The pharmacologic approach to airway clearance: Mucoactive agents Bruce K. Rubin * Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1081, USA INTRODUCTION The airway mucosa responds to infection and inflammation in a variety of ways. This response often includes surface mucous (goblet) cell and submucosal gland hyperplasia and hypertrophy with mucus hypersecretion. Products of inflammation including neutrophil derived DNA and fila- mentous actin (F-actin), effete cells, bacteria, and cell debris all contribute to mucus purulence and, when this is expec- torated it is called sputum. Mucoactive medications are intended to serve one of two purposes; either to increase the ability to expectorate sputum or to decrease mucus hypersecretion. Mucoactive medications have been classi- fied according to their proposed method of action. 1 Spu- tum is expectorated mucus mixed with inflammatory cells, cellular debris, polymers of DNA and F-actin, as well as bacteria. Mucus is usually cleared by airflow and ciliary movement, and sputum is cleared by cough. 2 In this review, I will discuss each of these classes of medication, their proposed mechanism of action, and their potential use in treating patients with chronic airways diseases associated with poor mucus clearance and with mucus hypersecretion. EXPECTORANTS Expectorants are defined as medications that are taken to improve the ability to expectorate purulent secretions. This term is now taken to mean medications that increase airway water or the volume of airway secretions. The most commonly used of these are simple hydration including both bland aerosol administration and oral hydration, iodide containing compounds such as SSKI or iodinated glycerol, glyceryl guaiacolate or guaifenesin, and the more recently developed ion channel modifiers such as the P2Y2 purinergic agonists. Most of these medications or maneu- vers are ineffective at adding water to the airway and those that are effective are also mucus secretagogues increasing the volume of both mucus and water in the airways. Despite widespread use, iodinated compounds, guaifene- sin, and simple hydration are ineffective as expectorants. 3 In fact, over-hydration has been shown to decrease airway mucus clearance in some patients with chronic airway disease, particularly with acute asthma. 4 For many years, sputum induction using hyperosmolar saline inhalation has been used to obtain specimens for the diagnosis of pneumonia. As summarized in the Cochrane Database, the long term use of inhaled hyperosmolar saline improves pulmonary function in patients with cystic fibrosis PAEDIATRIC RESPIRATORY REVIEWS (2006) 7S, S215–S219 KEYWORDS mucoactive medications; mucolytics; mucokinetics; mucoregulatory; surfactant; expectorant; mucociliary clearance; cough clearance Summary The term ‘‘mucoactive agent’’ refers to any medication used to improve the clearance of airway secretions. It is not synonymous with the word ‘‘mucolytic’’ as this strictly means a drug that decreases the viscosity of secretions. In many cases, decreased viscosity will adversely affect cough transport. For this reason many of the older mucolytic agents such as acetylcysteine are not effective for the therapy of lung disease and their use is not recommended. I review here the many classes of mucoactive agents and identify a number of medications with great promise for the treatment of chronic airway disease. ß 2006 Elsevier Ltd. All rights reserved. * Tel.: +1 336 716 0257; fax: +1 336 716 9229. E-mail address: brubin@wfubmc.edu. 1526-0542/$ – see front matter ß 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.prrv.2006.04.198