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 |