The Synergistic Role of Osteopontin and α-1-antitrypsin in Plasma in the Diagnosis of Unexplained COPD

Background: Osteopontin, a pleiotropic glycoprotein with roles in inflammation and tissue remodelling, and α‑1‑antitrypsin, an important anti-protease and acute phase reactant protein are novel biomarkers in respiratory disease. Their possible value in the evaluation of unexplained chronic obstructive pulmonary disease (COPD) is yet to be investigated. Materials and Methods: This case–control study consisted of 68 patients with idiopathic COPD and 77 age- and sex-matched controls who were healthy, conducted at Al-Shaab Hospital, Baghdad, Iraq between March 2024 and February 2025. The levels of serum osteopontin and α‑1‑antitrypsin were determined by enzyme linked immunosorbent assay (ELISA). Baseline demographic and clinical data were collected, and differences, correlations, and diagnostic performance were evaluated. Results: As compared to the controls, patients in whom COPD could not be established revealed significantly increased mean serum osteopontin (86.4 ± 18.7 pg/mL) levels as compared to control subjects (61.2 ± 14.9 pg/ mL, P <0.02), and significant higher mean α-1 antitrypsin (182.6 ± 34.1 mg/dL vs 154.8 ± 28.6 mg/dL, P < 0.03). A weak positive correlation was demonstrated between levels of osteopontin and α‑1‑antitrypsin in patients (r = 0.548, P = 0.002), indicating that an integrated inflammatory-protease antiprotease reaction occurred simultaneously. The ROC curve analysis showed a moderate diagnostic performance for both markers: OA, with an area under the curve (AUC) of 0.78 (cut‑off value, 72 pg/mL; sensitivity, 74%; specificity, 70.1%); and α-1-antitrypsin: AUC of 0.75 (cut‑off value, 165 mg/dL) sensitivity:,71% and the specificity was found to be at a level of 68.8%. Conclusion: Osteopontin and α‑1‑antitrypsin in serum are obviously increased in patients with COPD of unknown causes, and there is a certain correlation between them. Both biomarkers show diagnostic utility, and their joint assessment may be valuable in early detection and risk stratification of the patients suspected for unexplained copd. These results underline the need to include inflammatory and protease-antiprotease markers in the assessment of COPD.