Analysis of Genetic and Constitutional Factors for the Development of High-altitude Pulmonary Edema

我们在资助下进行了以下4个项目：(1)高原肺水肿（HAPE）人白细胞抗原（HLA）等位基因分析：分析30例高原肺水肿（HAPE）患者HLA等位基因频率，并与100例健康对照进行比较。HAPE与HLA-DR6和HLA-DQ4有显著相关性，肺动脉高压与HLA-DR6有显著相关性。(2)细胞内鸟分枝杆菌（Mycobacterium avium- intraculululum， MAI）肺部感染的HLA等位基因分析：我们对64例MAI疾病的HLA等位基因频率进行了评估，在间隔30±15个月后，27例出现恶化，37例无恶化。HLA -26抗原提示MAI肺部感染恶化。(3) HAPE患者支气管肺泡灌洗液分析：早期HAPE患者支气管肺泡灌洗液中细胞总数、中性粒细胞和淋巴细胞较恢复时和健康对照组明显增加。BAL液中总蛋白、LDH、IL-1β、IL-6、IL-8、TNF-α水平显著升高。(4)肺动脉重构和肺动脉高压：鼠兔是一种适应高海拔环境的啮齿动物，其肺血管收缩对缺氧和薄壁肺动脉的反应较低。10例重度肺气肿患者行肺减容手术后，肺动脉小动脉壁厚（WT）（27.5±4.5 μm）明显高于（16.5±42.8 μm）。外径WT的百分比与静止时的Ppa无关，但与运动时的Ppa高度相关。

We have performed the following 4 projects under the grant.(1) Analysis of human leukocyte antigen (HLA) alleles in high-altitude pulmonary edema (HAPE): We analyzed the frequencies of HLA alleles in 30 subjects with a history of HAPE, comparing with those in 100 bealthy controls. There were significantly associations of HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6.(2) Analysis of HLA alleles in Mycobacterium avium-intracellulare (MAI) pulmonary infection: We evaluated the frequencies of HLA alleles in 64 cases of MAI disease, showing deterioration in 27 and no deterioration in 37 subjects after an interval of 30 ± 15 months. The subjects with HLA A-26 antigens might indicate the deterioration of MAI pulmonary infection.(3) Analysis of bronchoalveolar lavage (BAL) fluid in patients with HAPE: During the early stage of HAPE the total cell counts, neutrophils and lymphocytes in the BAL fluid were significantly increased compared with those at the recovery and in healthy controls. Furthermore, the BAL fluid levels of total protein, LDH, IL-1β, IL-6, IL-8 and TNF-α were significantly elevated.(4) Pulmonary artery remodeling and pulmonary hypertension: The pika (Ochotona curzoniae), a family of rodent adapted to high altitude, has a lower response of pulmonary vasoconstriction to hypoxia and thin-walled pulmonary arteioles. In 10 patients with severe emphysema who underwent lung volume reduction surgery the wall thickness (WT) of small pulmonary artery was significantly increased (27.5 ± 4.5 μm) compared with that (16.5 ± 42.8 μm). The percent WT of the external diameter was not related to Ppa at rest, but was highly correlated with exercise Ppa.