Early Detection of Small Airway Dysfunction in Smokers and People with COPD via Forced Oscillation Technique and its Association with Biomarkers: a Pilot Study

Background: Early airflow changes associated with tobacco smoking often occur without observable obstruction or symptoms. Spirometry, the gold standard, has limitations in detecting early disease highlighting the need for sensitive diagnostic methods. We aimed to evaluate the utility of the forced oscillation technique (FOT) and biomarkers in detecting early airway abnormalities in smokers and patients with COPD, and to explore the correlation between FOT parameters, spirometry measures, and biomarkers of airway inflammation. Methods: A cross-sectional study was conducted on 71 participants divided into three groups: patients with COPD (CP, n=27), normal lung function smokers (NS, n=22), and healthy controls (HC, n=22). Lung function was assessed using spirometry and FOT, while biomarkers of inflammation (MMP-9, TIMP-1, TIMP-2) were measured. Statistical analyses included group comparisons and correlation between lung function parameters and biomarker levels. Results: Patients with COPD had significantly lower spirometry and higher FOT values compared to NS and HC (p<0.01). In contrast, NS participants had similar spirometry values to HC, except for FEF25-75% and PEF. The NS group exhibited significantly higher values for R5 compared to HC (p<0.05). FOT parameters, particularly R5, demonstrated comparable diagnostic accuracy to spirometry in smokers, and all other parameters showed excellent discriminatory ability in COPD patients. MMP-9 correlated positively with percentage predicted FOT parameters, R5-R20 and AX, and X5 (r‘=0.29,0.30, 0.31; p=0.02,0.04,0.02 respectively) in the combined group of smokers and COPD patients and positively with percentage predicted Fres (r‘=0.30; p=0.01) when all groups were analysed together. Conclusion: FOT may be a sensitive and complementary measure to detect early airway changes in smokers and patients with COPD. MMP-9 correlating with FOT further supports the role of FOT combined with biomarkers in detecting early airway abnormalities in smokers and earlier stages of COPD.