Recommendations for Guidelines on Clinical Trials of Mucoactive Drugs in Chronic Bronchitis and Chronic Obstructive Pulmonary Disease: Definition of Mucoactive Drugs

Recommendations for Guidelines on Clinical Trials of Mucoactive Drugs in Chronic Bronchitis and Chronic Obstructive Pulmonary Disease: General Principles Background InformationA mucoactive drug is an agent that possesses, as its primary action, the capability of modifying mucus production, secretion, its nature and composition, and/or interactions with the mucociliary epithelium.

Animal models are useful tools for pharmacodynamic investigations and assist the design of clinical studies. They should be chosen on consideration of the comparative anatomy of the respiratory tract, and the similarity in morphologic, biochemical, and physiologic determinants of the human and animal disease under investigation.
Nevertheless, even if the physiologic end points may be similar, animals cannot provide the ideal model of human CB with and without obstruction and COPD, but each model presents its own advantages and disadvantages review.

The morphologic and physiologic changes of human COPD can be reproduced in animals by intratracheal administration of elastase, neutrophil extracts, or by recruitment of neutrophils in bronchial airways. In fact, a large number of neutrophils and high concentrations of active proteases are known to exist in the sputum of patients with COPD. By varying the doses of instilled elastase, experimental models of COPD with or without emphysematous changes can be produced.

In animals, secretory cell metaplasia, a large number of atypical cilia, and impaired mucociliary clearance are usually observed in bronchial epithelium. Models based on the stimulation of hypersecretion based on demonstrated cause-effect relationship are the most appropriate ones. Mucus present in normal airways is composed of 95% water, 2% glycoproteins (mucins), 1% ions, 1% lipids, and 1% other proteins and proteoglycans. In conditions characterized by mucus hypersecretion, the relative proportion and the amount of mucus constituents are altered; the nature of the glycoproteins is altered and the protein content increased in noninfected mucoid sputum. In purulent sputum, DNA is present; a greater increase in proteins and lipids is also observed.

This entry was posted in Pulmonary Function and tagged airway obstruction, bronchitis, mucoactive drugs, pulmonary function.