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      International Journal of COPD (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

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

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          Abstract

          Introduction

          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.

          Results

          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).

          Conclusion

          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.

          Most cited references30

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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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              Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity.

              Chronic obstructive pulmonary disease (COPD) is characterized by a decline in forced expiratory volume in 1 s (FEV(1)) and, in many advanced patients, by arterial hypoxemia with or without hypercapnia. Spirometric and gas exchange abnormalities have not been found to relate closely, but this may reflect a narrow range of severity in patients studied. Therefore, we assessed the relationship between pulmonary gas exchange and airflow limitation in patients with COPD across the severity spectrum. Ventilation-perfusion (V(A)/Q) mismatch was measured using the multiple inert gas elimination technique in 150 patients from previous studies. The distribution of patients according to the GOLD stage of COPD was: 15 with stage 1; 40 with stage 2; 32 with stage 3; and 63 with stage 4. In GOLD stage 1, AaPo(2) and V(A)/Q mismatch were clearly abnormal; thereafter, hypoxemia, AaPo(2), and V(A)/Q imbalance increased, but the changes from GOLD stages 1-4 were modest. Postbronchodilator FEV(1) was related to Pa(O(2)) (r = 0.62) and Pa(CO(2)) (r = -0.59) and to overall V(A)/Q heterogeneity (r = -0.48) (P < 0.001 each). Pulmonary gas exchange abnormalities in COPD are related to FEV(1) across the spectrum of severity. V(A)/Q imbalance, predominantly perfusion heterogeneity, is disproportionately greater than airflow limitation in GOLD stage 1, suggesting that COPD initially involves the smallest airways, parenchyma, and pulmonary vessels with minimal spirometric disturbances. That progression of V(A)/Q inequality with spirometric severity is modest may reflect pathogenic processes that reduce both local ventilation and blood flow in the same regions through airway and alveolar disease and capillary involvement.
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                Author and article information

                Journal
                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
                1176-9106
                1178-2005
                2018
                06 March 2018
                : 13
                : 833-842
                Affiliations
                [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@ 123456uza.be
                Article
                copd-13-833
                10.2147/COPD.S153295
                5846311
                0edc7291-38fe-45e8-ba6a-06ce548ede59
                © 2018 Hajian et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). 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.

                History
                Categories
                Clinical Trial Report

                Respiratory medicine
                acute exacerbation,high-resolution computed tomography,functional respiratory imaging,ventilation–perfusion,airway resistance

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