Real-life evaluation of novel forced expiratory ratios with asthma exacerbations and symptoms.

Background: Small airways dysfunction (SAD) is an important treatable trait in persistent asthma but remains poorly captured by conventional spirometry. The (FEV3-FEV1)/FVC and FEV3/FEV6 ratios have been proposed as novel markers of peripheral airflow limitation.

Objective: We investigated the relationship between (FEV3-FEV1)/FVC and FEV3/FEV6 with symptom control and severe exacerbation frequency in patients with moderate-to-severe asthma.

Methods: Clinical, physiological and biomarker data were collected from adults with GINA-defined moderate-to-severe asthma visiting a specialist severe asthma centre in Scotland, UK. Associations between spirometric and oscillometric parameters with clinically relevant outcomes were retrospectively analysed using multivariate models.

Results: 294 patients were included in the analysis. The (FEV3-FEV1)/FVC and FEV3/FEV6 ratios were not significantly associated with asthma symptoms or severe exacerbation rates. Conversely, traditional measures such as FEV1/FVC [adjusted odds ratio (95%CI) 2.11 (1.27,3.50); p<0.01], FEF25-75/FVC [2.11 (1.27,3.50); p<0.01], and oscillometric Rrs5-20 [OR 1.90 (1.14,3.16); p<0.05] were significantly associated with ≥2 exacerbations in the previous year. High coefficient of determination (r2) values were observed between FEV1/FVC with (a) (FEV3-FEV1)/FVC r2=0.61 and (b) FEV3/FEV6r2=0.83, suggesting overlapping aspects of lung function being measured. There was a weak correlation between FEV1/FVC and Rrs5-20 values (r2=0.08) indicating that these parameters assess unique aspects of lung function and mechanics.

Conclusion: In moderate-to-severe asthma, the (FEV3-FEV1)/FVC and FEV3/FEV6 ratios were not independently associated with exacerbation risk or symptom control and did not provide additional clinical value compared to conventional lung function measures.