N-Acetyl Cysteine (NAC)

Cystic fibrosis (CF) is a genetic disease characterized by the buildup of thickened mucus in the lungs, pancreas, and other organs. In the lungs, this sticky mucus can block the airways, trap pathogens such as bacteria, and cause recurrent infections. Prolonged inflammation as a result of persistent infections contributes to lung injury and loss of lung function. CF patients are highly prone to sinus infections, bronchitis, and pneumonia, which can be severe and life-threatening.

Normal mucus is a complex, viscous secretion that contains proteins, lipids, ions, and water. A major component of mucous, mucins determine the thickness and elasticity of the mucus gel by creating complex polymeric networks. In CF patients, the mucus is thick and sticky because its ion and water composition is altered. The resulting thick and sticky mucus is difficult to cough out and is largely responsible for airway infections.

Mucus thinners or mucolytics are inhaled medications that help thin out the mucus in the airways so that it can be coughed out of the lungs more easily. Since the 1960s, N-acetyl cysteine (NAC) has been a commonly used mucolytic to clear the clogged airways in CF patients.

How NAC works

Aerosol administration of NAC loosens the thick and sticky mucus secretions in the airways of CF patients. It is sold as a 10 or 20 percent solution in the U.S under the brand name Mucomyst, and is generally administered by a nebulizer. The mucolytic effect of NAC is derived from its ability to break up the polymeric network between the mucin proteins, making mucus less dense and therefore easier to cough out. 

NAC in clinical trials for CF

In addition to its mucolytic properties, NAC has anti-inflammatory properties that can benefit CF patients. This is especially critical since persistent inflammation is one of the symptoms of CF.

A study, published in the Proceedings of the National Academy of Sciences, showed that oral administration of high doses of NAC (up to 1g per day) for four weeks reduced inflammation in the airways of 18 CF patients with stable disease.

A multicenter, randomized, double-blind study (NCT00809094) analyzed the long-term effects of oral NAC on lung function and inflammation in 70 CF patients who received NAC or a placebo orally three times daily for 24 weeks. The results showed stable or improved lung function in the NAC group compared with reduced lung function in the placebo group. However, inflammation in the sputum was similar for both groups. Further studies are necessary to determine the underlying mechanism and the clinical outcomes of long-term oral NAC treatment in CF patients.

The thick and sticky mucus of CF patients acts as an impermeable barrier for inhaled gene therapy of airway epithelial cells (inhaled gene therapy is the delivery of the healthy CFTR gene, which is mutated in CF, using inhaled vectors or carriers). In a mouse study, the use of NAC as a mucolytic enhanced the penetration of the CF sputum of the gene delivery vectors. Moreover, the production of the normal CFTR protein in the transformed cells was nearly 12 times greater than in the control. While this finding needs to be tested for clinical application, it highlights the possibility that NAC may enhance the effect of airway gene therapy in CF patients. 

Other information

Side effects of using NAC as an aerosol include inflammation and ulcers in the mouth, nausea, vomiting, fever, runny nose, drowsiness, clamminess, chest tightness, constriction of the airways, and, rarely, bronchospasms.

The oral administration of NAC, especially in large doses, may result in nausea, vomiting and other gastrointestinal symptoms. Though rare, rashes with or without mild fever are sometimes observed.


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