不同严重程度的晚期非小细胞肺癌患者免疫检查点抑制剂相关性肺炎的临床特征分析OA

Background and purpose:Currently,research on checkpoint inhibitor-associated pneumonia(CIP)primarily focuses on its clinical characteristics,risk factors,prognosis,and relationship to clinical efficacy.However,these studies fail to distinguish between low-grade and high-grade CIP.This study aims to explore the differences of clinical characteristics between low-grade and high-grade CIP in patients with advanced non-small cell lung cancer(NSCLC),as well as the risk factors for the development of high-grade CIP.Methods:We retrospectively collected the case records of 92 patients with advanced NSCLC who received treatment with immune checkpoint inhibitor(ICI)at the First Affiliated Hospital of Hebei North University from January 2018 to December 2023.CIP was graded according to the Common Terminology Criteria for Adverse Events(CTCAE)5.0:asymptomatic/mild(grade 1),moderate(grade 2),severe(grade 3),life-threatening(grade 4)and death(grade 5).Grades 1-2 were defined as low-grade CIP,and grades 3-5 were defined as high-grade CIP.The clinical characteristics,laboratory indicators,imaging features,treatment and prognosis of the two groups of patients were compared.Univariate and multivariate logistic regression analyses were used to screen the influencing factors of high-grade CIP in NSCLC patients.Spearman's correlation coefficient was used to analyze the correlation between neutrophil-lymphocyte ratio(NLR),platelet-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),Krebs von den Lungen-6(KL-6),and CIP grading.Receiver operating characteristic curve analysis was used to evaluate the predictive value of peripheral blood KL-6 levels for high-grade CIP,and Kaplan-Meier survival curve analysis was used for survival analysis.This study was approved by the Ethics Committee of the First Affiliated Hospital of Hebei North University(L2026025).Results:This study ultimately included 92 CIP patients,with 56 cases of low-grade CIP and 36 cases of high-grade CIP.Low-and high-grade CIP showed statistically significant differences in age,fever,performance status(PS)score and concurrent infections during CIP(P<0.05).The levels of NLR,PLR,SII and KL-6 were higher in high-grade CIP than in low-grade CIP(P<0.05).There were significant differences in nonspecific interstitial pneumonia,concurrent emphysema,concurrent pleural effusion and pleural thickening between low-and high-grade CIP(P<0.05).Univariate logistic regression analysis revealed that fever,PS score of 3-4,concurrent emphysema and high peripheral blood KL-6 levels were risk factors for the development of high-grade CIP in patients with advanced NSCLC(P<0.05).Multivariate logistic regression analysis indicated that concurrent emphysema and high peripheral blood KL-6 levels were independent risk factors for the development of high-grade CIP in patients with advanced NSCLC(P<0.05).Baseline NLR,PLR,SII and KL-6 levels were positively correlated with CIP grade(P<0.05).The area under the curve for KL-6 in predicting high-grade CIP was 0.895,with a sensitivity of 83.9%and a specificity of 86.1%.There were significant differences in the duration of methylprednisolone treatment≥80 mg/d,initial oral steroid dose>1 mg/kg/d,steroid response,use of immunosuppressants,immunoglobulin,antibiotics and antifungal treatment between low-and high-grade CIP(P<0.05).The main cause of death in high-grade CIP was the CIP disease itself,while the main cause of death in low-grade CIP was tumor progression,with a statistically significant difference(P<0.05).Kaplan-Meier survival curve analysis showed that the median overall survival(OS)for low-grade CIP was 19.20 months,while for high-grade CIP it was 16.60 months,with a statistically significant difference(P<0.05).Conclusion:Compared with patients with low-grade CIP,those with high-grade CIP were older,had higher PS scores,more frequently presented with fever and pulmonary infectious diseases,and had higher levels of NLR,PLR,SII and KL-6,which were positively correlated with CIP grade.Imaging findings were predominantly nonspecific interstitial pneumonia,with a high proportion of concurrent emphysema,pleural effusion and pleural thickening.Patients with high-grade CIP had higher steroid doses,longer treatment durations and poorer prognoses.High levels of KL-6 and emphysema were independent risk factors for high-grade CIP.