超高齢者感染症患者における循環性微小粒子の早期診断値

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Zhonghua Wei Zhong Bing Ji Jiu Yi Xue.2020 Jun;32(6):686-690. doi: 10.3760/cma.j.cn121430-20200326-00241.

超高齢者感染症患者における循環性微小粒子の早期診断値

[Early diagnostic value of circulating microparticles in super-elderly patients with infection].

Yaping Yuan
Tingting Liu
Jionghe Wu
Chao Wang
Xiangqun Fang
Hongxia Li

PMID: 32684213 DOI: 10.3760/cma.j.cn121430-20200326-00241.

抄録

目的:

超高齢者感染症患者における微小粒子（MP）のレベルとその変化傾向を調査し、感染症の早期診断効果を探る。

OBJECTIVE: To investigate the level and changing trend of microparticles (MPs) in super-elderly infected patients, and explore its early warning effect on infection.

方法:

2018年12月から2019年3月までに中国PLA総合病院第二医療センターに入院した感染者≧85歳を観察群とし、同期間の健康なボランティア≧85歳を対照群とした。発熱後2時間目、2日目、7日目に静脈採血を行い、白血球数（WBC）、好中球率（NEUT）、C反応性蛋白（CRP）、プロカルシトニン（PCT）などの炎症マーカーを測定した。MPのレベルはフローサイトメトリーによって決定した。アネキシンＶ標識ＣＤ１１ｂ陽性ＭＰ（アネキシンＶ／ＣＤ１１ｂＭＰ）は白血球微粒子（ＬＭＰ）を表し、アネキシンＶ標識ＣＤ６６ｂ陽性ＭＰ（アネキシンＶ／ＣＤ６６ｂＭＰ）は好中球微粒子（ＮＭＰ）を表した。両群間の異なる時点での各指標の差を比較し、高齢者の感染に対する各指標の予測値をレシーバー操作特性（ROC）曲線で解析した。

METHODS: The infected patients ≥ 85 years old admitted to the Second Medical Center of Chinese PLA General Hospital from December 2018 to March 2019 were selected as the observation group, and the healthy volunteers ≥ 85 years old in the same period were selected as the control group. Venous blood samples were collected at the 2nd hour, the 2nd day and the 7th day after fever, and the inflammatory markers such as white blood cell count (WBC), neutrophil percentage (NEUT), C-reactive protein (CRP) and procalcitonin (PCT) were measured. The levels of MPs were determined by flow cytometry. Annexin V labeled CD11b positive MPs (Annexin V/CD11b MPs) represented leukocyte microparticles (LMPs), and Annexin V labeled CD66b positive MPs (Annexin V/CD66b MPs) represented neutrophil microparticle (NMPs). The differences of each index at different time points between the two groups were compared, and the predictive value of each index to the infection of elderly patients was analyzed by receiver operating characteristic (ROC) curve.

結果:

観察群28例、対照群10例の計38例を登録した。観察群のLMPsとNMPsは発熱後2時間目をピークに上昇し，対照群と比較して有意に高値を示した［LMPs（細胞/μL）：55．0（28.8、197.2）対19.0（13.5、28.3）、NMPs（細胞/μL）：226.5（123.3、516.5）対26.5（22.0、48.8）、いずれもP＜0.01］。制圧に伴い、LMPsおよびNMPsは徐々に減少した。2日目のNMPsは発熱2時間目に比べて有意に低下した［cells/μL：106.0（40.0、309.0）vs.226.5（123.3、516.5）、P＜0．05]、7日目のLMPsとNMPsは2日目に比べて有意に低かった［LMPs（細胞/μL）：17.0（12.5、43.8）対42.0（13.0、117.0）、NMPs（細胞/μL）：30.0（15.8、62.0）対106.0（40.0、309.0）、いずれもP＜0.05］。7日目のLMPsとNMPsのレベルには両群間で有意差はなかった。炎症性マーカーのうち、発熱2時間目のNEUTは観察群が対照群に比べて有意に高かったが（0.70±0.09 vs. 0.59±0.04、P＜0.01）、WBC、CRP、PCTには両群間で有意差は認められなかった。2日目には観察群の炎症マーカーがピークに達し、対照群に比べて有意に高値を示した［WBC(×10/L)：9.33±2.44 vs. 6.37±2.44］。44 vs. 6.37±1.28、NEUT：0.78±0.08 vs. 0.57±0.04、CRP（mg/L）：5.67±2.99 vs. 0.33±0.18、PCT（μg/L）：0.80±0.67 vs. 0.07±0.03、いずれもP＜0.01］。7日目には、観察群の炎症マーカーが有意に減少し、観察群と対照群との間に有意差は認められなかった。ROC曲線解析の結果、発熱当日のLMPsおよびNMPsのROC曲線下面積（AUC）および95％信頼区間（95％CI）は、WBC、NEUT、CRPおよびPCTの値よりも高かった［0．888（0.763-1.000）、0.973（0.931-1.000）対0.679（0.346-0.811）、0.829（0.700-0.958）、0.607（0.404-0.811）、0.554（0.358-0.749）］であった。

RESULTS: A total of 38 subjects were enrolled, including 28 cases in the observation group and 10 cases in the control group. The levels of LMPs and NMPs in the observation group increased to the peak at the 2nd hour after fever, and were significantly higher than those in the control group [LMPs (cells/μL): 55.0 (28.8, 197.2) vs. 19.0 (13.5, 28.3), NMPs (cells/μL): 226.5 (123.3, 516.5) vs. 26.5 (22.0, 48.8), both P < 0.01]. With the control of the disease, LMPs and NMPs decreased gradually. The NMPs on the 2nd day was significantly lower than that at the 2nd hour of fever [cells/μL: 106.0 (40.0, 309.0) vs. 226.5 (123.3, 516.5), P < 0.05], and the LMPs and NMPs on the 7th day were significantly lower than those on the 2nd day [LMPs (cells/μL): 17.0 (12.5, 43.8) vs. 42.0 (13.0, 117.0), NMPs (cells/μL): 30.0 (15.8, 62.0) vs. 106.0 (40.0, 309.0), both P < 0.05]. There was no significant difference in the levels of LMPs and NMPs between the two groups on the 7th day. Among the inflammatory markers, the NEUT in the observation group was significantly higher than that in the control group at the 2nd hour of fever (0.70±0.09 vs. 0.59±0.04, P < 0.01), but there was no significant difference in WBC, CRP and PCT between the two groups. On the 2nd day, the inflammatory markers in the observation group reached the peak and were significantly higher than those in the control group [WBC (×10/L): 9.33±2.44 vs. 6.37±1.28, NEUT: 0.78±0.08 vs. 0.57±0.04, CRP (mg/L): 5.67±2.99 vs. 0.33±0.18, PCT (μg/L): 0.80±0.67 vs. 0.07±0.03, all P < 0.01]. On the 7th day, the inflammatory markers in the observation group decreased significantly, and there was no significant difference between the observation group and the control group. ROC curve analysis showed that the area under ROC curve (AUC) and 95% confidence interval (95%CI) of LMPs and NMPs on the day of fever were higher than those of WBC, NEUT, CRP and PCT [0.888 (0.763-1.000), 0.973 (0.931-1.000) vs. 0.679 (0.346-0.811), 0.829 (0.700-0.958), 0.607 (0.404-0.811), 0.554 (0.358-0.749)].

結論:

LMPとNMPは発熱初期に有意に増加しており，超高齢者の感染症発症を予測することができた．

CONCLUSIONS: LMPs and NMPs are significantly increased in the early stage of fever, which can predict the incidence of infection in the super-elderly patients.