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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Lung transplantation for lymphangioleiomyomatosis

  • Krishnan Warrior
    Affiliations
    Division of Pulmonary and Critical Care, Loyola University Chicago, Stritch School of Medicine, Maywood, IL
    Search for articles by this author
  • Daniel F. Dilling
    Correspondence
    Reprint requests: Daniel F. Dilling, MD, Division of Pulmonary and Critical Care, Loyola University Chicago, Stritch School of Medicine, 2160 S. 1st Avenue, Maywood, IL, 60153. Telephone: (708) 327-2181. Fax: (708) 327-2424.
    Affiliations
    Division of Pulmonary and Critical Care, Loyola University Chicago, Stritch School of Medicine, Maywood, IL
    Search for articles by this author
Published:October 08, 2022DOI:https://doi.org/10.1016/j.healun.2022.09.021
      Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease, associated with respiratory symptoms of dyspnea and spontaneous pneumothorax, along with various extra-thoracic manifestations. Often a progressive disease, albeit slowly, patients can develop chronic and severe respiratory failure and require supplemental oxygen. Lung transplantation (LTX) can offer improved duration and quality of life for patients with end-stage lung disease due to LAM. There are several unique considerations for LTX in LAM patients, and disease-specific complications of LAM prior to LTX can affect management decisions. Furthermore, there are several possible post-transplant issues specific to LAM. In this review, we discuss evaluation and management, disease-specific complications (both pre- and post-transplant), and outcomes for LAM patients undergoing lung transplantation.

      KEYWORDS

      List of non-standard abbreviation:

      LAM (Lymphangioleiomyomatosis), LTX (Lung transplantation), TSC (Tuberous sclerosis complex), mTOR (Mechanistic target of rapamycin)
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      References

        • McCarthy C
        • Gupta N
        • Johnson SR
        • Yu JJ
        • McCormack FX.
        Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management.
        Lancet Respir Med. 2021; (Published online August)https://doi.org/10.1016/S2213-2600(21)00228-9
        • Urban T
        • Lazor R
        • Lacronqiue J
        • et al.
        Pulmonary lymphangioleiomyomatosis: a study of 69 patients.
        Medicine (Baltimore). 1999; 78: 321-337
        • Schiavina M
        • di Scioscio V
        • Contini P
        • et al.
        Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without tuberous sclerosis complex.
        Am J Respir Crit Care Med. 2007; 176: 96-98https://doi.org/10.1164/rccm.200610-1408CR
        • Aubry MC
        • Myers JL
        • Ryu JH
        • et al.
        Pulmonary Lymphangioleiomyomatosis in a Man.
        Am J Respir Crit Care Med. 2000; 162: 749-752
        • Costello LC;
        • Hartman TE;
        • Ryu JH.
        High frequency of pulmonary lymphangioeiomyomatosis in women with tuberous sclerosis complex.
        Mayo Clin Proc. 2000; 75: 591
        • Moss J
        • Avila NA
        • Barnes PM
        • et al.
        Prevalence and Clinical Characteristics of Lymphangioleiomyomatosis (LAM) in Patients with Tuberous Sclerosis Complex.
        Am J Respir Crit Care Med. 2001; 164: 669-671
        • Goncharova EA
        • Goncharov DA
        • Eszterhas A
        • et al.
        Tuberin regulates p70 S6 kinase activation and ribosomal protein S6 phosphorylation: a role for the TSC2 tumor suppressor gene in pulmonary lymphangioleiomyomatosis (LAM).
        J Biol Chem. 2002; 277: 30958-30967https://doi.org/10.1074/jbc.M202678200
        • 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; 97: 6085-6090
        • Corrin B
        • Liebow AA
        • Friedman PJ.
        Pulmonary lymphangiomyomatosis: a review.
        Am J Pathol. 1975; 79: 348-382
        • Carrington CB
        • Cugell DW
        • Gaensler EA
        • et al.
        Lymphangioleiomyomatosis: physiologic-pathologic-radiologic correlations.
        Am Rev Respir Dis. 1977; 116: 977-995
        • Ferrans VJ
        • Yu ZX
        • Nelson WK
        • et al.
        Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features.
        J Nippon Med School. 2000; 67: 311-329
        • McCormack FX
        • Travis WD
        • Colby T.v.
        • Henske EP
        • Moss J.
        Lymphangioleiomyomatosis - Calling it what it is: a low-grade, destructive, metastasizing neoplasm.
        Am J Respir Crit Care Med. 2012; 186: 1210-1212https://doi.org/10.1164/rccm.201205-0848OE
        • Ryu JH
        • Moss J
        • Beck GJ
        • et al.
        The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment.
        Am J Respir Crit Care Med. 2006; 173: 105-111https://doi.org/10.1164/rccm.200409-1298OC
        • Taylor JR
        • Ryu J
        • Colby TV
        • Raffin TA.
        Lymphangioleiomyomatosis. Clinical course in 32 patients.
        N Engl J Med. 1990; 323: 1254-1260
        • Taveira-Da Silva AM
        • Jones AM
        • Julien-Williams P
        • Yao J
        • Stylianou M
        • Moss J
        Severity and outcome of cystic lung disease in women with tuberous sclerosis complex.
        Eur Respir J. 2015; 45: 171-180https://doi.org/10.1183/09031936.00088314
        • McCormack FX
        • Inoue Y
        • Moss J
        • et al.
        Efficacy and safety of sirolimus in lymphangioleiomyomatosis.
        N Engl J Med. 2011; 364: 1595-1606https://doi.org/10.1056/nejmoa1100391
        • McCormack FX
        • Gupta N
        • Finlay GR
        • et al.
        Official American thoracic society/Japanese respiratory society clinical practice guidelines: Lymphangioleiomyomatosis diagnosis and management.
        Am J Respir Crit Care Med. 2016; 194: 748-761https://doi.org/10.1164/rccm.201607-1384ST
        • Bissler JJ
        • Mccormack FX
        • Young LR
        • et al.
        Sirolimus for Angiomyolipoma in Tuberous Sclerosis Complex or Lymphangioleiomyomatosis.
        N Engl J Med. 2008; 358: 140-151
        • Bissler JJ
        • Kingswood JC
        • Radzikowska E
        • et al.
        Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial.
        Lancet North Am Ed. 2013; 381: 817-824https://doi.org/10.1016/S0140-6736(12)61767-X
        • Franz DN
        • Belousova E
        • Sparagana S
        • et al.
        Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial.
        Lancet North Am Ed. 2013; 381: 125-132https://doi.org/10.1016/S0140-6736(12)61134-9
        • Taveira-DaSilva AM
        • Stylianou MP
        • Hedin CJ
        • Hathaway O
        • Moss J.
        Decline in lung function in patients with lymphangioleiomyomatosis treated with or without progesterone.
        Chest. 2004; 126: 1867-1874https://doi.org/10.1378/chest.126.6.1867
        • Chambers DC
        • Cherikh WS
        • Harhay MO
        • et al.
        The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult lung and heart–lung transplantation Report—2019; Focus theme: donor and recipient size match.
        J Heart Lung Transplant. 2019; 38: 1042-1055https://doi.org/10.1016/j.healun.2019.08.001
        • Garami A
        • Zwartkruis FJT
        • Nobukuni T
        • et al.
        Insulin activation of Rheb, a mediator of mTOR:S6K:4E-BP signaling, is inhibited by TSC1 and 2.
        Mol Cell. 2003; 11: 1457-1466
        • Dibble CC
        • Elis W
        • Menon S
        • et al.
        TBC1D7 is a Third Subunit of the TSC1-TSC2 complex upstream of mTORC1.
        Mol Cell. 2012; 47: 535-546https://doi.org/10.1016/j.molcel.2012.06.009
        • Benvenuto G
        • Li S
        • Brown SJ
        • et al.
        The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination.
        Oncogene. 2000; 19: 6306-6316
        • Manning BD
        • Tee AR
        • Logsdon MN
        • Blenis J
        • Cantley LC.
        Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase:akt pathway.
        Mol Cell. 2002; 10: 151-162
        • Inoki K
        • Li Y
        • Zhu T
        • Wu J
        • Guan KL.
        TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.
        Nat Cell Biol. 2002; 4https://doi.org/10.1038/ncb839
        • O'mahony AM
        • Lynn E
        • Murphy DJ
        • Fabre A
        • McCarthy C
        Lymphangioleiomyomatosis: a clinical review.
        Breathe. 2020; 16: 1-11https://doi.org/10.1183/20734735.0007-2020
        • Sarbassov DD
        • Ali SM
        • Kim DH
        • et al.
        Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.
        Curr Biol. 2004; 14https://doi.org/10.1016/j.cub.2004.06.054
        • Ben-Sahra I
        • Manning BD.
        mTORC1 signaling and the metabolic control of cell growth.
        Curr Opin Cell Biol. 2017; 45: 72-82https://doi.org/10.1016/j.ceb.2017.02.012
        • Jacinto E
        • Facchinetti V
        • Liu D
        • et al.
        SIN1/MIP1 Maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity.
        Cell. 2006; 127: 125-137https://doi.org/10.1016/j.cell.2006.08.033
        • Ricoult SJH
        • Yecies JL
        • Ben-Sahra I
        • Manning BD.
        Oncogenic PI3K and K-Ras stimulate de novo lipid synthesis through mTORC1 and SREBP.
        Oncogene. 2016; 35: 1250-1260https://doi.org/10.1038/onc.2015.179
        • Dodd KM
        • Yang J
        • Shen MH
        • Sampson JR
        Tee AR. mTORC1 drives HIF-1α and VEGF-A signalling via multiple mechanisms involving 4E-BP1, S6K1 and STAT3.
        Oncogene. 2015; 34: 2239-2250https://doi.org/10.1038/onc.2014.164
        • Dilling DF.
        The 10,000-Piece Puzzle of Lymphangioleiomyomatosis.
        Chest. 2018; 153: 298-299https://doi.org/10.1016/j.chest.2017.07.027
        • Glasgow CG
        • Pacheco-Rodriguez G
        • Steagall WK
        • et al.
        CA-125 in Disease Progression and Treatment of Lymphangioleiomyomatosis.
        Chest. 2018; 153: 339-348https://doi.org/10.1016/j.chest.2017.05.018
        • Goncharova EA
        • Goncharov DA
        • Spaits M
        • et al.
        Abnormal growth of smooth muscle-like cells in lymphangioleiomyomatosis: role for tumor suppressor TSC2.
        Am J Respir Cell Mol Biol. 2006; 34: 561-572https://doi.org/10.1165/rcmb.2005-0300OC
        • Matsumoto Y
        • Horiba K
        • Usuki J
        • Chu SC
        • Ferrans VJ
        • Moss J.
        Markers of cell proliferation and expression of melanosomal antigen in lymphangioleiomyomatosis.
        Am J Respir Cell Mol Biol. 1999; 21: 327-336
        • Klarquist J
        • Barfuss A
        • Kandala S
        • et al.
        Melanoma-associated antigen expression in lymphangioleiomyomatosis renders tumor cells susceptible to cytotoxic T cells.
        Am J Pathol. 2009; 175: 2463-2472https://doi.org/10.2353/ajpath.2009.090525
        • Guo M
        • Yu JJ
        • Perl AK
        • et al.
        Single-cell transcriptomic analysis identifies a unique pulmonary lymphangioleiomyomatosis cell.
        Am J Respir Crit Care Med. 2020; 202: 1373-1387https://doi.org/10.1164/rccm.201912-2445OC
        • Maisel K
        • Merrilees MJ
        • Atochina-Vasserman EN
        • et al.
        Immune checkpoint ligand PD-L1 is upregulated in pulmonary lymphangioleiomyomatosis.
        Am J Respir Cell Mol Biol. 2018; 59: 723-732https://doi.org/10.1165/rcmb.2018-0123OC
        • Liu HJ
        • Lizotte PH
        • Du H
        • et al.
        TSC2-deficient tumors have evidence of T cell exhaustion and respond to anti-PD-1/anti-CTLA-4 immunotherapy.
        JCI Insight. 2018; 3https://doi.org/10.1172/jci.insight.98674
        • Osterburg AR
        • Nelson RL
        • Yaniv BZ
        • et al.
        NK cell activating receptor ligand expression in lymphangioleiomyomatosis is associated with lung function decline.
        JCI Insight. 2016; 1https://doi.org/10.1172/jci.insight.87270
        • Henske EP
        • McCormack FX.
        Lymphangioleiomyomatosis - A wolf in sheep's clothing.
        J Clin Invest. 2012; 122: 3807-3816https://doi.org/10.1172/JCI58709
        • Gu X
        • Yu JJ
        • Ilter D
        • Blenis N
        • Henske EP
        • Blenis J.
        Integration of mTOR and estrogen-ERK2 signaling in lymphangioleiomyomatosis pathogenesis.
        Proc Nat Sci Acad USA. 2013; 110: 14960-14965https://doi.org/10.1073/pnas.1309110110
        • Crooks DM
        • Pacheco-Rodriguez G
        • Decastro RM
        • et al.
        Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis.
        Proc Nat Acad Sci USA. 2004; 101: 17462-17467
        • Chang WYC
        • Cane JL
        • Blakey JD
        • Kumaran M
        • Pointon KS
        • Johnson SR.
        Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis.
        Respir Res. 2012; 13https://doi.org/10.1186/1465-9921-13-34
        • Johnson SR
        • Whale CI
        • Hubbard RB
        • Lewis SA
        • Tattersfield AE.
        Survival and disease progression in UK patients with lymphangioleiomyomatosis.
        Thorax. 2004; 59: 800-803https://doi.org/10.1136/thx.2004.023283
        • Gupta N
        • Langenderfer D
        • McCormack FX
        • Schauer DP
        • Eckman MH.
        Chest computed tomographic image screening for cystic lung diseases in patients with spontaneous pneumothorax is cost effective.
        Ann Am Thorac Soc. 2017; 14: 17-25https://doi.org/10.1513/AnnalsATS.201606-459OC
        • 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; 196: 1337-1348https://doi.org/10.1164/rccm.201709-1965ST
        • Gupta N
        • Meraj R
        • Tanase D
        • et al.
        Accuracy of chest high-resolution computed tomography in diagnosing diffuse cystic lung diseases.
        Eur Respir J. 2015; 46https://doi.org/10.1183/13993003.00570-2015
        • Johnson SR
        • Cordier JF
        • Lazor R
        • et al.
        European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis.
        Eur Respir J. 2010; 35: 14-26https://doi.org/10.1183/09031936.00076209
        • Zhe X
        • Schuger L.
        Combined smooth muscle and melanocytic differentiation in lymphangioleiomyomatosis.
        J Histochem Cytochem. 2004; 52: 1537-1542https://doi.org/10.1369/jhc.4A6438.2004
        • Matsui K
        • Takeda K
        • Yu ZX
        • et al.
        Downregulation of estrogen and progesterone receptors in the abnormal smooth muscle cells in pulmonary lymphangioleiomyomatosis following therapy an immunohistochemical study.
        Am J Respir Crit Care Med. 2000; 161: 1002-1009
        • Davies DM
        • Johnson SR
        • Tattersfield AE
        • et al.
        Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis.
        N Engl J Med. 2008; 358https://doi.org/10.1056/NEJMc072500
        • Weidman DR
        • Pole JD
        • Bouffet E
        • Taylor MD
        • Bartels U.
        Dose-level response rates of mtor inhibition in tuberous sclerosis complex (TSC) related subependymal giant cell astrocytoma (SEGA).
        Pediatr Blood Cancer. 2015; 62: 1754-1760https://doi.org/10.1002/pbc.25573
        • Hayashida M
        • Yasuo M
        • Hanaoka M
        • et al.
        Reductions in pulmonary function detected in patients with lymphangioleiomyomatosis: an analysis of the Japanese National Research Project on Intractable Diseases database.
        Respir Investig. 2016; 54https://doi.org/10.1016/j.resinv.2015.11.003
        • Gupta N
        • Lee HS
        • Ryu JH
        • et al.
        The NHLBI LAM registry: prognostic physiologic and radiologic biomarkers emerge from a 15-year prospective longitudinal analysis.
        Chest. 2019; 155: 288-296https://doi.org/10.1016/j.chest.2018.06.016
        • Gupta N
        • Lee HS
        • Young LR
        • et al.
        Analysis of the MILES cohort reveals determinants of disease progression and treatment response in lymphangioleiomyomatosis.
        Eur Respir J. 2019; 53https://doi.org/10.1183/13993003.02066-2018
        • Johnson SR
        • Tattersfield AE.
        Decline in lung function in lymphangioleiomyomatosis relation to menopause and progesterone treatment.
        Am J Respir Crit Care Med. 1999; 160: 628-633
        • Oprescu N
        • McCormack FX
        • Byrnes S
        • Kinder BW.
        Clinical predictors of mortality and cause of death in lymphangioleiomyomatosis: a population-based registry.
        Lung. 2013; 191https://doi.org/10.1007/s00408-012-9419-3
        • di Marco F
        • Terraneo S
        • Dias OM
        • et al.
        Natural history of incidental sporadic and tuberous sclerosis complex associated lymphangioleiomyomatosis.
        Respir Med. 2020; : 168https://doi.org/10.1016/j.rmed.2020.105993
        • Hayashida M
        • Seyama K
        • Inoue Y
        • Fujimoto K
        • Kubo K
        Respiratory Failure Research Group of the Japanese Ministry of Health L and W. The epidemiology of lymphangioleiomyomatosis in Japan: a nationwide cross-sectional study of presenting features and prognostic factors.
        respirol. 2007; 12https://doi.org/10.1111/j.1440-1843.2007.01101.x
        • Young LR
        • Almoosa KF
        • Pollock-BarZiv S
        • Coutinho M
        • McCormack FX
        • Sahn SA.
        Patient Perspectives on Management of Pneumothorax in Lymphangioleiomyomatosis.
        Chest. 2006; 129https://doi.org/10.1378/chest.129.5.1267
        • Almoosa KF
        • Ryu JH
        • Mendez J
        • et al.
        Management of pneumothorax in lymphangioleiomyomatosis: effects on recurrence and lung transplantation complications.
        Chest. 2006; 129: 1274-1281https://doi.org/10.1378/chest.129.5.1274
        • Ando K
        • Okada Y
        • Akiba M
        • et al.
        Lung transplantation for lymphangioleiomyomatosis in Japan.
        PLoS One. 2016; 11https://doi.org/10.1371/journal.pone.0146749
      1. OPTN Data. Organ Procurement and Transplantation Network website. Available at: https://optn.transplant.hrsa.gov/data/. Accessed May 1, 2022.

        • Estenne M
        • de Francquen P
        • Wellens F
        • et al.
        Combined heart-and-lung transplantation for lymphangioleiomyomatosis.
        Lancet. 1984; 1https://doi.org/10.1016/s0140-6736(84)90142-9
        • Boehler A
        • Speich R
        • Russi EW
        • Weder W.
        Lung transplantation for lymphangioleiomyomatosis.
        N Engl J Med. 1996; 335https://doi.org/10.1056/NEJM199610243351704
        • Pechet TT
        • Meyers BF
        • Guthrie TJ
        • et al.
        Lung transplantation for lymphangioleiomyomatosis.
        J Heart Lung Transpl. 2004; 23: 301-308https://doi.org/10.1016/S1053-2498(03)00195-5
        • Kpodonu J
        • Massad MG
        • Chaer RA
        • et al.
        The US experience with lung transplantation for pulmonary lymphangioleiomyomatosis.
        J Heart Lung Transpl. 2005; 24: 1247-1253https://doi.org/10.1016/j.healun.2004.09.013
        • Reynaud-Gaubert M
        • Mornex JF
        • Mal H
        • et al.
        Lung transplantation for lymphangioleiomyomatosis: the French experience.
        Transplantation. 2008; 86https://doi.org/10.1097/TP.0b013e31817c15df
        • Benden C
        • Rea F
        • Behr J
        • et al.
        Lung transplantation for lymphangioleiomyomatosis: the European experience.
        J Heart Lung Transplant. 2009; 28: 1-7https://doi.org/10.1016/j.healun.2008.09.014
        • Machuca TN
        • Losso MJ
        • Camargo SM
        • et al.
        Lung transplantation for lymphangioleiomyomatosis: Single-center Brazilian experience with no chylothorax.
        Transplant Proc. 2011; 43: 236-238https://doi.org/10.1016/j.transproceed.2010.12.051
        • Nakagiri T
        • Shintani Y
        • Minami M
        • et al.
        Lung transplantation for lymphangioleiomyomatosis in a single japanese institute, with a focus on late-onset complications.
        Transplant Proc. 2015; 47: 1977-1982https://doi.org/10.1016/j.transproceed.2015.04.103
        • Ussavarungsi K
        • Hu X
        • Scott JP
        • et al.
        Mayo clinic experience of lung transplantation in pulmonary lymphangioleiomyomatosis.
        Respir Med. 2015; 109: 1354-1359https://doi.org/10.1016/j.rmed.2015.08.014
        • Baldi BG
        • Samano MN
        • Campos SV
        • et al.
        Experience of lung transplantation in patients with lymphangioleiomyomatosis at a brazilian reference centre.
        Lung. 2017; 195https://doi.org/10.1007/s00408-017-0045-y
        • Oishi H
        • Watanabe T
        • Matsuda Y
        • et al.
        Single lung transplantation for lymphangioleiomyomatosis: a single-center experience in Japan.
        Surg Today. 2018; 48https://doi.org/10.1007/s00595-018-1678-z
        • Khawar MU
        • Yazdani D
        • Zhu Z
        • Jandarov R
        • Dilling DF
        • Gupta N.
        Clinical outcomes and survival following lung transplantation in patients with lymphangioleiomyomatosis.
        J Heart Lung Transplant. 2019; 38: 949-955https://doi.org/10.1016/j.healun.2019.06.015
        • Salman J
        • Ius F
        • Sommer W
        • et al.
        Long-term results of bilateral lung transplantation in patients with end-stage pulmonary lymphangioleiomyomatosis.
        Prog Transplant. 2019; 29https://doi.org/10.1177/1526924819835815
        • Kurosaki T
        • Otani S
        • Miyoshi K
        • et al.
        Favorable survival even with high disease-specific complication rates in lymphangioleiomyomatosis after lung transplantation—long-term follow-up of a Japanese center.
        Clinical Respiratory Journal. 2020; 14: 116-123https://doi.org/10.1111/crj.13108
        • Zhang J
        • Liu D
        • Yue B
        • et al.
        A retrospective study of lung transplantation in patients with lymphangioleiomyomatosis: challenges and outcomes.
        Front Med (Lausanne). 2021; 8https://doi.org/10.3389/fmed.2021.584826
        • Chang S
        • Choi JS
        • Leem AY
        • et al.
        Long-term clinical course and progression of lymphangioleiomyomatosis in a single lung transplant referral centre in Korea.
        Sci Rep. 2022; 12: 8260https://doi.org/10.1038/s41598-022-12314-1
        • Leard LE
        • Holm AM
        • Valapour M
        • et al.
        Consensus document for the selection of lung transplant candidates: an update from the International Society for Heart and Lung Transplantation.
        J Heart Lung Transplant. 2021; 40: 1349-1379https://doi.org/10.1016/j.healun.2021.07.005
        • Valapour M
        • Lehr CJ
        • Skeans MA
        • et al.
        OPTN/SRTR 2020 Annual Data Report: lung.
        Am J Transplant. 2022; 22: 438-518https://doi.org/10.1111/ajt.16991
        • Gonano C
        • Pasquier J
        • Daccord C
        • et al.
        Air travel and incidence of pneumothorax in lymphangioleiomyomatosis.
        Orphanet J Rare Dis. 2018; 13https://doi.org/10.1186/s13023-018-0964-6
        • Weill D
        • Benden C
        • Corris PA
        • et al.
        A consensus document for the selection of lung transplant candidates: 2014 - an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation.
        J Heart Lung Transpl. 2015; 34: 1-15https://doi.org/10.1016/j.healun.2014.06.014
        • El-Chemaly S
        • Goldberg HJ
        • Glanville AR.
        Should mammalian target of rapamycin inhibitors be stopped in women with lymphangioleiomyomatosis awaiting lung transplantation?.
        Expert Rev Respir Med. 2014; 8: 657-660https://doi.org/10.1586/17476348.2014.956728
        • Groetzner J
        • Kur F
        • Spelsberg F
        • et al.
        Airway anastomosis complications in de novo lung transplantation with sirolimus-based immunosuppression.
        J Heart Lung Transplant. 2004; 23: 632-638https://doi.org/10.1016/S1053-2498(03)00309-7
        • King-Biggs MB
        • Dunitz JM
        • Park SJ
        • Savik SK
        • Hertz MI.
        Airway anastomotic dehiscence associated with use of sirolimus immediately after lung transplantation.
        Transplantation. 2003; 75: 1437-1443https://doi.org/10.1097/01.TP.0000064083.02120.2C
      2. Rapamune. Black box warning in package insert. in Wyeth Pharmaceuticals Inc PA, Philadelphia.

        • Warrior K
        • Leard LE
        • Nair AR
        • et al.
        A survey of use of mTOR inhibitors in patients with lymphangioleiomyomatosis listed for lung transplant.
        Respir Med. 2022; : 195https://doi.org/10.1016/j.rmed.2022.106779
        • Malouf MA
        • Hopkins P
        • Snell G
        • Glanville AR.
        An investigator-driven study of everolimus in surgical lung biopsy confirmed idiopathic pulmonary fibrosis.
        respirol. 2011; 16: 776-783https://doi.org/10.1111/j.1440-1843.2011.01955.x
        • Warrior K
        • Darley DR
        • Glanville AR
        • et al.
        Continuation of mTOR inhibition in LAM patients listed for lung transplant is safe.
        J Heart Lung Transplant. 2020; 39: S324https://doi.org/10.1016/j.healun.2020.01.334
        • Freitas CSG
        • Baldi BG
        • Jardim C
        • et al.
        Pulmonary hypertension in lymphangioleiomyomatosis: prevalence, severity and the role of carbon monoxide diffusion capacity as a screening method.
        Orphanet J Rare Dis. 2017; 12https://doi.org/10.1186/s13023-017-0626-0
        • Taveira-DaSilva AM
        • Hathaway OM
        • Sachdev V
        • Shizukuda Y
        • Birdsall CW
        • Moss J.
        Pulmonary artery pressure in lymphangioleiomyomatosis: an echocardiographic study.
        Chest. 2007; 132: 1573-1578https://doi.org/10.1378/chest.07-1205
        • Lau EMT
        • Tamura Y
        • McGoon MD
        • Sitbon O.
        The 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: a practical chronicle of progress.
        Eur Respir J. 2015; 46 (European Respiratory Society): 879-882https://doi.org/10.1183/13993003.01177-2015
        • Cottin V
        • Harari S
        • Humbert M
        • et al.
        Pulmonary hypertension in lymphangioleiomyomatosis: characteristics in 20 patients.
        Eur Respir J. 2012; 40: 630-640https://doi.org/10.1183/09031936.00093111
        • Wu X
        • Xu W
        • Wang J
        • Tian X
        • Tian Z
        • Xu K.
        Clinical characteristics in lymphangioleiomyomatosis-related pulmonary hypertension: an observation on 50 patients.
        Front Med. 2019; 13: 259-266https://doi.org/10.1007/s11684-018-0634-z
        • Krymskaya VP
        • Snow J
        • Cesarone G
        • et al.
        mTOR is required for pulmonary arterial vascular smooth muscle cell proliferation under chronic hypoxia.
        FASEB J. 2011; 25: 1922-1933https://doi.org/10.1096/fj.10-175018
        • George MP
        • Champion HC
        • Pilewski JM.
        Lung transplantation for pulmonary hypertension.
        Pulm Circ. 2011; 1: 182-191https://doi.org/10.4103/2045-8932.83455
        • v Conte J
        • MJ Borja
        • Patel CB
        • Yang SC
        • Jhaveri RM
        • Orens JB
        Lung transplantation for primary and secondary pulmonary hypertension.
        Ann Thorac Surg. 2001; 72: 1673-1680https://doi.org/10.1016/S0003-4975(01)03081-8
        • Hayes D
        • Black SM
        • Tobias JD
        • Mansour HM
        • Whitson BA.
        Prevalence of pulmonary hypertension and its influence on survival in patients with advanced chronic obstructive pulmonary disease prior to lung transplantation.
        COPD: Journal of Chronic Obstructive Pulmonary Disease. 2016; 13: 50-56https://doi.org/10.3109/15412555.2015.1043425
        • Villavicencio MA
        • Axtell AL
        • Osho A
        • et al.
        Single- versus double-lung transplantation in pulmonary fibrosis: impact of age and pulmonary hypertension.
        Ann Thorac Surg. 2018; 106: 856-863https://doi.org/10.1016/j.athoracsur.2018.04.060
        • Shehata IM
        • Elhassan A
        • Urits I
        • et al.
        Postoperative management of hyperinflated native lung in single-lung transplant recipients with chronic obstructive pulmonary disease: a review article.
        Pulm Ther. 2021; 7: 37-46https://doi.org/10.1007/s41030-020-00141-6
        • Lane CR
        • Tonelli AR.
        Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations.
        Int J Chron Obstruct Pulmon Dis. 2015; 10: 2137-2146https://doi.org/10.2147/COPD.S78677
        • Liu F
        • Ruan Z
        • Wang S
        • Lin Q.
        Right native lung pneumonectomy due to over inflation three years after left single lung transplantation for pulmonary lymphangioleiomyomatosis.
        Ann Thorac Cardiovasc Surg. 2014; 20: 70-73https://doi.org/10.5761/atcs.cr.13-00133
        • Yoshizaki A
        • Yamamoto M
        • Hirabayashi A
        • et al.
        Fatal hemoptysis due to endobronchial aspergilloma in the hyperinflated native lung after single-lung transplantation for lymphangioleiomyomatosis: a case report.
        Kobe J Med Sci. 2020; 65: E114-E117
        • Doerr CH
        • Allen MS
        • Nichols FC
        • Ryu JH.
        Etiology of chylothorax in 203 patients.
        Mayo Clin Proc. 2005; 80https://doi.org/10.4065/80.7.867
        • Maldonado F
        • Cartin-Ceba R
        • Hawkins FJ
        • Ryu JH.
        Medical and surgical management of chylothorax and associated outcomes.
        Am J Med Sci. 2010; 339https://doi.org/10.1097/MAJ.0b013e3181cdcd6c
        • Cerfolio RJ
        • Allen MS
        • Deschamps C
        • Trastek VF
        • Pairolero PC.
        Postoperative chylothorax.
        J Thorac Cardiovasc Surg. 1996; 112https://doi.org/10.1016/S0022-5223(96)70152-6
        • Bryant AS
        • Minnich DJ
        • Wei B
        • Cerfolio RJ.
        The incidence and management of postoperative chylothorax after pulmonary resection and thoracic mediastinal lymph node dissection.
        Ann Thorac Surg. 2014; 98 (Elsevier USA): 232-237https://doi.org/10.1016/j.athoracsur.2014.03.003
        • Jacob S
        • Meneses A
        • Landolfo K
        • et al.
        Incidence, management, and outcomes of chylothorax after lung transplantation: a single-center experience.
        Cureus. 2019; (Published online July 22)https://doi.org/10.7759/cureus.5190
        • Doerr CH
        • Miller DL
        • Chylothorax Ryu JH.
        Semin Respir Crit Care Med. 2001; 22https://doi.org/10.1055/s-2001-18797
        • Smoke A
        • Delegge MH.
        Chyle leaks: consensus on management?.
        Nutr Clin Pract. 2008; 23: 529-532https://doi.org/10.1177/0884533608323424
        • Nair SK
        • Petko M
        • Hayward MP.
        Aetiology and management of chylothorax in adults.
        Eur J Cardiothorac Surg. 2007; 32https://doi.org/10.1016/j.ejcts.2007.04.024
        • Boffa DJ
        • Sands MJ
        • Rice TW
        • et al.
        A critical evaluation of a percutaneous diagnostic and treatment strategy for chylothorax after thoracic surgery.
        Eur J Cardiothorac Surg. 2008; 33https://doi.org/10.1016/j.ejcts.2007.11.028
        • Arndt A
        • Boffa DJ.
        Pleural space complications associated with lung transplantation.
        Thorac Surg Clin. 2015; 25: 87-95https://doi.org/10.1016/j.thorsurg.2014.09.005
        • 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; 154https://doi.org/10.7326/0003-4819-154-12-201106210-00007
        • Ando K
        • Kurihara M
        • Kataoka H
        • et al.
        Efficacy and safety of low-dose sirolimus for treatment of lymphangioleiomyomatosis.
        Respir Investig. 2013; 51https://doi.org/10.1016/j.resinv.2013.03.002
        • Suzuki Y
        • Matsuda Y
        • Watanabe Y
        • et al.
        Efficacy and tolerability of sirolimus in lymphangioleiomyomatosis patients after lung transplantation: single-center experience in Japan.
        J Heart Lung Transplant. 2021; 40: S335
        • Kurosaki T
        • Otani S
        • Sugimoto S
        • et al.
        Experience of Using mTOR Inhibitor in Lung Transplant at Recipients With Lymphangioleiomyomatosis.
        J Heart Lung Transpl. 2018; 37: S455-S456
        • Jacob S
        • Ali M
        • El-Sayed Ahmed MM
        • et al.
        Refractory chylous effusions in lymphangioleiomyomatosis patient post lung transplant.
        SAGE Open Med Case Rep. 2020; 8 (2050313X2092133)https://doi.org/10.1177/2050313x20921332
        • Fremont RD
        • Milstone AP
        • Light RW
        • Ninan M.
        Chylothoraces after lung transplantation for lymphangioleiomyomatosis: review of the literature and utilization of a pleurovenous shunt.
        J Heart Lung Transpl. 2007; 26https://doi.org/10.1016/j.healun.2007.07.008
        • Tang A
        • Siddiqui HU
        • Thuita L
        • et al.
        Natural history of pleural complications after lung transplantation.
        Ann Thorac Surg. 2021; 111 (Elsevier Inc): 407-415https://doi.org/10.1016/j.athoracsur.2020.06.052
        • Ferrer J
        • Roldan J
        • Roman A
        • et al.
        Acute and chronic pleural complications in lung transplantation.
        J Heart Lung Transplant. 2003; 22: 1217-1225https://doi.org/10.1016/S1053-2498(02)01230-5
        • Herridge MS
        • de Hoyos AL
        • Chaparro C
        • Winton TL
        • Kesten S
        • Maurer JR.
        Pleural complications in lung transplant recipients.
        J Thorac Cardiovasc Surg. 1995; 110https://doi.org/10.1016/S0022-5223(05)80005-4
        • Chhajed PN
        • Tamm M
        • Glanville AR.
        Role of flexible bronchoscopy in lung transplantation.
        Semin Respir Crit Care Med. 2004; 25https://doi.org/10.1055/s-2004-832714
        • Smith L
        • Singer JP
        • Hayes M
        • Golden JA
        • Leard LE.
        An analysis of potential risk factors for early complications from fiberoptic bronchoscopy in lung transplant recipients.
        Transpl Int. 2012; 25https://doi.org/10.1111/j.1432-2277.2011.01392.x
        • Venuta F
        • Rendina EA
        • de Giacomo T
        • Ciriaco PP
        • della Rocca G
        • Ricci C.
        Thoracoscopic treatment of recurrent contralateral pneumothorax after single lung transplantation.
        J Heart Lung Transpl. 1994; 13: 555-557
        • Waller DA
        • Conacher ID
        • Dark JH.
        Videothoracoscopic pleurectomy after contralateral single-lung transplantation.
        Ann Thorac Surg. 1994; 57https://doi.org/10.1016/0003-4975(94)90231-3
        • Nine JS
        • Yousem SA
        • Paradis IL
        • Keenan R
        • Griffith BP.
        Lymphangioleiomyomatosis: recurrence after lung transplantation.
        J Heart Lung Transpl. 1994; 13: 714-719
        • Chen F
        • Bando T
        • Fukuse T
        • et al.
        Recurrent lymphangioleiomyomatosis after living-donor lobar lung transplantation.
        Transplant Proc. 2006; 38https://doi.org/10.1016/j.transproceed.2006.08.145
        • Chen F
        • Omasa M
        • Kondo N
        • et al.
        Sirolimus treatment for recurrent lymphangioleiomyomatosis after lung transplantation.
        Ann Thorac Surg. 2009; 87https://doi.org/10.1016/j.athoracsur.2008.07.107
        • Bittmann I
        • Rolf B
        • Amann G
        • Löhrs U.
        Recurrence of lymphangioleiomyomatosis after single lung transplantation: new insights into pathogenesis.
        Hum Pathol. 2003; 34https://doi.org/10.1053/hupa.2003.50
        • Karbowniczek M
        • Astrinidis A
        • Balsara BR
        • et al.
        Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism.
        Am J Respir Crit Care Med. 2003; 167https://doi.org/10.1164/rccm.200208-969OC
        • Sugimoto R
        • Nakao A
        • Yamane M
        • et al.
        Sirolimus amelioration of clinical symptoms of recurrent lymphangioleiomyomatosis after living-donor lobar lung transplantation.
        J Heart Lung Transpl. 2008; 27https://doi.org/10.1016/j.healun.2008.05.012
        • Bissler JJ
        • Kingswood JC
        • Radzikowska E
        • et al.
        Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial.
        Nephrol Dialysis Transpl. 2016; 31: 111-119https://doi.org/10.1093/ndt/gfv249
        • Ryan JW
        • Farrelly C
        • Geoghegan T.
        What are the indications for prophylactic embolization of renal angiomyolipomas? A review of the current evidence in the literature.
        Can Assoc Radiol J. 2018; 69: 236-239https://doi.org/10.1016/j.carj.2018.01.002
        • Kato H
        • Kuwatsuru R
        • Inoue T
        • Okada S
        • Aida M
        • Yamashiro Y.
        Superselective Transcatheter Arterial Embolization for Large Unruptured Renal Angiomyolipoma in Lymphangioleiomyomatosis.
        J Vasc Interv Radiol. 2018; 29: 958-965https://doi.org/10.1016/j.jvir.2017.11.003
        • Lecuelle D
        • Basille D
        • Renard C
        • Saint F
        • Jounieaux V.
        Highly effective sirolimus therapy for abdominal lymphangioleiomyoma.
        Respir Med Res. 2019; : 75https://doi.org/10.1016/j.resmer.2019.02.002