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

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)401-413
Number of pages13
JournalInternational journal of chronic obstructive pulmonary disease
Accepted/In press2021

Bibliographical note

Funding Information: This project was funded by Department of Health, National Institute for Health Research (Grant Number: II-LA-0214-20005). Publisher Copyright: © 2021 Bruce et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.


King's Authors


Background: 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. Materials and Methods: The inspired sinewave test (IST) sinusoidally modulates the inspired concentration of a tracer gas (N 2O) over successive tidal breaths. A singlecompartment tidal-ventilation lung model processes the amplitude/phase of the expired N 2 O sinewave and estimates cardiopulmonary variables including: effective lung volume and indices of ventilatory heterogeneity (VH; ELV 180/FRC pleth and ELV 180/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). Results: ELV 180/FRC pleth and ELV 180/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 ELV 180/FRC pleth was a stronger and independent predictor of CAT, mMRC-DS and C+M score vs FEV 1%pred. ELV 180/ELV pred was a stronger and independent and better predictor of C+M score vs FEV 1%pred. Phenotyping patients, based upon ELV 180/ELV pred and FRC %pred, uncovered significant symptomatic differences between groups. Conclusion: 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.

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