Nasal Lavage Fluid Proteomics Reveals Potential Biomarkers of Asthma Associated with Disease Control

Meiping Chen,1,2 Yijun Ge,1,3 Wen Zhang,1 Ping Wu,4 Chao Cao1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310009, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Ninghai First Hospital, Ningbo, 315600, People’s Republic of China; 4National Facility for Protein in Shanghai, Zhangjiang Lab, Shanghai Advanced Research Institute, CAS, Shanghai, 201210, People’s Republic of ChinaCorrespondence: Chao Cao, The First Affiliated Hospital of Ningbo University, 59 Liuting Road, Ningbo, 315010, People’s Republic of China, Tel +86-574-87089878, Fax +86-0574-8729-1583, Email caocdoctor@163.comPurpose: Little research has explored the proteomic characteristics of nasal lavage fluid from asthmatic patients. This study aims to investigate whether differentially expressed proteins (DEPs) in nasal lavage fluid can serve as a biomarker to differentiate asthma patients from healthy controls (HCs) and to discern between individuals with well controlled and poorly controlled asthma.Patients and Methods: We enrolled patients with allergic rhinitis (AR), asthma, or both conditions, and HCs in this study. We recorded patients’ demographic and medical history data and administered asthma quality of life questionnaire (AQLQ) and asthma control questionnaire (ACQ). Nasal fluid samples were collected, followed by protein measurements, and proteomic analysis utilizing the data-independent acquisition (DIA) method.Results: Twenty-four with asthma, 27 with combined asthma+ AR, 25 with AR, and 12 HCs were enrolled. Four proteins, superoxide dismutase 2 (SOD2), serpin B7 (SERPINB7), kallikrein-13 (KLK13), and bleomycin hydrolase (BLMH) were significantly upregulated in nasal lavage fluid samples of asthma without AR, compared to HCs (Fold change ≥ 2.0, false-discovery rate [FDR] < 0.05). Conversely, 56 proteins including secretoglobin family 2A member 1 (SCGB2A1) were significantly downregulated (fold change ≥ 2.0, FDR < 0.05). Furthermore, 96.49% of DEPs including peptidase inhibitor 3 (PI3) and C-X-C motif chemokine 17 (CXCL17) were upregulated in poorly controlled asthma patients without AR relative those with well- or partly controlled asthma (fold change ≥ 1.5, FDR < 0.05). Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that PI3, with 18 connections, may be pivotal in asthma control.Conclusion: The study revealed significant alteration in the nasal lavage proteome in asthma without AR patients. Moreover, our results indicated a potential association between the expression of proteome in the upper airway and the level of asthma control. Specifically, PI3 appears to be a key role in the regulation of asthma without AR. Keywords: allergy, proteomic analysis, nasal lavage fluid, asthma control