RATIONALE Serum Immunoglobulin G (IgG) deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD) but it is unclear whether concentrations in the lower end of the normal range still confer risk. OBJECTIVES To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD. MEASUREMENTS AND MAIN RESULTS Former and current smokers in SPIROMICS (n=1,497) were studied, n=1,026 with and n=471 at risk for COPD. In a subset (n=1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographics, current smoking, smoking history, FEV1% predicted, inhaled corticosteroids, and serum IgA. RESULTS The 35th percentile (1225 mg/dL in this cohort) of IgG was the best cutoff by Akaike Information Criterion (AIC). Below this, there was increased exacerbation risk (IRR 1.28, 95% CI 1.08-1.51). Among subclasses, IgG1 and IgG2 below 35th percentile (354 and 105 mg/dL, respectively) were both associated with increased risk of severe exacerbation (IgG1: IRR 1.39, 95% CI 1.06-1.84; IgG2: IRR 1.50, 95% CI 1.14-1.1.97). These associations remained significant when additionally adjusting for history of exacerbations. CONCLUSIONS Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting subtle impairment of humoral immunity may be associated with exacerbations.

中文翻译：

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血清免疫球蛋白 G 水平与急性加重风险相关：SPIROMICS 分析。


基本原理血清免疫球蛋白 G （IgG） 缺乏与慢性阻塞性肺病 （COPD） 的发病率相关，但尚不清楚正常范围下限的浓度是否仍会带来风险。目的 确定高于血清 IgG 缺乏症传统临界值的水平是否与当前和既往患有 COPD 或有 COPD 风险的吸烟者的恶化有关。测量和主要结果研究了 SPIROMICS 中的既往和当前吸烟者 （n=1,497），n=1,026 有 COPD 风险，n=471 有 COPD 风险。在一个亚群 （n=1,031） 中，测量了 IgG 亚类。使用多变量模型评估总 IgG 或亚类与预期恶化之间的关联，这些模型调整了人口统计学、当前吸烟、吸烟史、预测的 FEV1%、吸入皮质类固醇和血清 IgA。结果 IgG 的第 35 个百分位数 （该队列中为 1225 mg/dL） 是 Akaike 信息标准 （AIC） 的最佳临界值。低于此水平，恶化风险增加 （IRR 1.28,95% CI 1.08-1.51）。在亚类中，低于第 35 个百分位数（分别为 354 和 105 mg/dL）的 IgG1 和 IgG2 均与严重恶化的风险增加相关（IgG1：IRR 1.39,95% CI 1.06-1.84;IgG2：IRR 1.50,95% CI 1.14-1.1.97）。在额外调整恶化史时，这些关联仍然很重要。结论 较低的血清 IgG 与 COPD 患者或有 COPD 风险的个体的恶化前瞻性相关。在亚类中，较低的 IgG1 和 IgG2 前瞻性地与严重恶化相关。最佳 IgG 临界值远高于传统的缺陷临界值，表明体液免疫的细微损害可能与恶化有关。