Potential for noninvasive assessment of lung inhomogeneity using highly precise, highly time-resolved measurements of gas exchange.

Inhomogeneity in the lung impairs gas exchange and can be an early marker of lung disease. We hypothesized that highly precise measurements of gas exchange contain sufficient information to quantify many aspects of the inhomogeneity noninvasively. Our aim was to explore whether one parameterization of lung inhomogeneity could both fit such data and provide reliable parameter estimates. A mathematical model of gas exchange in an inhomogeneous lung was developed, containing inhomogeneity parameters for compliance, vascular conductance, and dead space, all relative to lung volume. Inputs were respiratory flow, cardiac output, and the inspiratory and pulmonary arterial gas compositions. Outputs were expiratory and pulmonary venous gas compositions. All values were specified every 10 ms. Some parameters were set to physiologically plausible values. To estimate the remaining unknown parameters and inputs, the model was embedded within a nonlinear estimation routine to minimize the deviations between model and data for CO2, O2, and N2 flows during expiration. Three groups, each of six individuals, were studied: young (20-30 yr); old (70-80 yr); and patients with mild to moderate chronic obstructive pulmonary disease (COPD). Each participant undertook a 15-min measurement protocol six times. For all parameters reflecting inhomogeneity, highly significant differences were found between the three participant groups ( P < 0.001, ANOVA). Intraclass correlation coefficients were 0.96, 0.99, and 0.94 for the parameters reflecting inhomogeneity in deadspace, compliance, and vascular conductance, respectively. We conclude that, for the particular participants selected, highly repeatable estimates for parameters reflecting inhomogeneity could be obtained from noninvasive measurements of respiratory gas exchange. NEW & NOTEWORTHY This study describes a new method, based on highly precise measures of gas exchange, that quantifies three distributions that are intrinsic to the lung. These distributions represent three fundamentally different types of inhomogeneity that together give rise to ventilation-perfusion mismatch and result in impaired gas exchange. The measurement technique has potentially broad clinical applicability because it is simple for both patient and operator, it does not involve ionizing radiation, and it is completely noninvasive.

A mechanistic physicochemical model of carbon dioxide transport in blood.

A number of mathematical models have been produced that, given the Pco2 and Po2 of blood, will calculate the total concentrations for CO2 and O2 in blood. However, all these models contain at least some empirical features, and thus do not represent all of the underlying physicochemical processes in an entirely mechanistic manner. The aim of this study was to develop a physicochemical model of CO2 carriage by the blood to determine whether our understanding of the physical chemistry of the major chemical components of blood together with their interactions is sufficiently strong to predict the physiological properties of CO2 carriage by whole blood. Standard values are used for the ionic composition of the blood, the plasma albumin concentration, and the hemoglobin concentration. All Km values required for the model are taken from the literature. The distribution of bicarbonate, chloride, and H+ ions across the red blood cell membrane follows that of a Gibbs-Donnan equilibrium. The system of equations that results is solved numerically using constraints for mass balance and electroneutrality. The model reproduces the phenomena associated with CO2 carriage, including the magnitude of the Haldane effect, very well. The structural nature of the model allows various hypothetical scenarios to be explored. Here we examine the effects of 1) removing the ability of hemoglobin to form carbamino compounds; 2) allowing a degree of Cl- binding to deoxygenated hemoglobin; and 3) removing the chloride (Hamburger) shift. The insights gained could not have been obtained from empirical models. NEW & NOTEWORTHY: This study is the first to incorporate a mechanistic model of chloride-bicarbonate exchange between the erythrocyte and plasma into a full physicochemical model of the carriage of carbon dioxide in blood. The mechanistic nature of the model allowed a theoretical study of the quantitative significance for carbon dioxide transport of carbamino compound formation; the putative binding of chloride to deoxygenated hemoglobin, and the chloride (Hamburger) shift.

In-airway molecular flow sensing: A new technology for continuous, noninvasive monitoring of oxygen consumption in critical care.

There are no satisfactory methods for monitoring oxygen consumption in critical care. To address this, we adapted laser absorption spectroscopy to provide measurements of O2, CO2, and water vapor within the airway every 10 ms. The analyzer is integrated within a novel respiratory flow meter that is an order of magnitude more precise than other flow meters. Such precision, coupled with the accurate alignment of gas concentrations with respiratory flow, makes possible the determination of O2 consumption by direct integration over time of the product of O2 concentration and flow. The precision is illustrated by integrating the balance gas (N2 plus Ar) flow and showing that this exchange was near zero. Measured O2 consumption changed by <5% between air and O2 breathing. Clinical capability was illustrated by recording O2 consumption during an aortic aneurysm repair. This device now makes easy, accurate, and noninvasive measurement of O2 consumption for intubated patients in critical care possible.

A cross-sectional study of the prevalence and associations of iron deficiency in a cohort of patients with chronic obstructive pulmonary disease.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Iron deficiency, with or without anaemia, is associated with other chronic conditions, such as congestive heart failure, where it predicts a worse outcome. However, the prevalence of iron deficiency in COPD is unknown. This observational study aimed to determine the prevalence of iron deficiency in COPD and associations with differences in clinical phenotype. SETTING: University hospital outpatient clinic. PARTICIPANTS: 113 adult patients (65% male) with COPD diagnosed according to GOLD criteria (forced expiratory volume in 1 s (FEV1): forced vital capacity (FVC) ratio <0·70 and FEV1 <80% predicted); with age-matched and sex-matched control group consisting of 57 healthy individuals. MAIN OUTCOME MEASURES: Prevalence of iron deficiency, defined as: any one or more of (1) soluble transferrin receptor >28.1 nmol/L; (2) transferrin saturation <16% and (3) ferritin <12 µg/L. Severity of hypoxaemia, including resting peripheral arterial oxygen saturation (SpO2) and nocturnal oximetry; C reactive protein (CRP); FEV1; self-reported exacerbation rate and Shuttle Walk Test performance. RESULTS: Iron deficiency was more common in patients with COPD (18%) compared with controls (5%). In the COPD cohort, CRP was higher in patients with iron deficiency (median 10.5 vs 4.0 mg/L, p<0.001), who were also more hypoxaemic than their iron-replete counterparts (median resting SpO2 92% vs 95%, p<0.001), but haemoglobin concentration did not differ. Patients with iron deficiency had more self-reported exacerbations and a trend towards worse exercise tolerance. CONCLUSIONS: Non-anaemic iron deficiency is common in COPD and appears to be driven by inflammation. Iron deficiency associates with hypoxaemia, an excess of exacerbations and, possibly, worse exercise tolerance, all markers of poor prognosis. Given that it has been shown to be beneficial in other chronic diseases, intravenous iron therapy should be explored as a novel therapeutic option in COPD.

A three-state mathematical model of hyperthermic cell death.

Thermal treatments for tissue ablation rely upon the heating of cells past a threshold beyond which the cells are considered destroyed, denatured, or killed. In this article, a novel three-state model for cell death is proposed where there exists a vulnerable state positioned between the alive and dead states used in a number of existing cell death models. Proposed rate coefficients include temperature dependence and the model is fitted to experimental data of heated co-cultures of hepatocytes and lung fibroblasts with very small RMS error. The experimental data utilized include further reductions in cell viabilities over 24 and 48 h post-heating and these data are used to extend the three-state model to account for slow cell death. For the two cell lines employed in the experimental data, the three parameters for fast cell death appear to be linearly increasing with % content of lung fibroblast, while the sparse nature of the data did not indicate any co-culture make-up dependence for the parameters for slow cell death. A critical post-heating cell viability threshold is proposed beyond which cells progress to death; and these results are of practical importance with potential for more accurate prediction of cell death.

1-D steady state analysis of a two-equation coupled system for determination of tissue temperature in liver during radio frequency ablation.

An analytical solution is provided for a two-equation coupled model for determination of liver tissue temperature during radio frequency ablation in the steady state with one-dimension in space. Both analytical analysis and model simulation were conducted to investigate the effects of two crucial system parameters: blood perfusion rate and convective heat transfer coefficient on the tissue temperature field. The quantitative criteria were also derived, under which the two-equation coupled system can be approximated to a conventional single bio-heat equation system such as the Pennes model.