结缔组织病相关肺动脉高压合并与不合并肺间质病变患者临床特点与预后的比较

Characteristics and survival of connective tissue disease associated pulmonary arterial hypertension patients with and without interstitial lung disease

目的研究CTD同时合并肺动脉高压（PAH）及间质性肺病（ILD）患者的临床特征以及预后，并与单纯合并PAH的CTD患者进行比较。方法纳入2006年7月至2011年5月期间3个医学中心所有经右心导管确诊的CTD相关PAH的患者，根据胸部CT分为ILD组及无ILD组，比较这2组患者的临床特点及预后。采用t检验、Mann-Whitney U检验、χ^2检验、Kaplan-Meier生存分析以及Cox回归分析进行统计。结果126例患者被纳入研究，其中27例患者纳入ILD组，99例患者纳入无ILD组。ILD组患者年龄更大、肺功能指标显示用力肺活量[（75±18）%和（83±13）%，t=2.212，P=0.037]、一氧化碳弥散量[（54±22）%和（68±20）%，t=2.392，P=0.019]更差。尽管血流动力学指标肺动脉平均压（43±13和52±14，t=2.908，P=0.004）及肺血管阻力（9±6和12±7，t=2.205，P=0.029）在ILD组受损较轻，但Kaplan-Meier生存分析显示ILD组的短期生存率差于无ILD组（1年生存率72.7%和94.7%，3年生存率63.6%和81.1%，P=0.047）。对ILD患者进行Cox回归分析，显示混合静脉血氧饱和度（SvO2）是ILD患者死亡的独立影响因素[HR=0.19，95%CI（0.04，0.83），P=0.027]，SvO2〈60%的患者生存率显著低于SvO2≥60%的患者。结论同时合并PAH及ILD是CTD患者的一种特殊表型，尽管这组患者血流动力学恶化程度相对较轻，但预后较单纯合并PAH的患者更差。低SvO2是CTD同时合并PAH及ILD这组患者死亡的独立危险因素。

ObjectiveTo explore the characteristics and survival of connective tissue disease （CTD） patients with both of pulmonary arterial hypertension （PAH） and interstitial lung disease （ILD）, and to compare with CTD patients with isolated PAH.MethodsAll adult CTD patients who visited one of the three referral centers in China with a diagnosis of PAH confirmed by right heart catheterization from July 2006 to May 2011 were enrolled. They were then divided into two groups （ILD with and without-ILD group） based on chest CT and then the comparison of baseline characteristics and survival at the endpoint of follow up were made between the two groups. T test, Mann-Whitney U test, χ^2 test, Kaplan-Meier survival analysis and Cox regres-sion analysis were used for statistical analyses.ResultsOne hundred and twenty-six patients were recruited into the study. Patients with ILD （n=27） were older than those without ILD （n=99）. Lung function results including FVC [（75±18）% vs （83±13）%, t=2.212, P=0.037] and DLCO [（54±22）% vs （68±20）%, t=2.392, P=0.019] in ILD group were significantly worse than those without-ILD group. Although some important hemodynamic parameters such as mean pulmonary arterial pressure and pulmonary vascular resistance were better in the ILD group than the without-ILD group, Kaplan-Meier analysis showed that the short term survival of ILD group was significantly worse than that of the without-ILD group （72.7% versus 94.7% at 1 year and 63.6% versus 81.1% at 3 year, P=0.047）. In ILD group, Cox regression analysis showed that SvO2 was the only independent factor for the short term survival [HR=0.19, 95%CI （0.04, 0.83）, P=0.027], and Kaplan-Meier analysis showed patients with SvO2〈60% had significantly lower short term survival than patients with SvO2≥60% （1 and 2 year survival were 60.0% and 40.0% versus 92.9% and 77.4% respectively, P=0.002）.ConclusionPatients with both PAH and ILD is a special subtype in CTD. Although with the superiority of hemodynamics, these patients have significantly worse survival than CTD patients with isolated PAH. Low SvO2 is the independent risk factor for the short term mortality in patients of CTD complicated by both PAH and ILD. More attention should be paid to these patients and the management strategy should be investigated further.