COPD

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Discussion

The major findings of this study of exacerbations of COPD can be

summarised as follows:

(a) among patients with elevated CRP, those receiving NAC were more

likely to have this marker normalised than those receiving placebo,

with NAC1200 being more efficacious in this regard than NAC600;

( both dosages of NAC were superior to placebo in terms of

improving lung function and clinical outcomes; © NAC1200 was

superior to NAC600 in reducing IL-8 and difficulty of expectoration.

COPD is a disease characterised by a progressive decline in lung

function that is correlated with frequency of exacerbation.[1,2,18]

Exacerbations occur in response to a series of events including mucus

hypersecretion, reduced mucociliary clearance and viral or bacterial

infections.[4,18] The ensuing influx of inflammatory cells, namely

neutrophils, macrophages and T lymphocytes, may lead to damage of

bronchial mucosa and lung parenchyma through the release of protease,

myeloperoxidase and oxygen free radicals.[3,5]

In addition to its well known mucolytic activity,[19] NAC has been

shown to exert anti-inflammatory activity and antioxidant activity by

inhibiting neutrophil chemotaxis[10] and promoting the synthesis of

glutathione, which represents one of the most efficient antioxidant

cellular systems.[11]

The results of the present study, which is the first to demonstrate

the effects of NAC on lung function, support a role for NAC as an

anti-inflammatory agent in the treatment of COPD exacerbations.

NAC reduced CRP and IL-8 in a dose-dependent manner, which was

associated with a beneficial effect on clinical and functional

outcomes. The data presented here do not allow us to ascertain

whether NAC reduced CRP and IL-8 by a direct anti-inflammatory effect

or by improving mucociliary clearance, as suggested by the much

greater effect of NAC1200 than NAC600 on ease of expectoration.

The mode of action of NAC in COPD has not been elucidated. If the

effect is primarily a direct anti-inflammatory effect, the greatest

treatment effect may be seen in the first few days after treatment

initiation rather than at 5 or 10 days; however, this has not been

studied to date and was not measured in this study. Further research

is required to ascertain whether this is the case; such data would

shed more light on the likely mechanism of effect of NAC.

A possible confounding factor in any study of exacerbations of COPD

is use of concomitant treatments, which cannot be avoided for ethical

reasons. However, this does not appear to have been the case in the

present study as there were no significant differences in use of

antibacterial or bronchodilator treatments between the groups.

Furthermore, the number of patients receiving inhaled corticosteroids

was small in all treatment groups. Therefore, the differences between

treatments observed in the present study can be reasonably attributed

to NAC and its dosage. In this study, patients with at least two

exacerbations of COPD in the previous 2 years were included. It is

likely that patients with fewer previous exacerbations may also

benefit from this treatment. This is a matter for further study.

Both NAC600 and NAC1200 were equally well tolerated, as shown by the

constancy of vital signs and laboratory findings during the study,

and also by patients' opinions on treatment acceptability, which was

positive in >95% of patients for all groups.

http://www.medscape.com/viewarticle/508001_4