13 results on '"Tattersfield AE"'
Search Results
2. A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis.
- Author
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Chang WY, Cane JL, Kumaran M, Lewis S, Tattersfield AE, and Johnson SR
- Subjects
- Adult, Double-Blind Method, Enzyme Inhibitors therapeutic use, Exercise Tolerance, Female, Forced Expiratory Volume, Humans, Matrix Metalloproteinase Inhibitors therapeutic use, Matrix Metalloproteinases blood, Matrix Metalloproteinases urine, Middle Aged, Oxygen chemistry, Quality of Life, Spirometry, Surveys and Questionnaires, Doxycycline therapeutic use, Lymphangioleiomyomatosis drug therapy
- Abstract
Lymphangioleiomyomatosis (LAM) is characterised by lung cysts and airflow obstruction. Matrix metalloproteinases have been implicated in lung destruction in LAM. We performed a randomised, double-blind trial, comparing the matrix metalloproteinases inhibitor doxycycline with placebo on the progression of LAM. 23 females with LAM were randomised to doxycycline 100 mg daily for 3 months followed by 200 mg daily for 21 months, or matched placebo. Lung function, exercise capacity, quality of life and matrix metalloproteinases levels were measured. 21 patients completed 6 months of treatment, 17 completed 1 year of treatment and 15 completed 2 years of treatment. Eight withdrew from the trial due, four due to a pneumothorax and four because of other reasons. The mean±sd decline in FEV1, the primary endpoint, did not differ between the groups being -90±154 mL·year(-1) in the placebo group and -123±246 mL·year(-1) in the doxycycline group (difference -32.5, 95% CI -213-148; p=0.35). Doxycycline had no effect upon vital capacity, gas transfer, shuttle walk distance or quality of life. Urine matrix metalloproteinases-9 measurements were lower with doxycycline treatment (p=0.03). Although with limited numbers we cannot completely exclude an effect of doxycycline, the lack of effect on any outcome makes it unlikely that doxycycline has a useful effect in LAM.
- Published
- 2014
- Full Text
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3. Use of variability in national and regional data to estimate the prevalence of lymphangioleiomyomatosis.
- Author
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Harknett EC, Chang WY, Byrnes S, Johnson J, Lazor R, Cohen MM, Gray B, Geiling S, Telford H, Tattersfield AE, Hubbard RB, and Johnson SR
- Subjects
- Australia epidemiology, Canada epidemiology, Female, Germany epidemiology, Humans, Incidence, New Zealand epidemiology, Prevalence, Switzerland epidemiology, United Kingdom epidemiology, United States epidemiology, Lymphangioleiomyomatosis epidemiology, Registries statistics & numerical data
- Abstract
Background: Understanding the true prevalence of lymphangioleiomyomatosis (LAM) is important in estimating disease burden and targeting specific interventions. As with all rare diseases, obtaining reliable epidemiological data is difficult and requires innovative approaches., Aim: To determine the prevalence and incidence of LAM using data from patient organizations in seven countries, and to use the extent to which the prevalence of LAM varies regionally and nationally to determine whether prevalence estimates are related to health-care provision., Methods: Numbers of women with LAM were obtained from patient groups and national databases from seven countries (n = 1001). Prevalence was calculated for regions within countries using female population figures from census data. Incidence estimates were calculated for the USA, UK and Switzerland. Regional variation in prevalence and changes in incidence over time were analysed using Poisson regression and linear regression., Results: Prevalence of LAM in the seven countries ranged from 3.4 to 7.8/million women with significant variation, both between countries and between states in the USA. This variation did not relate to the number of pulmonary specialists in the region nor the percentage of population with health insurance, but suggests a large number of patients remain undiagnosed. The incidence of LAM from 2004 to 2008 ranged from 0.23 to 0.31/million women/per year in the USA, UK and Switzerland., Conclusion: Using this method, we have found that the prevalence of LAM is higher than that previously recorded and that many patients with LAM are undiagnosed.
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- 2011
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4. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial.
- Author
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Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, and Sampson JR
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- Adolescent, Adult, Aged, Angiomyolipoma pathology, Female, Humans, Lung physiopathology, Male, Middle Aged, Neuropsychological Tests, Sirolimus adverse effects, Treatment Outcome, Young Adult, Angiomyolipoma complications, Angiomyolipoma drug therapy, Lymphangioleiomyomatosis complications, Lymphangioleiomyomatosis pathology, Sirolimus therapeutic use, Tuberous Sclerosis complications, Tuberous Sclerosis pathology
- Abstract
Purpose: Renal angiomyolipomas are a frequent manifestation of tuberous sclerosis and sporadic lymphangioleiomyomatosis (LAM). These disorders are associated with mutations of TSC1 or TSC2 that lead to overactivation of mTOR complex 1 (mTORC1), suggesting an opportunity for targeted therapy by using mTORC1 inhibitors. This study investigated the efficacy and safety of the mTORC1 inhibitor sirolimus for treatment of renal angiomyolipomas in patients with these disorders., Experimental Design: In this multicenter phase 2 nonrandomized open label trial, 16 patients with tuberous sclerosis or sporadic LAM and renal angiomyolipoma(s) were treated with oral sirolimus for up to 2 years. Steady-state blood levels were 3 to 10 ng/mL. The primary outcome was change in size of renal angiomyolipomas measured by MRI and assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes included safety, neurocognitive function, and pulmonary function., Results: The response rate, by RECIST criteria, was 50%. Summated angiomyolipoma diameters were reduced in all 16 patients and by 30% or more in eight (all from the per protocol group of 10). Forty-one of 48 angiomyolipomas were smaller at the last measurement than at baseline. Most shrinkage occurred during the first year of treatment. There was little change in pulmonary function. Recall memory improved in seven of eight patients with tuberous sclerosis. Adverse events were consistent with the known toxicities of sirolimus., Conclusions: This study showed sustained regression of renal angiomyolipomas in patients with tuberous sclerosis or sporadic LAM receiving 2 years of sirolimus treatment. Possible effects on pulmonary function and neurocognition require further investigation., (©2011 AACR.)
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- 2011
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5. Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis.
- Author
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Davies DM, Johnson SR, Tattersfield AE, Kingswood JC, Cox JA, McCartney DL, Doyle T, Elmslie F, Saggar A, de Vries PJ, and Sampson JR
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- Angiomyolipoma etiology, Clinical Trials, Phase II as Topic, Humans, Immunosuppressive Agents adverse effects, Kidney Diseases etiology, Protein Kinases metabolism, Sirolimus adverse effects, TOR Serine-Threonine Kinases, Angiomyolipoma drug therapy, Immunosuppressive Agents therapeutic use, Kidney Diseases drug therapy, Lymphangioleiomyomatosis complications, Protein Kinase Inhibitors therapeutic use, Sirolimus therapeutic use, Tuberous Sclerosis complications
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- 2008
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6. Lymphangioleiomyomatosis: a national registry for a rare disease.
- Author
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Tattersfield AE and Glassberg MK
- Subjects
- Adult, Humans, Rare Diseases, United States, Lung Diseases, Lymphangioleiomyomatosis, Registries
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- 2006
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7. Survival and disease progression in UK patients with lymphangioleiomyomatosis.
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Johnson SR, Whale CI, Hubbard RB, Lewis SA, and Tattersfield AE
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- Cohort Studies, Disease Progression, Dyspnea epidemiology, Dyspnea mortality, Humans, Prognosis, Regression Analysis, Survival Analysis, United Kingdom epidemiology, Lung Neoplasms mortality, Lymphangioleiomyomatosis mortality
- Abstract
Background: Lymphangioleiomyomatosis (LAM) is a rare and progressive disease of young women with no effective treatment. Previous estimates of 10 year survival, based mostly on case series or patients from tertiary centres, have ranged from 40% to 79%; no data are available on the progression of respiratory disability. In order to provide data for patients and for planning intervention studies, we have looked at the time course of LAM using a national cohort., Methods: Time to death, time to MRC dyspnoea grades 2-5, and need for oxygen in patients on the UK LAM database were analysed using Kaplan-Meier analysis and Cox regression., Results: Fifty seven of 72 patients responded with a median duration of follow up of 12.6 years (range 2.3-37) from the onset of symptoms. Ten year survival was 91% from onset of symptoms but varied widely with 11 patients alive after 20 years. Median time to MRC grade 3 dyspnoea (breathless walking on the flat) was 9.3 years (95% CI 5.1 to 13.4) from onset of symptoms., Conclusions: Survival from LAM appears to be better than that reported in early studies. These data should be helpful for patients and for planning clinical trials.
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- 2004
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8. Lymphangioleiomyomatosis: a case-control study of perinatal and early life events.
- Author
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Whale CI, Johnson SR, Phillips KG, Newton SA, Lewis SA, and Tattersfield AE
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- Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, England epidemiology, Family Health, Female, Humans, Infant, Infant, Newborn, Life Change Events, Lymphangioleiomyomatosis epidemiology, Middle Aged, Pedigree, Regression Analysis, Risk Factors, Surveys and Questionnaires, Lymphangioleiomyomatosis etiology
- Abstract
Background: Lymphangioleiomyomatosis (LAM), a rare disease affecting women, is caused by somatic mutations in the tuberous sclerosis complex genes., Methods: A case-control questionnaire study was carried out examining parental and family history, prenatal events, and early life events to try to shed light on the aetiology of the condition. Forty five patients identified from a national LAM register completed a questionnaire and 31 were compared with 117 age and sex matched control subjects using conditional logistic regression., Results: No differences were found in perinatal events, childhood infections, and parental or family history, except that patients were more likely to be an only child (odds ratio (OR) 4.3 (95% confidence interval (CI), 1.5 to 11.8)) and have a relative with uterine fibroids (OR 4.2 (1.4 to 13)). Patients with LAM had had fewer pregnancies and fewer children but no differences in miscarriage rates. A non-matched analysis using all 45 cases and 117 controls gave similar results., Conclusions: No features in the family history, perinatal events, or early life events were detected that were associated with having LAM. Being more likely to be an only child and having an increased family history of uterine fibroids may, if confirmed, indicate some differences in reproductive function within the families of affected individuals.
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- 2003
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9. The TSC-2 product tuberin is expressed in lymphangioleiomyomatosis and angiomyolipoma.
- Author
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Johnson SR, Clelland CA, Ronan J, Tattersfield AE, and Knox AJ
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- Adult, Aged, Angiomyolipoma metabolism, Female, Humans, Immunohistochemistry, Kidney Neoplasms metabolism, Lung Neoplasms metabolism, Lymphangioleiomyomatosis metabolism, Male, Middle Aged, Tuberous Sclerosis Complex 2 Protein, Tumor Suppressor Proteins, Angiomyolipoma pathology, Kidney Neoplasms pathology, Lung Neoplasms pathology, Lymphangioleiomyomatosis pathology, Repressor Proteins biosynthesis
- Abstract
Aims: Lymphangioleiomyomatosis is categorized by proliferation of abnormal smooth muscle cells (LAM cells) in the lungs and lymphatics and the presence of angiomyolipomas. Recently mutations in the tuberous sclerosis complex-2 gene (TSC-2) have been described in LAM cells and angiomyolipomas. The TSC-2 protein tuberin is a tumour suppressor and its loss may result in cellular proliferation. We used immunohistochemistry to test the hypothesis that uncontrolled cellular proliferation in lymphangioleiomyomatosis is the result of reduced tuberin protein expression., Methods and Results: Tissue from normal lung, normal kidney, lymphangioleiomyomatosis and angiomyolipomas was immunostained with three separate anti-tuberin antibodies. Tuberin staining in normal tissues was similar to that previously described. Surprisingly, tuberin was strongly expressed in the LAM cells of all cases of lymphangioleiomyomatosis and angiomyolipoma at a greater level than in normal smooth muscle cells. The perivascular cells of angiomyolipomas, however, did not stain for tuberin., Conclusions: Our results suggest that a loss of tuberin protein in LAM cells is not the cause of the cellular proliferation seen in lymphangioleiomyomatosis. Lymphangioleiomyomatosis may result either from the expression of a mutant tuberin with abnormal function, as a result of mutations in functionally related proteins, or from more than one mechanism.
- Published
- 2002
- Full Text
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10. Clinical experience of lymphangioleiomyomatosis in the UK.
- Author
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Johnson SR and Tattersfield AE
- Subjects
- Adult, Female, Humans, Kidney Neoplasms diagnosis, Lung Neoplasms complications, Lung Neoplasms therapy, Lymphangioleiomyomatosis complications, Lymphangioleiomyomatosis therapy, Middle Aged, Pleural Effusion, Malignant etiology, Pneumothorax etiology, Pregnancy, Pregnancy Complications, Neoplastic, Skin Neoplasms diagnosis, Tuberous Sclerosis diagnosis, Lung Neoplasms diagnosis, Lymphangioleiomyomatosis diagnosis
- Abstract
Background: Lymphangioleiomyomatosis is a rare lung disease that affects only women. No controlled trials of management have been performed and, until such data are available, management must be based on clinical experience. This study provides data on the natural history of lymphangioleiomyomatosis in the UK and compares this with experience from other centres., Methods: We tried to identify all cases of lymphangioleiomyomatosis in the UK over a five year period by contacting all chest physicians. Cases were confirmed by lung biopsy or history and high resolution computed tomographic (CT) scanning. Details of disease and management were obtained from hospital notes., Results: The 50 patients who fitted the diagnostic criteria for lymphangioleiomyomatosis had a median age at onset of 35 years (range 22-50). Five presented when postmenopausal (four taking hormone replacement therapy). Pneumothorax and dyspnoea were the most common presenting features. Extrapulmonary presentations included renal angiomyolipomas (3) and lymphangiomyomas (2). Only half the patients were assessed for renal angiomyolipoma and six were identified. Thirty patients had had one or more pneumothoraces, of which two thirds recurred if treated conservatively. Chylous effusions occurred in 11 patients, five requiring surgery. Pregnancy was uncommon once the diagnosis was made (n=7), but was associated with an increase in complications. Half the patients were taking a beta agonist and many showed a bronchodilator response in the laboratory. Thirty six patients had received hormone treatment., Conclusions: Our UK five year period prevalence was one per 1.1 million population. Since prophylactic interventions are sometimes indicated for renal angiomyolipoma, these data suggest that screening for angiomyolipoma, ideally by CT scanning, may be underused. Patients need to be aware of the increase in complications associated with pregnancy. Recurrence rate of pneumothorax was high in those not treated surgically. Hormone treatment was used variably and controlled trials are needed to determine their role and the optimum duration and dose.
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- 2000
- Full Text
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11. Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment.
- Author
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Johnson SR and Tattersfield AE
- Subjects
- Adult, Female, Follow-Up Studies, Forced Expiratory Volume drug effects, Humans, Lung Neoplasms diagnosis, Lymphangioleiomyomatosis diagnosis, Middle Aged, Neoplasms, Hormone-Dependent diagnosis, Retrospective Studies, Total Lung Capacity drug effects, United Kingdom, Lung Neoplasms drug therapy, Lymphangioleiomyomatosis drug therapy, Menopause, Neoplasms, Hormone-Dependent drug therapy, Progesterone administration & dosage
- Abstract
The progression of lymphangioleiomyomatosis, a rare lung disease in women, is thought to be influenced by hormonal factors. We studied the rate of decline in FEV(1) and carbon monoxide transfer factor (TL(CO)) in a national cohort of patients with lymphangioleiomyomatosis in the United Kingdom and its relation to two factors that might influence the disease, menopausal status and progesterone treatment. We used retrospective data from hospital notes, and of the 50 patients identified 43 had suitable lung function data spanning at least 3 mo. Mean (SD) annual decline in FEV(1) was 118 (142) ml for all patients, and these figures changed little when only data spanning at least 2 and 3 yr were analyzed. There was considerable variation in the rate of decline between subjects, however, and although it tended to be less among postmenopausal women and those receiving progesterone, patient numbers were smaller and the findings were not significant. There was a significant reduction in decline in TL(CO) in premenopausal patients receiving progesterone and in both FEV(1) and TL(CO) after starting progesterone in six patients who had data before and after starting treatment. This study documents the rapid decline in lung function in lymphangioleiomyomatosis, confirms the wide variation between patients, and provides some support for the suggestion that disease progression may be reduced by progesterone. The data provide a basis for designing prospective studies of treatment for lymphangioleiomyomatosis.
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- 1999
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12. Relation of pulmonary lymphangio-leiomyomatosis to use of the oral contraceptive pill and fertility in the UK: a national case control study.
- Author
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Wahedna I, Cooper S, Williams J, Paterson IC, Britton JR, and Tattersfield AE
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- Abortion, Spontaneous, Adult, Age of Onset, Case-Control Studies, Female, Humans, Leiomyoma complications, Lung Neoplasms complications, Lung Neoplasms epidemiology, Lymphangioleiomyomatosis complications, Lymphangioleiomyomatosis epidemiology, Menstruation, Middle Aged, Ovarian Neoplasms complications, Parity, Pregnancy, United Kingdom epidemiology, Contraceptives, Oral adverse effects, Lung Neoplasms etiology, Lymphangioleiomyomatosis etiology
- Abstract
Background: Pulmonary lymphangioleiomyomatosis is a rare progressive disease of unknown aetiology affecting premenopausal women. Since the oral contraceptive pill has been implicated in its pathogenesis, a case control study was carried out to determine whether women with the disease were more likely to have taken the oral contraceptive pill, and whether the disease was associated with other conditions related to sex hormones including pregnancy, parity, and fibroids., Methods: All chest physicians in the UK were asked for details of all live patients with pulmonary lymphangioleiomyomatosis; the patient's family doctor was then asked for four age and sex matched control subjects from their patient register. Details of lifetime use of the oral contraceptive pill, pregnancy, parity, history of fibroids, and smoking were obtained from cases and controls. Relative odds of exposure to potential risk factors were estimated by conditional logistic regression., Results: Medical details were obtained from all 23 cases of lymphangioleiomyomatosis identified; questionnaires were completed by 21 cases (one by proxy) and by 46 matched controls of mean (SD) age 43 (10) and 44 (11) years, respectively. The patients had a mean age of 34 (9) years at onset of symptoms and a median (range) time of 2 (0-29) years from onset of symptoms to diagnosis. Compared with control subjects, cases did not differ in the use of the oral contraceptive pill (odds ratio (OR) 0.39, 95% CI 0.09 to 1.68), diagnosis of fibroids (OR 3.12; 95% CI 0.52 to 18.7), age of menarche, menstrual history, or lifetime smoking. They were, however, less likely to have been pregnant (OR 0.14, 95% CI 0.03 to 0.71) or to have had children (OR 0.13, 95% CI 0.03 to 0.67). More pregnancies had ended in spontaneous abortion (28% v 8%) but the proportion of women undergoing spontaneous abortion was similar in cases and controls (OR 2.13, 95% CI 0.47 to 9.3)., Conclusions: This study does not support the hypothesis that use of the oral contraceptive pill is causally associated with the development of pulmonary lymphangioleiomyomatosis. Sex hormones may be involved, however, since patients were less likely to have been pregnant or to have had children, and tended to have had more spontaneous abortions and an increased incidence of fibroids.
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- 1994
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13. European Respiratory Society guidelines for the diagnosis and management of lymphangioleiomyomatosis
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Johnson, Sr1, 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 including Johnson SR, Albera, Carlo, Bissler, J, Bouros, D, Corris, P, Donnelly, S, Durand, C, Egan, J, Grutters, Jc, Hodgson, U, Hollis, G, Korzeniewska Kosela, M, Kus, J, Lacronique, J, Lammers, Jw, Mccormack, F, Mendes, Ac, Moss, J, Naalsund, A, Pohl, W, Radzikowska, E, Robalo Cordeiro, C, Rouvière, O, Ryu, J, Schiavina, M, Tattersfield, Ae, Travis, W, Travis, P, Urban, T, Valeyre, D, Verleden, Gm, University of Nottingham, UK (UON), Rétrovirus et Pathologie Comparée, Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire Vaudois (CHUV), Universitätsklinikum Essen, Ospedale San Giuseppe, Hôpital Sainte Marguerite, University Hospital Zurich, Université Paris Nord (Paris 13), Karl-Franzens-Universität [Graz, Autriche], University of Verona (UNIVR), Bath, and University of Zurich
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Angiomyolipoma ,pneumothorax ,chylous effusions ,cystic lung disease ,lymphangioleiomyomatosis ,tuberous sclerosis ,Medizin ,610 Medicine & health ,Lung biopsy ,Cell morphology ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,03 medical and health sciences ,Tuberous sclerosis ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,Humans ,030212 general & internal medicine ,ComputingMilieux_MISCELLANEOUS ,business.industry ,Respiratory disease ,Chylothorax ,medicine.disease ,3. Good health ,030228 respiratory system ,Pneumothorax ,2740 Pulmonary and Respiratory Medicine ,Lymphangioleiomyomatosis ,lipids (amino acids, peptides, and proteins) ,10178 Clinic for Pneumology ,business ,Lung Transplantation - Abstract
Lymphangioleiomyomatosis (LAM) is a rare lung disease, which occurs sporadically or in association with the genetic disease tuberous sclerosis complex (TSC) 1, 2. Sporadic LAM affects ∼1 in 400,000 adult females; in TSC, LAM occurs in 30–40% of adult females 3, 4 and exceptionally in males and children 5, 6. Patients with LAM usually develop progressive dyspnoea and recurrent pneumothorax, chylous collections and occasional haemoptysis 1. Extra pulmonary lymphadenopathy and cystic masses of the axial lymphatics termed lymphangioleiomyomas can result in abdominal and pelvic lymphatic obstruction 7. LAM is often associated with angiomyolipoma in the kidneys 8, and an increased frequency of meningioma 9. LAM varies in clinical features and rate of progression: this together with an absence of clear prognostic factors results in patients being given conflicting information about prognosis. Diagnosis is made by tissue biopsy (generally from the lung but occasionally from lymph nodes or lymphangioleiomyomas) and/or a combination of history and high-resolution computed tomography scanning (HRCT). Pathological diagnosis relies on characteristic LAM cell morphology and positive immunoreactivity to smooth muscle actin and HMB-45 antibodies. Increasingly HRCT is used to diagnose LAM without resorting to lung biopsy; however a number of conditions with multiple pulmonary cysts can mimic LAM. As LAM is rare, there have been no controlled trials of its management. Supportive treatment includes management of airflow obstruction and hypoxaemia with bronchodilators and oxygen respectively, specific treatment for surgical or pleural complications including pneumo- and chylothorax, and interventional treatment of renal lesions 10, 11. As LAM is a disease of females and is thought to be accelerated by oestrogen, oophorectomy, tamoxifen, progesterone and gonadotropin-releasing hormone (GnRH) analogues have been used without evidence that they are effective. The recent finding of abnormalities in the TSC1/2 genes resulting …
- Published
- 2010
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