慢性阻塞性肺疾病急性加重继发肺真菌感染患者外周血辅助型T细胞17/调节型T细胞及血清细胞因子的变化

Changes of Th17/Treg and serum cytokines in peripheral blood of patients with acute exacerbation of chronic obstructive pulmonary disease and secondary pulmonary fungal infection

目的探讨慢性阻塞性肺疾病急性加重(acute exacerbation of chronic obstructive pulmonary disease,AECOPD)继发肺真菌感染患者外周血辅助型T细胞17(helper T cells 17,Th17)/调节型T细胞(regulatory T cells,Treg)比值及血清细胞因子的变化。方法选择南通大学附属海安人民医院呼吸内科2018年1月至2020年3月收治的AECOPD合并真菌感染27例患者(真菌感染组)的临床资料进行回顾性分析,采用病例对照研究的方法,收集同期接受治疗的AECOPD未合并真菌感染58例患者(非真菌感染组)临床资料,比较两组患者一般临床资料、外周血Th17、Treg水平、Th17/Treg比值及白细胞介素17(interleukin-17,IL-17)、白细胞介素23(interleukin-23,IL-23)、干扰素γ、转化生长因子β(transforming growth factor-β,TGF-β)水平,同时比较真菌感染组不同感染严重程度患者外周血Th17、Treg水平、Th17/Treg比值及血清细胞因子的变化。呈正态分布的计量资料两组间比较采用两独立样本t检验;多组间比较采用单因素方差分析,两两比较采用LSD-t检验。计数资料采用χ^(2)检验。结果27例AECOPD合并真菌感染组患者病原菌分布:白色假丝酵母菌占65.52%(19/27),热带假丝酵母菌占10.34%(3/27),近平滑假丝酵母菌占10.34%(3/27),曲霉菌占6.90%(2/27)。与非真菌感染组比较,真菌感染组患者Th17[(16.18±3.15)%与(12.34±2.64)%,t=5.87,P<0.001]、Th17/Treg比值[(4.70±0.85)与(2.41±0.51),t=22.87,P<0.001]、IL-17[(85.67±21.51)μg/L与(53.64±14.36)μg/L,t=8.12,P<0.001]、IL-23[(61.38±16.58)μg/L与(38.29±12.60)μg/L,t=7.10,P<0.001]均升高,Treg[(3.42±0.42)%与(5.13±0.51)%,t=20.77,P<0.001]、干扰素γ[(47.75±17.72)μg/L与(62.37±19.06)μg/L,t=3.37,P=0.001]、TGF-β[(110.34±26.03)μg/L与(131.40±35.03)μg/L,t=2.87,P=0.007]均降低,两组比较差异均有统计学意义。轻度、中度、重度真菌感染组患者Th17[(13.06±1.98)%、(15.94±2.11)%、(17.75±2.20)%,F=10.19,P<0.001]、Th17/Treg(5.01±0.60、5.66±0.69、6.52±0.65,F=10.77,P<0.001)、IL-17[(63.39±11.64)、(78.66±12.82)、(90.26±13.55)μg/L,F=9.01,P=0.001]、IL-23[(42.52±13.11)、(59.97±15.25)、(69.75±14.30)μg/L,F=7.41,P=0.003]随着感染严重程度的增加而升高;Treg[(4.33±0.39)%、(3.32±0.42)%、(2.50±0.35)%,F=44.42,P<0.001]、干扰素γ[(57.78±10.52)、(48.82±10.39)、(38.90±10.56)μg/L,F=6.50,P=0.006]、TGF-β[(126.62±18.94)、(115.34±13.66)、(102.52±17.73)μg/L,F=4.25,P=0.026]随着感染严重程度的增加而降低;差异均有统计学意义。结论Th17/Treg比值及相关炎症因子水平失衡可能对AECOPD继发真菌感染存在影响,且其失衡与真菌感染严重程度需密切监测患者外周血Th17、Treg水平及相关炎症因子的水平变化。

Objective To explore the changes of peripheral blood Th17/Treg and serum cytokines in AECOPD patients with secondary pulmonary fungal infection.Methods Selected the clinical data of 27 AECOPD patients who were admitted between January 2018 to March 2020 in the Department of Respiratory Medicine,Hai'an People's Hospital Affiliated to Nantong University with fungal infection(fungal infection group),and 58 AECOPD patients without fungal infection(non-fungal infection group)who received treatment in the hospital during the same period.Compared the general clinical data,peripheral blood Th17 and Treg cell levels,Th17/Treg ratio,interleukin-17(IL-17),interleukin-23(IL-23),interferon-γ(interferon-γ,IFN-γ),and transforming growth factor-β(TGF-β)levels.Meanwhile,compared the levels of Th17 and Treg cells in peripheral blood,the ratio of Th17/Treg and serum cytokines in patients with different infection severity in fungal infection group.The measurement data with normal distribution were compared by independent samplet t-test between the two groups,one-way ANOVA between multiple groups,LSD-t test for pairwise comparision,andχ^(2) test for counting data.Results In the 27 AECOPD patients with fungal infection group,the pathogen distribution was 65.52%(19/27)of candida albicans,10.34%(3/27)of candida tropicalis,10.34%(3/27)of candida albicans,and 6.90%(2/27)of Aspergillus.The level of Th17[(16.18±3.15)%and(12.34±2.64)%,t=5.87,P<0.001)],the ratio of Th17/Treg[(4.70±0.85)and(2.41±0.51),t=22.87,P<0.001]in Patients with fungal infection group were higher than those in the non-fungal group.The level of Treg[(3.42±0.42)%and(5.13±0.51)%,t=20.77,P<0.001]in Patients with fungal infection group was lower than those in the non-fungal group.The levels of IL-17[(85.67±21.51)μg/L and(53.64±14.36)μg/L,t=8.12,P<0.001],and IL-23[(61.38±16.58)μg/L and(38.29±12.60)μg/L,t=7.10,P<0.001]in Patients with fungal infection group were higher than those in non-fungal infection group,but the levels of IFN-γ((47.75±17.72)μg/L and(62.37±19.06)μg/L,t=3.37,P=0.001)and TGF-β((110.34±26.03)μg/L and(131.40±35.03)μg/L,t=2.87,P=0.007)were lower than those in non-fungal infection group,and the differences were statistically significant.There were statistically significant differences in the ratio of Th17/Treg,and the levels of Th17,Treg cells and cytokine among patients with different infection severity in the fungal infection group.With the increase of infection severity,the levels of Th17((13.06±1.98)%,(15.94±2.11)%,(17.75±2.20)%,F=10.19,P<0.001),the ratios of Th17/Treg((5.01±0.60),(5.66±0.69),(6.52±0.65),F=10.77,P<0.001),the levels of IL-17((63.39±11.64)μg/L,(78.66±12.82)μg/L,F=9.01,P=0.001),and IL-23((42.52±13.11)μg/L,(59.97±15.25)μg/L,(69.75±14.30)μg/L,F=7.41,P=0.003)were increase,the levels of Treg((4.33±0.39)%,(3.32±0.42)%,(2.50±0.35)%,F=44.42,P<0.001),IFN-γ((57.78±10.52)μg/L,(48.82±10.39)μg/L,(38.90±10.56)μg/L,F=6.50,P=0.006),TGF-β((126.62±18.94)μg/L,(115.34±13.66)μg/L,(102.52±17.73)μg/L,F=4.25,P=0.026)were significantly decreased.Conclusion The imbalance of Th17/Treg ratio and related serum cytokines play an important role in the process of lung fungal infection in AECOPD patients,and their imbalance is related to the severity of fungal infection.Therefore,the levels of Th17/Treg and serum cytokines should be closely monitored in AECOPD patients.