Traxler Denise, Zimmermann Matthias, Simader Elisabeth, Einwallner Elisa, Copic Dragan, Graf Alexandra, Mueller Thomas, Veraar Cecilia, Lainscak Mitja, Marčun Robert, Košnik Mitja, Fležar Matjaž, Rozman Aleš, Korošec Peter, Klepetko Walter, Moser Bernhard, Ankersmit Hendrik J
Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Medical University of Vienna, Austria.
Ann Transl Med. 2021 Jan;9(2):117. doi: 10.21037/atm-20-3683.
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is characterized by episodes of acute exacerbations. Finding a systemic biomarker that reliably predicts outcome after an acute exacerbation remains a major challenge. Heat shock protein 27 (HSP27) has been previously studied in COPD, however, urine excretion trajectory and prognostic value after an exacerbation is unknown.
In this retrospective post hoc analysis of a prospective study that included 253 COPD patients who were hospitalized for acute exacerbation, 207 patients were analyzed. Urine and serum were sampled at admission, discharge, and 180 days after discharge; urine excretion trajectory was analyzed and correlated with clinicopathological and survival data.
HSP27 urine excretion increased after an exacerbation episode [1.8% admission, 1.8% discharge, 2.3% 180 days after discharge (P=0.091)]. In severely ill patients (GOLD IV) this course was even more distinct [1.6% admission, 2.1% discharge, 2.8% 180 days after discharge (P=0.007)]. Furthermore, fractional HSP27 urine excretion at discharge was increased in GOLD IV patients (P=0.031). In Kaplan-Meier and univariable Cox proportional hazard models patients with HSP27 urine excretion below 0.845% showed significantly worse survival at 30, 90 and 180 days after discharge. In a multivariable Cox proportional hazard model including established COPD outcome parameters fractional HSP27 urine excretion remained a significant predictor of survival at 30 and 90 days after discharge. Comparing this model to our already published model that includes HSP27 serum concentration we could show that fractional HSP27 urine excretion performs better in short-term survival.
Our findings provide novel information about fractional HSP27 urine excretion trajectory in acute exacerbation of COPD. Fractional HSP27 urine excretion may be significantly reduced during an episode of acute exacerbation in COPD patients and may be used as a predictor of short-term all-cause mortality.
慢性阻塞性肺疾病（COPD）是发病和死亡的主要原因，其特征为急性加重发作。寻找一种能可靠预测急性加重后预后的系统性生物标志物仍然是一项重大挑战。热休克蛋白27（HSP27）此前已在COPD中进行过研究，然而，急性加重后尿液排泄轨迹及预后价值尚不清楚。
在这项对一项前瞻性研究的回顾性事后分析中，纳入了253例因急性加重住院的COPD患者，对其中207例患者进行分析。在入院时、出院时及出院后180天采集尿液和血清样本；分析尿液排泄轨迹，并将其与临床病理及生存数据相关联。
急性加重发作后HSP27尿液排泄增加[入院时1.8%，出院时1.8%，出院后180天2.3%（P = 0.091）]。在重症患者（GOLD IV级）中，这一过程更为明显[入院时1.6%，出院时2.1%，出院后180天2.8%（P = 0.007）]。此外，GOLD IV级患者出院时HSP27尿液排泄分数增加（P = 0.031）。在Kaplan-Meier和单变量Cox比例风险模型中，HSP27尿液排泄低于0.845%的患者在出院后30天、90天和180天的生存率显著更差。在一个包含已确定的COPD预后参数的多变量Cox比例风险模型中，HSP27尿液排泄分数仍然是出院后30天和90天生存的显著预测指标。将该模型与我们已发表的包含HSP27血清浓度的模型进行比较，我们发现HSP27尿液排泄分数在短期生存方面表现更好。
我们的研究结果提供了关于COPD急性加重时HSP27尿液排泄分数轨迹的新信息。COPD患者急性加重发作期间HSP27尿液排泄分数可能显著降低，并且可作为短期全因死亡率的预测指标。
