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

Background: Small airway dysfunction is an important treatable trait in persistent asthma but remains poorly captured by conventional spirometry. The (forced expiratory volume in 3 seconds [FEV₃]-FEV₁)/forced vital capacity (FVC) and FEV₃/FEV₆ ratios have been proposed as novel markers of peripheral airflow limitation. 

Objective: To investigate the relationship between (FEV₃-FEV₁)/FVC and FEV₃/FEV₆ with symptom control and the frequency of severe exacerbations in patients with moderate-to-severe asthma. 

Methods: Clinical, physiological, and biomarker data were collected from adults with Global Initiative for Asthma–defined moderate-to-severe asthma visiting a specialist severe asthma center in Scotland, United Kingdom. Associations between spirometric and oscillometric parameters with clinically relevant outcomes were retrospectively analyzed using multivariate models. 

Results: A total of 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 < .01), forced expiratory flow rate between 25% and 75% of the FVC/FVC (2.11 [1.27-3.50]; P < .01), and oscillometric Rrs_5-20 (1.90 [1.14-3.16]; P < .05) were significantly associated with more than or equal to 2 exacerbations in the previous year. High coefficient of determination ( r ²) values were observed between FEV₁/FVC with (1) (FEV₃-FEV₁)/FVC ( r ² = 0.61) and (2) FEV₃/FEV₆ ( r ² = 0.83), suggesting overlapping aspects of lung function being measured. There was a weak correlation between FEV₁/FVC and Rrs_5-20 values ( r ² = 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 with conventional lung function measures.