Muco-obstructive lung disease

Refers to a spectrum of lung diseases affecting the airways and include: COPD, cystic fibrosis, primary ciliary dyskinesia, and non-cystic fibrosis bronchiectasis.

Clinically these diseases are associated with cough, sputum production, episodic exacerbations.

The diffuse mucus obstruction is associated with airway ectasia, chronic inflammation, and bacterial infection.

Normally a normal hydrated mucus layer is transported rapidly at approximately 50 µm per second from the distal airways toward the trachea.

Muco-obstructive disease is associated with epithelial defects in ion-fluid transport, mucin secretions, or a combination of these processes that lead to dehydrated mucus, failed mucus transport, and mucus adhesion to airway services.

As a result of the above mucus accumulates in the trachea and is expectorated by cough as phlegm.

Mucus in the small airways cannot be cleared by cough as sputum and that causes airflow obstruction, infection and inflammation.

Mucus in the respiratory airway is composed of approximately 98% water, 0.9% salt, 0.8% globular proteins, and 0.3% high molecular weight mucin polymers.

In healthy individuals, airway epithelium can secrete or absorb ions and water, and probably do so simultaneously.

There are two major synthesized and secreted respiratory mucins: MUC5B and MUC5AC.

These mucins are physically large, spanning 0.2-10 µm in length for single polymers.

In the well hydrated normal state the mucus layer acts as a fluid buffer to ensure efficient mucus transport.

Secreted mucin polymers interweave to form mesh-like gels with sizes that are concentration dependent.

In muco-obstructive lung disease, abnormal epithelial fluid absorption depletes the airway surface of fluid, increases mucus concentrations, and raises osmotic pressures in the mucus layer to levels exceeding those in the pericilliary layer.

Hyperconcentrated mucus is associated with compressing cilia slows mucus transport, whereas severe hyperconcentration flattens cilia produces mucus adhesion.

This explains why small changes in hydration status can produce significant pulmonary disease.

MUC5B and MUC5AC I have high carbohydrate content.

MUC5B levels are elevated and is the dominant mucin by concentration in these diseases.

The elastic and osmotic properties of mucus manifest profound effects in bio physical and transport properties with changes in concentration, with higher concentrations dramatically decreasing transportability.

Mucus gels are modified by conditions that create inter-mucin polymer interactions producing sticky polymer gels with viscous properties that can scale to the eighth power of concentration.

Mucin concentrations are increased in the four mucoobstructive disease: COPD, cystic fibrosis, primary ciliary dyskinesia, and non-cystic fibrosis bronchiectasis.

Mucus lines all lung airway surfaces as it moves towards the throat via ciliary activity.

The superficial epithelial line large bronchial and small bronchiolar airways are believed to secrete MUC5AB.

Cough is a back up clearance mechanism when cilia depended mucus clearance fails.

The combination of the failure of cilia-dependent and cough-dependent clearance produces muo-obstructive disease.

Mucus concentration is a key determinant of the properties of mucus associated with cough dependent transport and includes friction, viscosity, cohesion, and adhesion.

Airways defend against infection by the mechanical clearance of mucus and by antimicrobial proteins and peptides secreted into the mucus by airway epithelial cells.

Antimicrobial molecules and antibodies that suppress bacterial infection replication is a short lived process in the order of hours.

The rate of acquisition of bacterial resistance to endogenous antimicrobial suppression versus the rate of mechanical bacterial clearance.

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