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一组新冠病毒肺炎患者出院六个月后的肺功能、影像学表现及纤维化生物标志物

Lung Function, Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge.

作者信息

Safont Belen, Tarraso Julia, Rodriguez-Borja Enrique, Fernández-Fabrellas Estrella, Sancho-Chust Jose N, Molina Virginia, Lopez-Ramirez Cecilia, Lope-Martinez Amaia, Cabanes Luis, Andreu Ada Luz, Herrera Susana, Lahosa Carolina, Ros Jose Antonio, Rodriguez-Hermosa Juan Luis, Soriano Joan B, Moret-Tatay Ines, Carbonell-Asins Juan Antonio, Mulet Alba, Signes-Costa Jaime

机构信息

Pulmonary Department, Hospital Clinico, INCLIVA, Valencia, Spain.

Laboratory of Biochemistry and Molecular Pathology, Hospital Clinico de Valencia, Valencia, Spain.

出版信息

Arch Bronconeumol. 2022 Feb;58(2):142-149. doi: 10.1016/j.arbres.2021.08.014. Epub 2021 Sep 3.

Abstract

INTRODUCTION

Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia.

METHODS

COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits.

RESULTS

In total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO < 80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74-5.06,  = 0.001), age (OR: 1.03, 95% CI: 1.01-1.05,  = 0.005), and peak RALE score (OR: 1.22, 95% CI 1.06-1.40,  = 0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54 ± 8.96 vs 6.71 ± 4.25,  = 0.001), and periostin (1.11 ± 0.07 vs 0.84 ± 0.40,  = 0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20 ± 9.20 vs 7.92 ± 6.32,  = 0.001), MMP1 (10.40 ± 8.21 vs 6.97 ± 8.89,  = 0.023), and periostin (1.36 ± 0.93 vs 0.87 ± 0.39,  = 0.001).

CONCLUSION

Almost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.

摘要

引言

肺功能测试受损和影像学异常是新冠病毒病康复者的主要关注点。我们的目的是评估新冠病毒肺炎患者在患病两个月和六个月后,其呼吸功能参数、胸部CT变化以及与肺纤维化相关的外周血生物标志物之间的相关性。

方法

COVID-FIBROTIC研究(clinicaltrials.gov NCT04409275)是一项多中心前瞻性观察队列研究,旨在评估出院患者。在门诊就诊时进行肺功能测试、循环血清生物标志物检测、胸部X线摄影和胸部CT检查。

结果

在纳入研究的481例患者中,共有313例(年龄61.12±12.26岁)患者可供分析。在60天和180天时,一氧化碳弥散量(DLCO)<80%的患者比例分别为54.6%和47%。六个月时与弥散功能障碍相关的因素包括女性(比值比:2.97,95%置信区间1.74-5.06,P=0.001)、年龄(比值比:1.03,95%置信区间:1.01-1.05,P=0.005)和啰音峰值评分(比值比:1.22,95%置信区间1.06-1.40,P=0.005)。肺弥散功能改变的患者基质金属蛋白酶-7(MMP-7)水平较高(11.54±8.96 vs 6.71±4.25,P=0.001),骨膜蛋白水平也较高(1.11±0.07 vs 0.84±0.40,P=0.001)。226例患者接受了CT扫描,其中149例(66%)有新冠病毒病的影像学后遗症。在重症患者中,68.35%有磨玻璃影表现,38.46%有实质条索影。早期纤维化改变与较高水平的MMP-7(13.20±9.20 vs 7.92±6.32,P=0.001)、MMP-1(10.40±8.21 vs 6.97±8.89,P=0.023)和骨膜蛋白(1.36±0.93 vs 0.87±0.39,P=0.001)相关。

结论

中度或重度新冠病毒肺炎患者出院六个月后,近一半患者存在肺弥散功能受损。重症患者CT扫描显示有纤维化病变,且参与肺纤维化的血清生物标志物升高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ed9/8414844/9b7133a29412/fx1_lrg.jpg

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