抽象
第3组肺动脉高压特发性NSIP常见复杂化,并与不良后果http://ow.ly/jsa930jMaSD
致编辑:
肺动脉高压(PH)与生活质量受损相关联,恶化功能状态和在特发性肺纤维化(IPF)死亡率增加[1]。以前尚未报道的患病率和其他特发性间质性肺炎(的IIP)的临床影响。由于PH的IPF预后的意义,我们试图确定世界卫生组织(WHO)第3组PH患者活检证实为特发性非特异性间质性肺炎(NSIP)队列的普遍性和严重性。我们认识到,PH在这一人群中晚期患者NSIP的发病率将是广大NSIP人口的高估,但认为强制外科肺活检和右心脏导管插入术(RHC)是确保NSIP的正确诊断的唯一途径和PH,分别。
患者的特发性NSIP回顾性诊断2002年至2016年间在执行我们的中心。所有病例均在我们的多学科的肺部病理会议审查。结缔组织病(CTD)被严格地排除在所有患者和RHC是必需的PH的确认。生殖健康药物供应不上在我院门诊所有病人进行标准地,并会为肺移植评估的一部分,或者通过临床参数或超声心动图的数据表明证实PH被执行。PH was defined as a resting mean pulmonary artery pressure (mPAP) ≥25 mmHg and severe PH as mPAP ≥35 mmHg. Patients with a pulmonary capillary wedge pressure >15 mmHg were excluded from the cohort as they were suspected to have left-heart disease associated (WHO group 2) PH. Chronic thromboembolic disease was excluded in all patients with ventilation/perfusion scanning. The primary endpoints of this study were the prevalence and impact of WHO Group 3 PH on patient outcomes in idiopathic NSIP. Secondary outcomes included the correlation of forced vital capacity (FVC) and mPAP in idiopathic NSIP patients, as well as the association between other demographics and PH in this population.
从我们的多学科的肺部病理会议记录审查确定95名潜在患者经活检证实NSIP。在这些患者中,35满足标准纳入研究。
11(31.4%)的35例患者WHO组3 PH。平均±SDmPAP for those with and without WHO group 3 PH were 32.0±10.3 mmHg and 18.1±3.1 mmHg, respectively. Of the 35 patients in the study, seven (20%) patients had a mPAP of 25–30 mmHg, two (5.7%) had a mPAP of 31–34 mmHg and two (5.7%) had a mPAP ≥35 mmHg.表格1详细的PH患者的特点与那些没有。Per cent predicted FVC was similar between the WHO group 3 PH and no PH cohorts, with r= −0.12 suggesting poor correlation between FVC per cent predicted and mPAP (p=0.48).
Median transplant-free survival was significantly lower in patients with WHO group 3 PH at 17.6 months as compared to 47.9 months in the cohort without PH (p=0.05). Severe PH (mPAP ≥35 mmHg or mPAP ≥25 mmHg with a low cardiac index) was only seen in two (5.7%) patients, both of whom expired without transplant, with an average adjusted survival time of 12.6 months. Both of these patients also suffered from severe functional impairment with a mean 6-min walk test distance of only 137.2 and 129 m, respectively. A competing risk analysis was performed to determine if the relationship between WHO group 3 PH and survival would persist after taking into account lung transplant as a competing event. The analysis confirmed that the presence of WHO group 3 PH was associated with an increased risk of death even after considering transplant as a competing risk (hazard ratio 3.73, 95% CI 1.32–10.55; p=0.013). Additionally, a multivariate competing risk analysis found WHO group 3 PH was still associated with an increased risk of death after adjusting for age and FVC per cent predicted.
我们发现,3组PH存在于谁接受RHC特发性NSIP患者的大约三分之一(31.4%)。据我们所知,这是第一个也是唯一研究,在NSIP严格评估PH。事实上,没有事先的研究报告PH的IPF比其他任何IIP流行。我们认为我们的研究有许多优势,其中包括用于确保只有特发性NSIP患者严格的入选标准包括:(需要手术肺活检,通过多学科的肺部病理委员会进行了广泛CTD血清学评价和审查),世界卫生组织第3组的确认通过RHC PH和长期随访。
从我们研究的主要发现是无移植生存显著减少特发性NSIP患者WHO组3 PH看到。Median transplant-free survival was over 30 months shorter in patients with WHO group 3 PH, at a mere 17.6 months. The association of WHO group 3 PH with increased mortality remained, even after adjusting for age and FVC % predicted, and treating lung transplant as a competing risk. The association between the development of PH is consistent with what has been demonstrated in the IPF population, where PH serves as a powerful predictor of mortality [1,2]。事实上,它似乎一旦PH在NSIP和IPF开发,成果是非常相似的,这也许是PH值就变成患者随后的临床过程中的主要驱动力。鉴于此关联,这是审慎的临床医生画面PH,并考虑肺移植在谁开发复杂PH NSIP病人上市。
PH在此特发性NSIP人群患病率很可能是什么将在一个不太选择,一般肺实践人口有几个原因可以看出高估。由于我们的诊所专门从事先进的肺部疾病和肺移植,还有它固有的转诊偏见和研究人群代表特发性NSIP患者更先进的子集,因为它们的平均FVC为53.3%的预测。此外,所有35例患者在我们的研究中有混合的细胞和纤维化或纤维化NSIP病理学,因此可能代表特发性NSIP的更难治的子集。最后,对纳入研究的RHC要求使得PH的预测试的概率较高为RHC指示通常已PH的临床或超声心动图怀疑,或作为移植前评估的一部分。无论如何,考虑到数据的缺乏对PH在NSIP的流行,我们觉得这些数据的价值,临床医生,尤其是那些谁与类似患者人群中的临床实践。
虽然不是我们的初衷,我们的研究也有助于特发性NSIP上生存的现有文献。Ťravis等。[3报道特发性纤维化NSIP 90%的5年存活率。Ťransplant-free survival in our cohort, even in those without PH, was <50% at 5 years. Ours most likely reflects a more advanced population, as noted by the moderately severe mean FVC, and its composition of only mixed cellular and fibrotic or fibrotic NSIP patients. In addition, Travis等。[3]专门评价了他们的生存分析,而不是肺移植死亡,而我们的研究既考虑后果,这可能有助于缩短无移植存活。最后,用于确定病人的生存方法的两项研究之间是不同的。经travis等。[3]的研究中所依据的病历审查,并与转诊医师,这可能低估相比,我们使用社会保障死亡指数,这可能是更准确的为患者搬迁或失去随访的死亡的发生率接触。然而,在我们的队列成果是显着低于NSIP之前报道更糟。
总之,我们已经表明,PH特发性纤维化NSIP的过程中常见的复杂化。在这个人口PH的发展与显着降低无移植生存率。事实上,与NSIP PH似乎也有类似的预后意义是什么有报道IPF-PH,支持包括治疗相同的临床试验两组的当前概念。
脚注
利益冲突:C.S.国王已经收到个人从收费勃林格殷格翰公司和法国基金会试点方案,提交作品之外。
利益冲突:O.A.Shlobin曾担任顾问,顾问委员会成员和扬声器拜耳,美国和治疗Actelion公司。
利益冲突:S.D.弥敦道是,已经获得的研究经费来自并且是扬声器局Boerhinger殷格翰公司,Gilead Sciences公司,罗氏基因泰克公司,拜耳制药和联合治疗的顾问。他也是Bellerophon的一个顾问。
- 收到2018年1月23日。
- 公认2018年4月5日。
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