Role of Serum Olfactomedin-4 as a Biomarker in Bronchial Asthma: A Pilot Cross-Sectional Comparative Study

Asthma is a heterogeneous chronic airway disease marked by variable airflow limitation and bronchial hyperresponsiveness. While eosinophilic inflammation is well studied, neutrophil-driven and mixed eosinophilic-neutrophilic patterns are increasingly recognized in severe or poorly controlled asthma. Olfactomedin-4 (OLFM4), a neutrophil-expressed glycoprotein involved in immune regulation, has emerged as a potential biomarker of neutrophilic inflammation, though its role in asthma is underexplored. This study aimed to evaluate serum OLFM4 levels in asthma patients and examine their association with disease severity and control.

A pilot cross-sectional, hospital-based comparative study was conducted at JSS Medical College, Mysore, between June 2023 and December 2024. Eighty participants were recruited: 60 asthmatics (20 each with mild, moderate, and severe asthma) and 20 healthy controls. Serum OLFM4 was measured using ELISA. Asthma severity was assessed by spirometry, and asthma control by the Asthma Control Test (ACT). Associations with hematological and pulmonary function parameters were analyzed.

Serum OLFM4 levels were significantly higher in asthmatics compared to controls (4,309.23 ± 1,533.97 vs. 1,344.41 ± 256.38 pg/mL; p < 0.001), with progressive elevation across severity (mild: 2,947.49; moderate: 4,371.45; severe: 5,608.75 pg/mL). OLFM4 correlated negatively with ACT scores (r = -0.820, p < 0.001) and lung function indices, and positively with leukocyte, neutrophil, and eosinophil counts. Multivariate Firth's penalized logistic regression identified serum OLFM4 as an independent predictor of asthma severity (p < 0.001). ROC analysis showed excellent discrimination between asthmatics and controls (AUC = 0.997) and between non-severe and severe asthma (AUC = 0.89).

Elevated serum OLFM4 levels correlate with asthma severity, poor control, and lower lung functions, highlighting its potential as a biomarker for disease stratification. These findings suggest that OLFM4 may be a useful biomarker reflecting overall disease burden and control status in asthma. Although the biological role of OLFM4 in asthma pathophysiology requires further investigation, its consistent association with clinical severity and control supports its potential utility in asthma stratification and monitoring.