Assessment of Ventilatory Heterogeneity in Chronic Obstructive Pulmonary Disease Using the Inspired Sinewave Test

There is marked variability in the symptoms and outcomes of patients with chronic obstructive pulmonary disease (COPD) which are poorly predicted by spirometry/FEV_1%pred. Furthermore, as spirometry requires the performance of potentially distressing respiratory manoeuvres which are to some extent user-effort dependent, there is need for non-invasive and simple-to-perform techniques to identify subtypes of COPD which are more closely related to clinically relevant outcomes.

The inspired sinewave test (IST) sinusoidally modulates the inspired concentration of a tracer gas (N₂O) over successive tidal breaths. A single-compartment tidal-ventilation lung model processes the amplitude/phase of the expired N₂O sinewave and estimates cardiopulmonary variables including: effective lung volume and indices of ventilatory heterogeneity (VH; ELV₁₈₀/FRC_pleth and ELV₁₈₀/ELV_pred). 83 COPD patients and 53 healthy controls performed the IST test, standard pulmonary function tests (Spirometry, body plethysmography and the single breath test of carbon monoxide uptake), and symptom severity questionnaires (COPD assessment test, CAT; mMRC dyspnoea-scale, mMRC-DS; Cough+Mucus score; C+M score).

ELV₁₈₀/FRC_pleth and ELV₁₈₀/ELV_pred were significantly lower in patients with COPD vs healthy participants (0.34±0.11 vs 0.68±0.14 and 0.7±0.27 vs 0.98±0.15, respectively; P<0.05). Multivariable regression analysis demonstrated that ELV₁₈₀/FRC_pleth was a stronger and independent predictor of CAT, mMRC-DS and C+M score vs FEV_1%pred. ELV₁₈₀/ELV_pred was a stronger and independent and better predictor of C+M score vs FEV_1%pred. Phenotyping patients, based upon ELV₁₈₀/ELV_pred and FRC_%pred, uncovered significant symptomatic differences between groups.

The IST indices of VH were superior and independent predictors of symptom severity vs FEV_1%pred and has potential as a non-invasive and simple-to-perform method to stratify patients into subgroups related to clinically relevant features of COPD.