Factors Influencing Respiratory Syncytial Virus Infection in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Correlation with Serum Levels of HSP70，KLF5，MIP-2

Xianbiao XU; Mingfang YANG; Ruidan LI; Li ZHANG

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Xianbiao XU, Mingfang YANG, Ruidan LI, Li ZHANG. Factors Influencing Respiratory Syncytial Virus Infection in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Correlation with Serum Levels of HSP70，KLF5，MIP-2[J]. Journal of Kunming Medical University.

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Factors Influencing Respiratory Syncytial Virus Infection in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Correlation with Serum Levels of HSP70，KLF5，MIP-2

1.
Department of Respiratory and Critical Care Medicine，General Hospital of Ordnance Industry，Shaanxi Xi’an 710065
2.
Department of Respiratory and Critical Care Medicine，Xi’an Daxing Hospital，Shaanxi Xi'an 710018，China

Received Date: 2025-07-21

Abstract

Abstract

Objective To explore the factors associated with respiratory syncytial virus （RSV） infection in patients with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） and its correlation with serum levels of heat shock protein 70 （HSP70）, Krüppel-like factor 5 （KLF5）, and macrophage inflammatory protein-2 （MIP-2）. Methods A total of 195 AECOPD patients were prospectively enrolled and categorized into an RSV-infected group （n = 95） and an uninfected group （n = 100） based on RSV infection status. The infected group was further subdivided by disease severity into mild, moderate, and severe subgroups （31 cases, 35 cases, 29 cases）, and by prognosis into poor prognosis （51 cases） and good prognosis subgroup （44 cases） . ELISA method was used to measure the serum levels of HSP70, KLF5, and MIP-2 in each group, and their correlation with relevant clinical indicators was analyzed. Multivariate Cox regression analysis was used to explore risk factors for RSV infection in AECOPD patients. Relative risk analysis was used to explore the impact of high and low levels of HSP70, KLF5, and MIP-2 on the prognosis of AECOPD patients with RSV infection. Kaplan-Meier survival curves analyzed patient survival outcomes. Receiver operating characteristic （ROC） curves were plotted to analyze the predictive value of serum HSP70, KLF5, and MIP-2 levels for the prognosis of AECOPD patients with RSV infection. Results The infected group had significantly higher proportions of smoking history and respiratory failure, higher number of exacerbations within one year, and higher levels of CRP, HSP70, KLF5, and MIP-2 compared to the non-infected group （P < 0.05）, while FEV1% pred and vaccination rate were significantly lower （P < 0.05）. Serum HSP70, KLF5, MIP-2 levels were positively correlated with respiratory failure, number of exacerbations within one year, and CRP levels （P < 0.05）, and negatively correlated with FEV1% pred （P < 0.05）. Multivariate Cox regression identified respiratory failure （HR = 2.118, 95% CI: 1.042～4.306）, number of AECOPD exacerbations within one year ≥ 3 times （HR = 2.475, 95% CI: 1.208～5.071）, low FEV1% pred （HR = 0.620, 95% CI: 0.404～0.952）, and high levels of CRP （HR = 2.301, 95% CI: 1.219～4.342）, HSP70 （HR = 2.221, 95% CI: 1.203～4.102）, KLF5 （HR = 2.600, 95% CI: 1.173～5.762）, and MIP-2 （HR = 2.291, 95% CI: 1.221～4.298） as independent risk factors for RSV infection in AECOPD patients （P < 0.05）. The severe subgroup had significantly higher serum HSP70, KLF5, and MIP-2 levels than the mild and moderate subgroups （P < 0.05）; levels in the moderate subgroup were significantly higher than in the mild subgroup （P < 0.05）. The poor prognosis subgroup had prominently higher serum HSP70, KLF5, and MIP-2 levels than the good prognosis subgroup（P < 0.05）. The risk of poor prognosis in patients with high levels of HSP70, KLF5, and MIP-2 was 2.431 times （95% CI: 1.576～3.748）, 2.054 times （95% CI: 1.331～3.168）, and 2.415 times （95% CI: 1.609～3.625） higher than in patients with low levels of HSP70, KLF5, and MIP-2, respectively （P < 0.05）. The 28-day progression-free survival rates were significantly lower in patients with high levels of HSP70, KLF5, and MIP-2 （Log-rank χ² = 22.719, 12.806, 23.457, P < 0.001）. The areas under the ROC curve （AUC） for predicting prognosis using HSP70, KLF5, and MIP-2 alone were 0.812, 0.820, and 0.814, respectively. The combined prediction model significantly increased the AUC to 0.922, which was superior to any single indicators （Z_joint-HSP70 = 2.762, P = 0.006, Z_joint-KLF5 = 2.467, P = 0.014, Z_joint-MIP-2 = 2.444, P = 0.015）. Conclusion Respiratory failure, the number of AECOPD exacerbations within one year ≥ 3 times, low FEV1% pred, high CRP level, and high serum levels of HSP70, KLF5, and MIP-2 are risk factors for RSV infection in AECOPD patients. Serum levels of HSP70, KLF5, MIP-2 are closely related to disease severity and prognosis in AECOPD patients with RSV infection. The combined detection of the three biomarkers has significant predictive value for patient prognosis, which is helpful for early clinical assessment and the formulation of intervention strategies.

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