State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, People's Republic of China.
Rehabilitation Clinical Trials Center, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Int J Chron Obstruct Pulmon Dis. 2020 Sep 30;15:2379-2388. doi: 10.2147/COPD.S266844. eCollection 2020.
We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotype in stable COPD patients ie, those with two or more exacerbations in the previous year.
Eighty-eight stable, severe, COPD patients (4 females) were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FNO); inflammatory variables were measured in venous blood. Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation.
Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%) had greater serum concentration (median (25th-75th quartile)) of serum amyloid A (SAA; 134 (84-178) vs 71 (38-116) ng/mL; P=0.024), surfactant protein D (SP-D; 15.6 (9.0-19.3) vs 8.5 (3.6-14.9) ng/mL; P=0.049) and interleukin-4 (IL-4; 0.12 (0.08-1.44) vs 0.03 (0.01-0.10) pg/mL; P=0.001). SAA, SP-D and IL-4 were not significantly correlated with FEV%predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012). The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (≥124.1 ng/mL) than the lowest SAA quartile (≤44.1 ng/mL) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008). For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators; an SAA cut-off of 87.0 ng/mL yielded an 80% sensitivity and 61.5% specificity.
In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA may be a useful serum biomarker to inform progression or management in COPD.
我们旨在确定循环炎症生物标志物是否与稳定 COPD 患者的频繁加重表型相关，即那些在过去一年中有两次或更多次加重的患者。
评估了 88 例稳定的重度 COPD 患者（4 名女性）的加重频率、肺功能、呼气一氧化氮分数（FNO）；在静脉血中测量了炎症变量。逻辑回归评估了频繁加重表型与全身炎症之间的关联。
与不频繁加重者相比，频繁加重者（n=10；11.4%）血清淀粉样蛋白 A（SAA）浓度（中位数（25%至 75%四分位数））更高[134（84-178）比 71（38-116）ng/mL；P=0.024]、表面活性剂蛋白 D（SP-D；15.6（9.0-19.3）比 8.5（3.6-14.9）ng/mL；P=0.049]和白细胞介素-4（IL-4；0.12（0.08-1.44）比 0.03（0.01-0.10）pg/mL；P=0.001）。SAA、SP-D 和 IL-4 与 FEV%predicted 或 FVC%predicted 无显著相关性。在校正性别、年龄、BMI、FEV/FVC 和吸烟包年数后，只有 SAA 仍与频繁加重表型独立相关（比值比 1.49[1.09-2.04]；P=0.012）。SAA 最高四分位数（≥124.1 ng/mL）的频繁加重者的可能性是 SAA 最低四分位数（≤44.1 ng/mL）的 18 倍（比值比 18.34[1.30-258.81]；P=0.031），且随着 SAA 四分位数的增加，比值比呈显著正趋势（P=0.008）。对于 SAA，识别频繁加重者的受试者工作特征曲线下面积为 0.721；SAA 截断值为 87.0 ng/mL 时，灵敏度为 80%，特异性为 61.5%。
在稳定的 COPD 患者中，SAA 与频繁加重表型独立相关，表明 SAA 可能是一种有用的血清生物标志物，可用于 COPD 的进展或管理。
