Advances in Mucomodulator Therapy for Treatment of Excess Airway Mucus in Patients with Asthma, Chronic Obstructive Pulmonary Disease and Cystic Fibrosis
Author(s):
Anpalaki J. Ragavan
Pages 222-240 (19)
Abstract:
Excessive mucus and subsequent airway plugging lead to airway mucus hyper-secretion, airway obstruction,
airflow limitation, ventilation-perfusion mismatch and impairment of gas exchange. Additionally, excess mucus prevents
proper deposition of inhaled medications on the airway epithelium thereby reducing the response of airway epithelial cells
to medication, and impairment of mucociliary function, encouraging bacterial colonization leading to repeated chest infections
and exacerbations. Several pharmacological agents currently in use for airway diseases have unfortunate side effects
and suboptimal pharmacokinetic properties with a narrow margin of safety. Airway inflammation and subsequent accumulation
of inflammatory products in expectorated secretions including polymeric DNA, actin, bacteria and bacterial
breakdown products mainly make the sputum purulent during airway diseases. The recent inventions to control inflammation
and accumulation of inflammatory products in airways of patients suffering from mucus hyper-secretion do not take
into consideration that defense and clearance of airways of patients with airway diseases are to a large extent dependent
on cough due to the damage to the ciliary mechanism and thickened mucus. Treatment of patents for excess mucus during
airway diseases should target first cough clearance leading progressively to mucociliary clearance. There is also evidence
from recent inventions that prevention or treatment of inflammation related disorders such as atopic allergy, asthma and
chronic obstructive pulmonary diseases can aggravate conditions related to cystic fibrosis through the down regulation of
calcium induced chloride channels. Treatment of airway mucus hyper-secretion and retention by simultaneously controlling
more than one mechanism involved may be a more effective therapeutic strategy.
Keywords:
Asthma, CF, COPD, cough clearance, mucociliary clearance, mucus hypersecretion, pulmonary inflammation, viscoelasticity of mucus, airway mucus hyper-secretion, airway plugging
Affiliation:
Department of Electrical and Biomedical Engineering, MS 400, University of Nevada, Reno, NV 89557, USA.