Application of N-Acetylcysteine in Pulmonary Disorders

Abstract

In clinical medicine, N-acetylcysteine (NAC), is frequently used for the treatment of acetaminophen overdose and as a renal protection medication for patients undergoing radiologic evaluation with contrast dyes, which can be nephrotoxic. For several decades now, NAC has also been routinely applied to the treatment of inflammatory pulmonary diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) to loosen thick mucus. The earliest published studies of the chemistry of NAC and its ability to reduce the viscosity of airway secretions were performed in 1963. However, only a few clinical studies have evaluated the efficacy of inhaled NAC in improving lung function over the long term, and none have determined that inhaled NAC is of obvious clinical benefit for CF patients when applied in this mode (Reas, J Pediatr 62:31, 1963; Duijvestijn and Brand, Acta Paediatr 88:38–41, 1999; Howatt and DeMuth, Univ Mich Med Cent J 32:82–85, 1966). In vitro, NAC has been demonstrated to reduce the viscosity and elasticity of mucus when directly in contact with airway secretions. This may make sputum easier to clear; however, thinner secretions could potentially be harder to expectorate due to this reduced viscosity. In addition, NAC is a very acidic compound (pH 2.2) and when inhaled results in airway irritation, induction of cough, and bronchospasm. Manufacturers therefore suggest that individuals receive pretreatment with a bronchodilator prior to inhalation. It has been suggested that induction of cough by inhaled NAC, rather than mucolysis, may explain any beneficial effect of NAC on expectoration. Thus, there is little published data to support using NAC in this mode.