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

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.

Noninvasive cardiac output monitoring in a porcine model using the inspired sinewave technique: a proof-of-concept study.

BACKGROUND: Cardiac output (Q˙) monitoring can support the management of high-risk surgical patients, but the pulmonary artery catheterisation required by the current 'gold standard'-bolus thermodilution (Q˙T)-has the potential to cause life-threatening complications. We present a novel noninvasive and fully automated method that uses the inspired sinewave technique to continuously monitor cardiac output (Q˙IST). METHODS: Over successive breaths the inspired nitrous oxide (N2O) concentration was forced to oscillate sinusoidally with a fixed mean (4%), amplitude (3%), and period (60 s). Q˙IST was determined in a single-compartment tidal ventilation lung model that used the resulting amplitude/phase of the expired N2O sinewave. The agreement and trending ability of Q˙IST were compared with Q˙T during pharmacologically induced haemodynamic changes, before and after repeated lung lavages, in eight anaesthetised pigs. RESULTS: Before lung lavage, changes in Q˙IST and Q˙T from baseline had a mean bias of -0.52 L min-1 (95% confidence interval [CI], -0.41 to -0.63). The concordance between Q˙IST and Q˙T was 92.5% as assessed by four-quadrant analysis, and polar plot analysis revealed a mean angular bias of 5.98° (95% CI, -24.4°-36.3°). After lung lavage, concordance was slightly reduced (89.4%), and the mean angular bias widened to 21.8° (-4.2°, 47.6°). Impaired trending ability correlated with shunt fraction (r=0.79, P<0.05). CONCLUSIONS: The inspired sinewave technique provides continuous and noninvasive monitoring of cardiac output, with a 'marginal-good' trending ability compared with cardiac output based on thermodilution. However, the trending ability can be reduced with increasing shunt fraction, such as in acute lung injury.

The inspired sine-wave technique: A novel method to measure lung volume and ventilatory heterogeneity.

NEW FINDINGS: What is the central question of this study? We present a new non-invasive medical technology, the inspired sine-wave technique, which involves inhalation of sinusoidally fluctuating concentrations of a tracer gas. The technique requires only passive patient cooperation and can monitor different cardiorespiratory variables, such as end-expired lung volume, ventilatory heterogeneity and pulmonary blood flow. What is the main finding and its importance? In this article, we demonstrate that the measurements of end-expired lung volume are repeatable and accurate, in comparison to whole-body plethysmography, and the technique is sensitive to the changes in ventilatory heterogeneity associated with advancing age. As such, it has the potential to provide clinically valuable information. ABSTRACT: The inspired sine-wave technique (IST) is a new method that can provide simple, non-invasive cardiopulmonary measurements. Over successive tidal breaths, the concentration of a tracer gas (i.e. nitrous oxide, N2 O) is sinusoidally modulated in inspired air. Using a single-compartment tidal-ventilation lung model, the resulting amplitude/phase of the expired sine wave allows estimation of end-expired lung volume (ELV), pulmonary blood flow and three indices for ventilatory heterogeneity (VH; ELV180 /FRCpleth , ELV180 /FRCpred and ELV60 /ELV180 ). This investigation aimed to determine the repeatability and agreement of ELV with FRCpleth and, as normal ageing results in well-established changes in pulmonary structure and function, whether the IST estimates of ELV and VH are age dependent. Forty-eight healthy never-smoker participants (20-86 years) underwent traditional pulmonary function testing (e.g. spirometry, body plethysmography) and the IST test, which consisted of 4 min of quiet breathing through a face mask while inspired N2 O concentrations were oscillated in a sine-wave pattern with a fixed mean (4%) and amplitude (3%) and a period of either 180 or 60 s. The ELV180 /FRCpleth and ELV180 /FRCpred were age dependent (average decreases of 0.58 and 0.48% year-1 ), suggesting an increase in VH with advancing age. The ELV showed a mean bias of -1.09 litres versus FRCpleth , but when normalized for the effects of age this bias reduced to -0.35 litres. The IST test has potential to provide clinically useful information necessitating further study (e.g. for mechanically ventilated or obstructive lung disease patients), but these findings suggest that the increases in VH with healthy ageing must be taken into account in clinical investigations.

The Inspired Sinewave Technique: A Comparison Study With Body Plethysmography in Healthy Volunteers.

The inspired sinewave technique is a noninvasive method to measure airway dead space, functional residual capacity, pulmonary blood flow, and lung inhomogeneity simultaneously. The purpose of this paper was to assess the repeatability and accuracy of the current device prototype in measuring functional residual capacity, and also participant comfort when using such a device. To assess within-session repeatability, six sinewave measurements were taken over two-hour period in 17 healthy volunteers. To assess day-to-day repeatability, measurements were taken over 16 days in 3 volunteers. To assess accuracy, sinewave measurements were compared to body plethysmography in 44 healthy volunteers. Finally, 18 volunteers who experienced the inspired sinewave device, body plethysmography and spirometry were asked to rate the comfort of each technique on a scale of 1-10. The repeatability coefficients for dead space, functional residual capacity, and blood flow were 48.7 ml, 0.48L, and 2.4L/min respectively. Bland-Altman analyses showed a mean BIAS(SD) of -0.68(0.42)L for functional residual capacity when compared with body plethysmography. 14 out of 18 volunteers rated the inspired sinewave device as their preferred technique. The repeatability and accuracy of functional residual capacity measurements were found to be as good as other techniques in the literature. The high level of comfort and the non-requirement of patient effort meant that, if further refined, the inspired sinewave technique could be an attractive solution for difficult patient groups such as very young children, elderly, and ventilated patients.

A modification of the Bohr method to determine airways deadspace for non-uniform inspired gas tensions.

BACKGROUND: The Bohr method is a technique to determine airways deadspace using a tracer gas such as carbon dioxide or nitrogen. It is based on the assumption that the inspired concentration of the tracer gas is constant throughout inspiration. However, in some lung function measurement techniques where inspired concentration of the tracer gas may be required to vary, or where rapid injection of the tracer gas is made in real time, uniform inspired concentration is difficult or impossible to achieve, which leads to inaccurate estimation of deadspace using the Bohr equation. One such lung function measurement technique is the inspired sinewave technique. OBJECTIVE: In this paper, we proposed a modification of the Bohr method, relaxing the requirement of absolute uniformity of tracer concentration in the inspired breath. METHOD: The new method used integration of flow and concentration. A computer algorithm sought an appropriate value of deadspace to satisfy the mass balance equation for each breath. A modern gas mixing apparatus with rapid mass flow controllers was used to verify the procedure. RESULT: Experiments on a tidally ventilated bench lung showed that the new method estimated dead space within 10% of the actual values whereas the traditional Bohr deadspace gave more than 50% error. CONCLUSION: The new method improved the accuracy of deadspace estimation when the inspired concentration is not uniform. This improvement would lead to more accurate diagnosis and more accurate estimations of other lung parameters such as functional residual capacity and pulmonary blood flow.

Modelling mixing within the dead space of the lung improves predictions of functional residual capacity.

Routine estimation of functional residual capacity (FRC) in ventilated patients has been a long held goal, with many methods previously proposed, but none have been used in routine clinical practice. This paper proposes three models for determining FRC using the nitrous oxide concentration from the entire expired breath in order to improve the precision of the estimate. Of the three models proposed, a dead space with two mixing compartments provided the best results, reducing the mean limits of agreement with the FRC measured by whole body plethysmography by up to 41%. This moves away from traditional lung models, which do not account for mixing within the dead space. Compared to literature values for FRC, the results are similar to those obtained using helium dilution and better than the LUFU device (Dräger Medical, Lubeck, Germany), with significantly better limits of agreement compared to plethysmography.