Therapeutics

Role of N-Acetylcysteine in the treatment of Acute Respiratory Disorders
6. Mucolytic Activity
NAC has two primary mechanisms of action as a
mucolytic (figure 5): [24]
• direct mucolytic activity. The thiol groups in NAC
rupture the disulfide bridges of proteins in the mucous,
resulting in smaller units of the protein and, therefore,
reduced viscosity and mucous that is easier to
expectorate
• activation of mucociliary clearance. The physiological
transport of mucous and, therefore, its removal is
improved by NAC.
The favourable effects of NAC as a mucolytic have been
shown in numerous in vitro and animal-model studies
and studies in patients (table III). [28-40] NAC reduced the
viscosity of mucous, improved its transport and
increased sputum volume.
NAC also had a beneficial effect on mucous induced by
cigarette smoke (table III). It improved mucociliary
action, [28] decreased the length of time necessary to
reverse mucous cell hyperplasia [29] and inhibited
hypersecretion of mucous in the larynx and trachea. [30]
6.1 Clinical Trials
The efficacy of NAC as a mucolytic in patients with
respiratory conditions, such as chronic obstructive
pulmonary disease (COPD) or chronic bronchitis, is well
established. [7,24,41] Oral NAC has favorable effects on
mucous and cough in patients, including children, with
acute or chronic respiratory disorders.
The focus of this monograph is the relatively short-term
(10–15 days) use of oral NAC in the treatment of acute
respiratory conditions. [42-44] In these trials, the efficacy of
treatment was assessed using the differences between
baseline and endpoint values in various clinical
parameters. [42-44] Sputum viscosity, cough severity,
difficulty of expectoration and dyspnea were each
scored on a 3- or 4-point scale, where the lowest scores
of 0 or 1 indicate ‘normal‘ function (e.g. absence of
cough) or few symptoms (e.g. very fluid sputum) and 3
points indicates highly pathological conditions (e.g.
very viscous sputum or intense cough during the day or
night).
NAC reduces the viscosity of expectorations, which
reduces the expectoration difficulties and the severity of
Table III Summary of mucolytic effects of N-acetylcysteine in
in vitro studies, animal models and studies in patients with excess
respiratory mucous
In vitro
Reduced viscosity of mucous [31-34]
Direct and immediate effect on decreasing the
viscoelastic properties of bronchial secretions [35]
Inhibited Na + absorption across human nasal epithelial
cells, which may increase mucous fluidity [36]
Reduced the deleterious effect of cigarette smoke
extract on mucociliary action [28]
Animal models
Increased mucous velocity and ciliary beat frequency [37]
Increased the volume of respiratory tract fluid and
decreased viscosity of sputum [38]
Reduced the time required to reverse smoke-induced
mucous cell hyperplasia [29]
Inhibited cigarette smoke-induced hypersecretion of
mucous in larynx and trachea [30]
Studies in patients
More effective than saline in reducing sputum viscosity
and consistency and increasing sputum volume in
patients with chronic bronchial disease [2,39]
Improved mucociliary transport in heavy smokers with
hypersecretory bronchitis and reduction in mucociliary
transport [40]
productive cough. In the short-term clinical trials, oral
NAC 200mg three times daily used alone or
concomitantly with antibiotics (amoxicillin 1.5 [42] or 2
g/day [43,44] ), decreased the consistency of sputum,
facilitated its expectoration and reduced cough and
thoracic physical symptoms. [42-44]
NAC was more effective than placebo in the largest of
the short-term trials. [42] In this trial in 215 patients with
acute bronchitis, superinfections of chronic bronchitis,
or complicated bronchitis in patients with severe
chronic respiratory insufficiency, patients received NAC
200mg three times daily for 10 days. Compared with
baseline, patients receiving NAC showed significant
improvements in all parameters (sputum expectoration,
sputum viscosity, cough and peak expiratory flow rate
[PEFR]). Moreover, NAC was significantly more
effective than placebo in decreasing sputum viscosity,
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