转化医学杂志

目的 分析人β防御素1(HBD1)单核苷酸多样性（SNP）与老年肺癌患者胸腔镜下肺癌根治术术后呼吸机相关肺炎（VAP）易感性及转归的相关性。方法 选取2022年1月至2024年12月空军军医大学唐都医院收治的胸腔镜下肺癌根治术术后需呼吸机辅助治疗的266例老年肺癌患者，根据是否并发VAP分为VAP组（41例）和对照组（225例），并根据VAP组患者预后不同分为死亡组（13例）和存活组（28例）。分析VAP患者病原菌及耐药性，采用聚合酶链反应(PCR)法测定HBD1基因第一外显子5′非编码区（-52A/G、-44C/G、-20A/G）SNP的基因型，采用Logistic回归分析SNP位点与老年肺癌患者胸腔下肺癌根治术后并发VAP和预后的关系。结果 41例VAP患者共分离出病原菌85株，其中革兰阴性菌占48.24%，革兰阳性菌占20.00%，真菌占31.76%。革兰阴性菌鲍曼不动杆菌对氨曲南、头孢唑啉、头孢曲松、头孢他啶、磺胺甲噁唑及氨苄西林耐药率均为100%，肺炎克雷伯菌对氨曲南、头孢唑啉、头孢曲松、头孢吡肟、头孢他啶、磺胺甲噁唑、氨苄西林耐药率均为100%，铜绿假单胞菌对头孢唑啉、头孢曲松、磺胺甲噁唑、氨苄西林/舒巴坦耐药率均为100%，大肠埃希菌对氨曲南、环丙沙星、头孢唑啉、头孢曲松、头孢吡肟、头孢他啶、左氧氟沙星、磺胺甲噁唑、氨苄西林及氨苄西林/舒巴坦耐药率均为100%。VAP组HBD1基因5′非编码区-44 SNP GG基因型及G等位基因频率高于对照组（P<0.05）；两组CC、CG基因型及其相应的C等位基因频率比较，差异无统计学意义（P>0.05）；多因素Logistic回归分析显示，HBD1基因5′非编码区-44 SNP位点GG基因型（OR=2.855,95%CI:1.347～6.083)患VAP的风险显著升高，而CC基因型(OR=0.440,95%CI:0.230～0.845)患VAP的风险显著降低（P<0.05）。VAP死亡组HBD1基因5′非编码区-44 SNP GG基因型及G等位基因频率高于存活组（P<0.05）；两组CC、CG基因型及其相应的C等位基因频率比较，差异均无统计学意义（P>0.05）；多因素Logistic回归分析显示，HBD1基因5′非编码区-44 SNP位点GG基因型（OR=4.392,95%CI:1.673～11.524）的死亡风险高，CC基因型（OR=0.291,95%CI:0.122～0.690）的死亡风险低（P<0.05）。结论 老年肺癌患者胸腔镜下肺癌根治术后VAP致病菌以革兰阴性菌为主，耐药性较高，临床应根据药敏试验合理应用抗菌药物，且HBD1基因-44C/G位点SNP与VAP易感性和预后具有一定的相关性，G等位基因可能会增加老年肺癌患者胸腔镜下肺癌根治术后VAP的易感性和死亡风险。

Objective To analyze the correlation between human beta-defensin 1(HBD1) single nucleotide polymorphisms(SNP) and susceptibility to ventilator-associated pneumonia(VAP) as well as outcomes in elderly lung cancer patients after thoracoscopic radical resection of lung cancer. Methods A total of 266 elderly lung cancer patients who required ventilator support after thoracoscopic radical resection of lung cancer at Tangdu Hospital, Air Force Medical University from January 2022 to December 2024 were selected. Based on the occurrence of VAP, they were divided into a VAP group(41 cases) and a control group(225 cases). According to prognosis, the VAP group was further divided into a death group(13 cases) and a survival group(28 cases). Pathogenic bacteria and drug resistance in VAP patients were analyzed. The genotypes of SNPs in the first exon 5′ non-coding region(-52A/G,-44C/G,-20A/G) of the HBD1 gene were determined by polymerase chain reaction(PCR). Logistic regression was used to analyze the relationship between SNP loci and the occurrence of VAP and prognosis in elderly lung cancer patients after radical resection. Results A total of 85 pathogenic strains were isolated from 41 VAP patients, including Gram-negative bacteria(48.24%), Gram-positive bacteria(20.00%), and fungi(31.76%). Acinetobacter baumannii showed 100% resistance to aztreonam, cefazolin, ceftriaxone, ceftazidime, sulfamethoxazole, and ampicillin. Klebsiella pneumoniae was 100% resistant to aztreonam, cefazolin, ceftriaxone, cefepime, ceftazidime, sulfamethoxazole, and ampicillin. Pseudomonas aeruginosa was 100% resistant to cefazolin, ceftriaxone, sulfamethoxazole, and ampicillin/sulbactam. Escherichia coli was 100% resistant to aztreonam, ciprofloxacin, cefazolin, ceftriaxone, cefepime, ceftazidime, levofloxacin, sulfamethoxazole, ampicillin, and ampicillin/sulbactam. The GG genotype and G allele frequency at the-44 SNP site in the 5′ non-coding region of the HBD1 gene were higher in the VAP group than in the control group(P<0.05). There were no significant differences in the frequencies of the CC and CG genotypes or the corresponding C allele between the two groups(P>0.05). Multivariate logistic regression analysis showed that the GG genotype at the-44 SNP site in the 5′ non-coding region of the HBD1 gene was associated with a significantly increased risk of VAP(OR=2.855, 95%CI: 1.347–6.083), while the CC genotype was associated with a significantly decreased risk(OR=0.440, 95%CI: 0.230–0.845)(P<0.05). In the VAP group, the GG genotype and G allele frequency at the-44 SNP site were higher in the death group than in the survival group(P<0.05). There were no significant differences in the frequencies of the CC and CG genotypes or the corresponding C allele between the two groups(P>0.05). Multivariate logistic regression analysis indicated that the GG genotype at the-44 SNP site was associated with a higher mortality risk(OR=4.392, 95%CI: 1.673–11.524), while the CC genotype was associated with a lower mortality risk(OR=0.291, 95%CI: 0.122–0.690)(P<0.05). Conclusions The main pathogens causing VAP in elderly lung cancer patients after thoracoscopic radical resection are Gram-negative bacteria, with high drug resistance. Antibiotics should be used rationally based on drug susceptibility testing. The SNP at the-44C/G locus of the HBD1 gene is correlated with susceptibility and prognosis of VAP. The G allele may increase the susceptibility to VAP and the risk of death in elderly lung cancer patients after thoracoscopic radical resection of lung cancer.