Department of Hematology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
PLoS Med. 2018 Nov 1;15(11):e1002685. doi: 10.1371/journal.pmed.1002685. eCollection 2018 Nov.
Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection and infection-related death in the general population.
Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401 infections and experienced 1,045 infection-related deaths. Due to the completeness of the Danish civil and health registries, none of the 98,344 individuals were lost to follow-up, and those emigrating (n = 385) or dying (n = 5,636) had their follow-up truncated at the day of emigration or death. At date of examination, mean age was 58 years, and 44,181 (44.9%) were men. Individuals with lymphopenia (lymphocyte count < 1.1 × 109/l, n = 2,352) compared to those with lymphocytes in the reference range (1.1-3.7 × 109/l, n = 93,538) had multivariable-adjusted hazard ratios of 1.41 (95% CI 1.28-1.56) for any infection, 1.31 (1.14-1.52) for pneumonia, 1.44 (1.15-1.79) for skin infection, 1.26 (1.02-1.56) for urinary tract infection, 1.51 (1.21-1.89) for sepsis, 1.38 (1.01-1.88) for diarrheal disease, 2.15 (1.16-3.98) for endocarditis, and 2.26 (1.21-4.24) for other infections. The corresponding hazard ratio for infection-related death was 1.70 (95% CI 1.37-2.10). Analyses were adjusted for age, sex, smoking status, cumulative smoking, alcohol intake, body mass index, plasma C-reactive protein, blood neutrophil count, recent infection, Charlson comorbidity index, autoimmune diseases, medication use, and immunodeficiency/hematologic disease. The findings were robust in all stratified analyses and also when including only events later than 2 years after first examination. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and reverse causation. In principle, fluctuating lymphocyte counts over time might also have influenced analyses, but lymphocyte counts in 5,181 individuals measured 10 years after first examination showed a regression dilution ratio of 0.68.
Lymphopenia was associated with increased risk of hospitalization with infection and increased risk of infection-related death in the general population. Notably, causality cannot be deduced from our data.
中性粒细胞减少会增加感染的风险，但淋巴细胞减少是否也会增加感染的风险尚不清楚。因此，我们检验了以下假设：淋巴细胞减少与普通人群感染风险和感染相关死亡风险增加有关。
在邀请的 220424 人中，有 99191 人参加了检查。我们分析了来自哥本哈根普通人群研究（丹麦）的 98344 个人的数据，这些人于 2003 年 11 月 25 日至 2013 年 7 月 9 日接受了检查，并且在检查日期时有可用的血液淋巴细胞计数。在中位数为 6 年的随访期间，他们发生了 8401 例感染，经历了 1045 例与感染相关的死亡。由于丹麦民事和卫生登记处的完整性，98344 人中没有人失访，那些移民（n=385）或死亡（n=5636）的人在移民或死亡之日截断了随访。在检查日期时，平均年龄为 58 岁，44181 人（44.9%）为男性。与淋巴细胞处于参考范围（1.1-3.7×109/l，n=93538）的个体相比，淋巴细胞减少症（淋巴细胞计数<1.1×109/l，n=2352）的个体发生任何感染的多变量调整后的危险比为 1.41（95%CI 1.28-1.56），肺炎为 1.31（1.14-1.52），皮肤感染为 1.44（1.15-1.79），尿路感染为 1.26（1.02-1.56），败血症为 1.51（1.21-1.89），腹泻病为 1.38（1.01-1.88），心内膜炎为 2.15（1.16-3.98），其他感染为 2.26（1.21-4.24）。与感染相关的死亡的危险比为 1.70（95%CI 1.37-2.10）。分析调整了年龄、性别、吸烟状况、累计吸烟量、饮酒量、体重指数、血浆 C 反应蛋白、血中性粒细胞计数、近期感染、Charlson 合并症指数、自身免疫性疾病、药物使用和免疫缺陷/血液疾病。在所有分层分析中以及在仅包括首次检查后 2 年以后的事件的分析中，结果均具有稳健性。然而，由于观察性设计，该研究无法解决因果关系问题，并且我们的分析理论上可能受到残余混杂和反向因果关系的影响。原则上，随着时间的推移淋巴细胞计数的波动也可能影响分析，但在首次检查 10 年后测量的 5181 个人的淋巴细胞计数显示回归稀释比为 0.68。
淋巴细胞减少与普通人群中感染住院风险增加和感染相关死亡风险增加有关。值得注意的是，我们的数据不能推断出因果关系。
