Feasibility of developing HAP risk warning model in critically ill patients based on genomic copy number polymorphisms of DEFA1/DEFA3

Abstract

Objective To evaluate the feasibility of developing hospital acquired pneumonia(HAP)risk warning model in critically ill patients based on genomic copy number polymorphisms(CNPs)of the genes encoding human neutrophil peptides 1-3(DEFA1/DEFA3). Methods Seventy-seven HAP patients(group HAP)and 109 non-HAP patients of matched age and sex in intensive care unit(ICU)(group NHAP)were enrolled in the study.The genomic CNPs of DEFA1/DEFA3 was determined by real-time quantitative polymerase chain reaction after extracting DNA from peripheral blood samples.The source of patients, condition of endotracheal intubation within 24 h after admission to ICU, Acute Physiology Score, Acute Physiology and Chronic Health Evaluation Ⅱ score, Sequential Organ Failure Assessment score, mechanical ventilation time, length of hospital and ICU stay and outcomes were obtained.The predictive model was developed using logistic regression through combining DEFA1/DEFA3 copy numbers and clinical characteristics(Acute Physiology Score and source of emergency)within 24 h after admission to ICU. The receiver operating characteristic curve was used to evaluate the predictive efficacy of the model. Results The copy numbers of DEFA1/DEFA3 were significantly lower in HAP group than in NHAP group(P <0.05). The area under the receiver operating characteristic curve of the predictive model developed through combining the DEFA1/DEFA3 copy numbers with clinical characteristics was 0.789(95% CI 0.724-0.854)when the model was used for predicting HAP. Conclusion CNPs of DEFA1/DEFA3 can be used to develop the HAP risk warning model in critically ill patients. Key words: alpha-Defensins; Crossinfection; Pneumonia; Hospitalization; Critical illness; DNA copy number variations