Ratio between forced expiratory flow between 25% and 75% of vital capacity and FVC is a determinant of airway reactivity and sensitivity to methacholine

Study objective: The ratio between forced expiratory flow between 25% and 75% of vital capacity (FEF_25-75) and FVC is thought to reflect dysanapsis between airway size and lung size. A low FEF_25-75/FVC ratio is associated with airway responsiveness to methacholine in middle-aged and older men. The current study was designed to assess this relationship in both male and female subjects over a broader range of ages. Study design: Data analysis of consecutive subjects who had a ≥ 20% reduction in FEV₁ after ≤ 189 cumulative units of methacholine over a 7-year period. Setting: Pulmonary function laboratory in a university-affiliated hospital. Patients: A total of 764 consecutive subjects aged 4 to 91 years (mean ± SD age, 40.8 ± 19.6 years). There were 223 male (29.3%) and 540 female (70.7%) subjects. Measurements and results: Airway reactivity was assessed as the dose-response slope of the reduction in FEV₁ from baseline vs the cumulative dose of inhaled methacholine. The cumulative dose of methacholine causing 20% reduction in FEV₁ (PD₂₀) was used as the indicator of airway sensitivity. In a linear regression model that included age, height, and percentage of predicted FEV₁, the FEF_25-75/FVC ratio accounted for 7.6% of variability in airway reactivity (p < 0.0001, r² = 0.076). Subjects with higher airway sensitivity, indicated by lower PD₂₀, also had a lower FEF_25-75/FVC ratio. Conclusions: A low FEF_25-75/FVC ratio, indicating small airway size relative to lung size, is associated with higher airway sensitivity and reactivity to methacholine in susceptible subjects.