Clinical Significance of Reduced Forced Expiratory Volume in 3 Seconds to Forced Expiratory Volume in 6 Seconds in Adults.

Background: The forced expiratory volume (FEV) in 3 seconds (FEV₃) to FEV₆ ratio (FEV₃/FEV₆) is a novel spirometry measure that identifies early airflow abnormalities, but its long-term prognosis value in the general population remains unclear. We aim to evaluated the long-term all-cause mortality risk among participants with reduced FEV₃/FEV₆.

Methods: Data were obtained from the National Health and Nutrition Examination Survey cycles 1988-1994 and 2007-2012 Reduced FEV₃/FEV₆ was defined as FEV₃/FEV₆ less than the lower limit of normal. Multivariable logistic regression was used to assess the relationship of reduced FEV₃/FEV₆ with comorbidities and chronic respiratory symptoms. The relationship between reduced FEV₃/FEV₆ and all-cause mortality was evaluated using Cox regression models. The non-linear relationship between FEV₃/FEV₆ and all-cause mortality was assessed using restricted cubic splines. Subgroup analyses and sensitivity analyses were conducted to validate the robustness of the relationship.

Results: Overall, 25,159 participants were enrolled in the 308-month median follow-up analysis, of whom 8.8% (2,225/25,159) had reduced FEV₃/FEV₆ Participants with reduced FEV₃/FEV₆ exhibited increased risks of congestive heart failure, asthma, chronic bronchitis, emphysema, respiratory symptoms, and all-cause mortality risk (hazard ratio=1.23, 95% confidence interval: 1.13-1.34, P<0.001). The findings remained consistent across subgroups. A non-linear U-shaped association was observed between FEV₃/FEV₆ and all-cause mortality, with the turning point at 1.04, and sensitivity analyses confirmed the robustness of this relationship.

Conclusion: Participants with reduced FEV₃/FEV₆ had worse respiratory health outcomes, suggesting that FEV₃/FEV₆ can be used as prognostic spirometry indicator.