Comprehensive Evaluation of 35 Patients With Lymphangioleiomyomatosis

Chu, Shan C.; Horiba, Koji; Usuki, Jiro; Avila, Nilo A.; Chen, Clara C.; Travis, William D.; Ferrans, Víctor J.; Moss, Joel

doi:10.1378/chest.115.4.1041

Cited by 296 publications

(282 citation statements)

References 27 publications

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“…Clinical manifestations of pulmonary LAM include recurrent spontaneous pneumothorax, progressive dyspnea on exertion, chylothorax, and hemoptysis (Corrin et al 1975;Silverstein et al 1974). The most common features of pulmonary function in patients with pulmonary LAM is the impairment of diffusing capacity and airflow obstruction (Chu et al 1999;Corrin et al 1975;Johnson and Tattersfield 1999;Silverstein et al 1974;Urban et al 1999). LAM has a diverse clinical course and some patients retain a good pulmonary function for a long period without antihormone therapy, although others show progressive deterioration leading to respiratory failure and cor pulmonale .…”

Section: Introductionmentioning

confidence: 99%

Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis

et al. 2002

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Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis

et al. 2002

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“…L ymphangioleiomyomatosis (LAM) is a multisystem disease of women, characterized by cystic degeneration of the lungs, renal angiomyolipomas (AML), and lymphatic lesions, e.g., thoracic and abdominal lymphangioleiomyomas (1)(2)(3). It occurs as a sporadic disease or with tuberous sclerosis complex (TSC), which can be inherited as an autosomal dominant disorder involving multiorgan hamartomas, in which patients frequently develop lung and kidney lesions pathologically and genetically similar to those seen in LAM (4)(5)(6).…”

mentioning

confidence: 99%

Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis

Crooks

Pacheco–Rodriguez²,

DeCastro³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…(2) The most common clinical profile is characterized by dyspnea, pneumothorax, and renal angiomyolipoma; however, involvement of the lymphatic system, in the form of chylothorax or lymphangioma, can also occur. (3)(4)(5)(6) Chest CT scans reveal diffusely distributed nodular cysts with thin, well-defined walls. (7) Histology reveals clusters of immature smooth muscle cells, which can be spindle-shaped, located adjacent to the nodules, or epithelioid, running along the peribronchovascular bundle.…”

Section: Introductionmentioning

confidence: 99%

Doxiciclina em pacientes com linfangioleiomiomatose: segurança e eficácia no bloqueio de metaloproteinases

et al. 2011

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Objective: Lymphangioleiomyomatosis (LAM) is characterized by lung cysts, whose development is associated with matrix metalloproteinase (MMP) hyperactivity, principally that of MMP-2 and MMP-9. Our objective was to compare LAM patients and controls in terms of the levels of these MMPs, as well as to determine the safety and efficacy of treatment with doxycycline, a potent MMP inhibitor. Methods: Prospective clinical study involving female LAM patients who received doxycycline (100 mg/day) for six months. Urine and blood samples were collected for the quantification of MMP-2 and MMP-9 before and after the treatment period. Samples from 10 healthy women were also collected. Results: Of the 41 LAM patients who started the treatment, 34 completed the protocol. Serum and urinary MMP-9 levels were significantly lower in the controls than in the LAM patients (p < 0.0001). Comparing pre-and post-treatment values, we found that the median level of MMP-9 in serum decreased from 919 ng/mL to 871 ng/mL (p = 0.05), whereas that of MMP-9 in urine decreased from 11,558 pg/mL to 7,315 pg/mL (p = 0.10). After treatment, the median level of MMP-2 in serum was significantly lower (p = 0.04) and urinary MMP-2 levels were undetectable. Nausea, diarrhea, and epigastric pain were the most prevalent adverse affects and were often self-limiting. There was only one case in which the patient discontinued the treatment because of side effects. Conclusions: We have demonstrated, for the first time, a decrease in serum and urine levels of MMPs in LAM patients treated with doxycycline, which proved to be a safe medication, with mild and well-tolerated side effects.Keywords: Lymphangioleiomyomatosis; Matrix metalloproteinases; Doxycycline. ResumoObjetivo: A linfangioleiomiomatose (LAM) é caracterizada pela presença de cistos pulmonares, cuja formação está associada à hiperreatividade de metaloproteinases de matriz (MMP), principalmente MMP-2 e MMP-9. Objetivamos comparar os níveis dessas MMPs entre pacientes com LAM e controles saudáveis, assim como avaliar, nas pacientes com LAM, a segurança e a eficácia do tratamento com doxiciclina, um potente inibidor de MMPs. Métodos: Estudo clínico prospectivo no qual as pacientes com LAM receberam doxiciclina (100 mg/dia) por seis meses, coletando-se amostras de urina e sangue para a dosagem de MMP-2 e MMP-9 antes e ao final do período. Foram ainda obtidas amostras de 10 mulheres saudáveis. Resultados: De 41 pacientes com LAM que iniciaram o tratamento, 34 concluíram o protocolo. Os níveis de MMP-9 sérica e urinária foram significativamente inferiores no grupo controle (p < 0,0001). Comparando-se os valores antes e após o tratamento, a mediana do nível sérico da MMP-9 reduziu de 919 ng/mL para 871 ng/mL (p = 0,05), enquanto a mediana da dosagem urinária de MMP-9 diminui de 11.558 pg/mL para 7.315 pg/mL (p = 0,10). A mediana da MMP-2 sérica apresentou um decréscimo significativo após o tratamento (p = 0,04). Não foram detectados níveis de MMP-2 urinária. Epigastralgia, náuseas e diarreia foram os...

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Comprehensive Evaluation of 35 Patients With Lymphangioleiomyomatosis

Cited by 296 publications

References 27 publications

Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis

Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis

Molecular and genetic analysis of disseminated neoplastic cells in lymphangioleiomyomatosis

Doxiciclina em pacientes com linfangioleiomiomatose: segurança e eficácia no bloqueio de metaloproteinases

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