Determinants of Progression and Mortality in Lymphangioleiomyomatosis

Xu, Wenshaui; Yang, Chaoyu; Cheng, Chongsheng; Wang, Yani; Hu, Danjing; Huang, Jiannan; He, Yudi; Wang, Jun; Chen, Keqi; Yang, Luning; Zhou, Wangji; Zhang, Tengyue; Liu, Song; Dai, Jianrong; Meng, Shu; Li, Xue; Yang, Yanli; Wang, Shao-Ting; Feng, Ru; Zhang, Weihong; Zhang, Hongbing; Wang, Li; Tian, Xinlun; Xu, Kai‐Feng

doi:10.1016/j.chest.2023.02.026

Cited by 13 publications

(9 citation statements)

References 27 publications

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“…Serum VEGF-D level is utilized as a diagnostic marker, severity indicator, and also as a prognostication tool. While some study described irrelevance of serum VEGF-D and decline rate of FEV 1 ( 14 ), correlation and usefulness of the VEGF-D level as a prognostic gauge is predominantly supported by other investigatory reports ( 47 , 48 ).…”

Section: Prognosismentioning

confidence: 97%

Lymphangioleiomyomatosis and mTOR inhibitors in real world—a narrative review

Park,

Lee

2023

J Thorac Dis

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Background and Objective Lymphangioleiomyomatosis (LAM) is a rare disease developing mostly on lung and leading to various pulmonary and extra-pulmonary manifestations. Management of this intractable illness has been mostly symptomatic and supplementary until the advent and application of a novel drug, i.e., the mechanistic target of rapamycin (mTOR) inhibitor, and successful disease control using mTOR inhibitors is improving LAM patients. Although mTOR inhibitors are showing remarkable results there are still many rooms for further progress, and partly solved issues on problems seen in LAM still remain. We searched multiple reports and investigational studies regarding LAM, especially the therapeutic achievement won by mTOR inhibitors. This article summarized several characteristics of LAM including pathogenesis, clinical manifestation, laboratory findings, and management. We also attempted to review the latest knowledge and efficacy of mTOR inhibitors and some new drugs. Methods Online searching of literature was performed. The National Center for Biotechnology Information (NCBI), PubMed, Cochrane Library, Google Scholar, and EMBASE were searched. Key Content and Findings LAM is a genetic disease with a high predilection toward female subjects. Not only lung but also other organs are involved, hence extrapulmonary symptoms and signs are also noted. Representative objective finding is a progressive deterioration of lung function, sometimes leading to respiratory failure. Supportive and symptomatic care has been the mainstay of therapy with suboptimal result, until a novel drug, the mTOR inhibitor, was developed. Successful deterrence of disease progression was achieved on management with mTOR inhibitors. Several unsolved problems using mTOR inhibitors are a pending issue, such as duration of treatment. Conclusions LAM has been a rare, stubborn disease to ameliorate in health due to its complex pathogenesis and accompanied by other manifestations. Adopting various tools for relief has been usually suboptimal, but mTOR inhibitors proved to achieve significant improvement in various aspects. Further investigation is needed including refinement of currently available therapeutic applications, development of novel remedies, and so on.

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Section: Prognosismentioning

confidence: 97%

Lymphangioleiomyomatosis and mTOR inhibitors in real world—a narrative review

Park,

Lee

2023

J Thorac Dis

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“…VEGF-D is a ligand for the lymphatic growth factor receptor 2 and vascular endothelial growth factor receptor 3 that induces formation of lymphatics and promotes the spread of tumor cells 10 . It is also reported that a high VEGF-D level predicts an involvement of lymphatic system and connects with the severity and progression of LAM [11][12][13] . However, normal VEGF-D concentration does not exclude LAM diagnosis 10 .…”

Section: Introductionmentioning

confidence: 95%

The Role of Moesin in Diagnosing and Assessing Severity of Lymphangioleiomyomatosis

Song,

Cai,

Peng

et al. 2023

Preprint

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Background Lymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM. Materials and methods The isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLD), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA assay. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM. Results The candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7-260.5) pg/mL] than in patients with OCLD (125.8 ± 59.9 pg/mL, P < 0.0001) and healthy women [49.6 (35.5–78.9) ng/mL, P < 0.0001]. Moesin had an area under the receiver operator characteristic curve (AUC) of 0.929 for predicting LAM diagnosis compared to healthy women (sensitivity 81.0%, specificity 94.6%). The combination of moesin and VEGF-D made a better prediction in differentiating LAM from OCLD than moesin or VEGF-D alone. Moreover, elevated levels of moesin were related to lymphatic involvement in patients with LAM. Moesin was found negatively correlated with FEV1%pred, FEV1/FVC, and DLCO%pred (P = 0.0181, r = -0.3398; P = 0.0067, r = -0.3863; P = 0.0010, r = -0.4744). A composite score combining moesin and VEGF-D improved prediction for sirolimus treatment, compared with each biomarker alone. Conclusion Higher levels of moesin in serum may indicate impaired lung function and lymphatic involvement in patients with LAM, suggest a more serious condition, and provide clinical guidance for sirolimus treatment.

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“…The late Paleozoic tectonic setting in the southeastern CAOB has been controversial for decades. One current view is that Carboniferous−Permian tectonic development was controlled by an intracontinental rift or nascent ocean basin after closure of the PAO in the middle Paleozoic (Li et al, 2012(Li et al, , 2014aXu et al, 2013Xu et al, , 2014Xu et al, , 2018Wang et al, 2014;Hu et al, 2015;Luo et al, 2016;Shao et al, 2017). The counter viewpoint is that there was a remnant ocean basin of the PAO, the tectonic development being controlled by oceanic crust subduction orogeny (Chen et al, 2000Xiao et al, 2003;Shang, 2004;Li, 2006;Miao et al, 2007;Liu et al, 2013;Liu R et al, 2016;.…”

Section: Implications For the Tectonic Framework Of The Southeastern ...mentioning

confidence: 99%

“…The first issue is the spatial distribution of the suture, for which there are three main viewpoints: 1) from northern Solonker via Xilinhot to Ulanhot (Xu and Chen, 1997;Xu et al, 2013), 2) from Solonker via Xilinhot to Horqinyouzhongqi (Li, 1987;Pan and Xiao, 2015;Fu et al, 2017) or via Sonidyouqi to Linxi (Wang and Liu, 1986;Xiao et al, 2003Xiao et al, ., 2009, 3) from southern Solonker to Xar-Moron River (Li, 2006;Jian et al, 2010;Liu et al, 2013;Pan and Xiao, 2015;Liu et al, 2017). Furthermore, the tectonic setting of the late Paleozoic magmatism, especially during the early Permian, is disputed, with conflicting interpretations such as: 1) continental arc or subduction setting (Miao et al, 2007;Tong et al, 2010;Liu J F et al, 2011Liu J F et al, , 2016Liu R et al, 2016), 2) post-orogenic extension setting (Li et al, 2012(Li et al, , 2014a, 3) intraplate rift or retro-arc basin setting Wang et al, 2014;Xu et al, 2014Xu et al, , 2018Song et al, 2015;Luo et al, 2016;Shao et al, 2017). In the present work, we present new zircon U-Pb ages, in-situ zircon Hf isotopes, whole-rock geochemistry and Sr-Nd isotopes for the early Permian intrusive rocks from Ar-Horqin, southeastern Inner Mongolia.…”

mentioning

confidence: 99%