Serum Parkin protein level is a potential differential diagnostic marker for asthma and chronic obstructive pulmonary disease

Abstract

In clinical practice, the differential diagnosis of asthma and chronic obstructive pulmonary disease (COPD) remains challenging. Differences in the serum proteomic profiles of patients with asthma and COPD may serve as a basis for identifying disease-specific markers. Objective. To evaluate the diagnostic potential of serum Parkin protein for differentiating between asthma and chronic obstructive pulmonary disease using research databases of patients with chronic respiratory diseases and the Biobank of the National Medical Research Center for Therapy and Preventive Medicine. Materials and methods. A comparative prospective study included outpatients with asthma (n=76) and COPD (n=68) outside of exacerbation, patients without chronic respiratory diseases (control; n=43); mean age 59±11 years, 52% men. The level of Parkin in blood serum was determined by an in-house ELISA using anti-Parkin primary antibodies and conjugated secondary antibodies, while the levels of immunoglobulin E, eosinophil cationic protein, alpha-1-antitrypsin, C-reactive protein, fibrinogen, lipopolysaccharide, and trimethylamine N-oxide were measured by means of commercial ready-to-use ELISA kits. Statistical analysis was performed using the SPSS software package (v. 23). Results. Parkin protein levels in patients with asthma were lower than in patients with COPD or control subjects (p<0.05; asthma vs. COPD: rho=0.200, p=0.016; asthma vs. control: rho=0.262, p=0.004), correlated with lymphocyte levels (r=0.352, p=0.004), and were not associated with asthma exacerbations. The ability to differentiate asthma from COPD using Parkin protein levels was confirmed by ROC analysis (AUC=0.35±0.04, p=0.002). Logistic regression analysis revealed an association between Parkin protein levels and asthma, adjusted for sex and age (B = –0.174; p=0.009). In the asthma group, the use of maintenance medications was not associated with Parkin protein levels; however, when the three groups were combined, the use of inhaled glucocorticoids correlated with these levels (rho= –0.171; p=0.019). Conclusion. The signaling pathway associated with the regulation of Parkin protein is involved in the pathogenesis of asthma. Presumably, the reduced level of Parkin in asthma (compared to chronic obstructive pulmonary disease and the absence of chronic respiratory diseases) is associated with impaired mitophagy — a critically important mechanism underlying asthma. Assessing the level of this protein in blood serum holds significant promise for the differential diagnosis of asthma, chronic obstructive pulmonary disease, and chronic respiratory symptoms.