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

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.

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.

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.

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 (r²) values were observed between FEV₁/FVC with (1) (FEV₃-FEV₁)/FVC (r² = 0.61) and (2) FEV₃/FEV₆ (r² = 0.83), suggesting overlapping aspects of lung function being measured. There was a weak correlation between FEV₁/FVC and Rrs_5-20 values (r² = 0.08) indicating that these parameters assess unique aspects of lung function and mechanics.

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.