血清 IgG 亚类水平与 COPD 患者加重和住院风险的关系。
Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD.
机构信息
Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC, V6Z 1Y6, Canada.
Department of Medicine (Division of Respiratory Medicine), University of British Columbia, Vancouver, BC, Canada.
出版信息
Respir Res. 2018 Feb 14;19(1):30. doi: 10.1186/s12931-018-0733-z.
BACKGROUND
The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts.
METHODS
We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders.
RESULTS
One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10-1.54, p < 0.01) and 1.19 (95% CI, 1.05-1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15-2.02, p < 0.01) and 1.33 (95% CI, 1.08-1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts.
CONCLUSIONS
Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts.
TRIAL REGISTRATION
This study used serum samples from participants of the MACRO ( NCT00325897 ) and STATCOPE ( NCT01061671 ) trials.
背景
关于 COPD 患者 IgG 亚类缺乏症的流行情况及其临床影响，文献资料相对较少。我们使用来自两个 COPD 队列的受试者，调查了 IgG 亚类缺乏症的流行情况及其与加重和住院的关系。
方法
我们使用免疫比浊法测量了先前两项 COPD 试验中参与者的血清 IgG 亚类水平：大环内酯类阿奇霉素预防 COPD 加重（MACRO；n=976）和辛伐他汀预防中重度 COPD 加重（STATCOPE；n=653）。所有样本均来自两项研究入组时处于临床稳定状态的参与者。当 IgG 亚类水平低于各自的正常下限值时，诊断为 IgG 亚类缺乏症：IgG1<2.8 g/L；IgG2<1.15 g/L；IgG3<0.24 g/L；IgG4<0.052 g/L。为了研究 IgG 亚类水平对首次加重或住院时间的影响，我们对 IgG 水平进行了对数转换，并使用 Cox 回归模型进行了分析，同时对混杂因素进行了调整。
结果
MACRO 和 STATCOPE 研究中，分别有 173（17.7%）和 133（20.4%）名参与者存在 1 种或多种 IgG 亚类缺乏症。MACRO 研究中，较低的 IgG1 或 IgG2 水平导致加重的风险增加，调整后的危险比（HR）分别为 1.30（95%CI，1.10-1.54，p<0.01）和 1.19（95%CI，1.05-1.35，p<0.01），STATCOPE 研究结果类似。较低的 IgG1 或 IgG2 水平也与住院风险增加相关：IgG1 和 IgG2 的调整 HR 分别为 1.52（95%CI：1.15-2.02，p<0.01）和 1.33（95%CI，1.08-1.64，p<0.01），MACRO 研究；在 STATCOPE 中，仅 IgG2 是住院的独立预测因子。在我们的多变量 Cox 模型中，MACRO 和 STATCOPE 队列中 IgG3 和 IgG4 水平均与两个结局无显著相关性。
结论
大约每 5 名 COPD 患者中就有 1 名存在 1 种或多种 IgG 亚类缺乏症。较低的 IgG 亚类水平是两个 COPD 队列中加重（IgG1 和 IgG2）和住院（IgG2）的独立危险因素。
试验注册
本研究使用了来自 MACRO（NCT00325897）和 STATCOPE（NCT01061671）试验的参与者的血清样本。
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