Comparing Changes in FEV1 and Impulse Oscillometry Parameters Following Methacholine Challenge Testing: Physiological Correlates, Clinical Markers, and Pulmonary Symptoms

<b>Background:</b> Spirometry-based methacholine challenge testing using the provocative dose causing a 20% decline in forced expiratory volume in 1 s (FEV₁, PD₂₀) is a reference method for assessing airway hyperresponsiveness. Impulse oscillometry (IOS), performed during tidal breathing, may capture airway mechanical changes not fully reflected by spirometry. We compared FEV₁- and IOS-based methacholine responsiveness in a large, real-world adult cohort and examined associations with clinical markers and symptoms. <b>Methods:</b> We analyzed 794 consecutively referred adults undergoing standardized methacholine challenge testing with concurrent spirometry and IOS. IOS positivity was defined as a ≥40% increase in resistance at 5 Hz (ΔR₅ ≥ 40%). Agreement between FEV₁-PD₂₀ positivity (PD₂₀ ≤ 1440 µg) and IOS positivity was evaluated using cross-classification and Cohen's κ. Associations between continuous responses were assessed using Pearson and Spearman correlations. The relationship between ΔR₅ and the probability of a ≥20% decline in FEV₁ was examined using logistic regression. Predictors of ΔR₅ were assessed using multivariable linear regression. Symptom severity was recorded immediately post-challenge using a five-point Likert scale and related to physiological responses. <b>Results:</b> FEV₁-PD₂₀ classified 37.5% of participants as hyperresponsive, whereas IOS positivity (ΔR₅ ≥ 40%) classified 70.6%. Agreement between methods was limited (κ = 0.09; <i>p</i> < 0.01). ΔFEV₁ and ΔR₅ were weakly correlated (r = -0.287; ρ = -0.306; both <i>p</i> < 0.001; R² = 0.08). A 20% decline in FEV₁ corresponded on average to a 74% increase in R₅, whereas ΔR₅ ≥ 40% corresponded to an average FEV₁ decline of 7.6%. In multivariable models, referral diagnosis group and age independently predicted ΔR₅, whereas FeNO and baseline FEV₁% predicted did not. Baseline FEV₁% predicted modified the ΔFEV₁-ΔR₅ slope (interaction β = -0.0317; <i>p</i> = 0.0028). Post-challenge symptom (5-point Likert) related to MCT was associated with both ΔFEV₁ and IOS responses; ΔFEV₁ showed a stronger linear association with symptoms, whereas IOS measures showed larger stepwise differences across symptom categories. <b>Conclusions:</b> IOS identifies a larger, partly distinct subset of methacholine-responsive individuals compared with conventional FEV₁-PD₂₀ criteria and detects mechanical changes at lower levels of spirometric impairment. Despite limited concordance, IOS provides complementary physiological and symptom-relevant information when used alongside spirometry. Standardized IOS response definitions and prospective validation are needed to establish clinical utility.