Doxiciclina em pacientes com linfangioleiomiomatose: biomarcadores e resposta funcional pulmonar

Pimenta, Suzana Pinheiro; Baldi, Bruno Guedes; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

doi:10.1590/s1806-37132013000100002

Cited by 33 publications

(13 citation statements)

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“…al. [19] and although this may reflect our smaller numbers and intra-subject variability, there must be doubt as to whether a change of 5% would result in clinical benefit. The lack of efficacy of doxycycline in preventing decline in lung function raises questions about the role of MMPs in lung destruction in LAM.…”

Section: Discussionmentioning

confidence: 85%

“…In a single patient with severe disease, lung function and oxygenation improved after doxycycline treatment although this may have been due treatment of a co-existing infection [17]. In a series of 38 patients all treated with doxycycline for 12 months, PIMENTA et al [19] observed that some patients remained stable on treatment and these tended to be those with better lung function. A relatively benign clinical course in some patients with LAM is well documented, and without a control group the significance of these findings is difficult to assess [28].…”

Section: Discussionmentioning

confidence: 97%

“…Doxycycline is the only MMP inhibitor licensed for clinical use and MOSES et al [17] described a large improvement in spirometry and oxygenation in a patient with advanced LAM following treatment with doxycycline. In an observational study of patients with mild LAM, doxycycline was associated with a reduction in urine MMP-9 and a relatively slow decline in mean FEV1 of 70 mL over 12 months [18,19]. As a consequence of these reports, some females with LAM have been taking doxycycline off label.…”

Section: Introductionmentioning

confidence: 99%

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A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis

Chang

Cane

Kumaran

et al. 2013

European Respiratory Journal

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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; p50.35). 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 (p50.03).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. @ERSpublications Doxycycline does not prevent progression of lung disease in LAM http://ow.ly/tiMqo

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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A 2-year randomised placebo-controlled trial of doxycycline for lymphangioleiomyomatosis

Chang

Cane

Kumaran

et al. 2013

European Respiratory Journal

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“…Currently, trial is closed for enrollment and results were reported by Johnson and colleagues [48]. Another doxycycline trial has been completed in Brasil [49]. In this open label trial, 31 LAM patients were treated with 100 mg daily doxycycline for 12 months.…”

Section: Targeting Lung Destruction In Lam?mentioning

confidence: 99%

Therapeutic strategies for treatment of pulmonary lymphangioleiomyomatosis

Krymskaya

2014

Expert Opinion on Orphan Drugs

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Introduction Pulmonary lymphangioleiomyomatosis (LAM) is a rare progressive lung disease affecting almost exclusively women. Neoplastic growth of atypical smooth muscle-like cells in the lung induces destruction of lung parenchyma leading to the formation of lung cysts, rupture of which results in spontaneous pneumothorax. LAM occurs sporadically or in association with inherited hamartoma syndrome tuberous sclerosis complex (TSC). Progression of LAM often results in loss of pulmonary function and death. Increasing understanding of neoplastic LAM cell growth is driving the development of therapeutic approaches targeting the disease progression. Areas covered This review provides background to understand the rationale for current treatments used in patients with LAM, to critically appraise the evidence for these treatments, and to discuss future treatment approaches. The literature review includes publications from PubMed and clinicaltrials.gov/. Expert Opinion Targeting mTOR activation with rapamycin analogs sirolimus and everolimus are awaiting approval by the FDA for treatment of LAM. A number of other treatment options have been investigated and are currently tested in clinical trials to target LAM cell survival and metastasis. Key remaining and poorly understood areas for development and validation of therapeutic targeting in LAM are destruction of lungs, pathological lymphangiogenesis, and hormonal regulation. Future will reveal whether they could be targeted therapeutically.

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“…In B.G. Baldi's study, 41 patients received doxycycline in an open-labelled manner, 31 patients completed 1 year of therapy and were then divided into those with a fall in forced expiratory volume in 1 s (FEV1) or those whose FEV1 did not fall, termed ''nonresponders'' and ''responders'' respectively, with responders tending to have a better baseline lung function [2,3]. Although, these data would be consistent with B.G.…”

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confidence: 99%