Cystic fibrosis mucociliary clearance

Chronic diseases include cystic fibrosis in which nasal mucus is thick and viscous as a result of abnormal chloride transport across the membrane of the epithelial cells, leading to reduced water secretion. Similarly, chronic sinusitis also reduces nasal mucociliary clearance due to an increase in the rheological properties of mucus. 

The rate of removal of mucus from the airways is determined by such factors as mucus viscosity, the amount of mucus produced, and the degree of ciliary activity. These processes may be influenced by a variety of diseases, including asthma, cystic fibrosis, and chronic bronchitis [82,83], In patients suffering from cystic fibrosis or chronic bronchitis, mucus hypersecretion is evident and mucociliary function is impaired. The failure to clear mucus from the airways leads to airway obstruction and to chronic colonization of the airways with bacterial organisms (which leads to lung infections and airway inflammation and damage). In asthmatic subjects, airway mucus is more viscous and ciliary transport mechanisms are inhibited [82,83]. In these diseases, the therapeutic objective is to improve mucus clearance from the airways. For example, aerosols of water or saline (especially hypertonic saline) promote clearance of mucus by... 

Robinson M, Bye PT. Mucociliary clearance in cystic fibrosis. Pediatr Pulmonol 2002 33(4) 293-306. 

Regnis JA, Robinson M, Bailey DL, Cook P, Hooper P, Chan HK, Gonda I, Bautovich G, Bye PT. Mucociliary clearance in patients with cystic fibrosis and in normal subjects. Am J Respir Crit Care Med 1994, 150, 66-71. 

Cystic fibrosis is a hereditary disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene that encodes a cyclic adenosine monophosphate-regulated chloride channel. Defects in chloride ion transport in the airway epithelia lead to abnormal airway secretions, impaired mucociliary clearance, chronic bacterial infection, bronchiectasis, and premature death. Delivery of the cystic fibrosis transmembrane conductance regulator cDNA by adenovirus vectors or the plasmid-liposome complex resulted in transient correction of the defects in patients with cystic fibrosis. Formulations of cationic lipid-DNA complexes for aerosol delivery are being explored to improve on the gene therapy approach. 

Bennett WD, Olivier KN, Zeman KL, et al. Effect of uridine 5 -triphosphate plus amiloride on mucociliary clearance in adult cystic fibrosis. Am J Respir Crit Care Med 1996 153 1796-1801. 

Respiratory Inhaled mannitol as a dry powder has been used to treat patients with cystic fibrosis, since it increases mucociliary clearance by rehydrating the airways. In 39 children with cystic fibrosis, aged 8-18 years, a bronchial provocation... 

Pryor JA, Webber BA, Hodson BA, et al. Evaluation of the forced expiration technique as an adjunet to postural drainage in treatment of cystic fibrosis. BMJ 1979 2(6187) 417-418. American ThOTacic Society. Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 1995 152(5 pt 2) S77-S121. Clarke SW, Pavia D. Lung mucus jnoduction and mucociliary clearance methods of assessment. Br J Clin Pharmacol 1980 9(6) 537-546. 

Cystic fibrosis and bronchopulmonary disease, resulting in compromised mucociliary clearance... 

The relationship between these defects and the clirrical marrifestations of cystic fibrosis still remains speculative. However, a reasonable hypothesis is that the ion transport defects may lead to suboptimal volttmes of airways surface liquid resulting in impaired mucociliary clearance, bacterial colonization, and... 

Particle clearance by cough supports mucociliary clearance, especially under pathophysiological conditions of diseased lungs (60), such as chronic obstructive pulmonary disease (COPD), immotile cilia syndrome (ICS), and cystic fibrosis (CF). An increased secretion in the airways seems to be necessary. During cough, mucus is propelled toward the larynx by the very fast exhalation, with linear air... 

Water can bind to mucous glycoprotein (MGP) macromolecules and influence viscosity. Viscosity can be increased by dehydration of the mucus, as can adhesion of mucus-epithelium. In purulent sputum, the correlation between viscosity and dry weight of solids is poor and may explain why mucous glycoprotein content is a poor index of viscoelasticity in chronic bronchitis, bronchiectasis, and cystic fibrosis. Mucus s viscoelasticity increases with acidic pH (3), causing reduced mucociliary clearance. Its viscoelasticity is also dependent on the content of low molecular weight electrolytes. These properties reflect the polyelectrolyte nature of mucins (4-6). 

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