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Author |
de Backer, J.; Vos, W.; Van Holsbeke, C.; Vinchurkar, S.; Claes, R.; Parizel, P.M.; de Backer, W. |
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Title |
Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients |
Type |
A1 Journal article |
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Year  |
2013 |
Publication |
International Journal Of Chronic Obstructive Pulmonary Disease |
Abbreviated Journal |
Int J Chronic Obstr |
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Volume |
8 |
Issue |
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Pages |
569-579 |
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Keywords |
A1 Journal article; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP) |
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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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Wos |
000327537300001 |
Publication Date |
2013-11-21 |
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1178-2005; |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
3.157 |
Times cited |
21 |
Open Access |
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Notes |
; JDB is a founder/shareholder of FluidDA NV, Kontich, Belgium. WV, SV, and CVH are employed by FluidDA NV, and WDB is the director of FluidDA NV. PMP and RC have no conflicts of interest to report. The study was supported by Zambon SpA, Bresso, Italy. ; |
Approved |
Most recent IF: 3.157; 2013 IF: NA |
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Call Number |
UA @ lucian @ c:irua:112799 |
Serial |
813 |
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Author |
De Backer, L.A.; Vos, W.G.; Salgado, R.; de Backer, J.W.; Devolder, A.; Verhulst, S.L.; Claes, R.; Germonpré, P.R.; de Backer, W.A. |
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Title |
Functional imaging using computer methods to compare the effect of salbutamol and ipratropium bromide in patient-specific airway models of COPD |
Type |
A1 Journal article |
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Year |
2011 |
Publication |
International journal of chronic obstructive pulmonary disease |
Abbreviated Journal |
Int J Chronic Obstr |
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Volume |
6 |
Issue |
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Pages |
637-646 |
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Keywords |
A1 Journal article; Condensed Matter Theory (CMT); Vision lab; Laboratory Experimental Medicine and Pediatrics (LEMP) |
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Background: Salbutamol and ipratropium bromide improve lung function in patients with chronic obstructive pulmonary disease (COPD). However, their bronchodilating effect has not yet been compared in the central and distal airways. Functional imaging using computational fluid dynamics offers the possibility of making such a comparison. The objective of this study was to assess the effects of salbutamol and ipratropium bromide on the geometry and computational fluid dynamics-based resistance of the central and distal airways.Methods: Five patients with Global Initiative for Chronic Obstructive Lung Disease Stage III COPD were randomized to a single dose of salbutamol or ipratropium bromide in a crossover manner with a 1-week interval between treatments. Patients underwent lung function testing and a multislice computed tomography scan of the thorax that was used for functional imaging. Two hours after dosing, the patients again underwent lung function tests and repeat computed tomography.Results: Lung function parameters, including forced expiratory volume in 1 second, vital capacity, overall airway resistance, and specific airway resistance, changed significantly after administration of each product. On functional imaging, the bronchodilating effect was greater in the distal airways, with a corresponding drop in airway resistance, compared with the central airways. Salbutamol and ipratropium bromide were equally effective at first glance when looking at lung function tests, but when viewed in more detail with functional imaging, hyporesponsiveness could be shown for salbutamol in one patient. Salbutamol was more effective in the other patients.Conclusion: This pilot study gives an innovative insight into the modes of action of salbutamol and ipratropium bromide in patients with COPD, using the new techniques of functional imaging and computational fluid dynamics. |
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000208709800068 |
Publication Date |
2011-11-28 |
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ISSN |
1178-2005; |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
3.157 |
Times cited |
25 |
Open Access |
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Notes |
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Approved |
Most recent IF: 3.157; 2011 IF: NA |
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Call Number |
UA @ lucian @ c:irua:93165 |
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1300 |
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De Backer, L.; Vos, W.; Dieriks, B.; Daems, D.; Verhulst, S.; Vinchurkar, S.; Ides, K.; de Backer, J.; Germonpré, P.; de Backer, W. |
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Title |
The effects of long-term noninvasive ventilation in hypercapnic COPD patients : a randomized controlled pilot study |
Type |
A1 Journal article |
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Year |
2011 |
Publication |
International journal of chronic obstructive pulmonary disease |
Abbreviated Journal |
Int J Chronic Obstr |
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Volume |
6 |
Issue |
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Pages |
615-624 |
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Keywords |
A1 Journal article; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP) |
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Abstract |
Introduction: Noninvasive ventilation (NIV) is a well-established treatment for acute-on-chronic respiratory failure in hypercapnic COPD patients. Less is known about the effects of a long-term treatment with NIV in hypercapnic COPD patients and about the factors that may predict response in terms of improved oxygenation and lowered CO2 retention.Methods: In this study, we randomized 15 patients to a routine pharmacological treatment (n = 5, age 66 [standard deviation ± 6] years, FEV1 30.5 [±5.1] %pred, PaO2 65 [±6] mmHg, PaCO2 52.4 [±6.0] mmHg) or to a routine treatment and NIV (using the Synchrony BiPAP device [Respironics, Inc, Murrsville, PA]) (n = 10, age 65 [±7] years, FEV1 29.5 [±9.0] %pred, PaO2 59 [±13] mmHg, PaCO2 55.4 [±7.7] mmHg) for 6 months. We looked at arterial blood gasses, lung function parameters and performed a low-dose computed tomography of the thorax, which was later used for segmentation (providing lobe and airway volumes, iVlobe and iVaw) and post-processing with computer methods (providing airway resistance, iRaw) giving overall a functional image of the separate airways and lobes.Results: In both groups there was a nonsignificant change in FEV1 (NIV group 29.5 [9.0] to 38.5 [14.6] %pred, control group 30.5 [5.1] to 36.8 [8.7] mmHg). PaCO2 dropped significantly only in the NIV group (NIV: 55.4 [7.7] → 44.5 [4.70], P = 0.0076; control: 52.4 [6.0] → 47.6 [8.2], NS). Patients actively treated with NIV developed a more inhomogeneous redistribution of mass flow than control patients. Subsequent analysis indicated that in NIV-treated patients that improve their blood gases, mass flow was also redistributed towards areas with higher vessel density and less emphysema, indicating that flow was redistributed towards areas with better perfusion. There was a highly significant correlation between the % increase in mass flow towards lobes with a blood vessel density of >9% and the increase in PaO2. Improved ventilation–perfusion match and recruitment of previously occluded small airways can explain the improvement in blood gases.Conclusion: We can conclude that in hypercapnic COPD patients treated with long-term NIV over 6 months, a mass flow redistribution occurs, providing a better ventilation–perfusion match and hence better blood gases and lung function. Control patients improve homogeneously in iVaw and iRaw, without improvement in gas exchange since there is no improved ventilation/perfusion ratio or increased alveolar ventilation. These differences in response can be detected through functional imaging, which gives a more detailed report on regional lung volumes and resistances than classical lung function tests do. Possibly only patients with localized small airway disease are good candidates for long-term NIV treatment. To confirm this and to see if better arterial blood gases also lead to better health related quality of life and longer survival, we have to study a larger population. |
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000208709800066 |
Publication Date |
2011-11-18 |
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ISSN |
1178-2005; |
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Additional Links |
UA library record; WoS full record; WoS citing articles |
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Impact Factor |
3.157 |
Times cited |
28 |
Open Access |
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Notes |
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Approved |
Most recent IF: 3.157; 2011 IF: NA |
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Call Number |
UA @ lucian @ c:irua:93164 |
Serial |
866 |
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