血清 IgA 水平降低与 SPIROMICS 中 COPD 加重风险相关。
Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS.
机构信息
Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
出版信息
PLoS One. 2018 Apr 12;13(4):e0194924. doi: 10.1371/journal.pone.0194924. eCollection 2018.
BACKGROUND
Decreased but measurable serum IgA levels (≤70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD. This study tested the hypothesis that subnormal serum IgA levels would be associated with exacerbation risk in COPD.
METHODS
Data were analyzed from 1,049 COPD participants from the observational cohort study SPIROMICS (535 (51%) women; mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA measured using the Myriad RBM biomarker discovery platform. Exacerbation data was collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear, logistic and zero-inflated negative binomial regressions were performed.
RESULTS
Mean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum IgA (<7 mg/dL) and 25 (2.4%) had IgA level ≤70 mg/dL. Participants with IgA ≤70 mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those with higher IgA. In adjusted models, IgA ≤70 mg/dL was associated with higher exacerbation incidence rates (IRR 1.71, 95% CI 1.01-2.87, p = 0.044) and greater risk for any severe exacerbation (OR 2.99, 95% CI 1.30-6.94, p = 0.010). In adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL decrement in IgA (analyzed continuously) was associated with more exacerbations during follow-up (β 0.24, 95% CI 0.017-0.46, p = 0.035).
CONCLUSIONS
Subnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity. Additionally, a dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk. Future COPD studies should more comprehensively characterize immune status to define the clinical relevance of these findings and their potential for therapeutic correction.
背景
在一些人群中，血清 IgA 水平降低（≤70mg/dL）与感染风险相关，但在 COPD 中尚未研究。本研究检验了假设，即亚正常血清 IgA 水平与 COPD 加重风险相关。
方法
使用 Myriad RBM 生物标志物发现平台，对来自观察性队列研究 SPIROMICS 的 1049 名 COPD 参与者（535 名（51%）女性；平均年龄 66.1（SD 7.8），338 名（32%）当前吸烟者）的基线血清 IgA 进行数据分析。前瞻性收集加重数据（平均 944.3（SD 281.3）天），并进行调整线性、逻辑和零膨胀负二项回归分析。
结果
平均 IgA 为 269.1mg/dL（SD 150.9）。1 人血清 IgA 水平低于正常值（<7mg/dL），25 人（2.4%）血清 IgA 水平≤70mg/dL。IgA≤70mg/dL 的参与者年龄较小（62 岁 vs. 66 岁，p=0.01），但其他方面与 IgA 较高的参与者相似。在调整后的模型中，IgA≤70mg/dL 与较高的加重发生率（IRR 1.71，95%CI 1.01-2.87，p=0.044）和更严重的加重风险（OR 2.99，95%CI 1.30-6.94，p=0.010）相关。在最低十分位数（<120mg/dL）的参与者中，调整后的模型中，IgA 每降低 10mg/dL（连续分析）与随访期间的加重次数增加相关（β 0.24，95%CI 0.017-0.46，p=0.035）。
结论
亚正常血清 IgA 水平与急性加重风险增加相关，支持轻度受损的 IgA 水平是 COPD 发病率的一个促成因素。此外，在血清 IgA 处于最低十分位数的个体中，发现血清 IgA 水平与加重次数之间存在剂量-反应关系，进一步支持了血清 IgA 与加重风险之间的联系。未来的 COPD 研究应更全面地描述免疫状态，以确定这些发现的临床意义及其治疗纠正的潜力。
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