Therapeutics

Role of N-Acetylcysteine in the treatment of Acute Respiratory Disorders
8.1 Clinical Trials
8.1.1 Effect on Influenza-like Symptoms
NAC reduced both the frequency and severity of
influenza-like episodes in a randomized, double-blind
trial (table VIII). [71] Treatment with oral NAC 600mg
twice daily for 6 months attenuated influenza-like
symptomatology relative to placebo in patients without
chronic respiratory diseases (the majority of the 190
evaluable patients were aged ≥ 65 years). [72] The frequency
of influenza-like symptoms was significantly less with
NAC than with placebo (figure 14). When assessed on a
monthly basis, significant between-group differences in the
frequency of influenza-like episodes were shown during
the period of greatest seasonal incidence of influenza in
Europe (i.e. during the winter months of December to
March [2–4 months after beginning treatment]).
The severity of influenza-like symptoms was also less
Table VIII Summary of the immunomodulatory activity of
N-acetylcysteine in patients with nonrespiratory chronic
degenerative diseases [71]
Decreased the severity of influenza-like episodes
Decreased the incidence of specific local and general
influenza-like symptoms
Decreased the length of time spent in bed due to
influenza-like symptoms
Protective effect with respect to clinically evident
disease
Shift from anergy to normergy in cell-mediated
immunity
with NAC than with placebo. [72] Of the 46 influenza-like
episodes in the NAC-treatment group, 72% were
classified as mild, 25% as moderate, and 2% as severe. In
comparison, of the 99 episodes within the placebo group,
48%, 47%, and 6% were classified as mild, moderate, or
severe, respectively.
The incidence of specific local influenza-like symptoms
(coryza/rhinorrhea, sore throat, catarrh and cough) and
general influenza-like symptoms (headache, myalgia)
was significantly lower with NAC than with placebo
(all p < 0.05). [72] This indicates that NAC, in addition
to its mucolytic effects, also has antioxidant and
immunomodulatory activity.
Relative to placebo, NAC also significantly reduced the
length of time spent in bed due to influenza-like
symptoms. [72] Indeed, 9 of the 10 patients with influenzalike
symptoms who were not bedridden were receiving
NAC. Conversely, of the 25 patients who were
bedridden for ≥ 6 days, only 3 patients were in the
NAC-treatment group.
The frequency of seroconversion towards influenza virus
was similar in the NAC and placebo-treatment groups
(29% vs 24%), indicating that NAC did not prevent
subclinical infections. However, significantly fewer NAC
recipients developed a symptomatic form of the condition
(figure 15). This indicates that NAC had a protective effect
with respect to clinically evident disease. In those patients
who did not undergo seroconversion towards the virus
(71% vs 76%), the proportion of patients experiencing an
influenza-like episode was numerically, but not
Fig. 14
Efficacy of oral N-acetylcysteine
(NAC) 600mg twice daily
compared with placebo in the
attenuation of influenza-like
symptoms. Proportion of
patients experiencing influenzalike
symptoms during the total
duration of ≥ 5 months
treatment and on a monthly
basis. [71]
* p < 0.05, ** p < 0.01,
*** p = 0.0006 vs placebo.
Influenza-like episodes (% of patients)
60
50
40
30
20
10
***
* **
NAC
**
Placebo
0
Total treatment
duration
1 month 2 months 3 months
Monthly assessment
4 months 5 months 6 months
19