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

高原肺水肿发生的遗传及体质因素分析

• 批准号: 09470539
• 负责人: KUBO Keishi
• 金额: $ 4.22万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470539/
• 关键词: High-altitude pulmonary edema; Individual difference; HLA analysis; Bronchoalveolar lavage; Pulmonary artery remodeling; Pulmonary hypertension; Exercise; 肺MAC症; 肺動脈圧; 高山病; HLA-typing; ANP; 2,3-DPG; 肺水腫; 高地; HLA; 低酸素換気応答能; 肥満細胞; 右室肥大; 低

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.

我们已经完成了以下4个项目的赠款。(1)人类白细胞抗原（HLA）等位基因在高原肺水肿（HAPE）中的分布：分析了30例有高原肺水肿病史者和100例健康对照者的HLA等位基因频率。HAPE与HLA-DR 6和HLA-DQ 4显著相关，肺动脉高压与HLA-DR 6显著相关。(2)鸟细胞内分枝杆菌（MAI）肺部感染的HLA等位基因分析：我们评估了64例MAI疾病患者的HLA等位基因频率，在间隔30 ± 15个月后，27例患者恶化，37例患者无恶化。HLA-A-26抗原阳性者可能提示MAI肺部感染的恶化。(3)HAPE患者支气管肺泡灌洗液（BAL）分析：HAPE早期BAL液中细胞总数、中性粒细胞和淋巴细胞计数均较恢复期和健康对照组显著增高。BALF中总蛋白、LDH、IL-1β、IL-6、IL-8和TNF-α水平显著升高。(4)肺动脉重塑和肺动脉高压：鼠兔（Ochotona curzaleae）是一种适应高海拔的啮齿动物家族，对缺氧和薄壁肺动脉的肺血管收缩反应较低。10例重度肺气肿患者行肺减容术后，肺小动脉壁厚度（WT）由术前的（16.5 ± 42.8）μ m增加到（27.5 ± 4.5）μ m。外径的百分比WT与静息Ppa无关，但与运动Ppa高度相关。

项目成果

Kubo et al.: "Pulmonary artery remodeling modifies pulmonary hypertension during exercise in severe emphysema"Respir Physiol. (in press).

Kubo 等人：“肺动脉重塑可改善严重肺气肿运动期间的肺动脉高压”Respir Physiol。

Kubo et al.: "Pulmonary artery remodeling modifies pulmonary hypertension during exercise in severe emphysema."Respir Physiol. (in press).

Kubo 等人：“肺动脉重塑可改善严重肺气肿运动期间的肺动脉高压。”Respir Physiol。

Kubo et al.: "Analysis of HLA antigens in Mycobacterium-intracellulare pulmonary infection"Am J Respir Crit Care Med. (in press).

Kubo 等人：“细胞内分枝杆菌肺部感染中 HLA 抗原的分析”Am J Respir Crit Care Med。

Ge et al.: "Blunted hypoxic pulmonary vasoconstrictive response in the rodent Ochotona curzoniae (pika) at high altitude"Am J Physiol. 274. H1792-H1799 (1998)

Ge 等人：“高海拔啮齿动物鼠兔 (Ochotona curzoniae) (鼠兔) 的缺氧肺血管收缩反应减弱”Am J Physiol。

Yamazaki Y: "Pulmonary function tests of M. avium-intracellulare infection: correlation with BAL fluid findings."Respiration. (in press).

Yamazaki Y：“鸟分枝杆菌胞内感染的肺功能测试：与支气管肺泡灌洗液检查结果的相关性。”呼吸。