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      Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients

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          Abstract

          Background

          Previous studies have demonstrated the potential beneficial effect of N-acetylcysteine (NAC) in chronic obstructive pulmonary disease (COPD). However, the required dose and responder phenotype remain unclear. The current study investigated the effect of high-dose NAC on airway geometry, inflammation, and oxidative stress in COPD patients. Novel functional respiratory imaging methods combining multislice computed tomography images and computer-based flow simulations were used with high sensitivity for detecting changes induced by the therapy.

          Methods

          Twelve patients with Global Initiative for Chronic Obstructive Lung Disease stage II COPD were randomized to receive NAC 1800 mg or placebo daily for 3 months and were then crossed over to the alternative treatment for a further 3 months.

          Results

          Significant correlations were found between image-based resistance values and glutathione levels after treatment with NAC ( P = 0.011) and glutathione peroxidase at baseline ( P = 0.036). Image-based resistance values appeared to be a good predictor for glutathione peroxidase levels after NAC ( P = 0.02), changes in glutathione peroxidase levels ( P = 0.035), and reduction in lobar functional residual capacity levels ( P = 0.00084). In the limited set of responders to NAC therapy, the changes in airway resistance were in the same order as changes induced by budesonide/formoterol.

          Conclusion

          A combination of glutathione, glutathione peroxidase, and imaging parameters could potentially be used to phenotype COPD patients who would benefit from addition of NAC to their current therapy. The findings of this small pilot study need to be confirmed in a larger pivotal trial.

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          Most cited references 33

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          Health status measurement in chronic obstructive pulmonary disease.

           G Jones (2001)
          Health status measurement is a common feature of studies in chronic obstructive pulmonary disease (COPD). This review assesses recent evidence for the validity of these measurements and their role as measures of the overall impact of the disease on the patient's daily life and wellbeing. It reviews the mostly widely used COPD specific questionnaires and examines the contribution that they make to an assessment of the overall effect of treatment. Finally, it addresses the question of how symptomatic benefit may be assessed in individual patients in routine practice.
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            Small airways dimensions in asthma and in chronic obstructive pulmonary disease.

             P Pare,  Simon Hogg,  K Kuwano (1993)
            The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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              Validation of computational fluid dynamics in CT-based airway models with SPECT/CT.

              To compare the results obtained by using numerical flow simulations with the results of combined single photon emission computed tomography (SPECT) and computed tomography (CT) and to demonstrate the importance of correct boundary conditions for the numerical methods to account for the large amount of interpatient variability in airway geometry. This study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, six patients with mild asthma (three men; three women; overall mean age, 46 years ± 17 [standard deviation]) underwent CT at functional residual capacity and total lung capacity, as well as SPECT/CT. CT data were used for segmentation and computational fluid dynamics (CFD) simulations. A comparison was made between airflow distribution, as derived with (a) SPECT/CT through tracer concentration analysis, (b) CT through lobar expansion measurement, and (c) CFD through flow computer simulation. Also, the heterogeneity of the ventilation was examined. Good agreement was found between SPECT/CT, CT, and CFD in terms of airflow distribution and hot spot detection. The average difference for the internal airflow distribution was less than 3% for CFD and CT versus SPECT/CT. Heterogeneity in ventilation patterns could be detected with SPECT/CT and CFD. This results of this study show that patient-specific computer simulations with appropriate boundary conditions yield information that is similar to that obtained with functional imaging tools, such as SPECT/CT. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100322/-/DC1. © RSNA, 2010
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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
                2013
                2013
                22 November 2013
                : 8
                : 569-579
                Affiliations
                [1 ]FluidDA nv, Kontich, Belgium
                [2 ]Department Respiratory Medicine, University Hospital, Antwerp, Belgium
                [3 ]Department Radiology, University Hospital, Antwerp, Belgium
                Author notes
                Correspondence: Jan De Backer, FluidDA nv, Groeningenlei 132, 2550 Kontich, Belgium, Tel +32 3450 8720, Fax +32 3450 8729, Email jan.debacker@ 123456fluidda.com
                Article
                copd-8-569
                10.2147/COPD.S49307
                3842218
                © 2013 De Backer et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

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