Effect of deep inspiration on impulse oscillometry responses to methacholine in healthy adults

Impulse oscillometry (IOS) detects small-airway hyperresponsiveness during methacholine challenge testing (MCT). Deep inspiration (DI) may attenuate these responses, but the magnitude and interpretive impact of this effect in healthy adults remain uncertain.

We conducted a prospective two-period crossover study in 38 healthy, non-smoking adults (median age 34.8 years; 53% female). Each participant completed two standardized five-dose MCT protocols: (i) IOS-only and (ii) IOS immediately followed by spirometry (IOS + DI). The primary endpoint was the within-subject difference in total resistance at 5 Hz (ΔR₅) at the maximum methacholine dose. Secondary analyses included R₅-R₂₀, AX, Fres, and bootstrap-derived upper limits of normal (ULNs).

No participant met the PD₂₀FEV₁ criterion. At the final dose, the IOS-only protocol elicited larger responses than IOS + DI (median ΔR₅% + 87% vs. +60%; paired difference +27%, 95% CI +12 to +44; p = 0.002). Similar attenuation was observed for R₅-R₂₀, AX, and Fres (all p ≤ 0.001), while central resistance (R₂₀) remained unaffected. Baseline R₅ correlated with ΔR₅ under both protocols (ρ ≈ 0.5, p < 0.01). Bootstrap-derived ULNs exceeded manufacturer thresholds, particularly under IOS-only conditions.

Deep inspiration substantially attenuates methacholine-induced IOS responses, underscoring the need for protocol-specific diagnostic thresholds. IOS-only MCT provides sensitive, effort-independent information and may be particularly valuable when spirometry is impracticable.Clinical Trial Registration: ClinicalTrials.gov NCT05012345.