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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

Glutathione after NAC treatment was significantly different for patients who experienced a decrease in iRawcent (top) and an increase in iVawcent (bottom).Abbreviations: iRaw, image-based resistance; GSH, glutathione; iVaw, image-based volume.
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f6-copd-8-569: Glutathione after NAC treatment was significantly different for patients who experienced a decrease in iRawcent (top) and an increase in iVawcent (bottom).Abbreviations: iRaw, image-based resistance; GSH, glutathione; iVaw, image-based volume.

Mentions: The study showed a significant correlation (R = −0.7, P = 0.011) between the level of glutathione after NAC treatment and the change in resistance of the central airways (iRawcent) measured using imaging and computational fluid dynamics (Figure 4). No correlation was found between glutathione after placebo and iRawcent after placebo. The level of glutathione peroxidase at baseline (R = 0.61, P = 0.036) and after placebo treatment (R = 0.67, P = 0.017) correlated with the change in distal airway resistance (iRawdist) after NAC treatment (Figure 5). No significant correlation was found between the baseline and placebo values for glutathione peroxidase and the change in iRawdist after placebo. Using the Mann–Whitney U test, it could be observed that the level of glutathione after treatment was significantly higher (P = 0.020) in patients who demonstrated a reduction in iRawcent compared with patients in whom iRawcent stayed constant or increased (Figure 6). A similar result was found based on the segmented airway volume of the central airways (iVawcent). Glutathione after NAC treatment was significantly higher (P = 0.042) in patients with an increase in iVawcent. In patients who demonstrated a reduction in total (central + distal) image-based airway resistance (iRawtot), the change in glutathione peroxidase was significantly (P = 0.035) higher compared with patients in whom iRawtot did increase. On average, glutathione peroxidase levels increased in the group with reduced iRawtot and decreased in the group with elevated iRawtot after treatment. FEV1 also increased slightly in the group with reduced iRawtot and decreased in the group with higher iRawtot after NAC treatment, although the difference between the two groups was not significant (Figure 7).


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)

Glutathione after NAC treatment was significantly different for patients who experienced a decrease in iRawcent (top) and an increase in iVawcent (bottom).Abbreviations: iRaw, image-based resistance; GSH, glutathione; iVaw, image-based volume.
© Copyright Policy
Related In: Results  -  Collection

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

f6-copd-8-569: Glutathione after NAC treatment was significantly different for patients who experienced a decrease in iRawcent (top) and an increase in iVawcent (bottom).Abbreviations: iRaw, image-based resistance; GSH, glutathione; iVaw, image-based volume.
Mentions: The study showed a significant correlation (R = −0.7, P = 0.011) between the level of glutathione after NAC treatment and the change in resistance of the central airways (iRawcent) measured using imaging and computational fluid dynamics (Figure 4). No correlation was found between glutathione after placebo and iRawcent after placebo. The level of glutathione peroxidase at baseline (R = 0.61, P = 0.036) and after placebo treatment (R = 0.67, P = 0.017) correlated with the change in distal airway resistance (iRawdist) after NAC treatment (Figure 5). No significant correlation was found between the baseline and placebo values for glutathione peroxidase and the change in iRawdist after placebo. Using the Mann–Whitney U test, it could be observed that the level of glutathione after treatment was significantly higher (P = 0.020) in patients who demonstrated a reduction in iRawcent compared with patients in whom iRawcent stayed constant or increased (Figure 6). A similar result was found based on the segmented airway volume of the central airways (iVawcent). Glutathione after NAC treatment was significantly higher (P = 0.042) in patients with an increase in iVawcent. In patients who demonstrated a reduction in total (central + distal) image-based airway resistance (iRawtot), the change in glutathione peroxidase was significantly (P = 0.035) higher compared with patients in whom iRawtot did increase. On average, glutathione peroxidase levels increased in the group with reduced iRawtot and decreased in the group with elevated iRawtot after treatment. FEV1 also increased slightly in the group with reduced iRawtot and decreased in the group with higher iRawtot after NAC treatment, although the difference between the two groups was not significant (Figure 7).

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