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

(1)高原肺水肿(HAPE)患者的人类白细胞抗原(人类白细胞抗原)等位基因频率分析：对30例有高原肺水肿病史的受试者和100例健康体检者进行了等位基因频率分析。HAPE与HLADR6、HLADQ4及肺动脉高压与HLADR6的相关性显著。(2)鸟型分枝杆菌肺部感染的等位基因分析：我们对的MAI患者进行了等位基因频率的检测，发现27例MAI恶化，37例未恶化。HLAA-26抗原阳性者提示MAI肺部感染加重。(3)HAPE患者支气管肺泡灌洗液分析：HAPE早期，BAL液中细胞总数、中性粒细胞和淋巴细胞均显著高于恢复期和健康对照组。肺泡灌洗液中总蛋白、乳酸脱氢酶、IL-1β、IL-6、IL-8和肿瘤坏死因子-α水平显著升高。(4)肺血管重塑与肺动脉高压：高原鼠兔对低氧和薄壁肺小动脉的肺血管收缩反应较弱。10例重度肺气肿患者行肺减容术后，小动脉壁厚度(WT)明显增加，分别为(2 7.5±4.5)μm和(16.5±42.8)μm。静息时外径百分比WT与PPA无关，但与运动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.