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

Abstract

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, UKCorrespondence: Richard M BruceKing’s College London, Shepherd’s House, Guy’s Campus, London, SE1 1UL, UKTel [phone]Email [email protected]: 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

Keywords

• copd
• lung function test
• nitrous oxide
• medical device
• ventilatory heterogeneity