Hepatopulmonary Syndrome Is a Frequent Cause of Dyspnea in the Short Telomere Disorders
Hepatopulmonary Syndrome Is a Frequent Cause of Dyspnea in the Short Telomere Disorders
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DOI：
10.1378/chest.15-0825
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发表时间：
2015-10-01
期刊：
影响因子：
9.6
通讯作者：
Armanios, Mary
中科院分区：
文献类型：
--
作者：
Gorgy, Amany I.;Jonassaint, Naudia L.;Armanios, Mary
背景：端粒综合征最常见于特发性肺纤维化和肺气肿。这些患者的短端粒缺陷可能表现为骨髓衰竭和肝脏疾病。我们试图了解端粒酶和端粒基因突变携带者呼吸困难的原因，他们没有实质性的肺diseases.METHODS：临床和病理数据进行了审查，作为一个基于Johns Hopkins的短端粒综合征，包括先天性角化不良的自然史研究的一部分。他们的发病年龄明显小于最初表现为肺纤维化和肺气肿的病例（中位数，25岁对55岁; P <0.001）。病例有肺内和肺外动脉血管畸形的证据，导致分流生理学。结节性再生性增生是最常见的组织病理学异常，它被认为是在没有肝硬化。呼吸困难和门静脉高压症是进行性的，死亡或肝移植的中位时间为6年（范围，4-10年; n = 6）。在接受肝移植，呼吸困难和缺氧的情况下，改善，但肺纤维化随后developed.CONCLUSIONS：本报告确定HPS作为一个常见的原因，端粒酶和端粒基因突变携带者呼吸困难。虽然它通常先于实质性肺病的发展，但HPS也可能与肺纤维化和肺气肿同时发生。认识到这一基因诊断是至关重要的管理，特别是在肺和肝移植设置。
BACKGROUND: Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease.METHODS: Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita.RESULTS: Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21 %). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P < .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed.CONCLUSIONS: This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.