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

Authors
  • Mountain, James E1, 2
  • Santer, Peter1
  • O'Neill, David P1
  • Smith, Nicholas M J3
  • Ciaffoni, Luca3
  • Couper, John H3
  • Ritchie, Grant A D3
  • Hancock, Gus3
  • Whiteley, Jonathan P2
  • Robbins, Peter A1
  • 1 Department of Physiology, Anatomy and Genetics, University of Oxford , Oxford , United Kingdom. , (United Kingdom)
  • 2 Department of Computer Science, University of Oxford , Oxford , United Kingdom. , (United Kingdom)
  • 3 Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford , Oxford , United Kingdom. , (United Kingdom)
Type
Published Article
Journal
Journal of Applied Physiology
Publisher
American Physiological Society
Publication Date
Mar 01, 2018
Volume
124
Issue
3
Pages
615–631
Identifiers
DOI: 10.1152/japplphysiol.00745.2017
PMID: 29074714
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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