Spittle Daniella A, Mansfield Alison, Pye Anita, Turner Alice M, Newnham Michael
Institute of Applied Health Research, University of Birmingham, Birmingham B15 2TT, UK.
Biomedicines. 2023 Jul 15;11(7):2001. doi: 10.3390/biomedicines11072001.
Lung disease progression in alpha-1 antitrypsin deficiency (AATD) is heterogenous and manifests in different ways. Blood biomarkers are an attractive method of monitoring diseases as they are easy to obtain and repeatable. In non-AATD COPD, blood biomarker panels have predicted disease severity, progression, and mortality. We measured a panel of seven serum biomarkers in 200 AATD patients and compared levels between those with COPD and those without. We assessed whether biomarkers were associated with baseline lung function parameters (FEV1 and TLco) or absolute change in these parameters. In total, 111 patients with a severely deficient genotype of AATD (PiZZ) and COPD were included in the analyses. Pearson's correlation coefficient was measured for biomarker correlations and models were compared using ANOVA. CRP and CCL18 were significantly higher in the serum of AATD COPD versus AATD with no COPD. Biomarkers were not predictive of cross-sectional lung function measurements, however, CC16 was significantly associated with an absolute change in TLco ( = 0.018). An addition of biomarkers to the predictive model for TLco added significant value over covariates alone (R 0.13 vs. 0.02, = 0.028). Our findings suggest that CC16 is predictive of emphysema progression in AATD COPD. Proteomics data may reveal alternative candidate biomarkers and further work should include the use of longitudinal biomarker measurements.
α-1抗胰蛋白酶缺乏症（AATD）患者的肺部疾病进展具有异质性，且表现形式各异。血液生物标志物是一种颇具吸引力的疾病监测方法，因为它们易于获取且具有可重复性。在非AATD慢性阻塞性肺疾病（COPD）中，血液生物标志物组合可预测疾病严重程度、进展及死亡率。我们对200例AATD患者的一组七种血清生物标志物进行了检测，并比较了COPD患者与非COPD患者的标志物水平。我们评估了这些生物标志物是否与基线肺功能参数（第一秒用力呼气容积[FEV1]和一氧化碳肺弥散量[TLco]）或这些参数的绝对变化相关。分析共纳入了111例AATD基因严重缺陷型（PiZZ）且患有COPD的患者。采用Pearson相关系数测定生物标志物之间的相关性，并使用方差分析比较模型。与无COPD的AATD患者相比，AATD合并COPD患者血清中的C反应蛋白（CRP）和CC趋化因子配体18（CCL18）显著升高。生物标志物无法预测横断面肺功能测量结果，然而，CC16与TLco的绝对变化显著相关（P = 0.018）。在TLco预测模型中加入生物标志物比仅使用协变量具有更高的价值（R²分别为0.13和0.02，P = 0.028）。我们的研究结果表明，CC16可预测AATD合并COPD患者的肺气肿进展。蛋白质组学数据可能会揭示其他候选生物标志物，进一步的研究应包括使用纵向生物标志物测量。
