Back to Journals » International Journal of Chronic Obstructive Pulmonary Disease » Volume 16

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

Authors Bruce RM, Phan PA, Rigolli M, Tran MC, Pacpaco E, Rahman NM, Farmery AD

Received 28 May 2020

Accepted for publication 22 September 2020

Published 23 February 2021 Volume 2021:16 Pages 401—413


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Richard Russell

Richard M Bruce,1,2 Phi Anh Phan,2 Marzia Rigolli,3 Minh C Tran,2 Edmund Pacpaco,4 Najib M Rahman,4 Andrew D Farmery2

1Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, King’s College London, London, UK; 2Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK; 3University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, UK; 4Oxford University Hospitals NHS Foundation Trust, Oxford Centre for Respiratory Medicine, Oxford, UK

Correspondence: Richard M Bruce
King’s College London, Shepherd’s House, Guy’s Campus, London, SE1 1UL, UK
Tel +44 20 7848 6324

Background: There is marked variability in the symptoms and outcomes of patients with chronic obstructive pulmonary disease (COPD) which are poorly predicted by spirometry/FEV1%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 (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/FRCpleth and ELV180/ELVpred). 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: ELV180/FRCpleth and ELV180/ELVpred 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/FRCpleth was a stronger and independent predictor of CAT, mMRC-DS and C+M score vs FEV1%pred. ELV180/ELVpred was a stronger and independent and better predictor of C+M score vs FEV1%pred. Phenotyping patients, based upon ELV180/ELVpred and FRC%pred, uncovered significant symptomatic differences between groups.
Conclusion: The IST indices of VH were superior and independent predictors of symptom severity vs FEV1%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.

Keywords: COPD, lung function test, nitrous oxide, medical device, ventilatory heterogeneity

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]