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

De Backer J, Vos W, Van Holsbeke C, Vinchurkar S, Claes R, Parizel PM, De Backer W - Int J Chron Obstruct Pulmon Dis (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: FluidDA nv, Kontich, Belgium.

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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Related in: MedlinePlus

Changes in iRaw and iVaw for all patients.Abbreviations: iRaw, image-based resistance; iVaw, image-based volume.
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f1-copd-8-569: Changes in iRaw and iVaw for all patients.Abbreviations: iRaw, image-based resistance; iVaw, image-based volume.

Mentions: Figure 1 shows image-based resistance (iRaw) and volume (iVaw) measurements for the individual patients. The left hand side depicts iRaw, while the right hand side shows iVaw. The left upper quadrant indicates an increase in iRaw, hence nonresponders. The left lower quadrant indicates a decline in iRaw, hence responders. For iVaw it is reversed, whereby the right upper quadrant indicates an increase in iVaw, therefore identifying responders, and the right lower quadrant indicates an decline in iVaw, hence nonresponders. From Figure 1, it can be seen that there was a relatively even distribution between patients who responded in terms of iRaw and iVaw measurements. There were six patients with a reported reduction in iRawcent and four with a reported reduction in iRawdist. In total, five patients demonstrated an increase in iVawdist and three patients showed an increase in iVawcent. In general, the changes could be considered small. However, the differences are considerable for individual patients on a local scale. Figure 2 shows the changes in airway resistance after placebo and NAC treatment for a patient who could be considered an iRaw or NAC responder. It could be observed that the changes are not homogeneously distributed throughout the airway system with a general decline in airway resistance up to 50% after NAC treatment and an increase in airway resistance up to 20% after placebo. Figure 3 shows the results for a nonresponder in terms of iRaw after NAC treatment. It could be observed that local resistance tended to increase up to 20% both after placebo and after NAC treatment.


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

De Backer J, Vos W, Van Holsbeke C, Vinchurkar S, Claes R, Parizel PM, De Backer W - Int J Chron Obstruct Pulmon Dis (2013)

Changes in iRaw and iVaw for all patients.Abbreviations: iRaw, image-based resistance; iVaw, image-based volume.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842218&req=5

f1-copd-8-569: Changes in iRaw and iVaw for all patients.Abbreviations: iRaw, image-based resistance; iVaw, image-based volume.
Mentions: Figure 1 shows image-based resistance (iRaw) and volume (iVaw) measurements for the individual patients. The left hand side depicts iRaw, while the right hand side shows iVaw. The left upper quadrant indicates an increase in iRaw, hence nonresponders. The left lower quadrant indicates a decline in iRaw, hence responders. For iVaw it is reversed, whereby the right upper quadrant indicates an increase in iVaw, therefore identifying responders, and the right lower quadrant indicates an decline in iVaw, hence nonresponders. From Figure 1, it can be seen that there was a relatively even distribution between patients who responded in terms of iRaw and iVaw measurements. There were six patients with a reported reduction in iRawcent and four with a reported reduction in iRawdist. In total, five patients demonstrated an increase in iVawdist and three patients showed an increase in iVawcent. In general, the changes could be considered small. However, the differences are considerable for individual patients on a local scale. Figure 2 shows the changes in airway resistance after placebo and NAC treatment for a patient who could be considered an iRaw or NAC responder. It could be observed that the changes are not homogeneously distributed throughout the airway system with a general decline in airway resistance up to 50% after NAC treatment and an increase in airway resistance up to 20% after placebo. Figure 3 shows the results for a nonresponder in terms of iRaw after NAC treatment. It could be observed that local resistance tended to increase up to 20% both after placebo and after NAC treatment.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: FluidDA nv, Kontich, Belgium.

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.

Show MeSH
Related in: MedlinePlus