Peripheral neutrophils and oxidative stress-associated molecules for predicting the severity of asthma: a cross-sectional study based on multidimensional assessment

Ruolin Mao; Zhilong Jiang; Zhihui Min; Gang Wang; Min Xie; Peng Gao; Lei Zhu; Huayin Li; Zhihong Chen

doi:10.3389/fmed.2023.1240253

Peripheral neutrophils and oxidative stress-associated molecules for predicting the severity of asthma: a cross-sectional study based on multidimensional assessment

Front Med (Lausanne). 2023 Dec 7:10:1240253. doi: 10.3389/fmed.2023.1240253. eCollection 2023.

Authors

Ruolin Mao^#^{1

2}, Zhilong Jiang^#¹, Zhihui Min³, Gang Wang⁴, Min Xie⁵, Peng Gao⁶, Lei Zhu⁷, Huayin Li¹, Zhihong Chen¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Research Center of Zhongshan Hospital, Fudan University, Shanghai, China.
⁴ Department of Respiratory and Critical Care Medicine, Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu, China.
⁵ Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁶ Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, Changchun, China.
⁷ Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, China.

^# Contributed equally.

Abstract

Objectives: This study aims to explore the relationship between the severity of asthma and neutrophils and related oxidative stress-associated molecules in peripheral blood and induced sputum.

Methods: A total of 67 subjects were included in this study, namely, 25 patients with severe asthma and 42 patients with non-severe asthma. Clinical data, induced sputum and peripheral blood were collected. Lung function and molecules related to oxidative stress in induced sputum and peripheral blood of asthma patients were detected. The relationship between neutrophils and asthma severity was analyzed. HDAC2 mRNA and protein expression levels and HDAC2 activity were also analyzed. Multivariate logistic regression was performed to select statistically significant variables.

Results: The absolute value of neutrophils and percentage of neutrophils were higher in the severe asthma patients. These two values were used to predict the severity of asthma by ROC analysis, with the best cutoff values being 4.55 × 10⁹/L (sensitivity 83.3%, specificity 64.0%) and 55.15% (sensitivity 54.8%, specificity 88.0%). The ROS concentration of neutrophils in the induced sputum samples and the 8-iso-PGF2α concentration in the peripheral blood samples were higher in the severe asthma group (P = 0.012; P = 0.044), whereas there was reduced HDAC2 protein activity in PBMCs (P < 0.001). A logistic equation and a nomogram were created to give a precise prediction of disease severity.

Conclusion: Oxidative stress is increased in severe asthma patients. Peripheral blood neutrophils and 8-iso-PGF2α can be used as biomarkers to predict the severity of asthma. A prediction model was created for evaluating asthma severity.

Keywords: 8-iso-prostaglandin F2alpha; histone deacetylase 2; neutrophil; oxidative stress; severe asthma.

Grants and funding

This work was supported by the National Natural Science Foundation of China [81970023], the Shanghai Top-Priority Clinical Key Disciplines Construction Project [2017ZZ02013], the Shanghai Municipal Key Clinical Specialty [shslczdzk02201], and the Youth Fund of Zhongshan Hospital [2021-015].