The Science Journal of the American Association for Respiratory Care

Symposium Papers

July 2002 / Volume 47 / Number 7 / Page 818

The Pharmacologic Approach to Airway Clearance: Mucoactive Agents

Bruce K Rubin MEngr MD FAARC

Introduction
Expectorants
Medications That Change the Biophysical Properties of Secretions
      Mucolytics
Mucokinetic Agents
Cough Clearance Promoters
Mucoregulatory Medications
Summary
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 deoxyribonucleic acid (DNA) and filamentous actin (F-actin), effete cells, bacteria, and cell debris, all contribute to mucus purulence and, when this mucus is expectorated it is called sputum. Mucoactive medications are intended to serve one of 2 purposes; either to increase the ability to expectorate sputum or to decrease mucus hypersecretion. Mucoactive medications have been classified according to their proposed mechanisms of action. Increased knowledge of the properties of mucus has given us tools to better understand the mechanisms of airway disease and mucoactive therapy. Expectorants are thought to increase the volume or hydration of airway secretions. Systemic hydration and classic expectorants have not been demonstrated to be clinically effective. Modifiers of airway water transport are being clinically investigated as expectorants. Mucolytics degrade polymers in secretions. The classic mucolytics have free thiol groups to degrade mucin. Peptide mucolytics break pathologic filaments of neutrophil-derived DNA and actin in sputum. Nondestructive mucolysis includes mucin dispersion by means of charge shielding. Mucokinetics are medications that increase mucociliary efficiency or cough efficiency. Cough flow can be increased by bronchodilators in patients with airway hyperreactivity. Abhesives such as surfactants decrease mucus attachment to the cilia and epithelium, augmenting both cough and mucociliary clearance. Mucoregulatory agents reduce the volume of airway mucus secretion and appear to be especially effective in hypersecretory states such as bronchorrhea, diffuse panbronchiolitis, and some forms of asthma. Mucoregulatory agents include anti-inflammatory agents (indomethacin, glucocorticosteroids), anticholinergic agents, and some macrolide antibiotics. Classifying mucoactive agents should help us to develop and evaluate new types of therapy and to better direct therapy toward the patients who are most likely to benefit.
Key words: mucoactive medications, expectorants, mucolytics, mucokinetics, mucoregulatory medications, macrolides, surfactants, abhesives, ion transport, cough, mucociliary clearance, cystic fibrosis, chronic bronchitis.
[Respir Care 2002;47(7):808–817]

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 deoxyribonucleic acid [DNA] and filamentous actin [F-actin], effete cells, bacteria, and cell debris) all contribute to mucus purulence, and when this mucus is expectorated it is called sputum. Mucoactive medications are intended to serve one of 2 purposes; either to increase the ability to expectorate sputum or to decrease mucus hypersecretion. Mucoactive medications have been classified according to their proposed mechanisms of action (Table 1). In this review I discuss each of these classes of medication, their proposed mechanisms of action, and their potential uses in treating chronic airways diseases associated with poor mucus clearance and mucus hypersecretion.

The entire text of this article is available in the printed version of the July 2002 RESPIRATORY CARE.

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