Clinical Value Of Exhaled Breath Condensate-GM In The Diagnosis Of Invasive Pulmonary Aspergillosis

Objective: It is for quantitative analysis of the level of galactomannan(GM)of exhaled breath condensate(EBC)and GM of bronchoalveolar lavage fluid(BALF),to evaluate the diagnostic value of both in invasive pulmonary aspergillosis(IPA).Method: Clinical experiment part: the IPA group selected patients with confirmed aspergillus pneumonia and received mechanical ventilation therapy in MICU/RICU of Sichuan Provincial People’s Hospital from May 2022 to January 2023,and the control group included mechanical ventilation treated patients who had been excluded aspergillus infection.EBC and BALF were collected on the same day in both groups,and EBC-BM and BALF-GM levels were determined by chemiluminescence method.Animal experiment part: normal SD rats of 12-14 weeks were selected to construct IPA rat model(IPA group)and saline control group.The EBC,BALF and serum samples were collected,and the concentrations of IL-6,IL-8 and TNF-α were determined by ELISA,and the level of GM was determined by chemiluminescence method.And the differences between the different cytokines in EBC and BALF and the differences of the infectious condition of GM on animal Aspergillus pulmonary infection and that of the control group,as well as the diagnostic efficacy of EBC-GM and BALF-GM on aspergillus pneumonia.Result: In clinical experiments,EBC-GM and BALF-GM levels were significantly higher in the IPA group than that in the control group(P <0.05).EBC-GM(AUC=0.893,95%CI of 0.745-1.000)and BALF-GM(AUC=0.887,95%CI: 0.729-1.000)had high diagnostic value for IPA.When EBC-GM≥ 0.235ng/ml was used as the positive cut-off value,its sensitivity,specificity,positive predictive value,and negative predictive value were 92.8%,66.7%,86.7%,and 80%,respectively.When BALF-GM≥1.365ng/ml was used as the positive cut-off value,its sensitivity,specificity,positive predictive value,and negative predictive value were 78.5%,83.3%,91.6%,and 62.5%,respectively.In the animal experiment,IL-6,IL-8,TNF α and GM levels were significantly increased in EBC,BALF and serum,compared with the control group(P <0.05).EBC-GM had high diagnostic value for IPA(AUC = 0.88,95%CI: 0.681-1.000),when the optimal cut-off value of EBC-GM was 1.385 ng/ml,the sensitivity,specificity,positive predictive value of EBC-GM on IPA diagnosis were 90.0%,80.0%,90.0% and80.0%.BALF-GM also had high diagnostic value for IPA(AUC=0.88,0.706-1.00),when taking the 1.01 ng/ml as positive threshold,the specificity,positive predictive value were 80.0%,60.0%,80.0% and 60.0%.The diagnostic efficacy of EBC-GM and BALF-GM combined with cytokines was better for IPA diagnosis than a single index,and the diagnosis efficacy was significantly improved after EBC-GM combined with serum IL-6 and serum TNFα(AUC=0.960,95%CI:0.863-1).Conclusion: IL-6,IL-8 and TNF α were elevated in EBC of invasive pulmonary aspergillosis,consistent with the expression of cytokines in serum and BALF.EBC-GM has a high diagnostic efficacy for IPA.Cytokines and EBC-GM combination has important clinical value in the diagnosis of IPA,and the diagnostic efficacy is higher than the single EBC-GM,which can improve the clinical diagnostic accuracy,among which the combination of EBC-GM,serum IL 6 and serum TNFα(AUC=0.960,95%CI:0.863-1)is the best combination method.