|Classification and external resources|
Figure A shows the location of the lungs and airways in the body. The inset image shows a cross-section of a healthy lung. Figure B shows a view of the lungs with LAM and a collapsed lung (pneumothorax). The inset image shows a cross-section of a lung with LAM.
Lymphangioleiomyomatosis (LAM) is a rare lung disease that results in a proliferation of disorderly smooth muscle growth (leiomyoma) throughout the lungs, in the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways (leading to pulmonary cyst formation and pneumothorax) and lymphatics (leading to chylous pleural effusion). LAM occurs in a sporadic form, which affects only females, usually of childbearing age; LAM also occurs in patients who have tuberous sclerosis.
Signs and symptoms
- shortness of breath on exertion
- hemoptysis, as a result of vascular congestion
- recurrent pneumothorax
- chylous pleural effusion and chylous ascites, as a result of lymphatic obstruction.
Symptoms are more likely in women, with average age at onset 34 years. Symptoms may precede radiographic abnormalities.
The proliferating smooth muscle that occurs in the type of LAM seen in patients with tuberous sclerosis (TSC-LAM) has been shown to represent clones of the smooth muscle in those patients' renal angiomyolipomas. Thus it is believed to represent metastases of this "benign" tumor. There is a female preponderance to TSC-LAM.
Investigations may include:
- Spirometry studies, which may include an increased FVC, with a decreased FVC1/FVC ratio.
- High-Resolution CT, which may demonstrate an interstitial pattern with cystic changes 
- Vascular endothelial growth factor D, which is typically elevated.
In patients with typical cystic changes on high resolution CT scanning serum levels of vascular endothelial growth factor-D greater than 800 pg/ml are considered to be diagnostic for LAM.
In some cases, the diagnosis of LAM can be made with confidence on clinical grounds (without biopsy) in patients with typical cystic changes on high resolution CT scanning of the lung and findings of tuberous sclerosis, angiomyolipoma or chylothorax
LAM may be treated with a number of therapies.
Anti-estrogen therapy. This may include use of tamoxifen or surgical removal of the ovaries. Other drugs may include progesterone or GnRH agonists. This therapy has been in use since the 1980s, and was developed in light of reports of LAM worsening during pregnancy. None of these therapies has been shown to be clearly efficacious, and all have undesirable side-effects. There is some evidence which shows that tamoxifen may actually cause worsening of LAM in some patients.
Sirolimus. Sirolimus is an antiproliferative and immunosuppressant interleukin-2 inhibitor that is used in some patients with LAM. Unlike anti-estrogen therapy, Sirolimus has statistically significant efficacy, improving quality of life in mild-to-moderately severe LAM patients.
Lung transplantation may be considered when pulmonary function has sufficiently deteriorated. Following lung transplant, LAM patients have Kaplan-Meier estimators (survival curves) similar to other lung transplant patients. Although LAM has been reported to recur in the transplanted lung , there have been no reported cases of graft failure or death due to recurrence. LAM-specific complications may occur secondary to transplantation, include pneumothorax secondary to a ruptured cyst, chylothorax, LAM recurrence, and abdominal complications[which?]. General transplant-related may include bacterial, viral and fungal lung infections, and rejection of the lung, including graft-versus-host disease and host-versus-graft disease.
A chylothorax should be managed conservatively. Surgical interventions may be pursued, including pleural abrasion, pleurodesis and pleurectomy, however these should be avoided in early stages of the disease, as intervention may impact on future lung transplantation.
10-year survival figures range from 49-79%, with LAM believed to be progressive, ultimately leading to respiratory failure. High reported survival may stem from improvements in diagnosis, allowing for earlier diagnosis of LAM at a less severe change. Thus survival differences may not reflect changes in treatment, but rather earlier diagnosis.
LAM almost always affects women, with only a handful of cases reported in men. The first of these was in a man with tuberous sclerosis, reported in 2000 from the Mayo Clinic by a team led by Henry Tazelaar
- Johnson, SR; Cordier, JF, Lazor, R, Cottin, V, Costabel, U, Harari, S, Reynaud-Gaubert, M, Boehler, A, Brauner, M, Popper, H, Bonetti, F, Kingswood, C, Review Panel of the ERS LAM Task, Force (2010 Jan). "European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis.". The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 35 (1): 14–26. doi:10.1183/09031936.00076209. PMID 20044458.
- Yu, J; Astrinidis, A; Howard, S; Henske, EP (2004 Apr). "Estradiol and tamoxifen stimulate LAM-associated angiomyolipoma cell growth and activate both genomic and nongenomic signaling pathways.". American journal of physiology. Lung cellular and molecular physiology 286 (4): L694–700. PMID 12922981.
- Pallisa, E; Sanz, P; Roman, A; Majó, J; Andreu, J; Cáceres, J (2002 Oct). "Lymphangioleiomyomatosis: pulmonary and abdominal findings with pathologic correlation.". Radiographics : a review publication of the Radiological Society of North America, Inc. 22 Spec No: S185–98. PMID 12376610.
- Clemm, C; Jehn, U; Wolf-Hornung, B; Siemon, G; Walter, G (1987 Apr 15). "Lymphangiomyomatosis: a report of three cases treated with tamoxifen.". Klinische Wochenschrift 65 (8): 391–3. PMID 3586575.
- 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 (2010 Sep). "Serum vascular endothelial growth factor-D prospectively distinguishes lymphangioleiomyomatosis from other diseases.". Chest 138 (3): 674–81. PMID 20382711.
- Ye, L; Jin, M, Bai, C (2010 Oct). "Clinical analysis of patients with pulmonary lymphangioleiomyomatosis (PLAM) in mainland China.". Respiratory medicine 104 (10): 1521–6. doi:10.1016/j.rmed.2010.05.003. PMID 20627505.
- Torre, O; Harari, S (2010 Jul). "The diagnosis of cystic lung diseases: a role for bronchoalveolar lavage and transbronchial biopsy?". Respiratory medicine. 104 Suppl 1: S81–5. doi:10.1016/j.rmed.2010.03.021. PMID 20430602.
- Clemm C, Jehn U, Wolf-Hornung B, Siemon G, Walter G (Apr 1987). "Lymphangiomyomatosis: a report of three cases treated with tamoxifen". Klin Wochenschr 65 (8): 391–3. doi:10.1007/BF01745582. PMID 3586575.
- 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 (2011 Apr 28). "Efficacy and safety of sirolimus in lymphangioleiomyomatosis.". The New England journal of medicine 364 (17): 1595–606. PMID 21410393.
- Boehler, A; Speich, R; Russi, EW; Weder, W (1996 Oct 24). "Lung transplantation for lymphangioleiomyomatosis.". The New England journal of medicine 335 (17): 1275–80. PMID 8857007.
- Moses, MA; Harper, J, Folkman, J (2006-06-15). "Doxycycline treatment for lymphangioleiomyomatosis with urinary monitoring for MMPs.". The New England Journal of Medicine 354 (24): 2621–2. doi:10.1056/NEJMc053410. PMID 16775248.
- Aubry, MC; Myers, JL; Ryu, JH; Henske, EP; Logginidou, H; Jalal, SM; Tazelaar, HD (2000 Aug). "Pulmonary lymphangioleiomyomatosis in a man.". American journal of respiratory and critical care medicine 162 (2 Pt 1): 749–52. PMID 10934115.
- The LAM Foundation (US)
- LAM Treatment Alliance
- LAM Action (UK)
- J-LAM (Japan)
- LAM Australasia Research Alliance (LARA)
- LAM Trust of New Zealand
- LAM Italia Non Profit of Italy