What is the use of N-acetylcysteine (NAC) oral inhalation as a mucolytic agent?

From the Guidelines

N-acetylcysteine (NAC) oral inhalation is not the preferred route of administration for mucolytic therapy, as the evidence supports oral administration for reducing exacerbations in COPD patients. The typical dosage for oral NAC is 600 mg twice daily, as seen in the study by Zheng et al 1. This study demonstrated a reduction in the rate of exacerbations in COPD patients, with a relative risk of 0.78 for the NAC group compared to the placebo group.

Key Points

• Oral NAC has been shown to reduce the viscosity of respiratory secretions by breaking disulfide bonds in mucus proteins, making secretions easier to clear 1.
• The evidence from the study by Zheng et al 1 suggests that oral NAC is effective in reducing the rate of exacerbations in COPD patients, particularly those with moderate to severe disease.
• NAC is well tolerated, with no significant difference in adverse events between the NAC and placebo groups 1.
• The European Respiratory Society/American Thoracic Society guideline also supports the use of mucolytic therapy, including NAC, for reducing the likelihood of hospitalization and COPD exacerbations 1.

Administration and Side Effects

When administering oral NAC, it's essential to note that gastrointestinal side effects can occur, although they are rare 1. The solution may have an unpleasant sulfur odor, which patients should be warned about. For optimal effectiveness, proper administration technique should be used, and the treatment should be followed by chest physiotherapy or postural drainage when possible to enhance mucus clearance.

Quality of Life and Mortality

The evidence suggests that mucolytic therapy, including NAC, does not have a significant effect on mortality, although the number of deaths in the trials was low 1. Additionally, there is no evidence that mucolytic therapy alters quality of life or increases adverse effects 1. Therefore, oral NAC can be recommended as a mucolytic treatment for patients with COPD, particularly those with moderate to severe disease, to reduce the rate of exacerbations and improve quality of life.

From the FDA Drug Label

Acetylcysteine is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as: Acetylcysteine Solution, USP is oxygen sensitive. Acetylcysteine As A Mucolytic Agent

NAC oral inhalation for mucolytic is indicated for patients with abnormal, viscid, or inspissated mucous secretions in various conditions, including chronic and acute bronchopulmonary diseases, pulmonary complications of cystic fibrosis, and others 2 2.

• Key uses include:
  • Chronic bronchopulmonary disease
  • Acute bronchopulmonary disease
  • Pulmonary complications of cystic fibrosis
  • Tracheostomy care
  • Pulmonary complications associated with surgery
  • Use during anesthesia
  • Post-traumatic chest conditions
  • Atelectasis due to mucous obstruction
  • Diagnostic bronchial studies Mucolytic agent is used for inhalation or oral administration.

From the Research

NAC Oral Inhalation for Mucolytic

• NAC oral inhalation has been studied as a mucolytic agent in various respiratory conditions, including chronic bronchitis and COPD 3, 4, 5.
• A case report published in 2020 found that nebulised N-acetylcysteine was effective in treating a patient with critical airway obstruction secondary to a solid tracheal mucus plug 3.
• A meta-analysis published in 2015 found that NAC treatment was effective in preventing exacerbations of chronic bronchitis or COPD, with a significant reduction in relative risk 4.
• However, a study published in 1995 found that intravenous administration of NAC had no clinically relevant effect on glutathione levels, lipid peroxidation products, tracheobronchial mucus, and clinical condition in ventilated patients 6.
• Another study published in 2012 reviewed the use of NAC as a mucolytic agent in the management of COPD, highlighting its potential to influence mucin expression by acting on oxidative stress and inflammation 5.
• A study published in 1985 found that oral N-acetylcysteine had no significant effect on lung function, mucociliary clearance, or sputum viscosity in patients with chronic bronchitis 7.

Mechanism of Action

• NAC is thought to act as a mucolytic agent by breaking down mucus and making it easier to clear from the airways 3, 5.
• It is also believed to have antioxidant properties, which can help reduce oxidative stress and inflammation in the airways 4, 5.

Dosage and Administration

• The optimal dosage and administration of NAC for mucolytic use is not well established, with varying doses and routes of administration used in different studies 3, 4, 6, 5, 7.
• Further research is needed to determine the most effective dosage and administration regimen for NAC as a mucolytic agent.