Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis
Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis
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DOI：
10.1164/ajrccm.164.4.2011025
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发表时间：
2001-08-15
影响因子：
24.7
通讯作者：
McCormack, FX
中科院分区：
文献类型：
--
作者：
Franz, DN;Brody, A;McCormack, FX
淋巴管平滑肌瘤病（LAM）和多灶性微结节性肺泡细胞增生（MMPH）分别在结节性硬化症患者的肺部产生囊性和结节性病变。本研究的目的是前瞻性地描述结节性硬化症（TSC）中肺部疾病的患病率、临床表现和遗传基础。我们对23名无症状的结节性硬化症复合物（TSC）女性进行了基因分型和胸部计算机断层扫描（CT）。在9名患者（39%）中发现了与LAM一致的囊性肺实质改变。这些患者往往比无囊肿患者年龄更大（31.9±7.6岁对24.8±11.6岁，p = 0.09）。囊肿的存在与吸烟、月经初潮年龄、妊娠史或含雌激素药物之间没有相关性。3名囊肿阳性患者有气胸病史。肺功能研究显示，囊肿阳性组有气体潴留的证据，但肺量测定指标正常。所有9名囊肿阳性患者都有血管平滑肌脂肪瘤（AML），与无囊肿患者相比，其体积更大（p < 0.05），更常需要干预（p = 0.08）（14名中有8名有AML，p < 0.05）。10名患者（43%）有肺实质结节。有囊肿的女性中肺结节更常见（78%对21%，p < 0.05），所有患者中有52%有囊性或结节性改变。在所有接受检测的囊肿阳性患者（n = 8）中都发现了TSC2突变，而在结节性疾病患者中发现了TSC1和TSC2突变。突变数据和影像学数据的相关性显示，有一对姐妹在囊性疾病方面不一致，两对母女在结节性疾病方面不一致，囊肿的发展与特定突变类型之间没有明确的关联。这项前瞻性分析表明，与LAM和MMPH一致的囊性和结节性肺部改变在结节性硬化症女性中很常见。
Lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH) produce cystic and nodular disease, respectively, in the lungs of patients with tuberous sclerosis. The objective of this study was to prospectively characterize the prevalence, clinical presentation, and genetic basis of lung disease in TSC. We performed genotyping and computerized tomographic (CT) scanning of the chest on 23 asymptomatic women with tuberous sclerosis complex (TSC). Cystic pulmonary parenchymal changes consistent with LAM were found in nine patients (39%). These patients tended to be older than cyst-negative patients (31.9 +/- 7.6 yr versus 24.8 +/- 11.6 yr, p = 0.09). There was no correlation between presence of cysts and tobacco use, age at menarche, history of pregnancy, or estrogen-containing medications. Three of the cyst-positive patients had a prior history of pneumothorax. Pulmonary function studies revealed evidence of gas trapping but normal spirometric indices in the cyst-positive group. All nine cyst-positive patients had angiomyolipomas (AML), which were larger (p < 0.05) and more frequently required intervention (p = 0.08) than cyst-negative patients (8 of 14 with AMLs p < 0.05). Ten patients (43%) had pulmonary parenchymal nodules. Pulmonary nodules were more common in women with cysts (78% versus 21%, p < 0.05), and 52% of all patients had either cystic or nodular changes. TSC2 mutations were identified in all cyst-positive patients who were tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with nodular disease. Correlation of the mutational and radiographic data revealed one pair of sisters who were discordant for cystic disease, two mother-daughter pairs who were discordant for nodular disease, and no clear association between cyst development and a specific mutational type. This prospective analysis demonstrates that cystic and nodular pulmonary changes consistent with LAM and MMPH are common in women with TSC.