Orriols Gerard, Aljama Cristina, Rodriguez-Frias Francisco, Medina Pablo-Gabriel, Ferrer-Costa Roser, Granados Galo, Nuñez Alexa, López-González Ane, Ruiz-Satelinas Gerardo, Miravitlles Marc, Barrecheguren Miriam, Esquinas Cristina
Department of Pneumology, Hospital Universitari Vall d'Hebron/ Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
PLoS One. 2025 Jun 5;20(6):e0324237. doi: 10.1371/journal.pone.0324237. eCollection 2025.
Pulmonary emphysema, a component of chronic obstructive pulmonary disease (COPD) is characterised by irreversible alveolar tissue destruction and is produced by an imbalance between proteolytic enzymes, mostly neutrophil elastase (NE), and its inhibitors, mainly alpha-1 antitrypsin (AAT). We measured elastase-inhibitory activity (EIA) in serum samples and determined whether there is an association between EIA and COPD severity. This cross-sectional study recruited COPD patients with and without severe alpha-1 antitrypsin deficiency (AATD) and healthy controls. A semi-automated method assessed EIA using a porcine elastase inhibition assay. EIA levels and the EIA/AAT ratio were compared across groups and the correlation with clinical variables was analysed. A total of 86 individuals were recruited: 36 COPD patients, 20 individuals with COPD associated with AATD (PiZZ mutation), of whom 11 were on augmentation therapy, and 30 healthy controls. Positive, linear and significant relationships were observed between EIA and AAT levels. The EIA/AAT ratio was higher in non AATD-related COPD patients compared to untreated PiZZ patients and controls. Further analysis in non-AATD-related COPD patients revealed a higher EIA/AAT ratio associated with older age, higher comorbidity burden and a trend towards higher severity of lung disease. The strong correlation between AAT levels and EIA suggests that the assay technique employed is robust and effective for assessing EIA. The EIA assay may serve as a potential biomarker for the assessment of the severity and prognosis of emphysema.
肺气肿是慢性阻塞性肺疾病(COPD)的一个组成部分,其特征是肺泡组织不可逆性破坏,由蛋白水解酶(主要是中性粒细胞弹性蛋白酶(NE))与其抑制剂(主要是α-1抗胰蛋白酶(AAT))之间的失衡所致。我们测量了血清样本中的弹性蛋白酶抑制活性(EIA),并确定EIA与COPD严重程度之间是否存在关联。这项横断面研究招募了有和没有严重α-1抗胰蛋白酶缺乏症(AATD)的COPD患者以及健康对照。采用半自动化方法,通过猪弹性蛋白酶抑制试验评估EIA。比较了各组的EIA水平和EIA/AAT比值,并分析了其与临床变量的相关性。共招募了86名个体:36名COPD患者、20名与AATD相关的COPD患者(PiZZ突变),其中11名接受了强化治疗,以及30名健康对照。观察到EIA与AAT水平之间存在正相关、线性且显著的关系。与未经治疗的PiZZ患者和对照相比,非AATD相关的COPD患者的EIA/AAT比值更高。对非AATD相关的COPD患者的进一步分析显示,EIA/AAT比值较高与年龄较大、合并症负担较重以及肺部疾病严重程度较高的趋势相关。AAT水平与EIA之间的强相关性表明,所采用的检测技术对于评估EIA是可靠且有效的。EIA检测可能作为评估肺气肿严重程度和预后的潜在生物标志物。