Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Nicotine Tob Res. 2019 Jul 17;21(8):1036-1044. doi: 10.1093/ntr/nty077.
Smoking is associated with systemic and local inflammation in the lungs. Furthermore, in chronic obstructive pulmonary disease, which is often caused by smoking, there is often systemic inflammation that is linked to lung function impairment. However, the causal pathways linking smoking, systemic inflammation, and airflow limitation are still unknown. We tested whether higher tobacco consumption is associated with higher systemic inflammation, observationally and genetically and whether genetically higher systemic inflammation is associated with airflow limitation.
We included 98 085 individuals aged 20-100 years from the Copenhagen General Population Study; 36589 were former smokers and 16172 were current smokers. CHRNA3 rs1051730 genotype was used as a proxy for higher tobacco consumption and the IL6R rs2228145 genotype was used for higher systemic inflammation. Airflow limitation was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <70%.
Difference in plasma level of C-reactive protein was 4.8% (95% CI = 4.4% to 5.2%) per 10 pack-year increase and 1.6% (95% CI = 0.4% to 2.8%) per T allele. Corresponding differences were 1.2% (95% CI = 1.1% to 1.3%) and 0.5% (95% CI = 0.3% to 0.8%) for fibrinogen, 1.2% (95% CI = 1.2% to 1.3%) and 0.7% (95% CI = 0.5% to 1.0%) for α1-antitrypsin, 2.0% (95% CI = 1.8% to 2.1%) and 0.7% (95% CI = 0.4% to 1.1%) for leukocytes, 1.9% (95% CI = 1.8% to 2.1%) and 0.8% (95% CI = 0.4% to 1.2%) for neutrophils, and 0.8% (95% CI = 0.7% to 1.0%) and 0.4% (95% CI = 0.1% to 0.7%) for thrombocytes. The differences in these levels were lower for former smokers compared with current smokers. The IL6R rs2228145 genotype was associated with higher plasma acute-phase reactants but not with airflow limitation. Compared with the C/C genotype, the odds ratio for airflow limitation was 0.95 (95% CI = 0.89 to 1.02) for A/C genotype and 0.94 (95% CI = 0.87 to 1.01) for A/A genotype.
Higher tobacco consumption is associated with higher systemic inflammation both genetically and observationally, whereas systemic inflammation was not associated with airflow limitation genetically.
The association between higher tobacco consumption and higher systemic inflammation may be causal, and the association is stronger among current smokers compared to former smokers, indicating that smoking cessation may reduce the effects of smoking on systemic inflammation. Systemic inflammation does not seem to be a causal driver in development of airflow limitation. These findings can help to understand the pathogenic effects of smoking and the interplay between smoking, systemic inflammation, and airflow limitation and hence development and progression of chronic obstructive pulmonary disease.
吸烟与肺部的全身和局部炎症有关。此外，在常由吸烟引起的慢性阻塞性肺疾病中，常存在与肺功能损害相关的全身炎症。然而，将吸烟、全身炎症和气流受限联系起来的因果途径仍不清楚。我们观察和遗传上测试了较高的烟草消费是否与较高的全身炎症相关，以及遗传上较高的全身炎症是否与气流受限相关。
我们纳入了来自哥本哈根普通人群研究的 98085 名 20-100 岁的个体；其中 36589 名为曾经吸烟者，16172 名为当前吸烟者。CHRNA3 rs1051730 基因型被用作较高烟草消费的替代物，IL6R rs2228145 基因型被用于较高的全身炎症。气流受限定义为 1 秒用力呼气量（FEV1）/用力肺活量（FVC）<70%。
每增加 10 包年，血浆 C-反应蛋白水平差异为 4.8%（95%CI=4.4%至 5.2%），每增加一个 T 等位基因差异为 1.6%（95%CI=0.4%至 2.8%）。相应的差异为 1.2%（95%CI=1.1%至 1.3%）和 0.5%（95%CI=0.3%至 0.8%）的纤维蛋白原，1.2%（95%CI=1.2%至 1.3%）和 0.7%（95%CI=0.5%至 1.0%）的α1-抗胰蛋白酶，2.0%（95%CI=1.8%至 2.1%）和 0.7%（95%CI=0.4%至 1.1%）的白细胞，1.9%（95%CI=1.8%至 2.1%）和 0.8%（95%CI=0.4%至 1.2%）的中性粒细胞，以及 0.8%（95%CI=0.7%至 1.0%）和 0.4%（95%CI=0.1%至 0.7%）的血小板。与当前吸烟者相比，曾经吸烟者的这些水平差异较低。IL6R rs2228145 基因型与较高的血浆急性期反应物相关，但与气流受限无关。与 C/C 基因型相比，A/C 基因型的气流受限比值比为 0.95（95%CI=0.89 至 1.02），A/A 基因型的比值比为 0.94（95%CI=0.87 至 1.01）。
无论在遗传上还是观察上，较高的烟草消费都与全身炎症有关，而全身炎症与气流受限在遗传上没有关联。
较高的烟草消费与较高的全身炎症之间的关联可能是因果关系，与曾经吸烟者相比，当前吸烟者之间的关联更强，这表明戒烟可能会降低吸烟对全身炎症的影响。全身炎症似乎不是气流受限发展的因果驱动因素。这些发现有助于理解吸烟的致病作用以及吸烟、全身炎症和气流受限之间的相互作用，以及慢性阻塞性肺疾病的发生和发展。
