with lymphangioleiomyomatosis: a patient perspective
    Iris Bassi, Gill Hollis, Vincent Cottin, Sergio Harari, Elma Zwanenburg, Marcel Veltkamp, Alvaro Casanova, Monica Fletcher, Sarah Masefield, Pippa Powell, Jeanette Boyd. DOI: 10.1183/23120541.00102-2015 Published 21 April 2016
  18. Patient Organizations and Research on Rare Diseases
    Ingelfinger, Julie R., and Jeffrey M. Drazen. 2011 The New England Journal of Medicine 364 (17): 1670–71. doi:10.1056/NEJMe1102290. 18 a)How Much Would You Give to Save a Dying Bird? Patient Advocacy and Biomedical Research Rosenbaum, Lisa. 2012. The New England Journal of Medicine 367 (18): 1755–59. doi:10.1056/NEJMms1207114.
Menu