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August 2004

LE Magazine August 2004

Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases.
This multicentre trial was undertaken to confirm previous results indicating that long-term treatment with oral acetylcysteine reduces the exacerbation rate in patients with chronic bronchitis. Two hundred and eighty-five patients, smokers or ex-smokers, with chronic bronchitis started a pre-trial placebo-period of 1 month. After this run-in period 259 patients were included in the trial and randomized into two parallel groups. The patients were treated in a double-blind way either with acetylcysteine 200 mg b.i.d. or placebo b.i.d. for 6 months. The trial was completed by 98 patients in the acetylcysteine group and by 105 patients in the placebo group. Initially, there were no significant differences between the groups. Twice weekly, the patients filled in a diary card concerning symptoms. The number of exacerbations was assessed from these cards and at visits 2, 4, and 6 months after institution of therapy. The exacerbation rate was significantly lower in the acetylcysteine group in which 40% of the patients remained free from exacerbations compared to 19% in the placebo group. Sick-leave due to acute exacerbation was significantly less common in the acetylcysteine group. The drug was well tolerated.

Eur J Respir Dis. 1983 Aug;64(6):405-15

Are anti-oxidant and anti-inflammatory treatments effective in different subgroups of COPD? A hypothesis.
The treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids or anti-oxidants is still under debate and the identification of sub-groups of COPD patients who may benefit from either anti-inflammatory or anti-oxidant treatment is needed. We re-analysed data from an earlier study of inhaled beclomethasone therapy in COPD (n = 28) and asthma (n = 28) patients in order to determine patient characteristics that predict a favourable inhaled steroid treatment effect. A higher bronchodilatory response, a faster decline of FEV1 prior to the treatment period and a lower Tiffeneau index were significantly related to more beneficial treatment effects. Increased smoking tended to be related to less steroid treatment benefits, though it was not statistically significant. In this paper these findings are presented in light of the available literature on anti-inflammatory and anti-oxidant COPD treatment. On this basis the hypothesis is presented that anti-oxidant treatment might be relatively more effective among those COPD patients who respond less well to inhaled steroids (low reversibility and heavy smoking).

Respir Med. 1998 Nov;92(11):1259-64

N-acetylcysteine: potential for AIDS therapy.
The observations that people infected with HIV suffer not only from an inflammatory stress but also from depleted glutathione levels have led to a general hypothesis that these two are causally related, and that treatment of AIDS should include thiol-replenishment therapy. In particular, inflammatory stimulations are dependent on intracellular thiol levels, as they are potentiated at low glutathione levels (oxidative stress) and inhibited at high glutathione levels. Inflammatory stress may itself lead to decreased levels of glutathione. HIV has taken advantage of inflammatory signals to regulate its own replication; thus, the HIV infection is exacerbated by low levels of glutathione. We have shown that N-acetylcysteine can inhibit inflammatory stimulations, including that of HIV replication. Since N-acetylcysteine can replenish depleted glutathione levels in vivo, we suggest that it be used as an adjunct in the treatment of AIDS.

Pharmacology. 1993;46(3):121-9

Significance of glutathione in lung disease and implications for therapy.
Glutathione is a tripeptide that contains an important thiol (sulfhydryl) group within the central cysteine amino acid. Glutathione is involved in numerous vital processes where the reducing potential of the thiol is used. Several lung disorders are believed to be characterized by an increase in alveolar oxidant burden, potentially depleting alveolar and lung glutathione. Low glutathione has been linked to abnormalities in the lung surfactant system and the interaction between glutathione and antiproteases in the epithelial lining fluid of patients. Normal levels of intracellular glutathione may exert a critical negative control on the elaboration of proinflammatory cytokines. The increase of intracellular reactive oxygen species is believed to correlate with the activation of NF-kappa B, a transcription activator linked to the elaboration of several cytokines. There is now sufficient data to strongly implicate free radical injury in the genesis and maintenance of several lung disorders in humans. This information is substantial and will help the development of clinical studies examining a variety of inflammatory lung disorders.

Am J Med Sci. 1994 Feb;307(2):119-27

Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure.
OBJECTIVES: We sought to evaluate the efficacy of the antioxidant acetylcysteine in limiting the nephrotoxicity after coronary procedures. BACKGROUND: The increasingly frequent use of contrast-enhanced imaging for diagnosis or intervention in patients with coronary artery disease has generated concern about the avoidance of contrast-induced nephrotoxicity (CIN). Reactive oxygen species have been shown to cause CIN. METHODS: We prospectively studied 121 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration 2.8 +/- 0.8 mg/dl) who underwent a coronary procedure. Patients were randomly assigned to receive either acetylcysteine (400 mg orally twice daily) and 0.45% saline intravenously, before and after injection of the contrast agent, or placebo and 0.45% saline. Serum creatinine and blood urea nitrogen were measured before, 48 h and 7 days after the coronary procedure. RESULTS: Seventeen (14%) of the 121 patients had an increase in their serum creatinine concentration of at least 0.5 mg/dl at 48 h after administration of the contrast agent: 2 (3.3%) of the 60 patients in the acetylcysteine group and 15 (24.6%) of the 61 patients in the control group (p < 0.001). In the acetylcysteine group, the mean serum creatinine concentration decreased significantly from 2.8 +/- 0.8 to 2.5 +/- 1.0 mg/dl (p < 0.01) at 48 h after injection of the contrast medium, whereas in the control group, the mean serum creatinine concentration increased significantly from 2.8 +/- 0.8 to 3.1 +/- 1.0 mg/dl (p < 0.01). CONCLUSIONS: Prophylactic oral administration of the antioxidant acetylcysteine, along with hydration, reduces the acute renal damage induced by a contrast agent in patients with chronic renal insufficiency undergoing a coronary procedure.

J Am Coll Cardiol. 2002 Oct 16;40(8):1383-8