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

TL;DR

This study compares two methods for measuring airway responsiveness to methacholine and finds that impulse oscillometry detects more cases than traditional spirometry.

Contribution

The study demonstrates that impulse oscillometry identifies a larger and partly distinct group of methacholine-responsive individuals compared to FEV1-based testing.

Findings

Impulse oscillometry (IOS) identified 70.6% of participants as hyperresponsive, compared to 37.5% using FEV1–PD20 criteria.

IOS responses showed larger stepwise differences in symptom categories compared to FEV1 declines.

A 20% decline in FEV1 corresponded to a 74% increase in R5, while a 40% increase in R5 corresponded to only a 7.6% FEV1 decline.

Abstract

Background: 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. Methods: 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. Results: 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; p < 0.01). ΔFEV1 and ΔR5 were weakly correlated (r = −0.287; ρ = −0.306; both p < 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; p = 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. Conclusions: 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.

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