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      Changes in ventilation–perfusion during and after an COPD exacerbation: an assessment using fluid dynamic modeling

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          Severe exacerbations associated with chronic obstructive pulmonary disease (COPD) that require hospitalization significantly contribute to morbidity and mortality. Definitions for exacerbations are very broad, and it is unclear whether there is one predominant underlying mechanism that leads to them. Functional respiratory imaging (FRI) with modeling provides detailed information about airway resistance, hyperinflation, and ventilation–perfusion (V/Q) mismatch during and following an acute exacerbation.

          Materials and methods

          Forty-two patients with COPD participating in a multicenter study were assessed by FRI, pulmonary function tests, and self-reported outcome measures during an acute exacerbation and following resolution. Arterial blood gasses and lung function parameters were measured.


          A significant correlation was found between alveolar–arterial gradient and image-based V/Q (iV/Q), suggesting that iV/Q represents V/Q mismatch during an exacerbation ( p<0.05).


          Recovery of an exacerbation is due to decreased (mainly distal) airway resistance ( p<0.05). Improvement in patient-reported outcomes were also associated with decreased distal airway resistance ( p<0.05), but not with forced expiratory volume. FRI is, therefore, a sensitive tool to describe changes in airway caliber, ventilation, and perfusion during and after exacerbation. On the basis of the fact that FRI increased distal airway resistance seems to be the main cause of an exacerbation, therapy should mainly focus on decreasing it during and after the acute event.

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          Most cited references 30

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          Characterization of pulmonary vascular remodelling in smokers and patients with mild COPD.

          Intimal enlargement of pulmonary arteries is an early change in chronic obstructive pulmonary disease (COPD). The cellular and extracellular components that are involved in this enlargement are unknown. The present study was designed to characterize the structural changes occurring in pulmonary muscular arteries in the initial disease stages. Lung specimens from patients with moderate COPD (n=8; forced expiratory volume in one second (FEV1), 66 +/- 10% predicted) and smokers without airflow obstruction (n=7; FEV1, 86 +/- 6% pred), were investigated by histochemistry to characterize extracellular matrix proteins and by immunohistochemistry to identify intrinsic cells of the vascular wall. In both COPD patients and smokers, the majority of cells present in the enlarged intimas were stained by specific smooth muscle cell (SMC) markers. No staining with endothelial or fibroblast markers was shown. A proportion of SMCs did not stain with desmin, suggesting cellular heterogeneity in this population. Elastin was the most abundant extracellular matrix protein and collagen was seen in a lower proportion. The amount of collagen was related to the intimal thickness (p<0.001). The findings demonstrated smooth muscle cell proliferation, as well as elastin and collagen deposition, in the thickened intimas of pulmonary arteries in moderate chronic obstructive pulmonary disease patients and smokers, suggesting that these abnormalities may originate at an early stage in cigarette smoke-induced respiratory disease.
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            Daily physical activity in patients with chronic obstructive pulmonary disease is mainly associated with dynamic hyperinflation.

            Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation, little is known about its relation to daily physical activity. To analyze the contribution of dynamic hyperinflation, exercise tolerance, and airway oxidative stress to physical activity in patients with COPD. In a cross-sectional study, we included 110 patients with moderate to very severe COPD. Daily physical activity was measured using a triaxial accelerometer providing a mean of 1-minute movement epochs as vector magnitude units (VMU). Patients performed the 6-minute walk test, incremental exercise test with measurement of breathing pattern and operating lung volumes, and constant-work rate test at 75% of maximal work rate. Using the GOLD stage and BODE index, we determined arterial blood gases, lung volumes, diffusing capacity, and biomarkers in exhaled breath condensate. Daily physical activity was lower in the 89 patients who developed dynamic hyperinflation than in the 21 who did not (n =161 [SD 70] vs. n = 288 [SD 85] VMU; P = 0.001). Physical activity was mainly related to distance walked in 6 minutes (r = 0.72; P = 0.001), Vo(2) (r = 0.63; P = 0.001), change in end-expiratory lung volume during exercise (r = -0.73; P = 0.001), endurance time (r = 0.61; P = 0.001), and 8-isoprostane in exhaled breath condensate (r = -0.67; P = 0.001). In a multivariate linear regression analysis using VMU as a dependent variable, dynamic hyperinflation, change in end-expiratory lung volume, and distance walked in 6 minutes were retained in the prediction model (r(2) = 0.84; P = 0.001). Daily physical activity of patients with COPD is mainly associated with dynamic hyperinflation, regardless of severity classification.
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              Clinical applications of forced oscillation to assess peripheral airway function.

              Forced oscillation applies external pressures to the respiratory system to measure respiratory impedance. Impedance of larger central airways may be dissected from that of peripheral airways using multiple oscillation frequencies. Respiratory impedance is calculated by computer-assisted methods that yield separate resistive and reactive components. The reactive component includes respiratory system capacitative and inertive properties, which may be separately visualized for clinical purposes using resonance as a rough dividing line. Low oscillation frequencies comprise those below resonance, and relate most prominently to capacitative properties of peripheral airways. High oscillation frequencies comprise those greater than resonance, which relate most prominently to inertial properties of larger central airways. Measurements of resistance and reactance in patients with peripheral airway disease, before and after therapeutic intervention, manifest characteristic patterns of response in low frequency resistance and reactance measures that appear to be closely correlated with each other. In contrast, changes in large central airways manifest resistance change uniformly over low and high frequencies.

                Author and article information

                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                06 March 2018
                : 13
                : 833-842
                [1 ]Department of Respiratory Medicine, University Hospital Antwerp, Edegem, Belgium
                [2 ]FLUIDDA nv, Kontich, Belgium
                [3 ]Department of Respiratory Medicine, University Medical Center Groningen, Groningen, the Netherlands
                [4 ]Department of Pulmonology, Brompton Hospital, London, UK
                [5 ]GSK, London, UK
                [6 ]Department of Pulmonary Diseases, University of Firenze, Florence, Italy
                Author notes
                Correspondence: Bita Hajian, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium, Tel +32 3 821 3656, Email bita.hajian@
                © 2018 Hajian et al. 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.

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