Efficacy of thymalfasin combined with voriconazole in treating chronic obstructive pulmonary disease patients with invasive pulmonary aspergillosis

Wang Liyang; Li Guizhen; Zhang Yusai; Zhang Jiamin; Zhou Zhiwen; Wang Chaokun; Meng Lijie

doi:10.3969/j.issn.1672-8521.2025.03.009

Abstract：Objective:To evaluate the efficacy of thymalfasin combined with voriconazole in chronic obstructive pulmonary disease(COPD)patients with invasive pulmonary aspergillosis(IPA).Methods:A retrospective study enrolled IPA patients secondary to COPD treated at Shangqiu Municipal Hospital from May 2021 to February 2023.Patients who received voriconazole alone or voriconazole combined with thymalfasin were selected.The patients were divided into combined group and control group according to whether they were treated with thymalfasin.Using propensity score matching(caliper=0.2,1∶1 nearest-neighbor),52 patients receiving voriconazole monotherapy(control group)were matched with 52 patients receiving voriconazole plus thymalfasin(combination group).The clinical efficacy of the two groups after 2 weeks of treatment,symptom improvement time,immune function indicators such as peripheral blood T lymphocyte subsets CD8+,CD4+,CD3+and the ratio of CD4+/CD8+,and interleukin-12(IL-12),IL-6,interferon-γ(IFN-γ),white blood cell count(WBC)and percentage of neutrophil(NEUT%)and occurrence of treatment-related adverse reactions in the two groups were compared.Results:After 2 weeks of treatment,the total effective rate in combined group was 90.38%(47/52 cases),which was higher than 73.08%(38/52 cases)in control group(P＜0.05).The imaging performance improvement time,significant improvement time of cough and expectoration,body temperature normal recovery time,dyspnea relief time and IPA treatment time in the control group were longer than those in the combined group(t=4.873,3.116,2.912,2.801,5.740,P＜0.01).After treatment in both groups,CD3+and CD4+T cells and the ratio of CD4+/CD8+increased,while CD8+T cells decreased.CD3+and CD4+T cells and the ratio of CD4+/CD8+in the combined group were(61.02±3.26)%(36.03±2.25)%and(1.58±0.17),respectively,which were higher than(58.87±3.64)%,(33.67±2.57)%and(1.39±0.19)in control group.While CD8+T cells[(22.86±2.17)%]was lower than that of the control group[(24.44±2.11)%;t=3.173,4.980,5.374,3.764,P＜0.01].After 2 weeks of treatment,the levels of WBC,NEUT%and IL-6 in the two groups decreased,while the levels of IL-12 and IFN-γ increased.Moreover,the levels of WBC,NEUT%and IL-6 in the combined group after treatment[(9.13±2.95)×109/L,(0.690 8±0.029 4),(29.64±4.21)ng/L,respectively]were lower than that of the control group[(12.36±3.66)×109/L,(0.721 6±0.032 6),(33.64±4.89)ng/L,respectively],while the levels of IL-12 and IFN-γ[(49.17±3.54)ng/L and(16.02±4.35)ng/L were higher than those in the control group[(46.24±3.75)ng/L and(12.86±4.75)ng/L;t=4.955,5.059,4.470,4.097,3.538,P＜0.001].There was no statistical difference in the incidence of adverse reactions between the two groups(21.15%vs.15.38%;χ2=0.580,P=0.446).Conclusions:Thymalfasin combined with voriconazole has a significant clinical effect in the treatment of IPA secondary to COPD.It can shorten the symptom recovery time,enhance the immune function,improve the levels of inflammatory factors,and promote rehabilitation.