Drug Control of Mucus

Drug Control of Mucus: A Perspective

• The mucociliary escalator is the major defense system in the airways.
• Failure of the mucociliary escalator can lead to mechanical obstruction of the airway.
• Mucus properties include protection, lubrication, waterproofing, and the ability to entrap microorganisms.

Clinical Indication for Use

• Mucoactive drugs are used to reduce accumulation of airway secretions.
• Mucoactive drugs are used to improve pulmonary function and gas exchange.
• Mucoactive drugs are used to prevent repeated infection and airway damage.
• Mucoactive drugs are used to treat Cystic fibrosis (CF), chronic bronchitis, pneumonia, primary ciliary dyskinesia, asthma, and bronchiectasis.
• Mucoactive drugs should be considered only after therapy to decrease infection/inflammation and removal of irritants such as tobacco smoke.

Identification of Agents

• N-Acetylcysteine (NAC) is a type of agent.
• Dornase alfa is a type of agent.
• Aqueous aerosols are a type of agent.
• Water, saline, and hyperosmolar saline (Hypertonic Saline) are aqueous aerosols.

Physiology of the Mucociliary System

• Airway secretions come from the gel layer (0.5–20 μm), periciliary layer (sol layer) (7 µm), surface epithelial cells, and submucosal glands.
• Surface epithelial cells are pseudostratified, columnar, ciliated epithelial cells including surface goblet cells and Clara cells in the distal airway.
• Submucosal glands include serous and mucous cells.

Surface-Active Phospholipids

• A thin surfactant layer exists between the periciliary fluid and mucus gel.
• The surfactant layer prevents airway dehydration and permits mucus spreading on extrusion from glands.
• The surfactant layer allows efficient ciliary coupling with mucus, and allows ciliary release from mucus once kinetic energy is transmitted.
• Surfactant therapy is effective in treating chronic bronchitis and CF.

Terminology

• Mucoactive agents affect mucus secretion, viscosity or clearance.
• Mucokinetic agents increase cough or ciliary clearance of respiratory secretions.
• Mucoregulatory agents reduce mucus hypersecretion.
• Mucospissic agents increase the viscosity of mucus.
• Mucolytic agents are designed to break down mucus.
• Most of these medications mobilize secretions via mechanisms other than directly thinning mucus.

Physiology of the Mucociliary System

• Factors that slow the mucociliary transport rate include chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), airway drying, narcotics, and endotracheal suctioning.
• Factors affecting mucociliary transport also include airway trauma, tracheostomy, cigarette smoke, hyperoxia, and hypoxia.
• Atmospheric pollutants (SO2, NO2, ozone) may increase transport transiently at low concentration, but decrease transport rates at toxic concentrations or with prolonged exposure.
• Normal hydration is necessary to maintain normal properties of mucus.
• There is no reported association between milk/dairy product intake and congestion or nasal secretion weight.

Nature of Mucus Secretion

• Healthy individuals secrete approximately 100 mL of mucus per 24 hours.
• Healthy mucus is clear, viscoelastic, and sticky.
• Mucus consists of two major classes of mucins: secreted mucins and membrane-tethered mucins.

Epithelial Ion Transport

• Under normal conditions, healthy airway epithelia can absorb salt and water via active sodium transport.
• Normal epithelia can secrete liquid into periciliary fluid via active chloride transport and passively through aquaporins or water channels.

Mucoactive Agents

• Mucolytic agents decrease elasticity and viscosity of mucus, breaking down the gel structure.
• Therapeutic options for controlling hypersecretion include removing causative factors, optimizing tracheobronchial clearance, and using mucoactive agents when indicated.
• Mucolytics and expectorants are types of mucoactive agents.

N-Acetylcysteine (NAC)

• NAC is indicated for conditions with viscous secretions and acetaminophen overdose.
• No data shows oral or aerosolized NAC is effective for any lung disease.
• NAC disrupts the structure of the mucus polymer by substituting free thiol groups for disulfide bonds connecting mucin proteins.
• Hazards of using NAC include bronchospasm (less common with 10% solution), mechanical obstruction of the airway, and incompatibility with antibiotics in mixture.

Dornase Alfa (Pulmozyme)

• Dornase Alfa is used in CF for clearance of purulent secretions and to reduce frequency of respiratory infections requiring parenteral antibiotics.
• Dornase Alfa can improve or preserve pulmonary function in these subjects.
• When given by aerosol, it reduces viscosity and adhesivity by breaking down DNA.
• Dornase Alfa is available as a single-use ampule containing 2.5 mg of drug in 2.5 mL of clear, colorless solution and should be refrigerated, protected from light.

Mucoactive Agents

• Hyperosmolar saline (7%) (HTS: Hypertonic Saline) may increase FEV₁ in patients.
• An alternate effect of hyperosmolar saline is an acute decrease in FEV₁.
• Its unpleasant taste and the coughing it induces may render it unsuitable for long-term use.

Mucokinetic Agents

• Mucokinetic agents increase cough clearance by increasing expiratory airflow or by reducing sputum adhesivity and tenacity.
• Bronchodilators increase ciliary beat, but this has little effect, and may increase mucus production.

Mucoregulatory Medications

• Mucoregulatory medications decrease mucus hypersecretion.
• Steroids, anticholinergics (atropine, ipratropium bromide, tiotropium), and macrolide antibiotics can be utilized.

Mucoactive Therapy

• Gravity is not a primary mechanism for normal mucociliary transport.
• Postural drainage may benefit when incorporated into conventional chest physiotherapy (CPT).
• Insufflation-Exsufflation inflates lungs with positive pressure followed by negative pressure to simulate cough.
• The I-E cycle begins with inspiratory pressure of 25–35 cm H2O for 1-2 seconds, followed by expiratory pressure of -30–-40 cm H2O for 1-2 seconds.
• I-E therapy's primary application is in patients with neurological muscular weakness.
• Autogenic drainage aims to "optimize” airflow in various generations of bronchi to move secretions.
• Active cycle of breathing (ACB) and forced expiratory technique (FET) utilizes breathing control (relaxed diaphragmatic breathing), thoracic expansion control (deep breaths), and progressive volume forced expiration.
• The Active cycle of breathing (ACB) and forced expiratory technique (FET) has no documented studies showing benefit.

Mucoactive Therapy (Cont.)

• Chest wall compression using devices such as The Vest® are reported to be effective for secretion clearance in patients with CF.
• The Vest® may have a role in lung expansion for patients other than those with cystic fibrosis in acute care settings.
• Positive airway pressure techniques are effective alternatives to chest physical therapy in expanding lungs and mobilizing secretions, including cough, FET, and pursed-lipped breathing.
• Oscillation of airway can be utilized via the FLUTTER® or the Percussionator®.
• Exercise causes increased sputum production with rest and appears to augment bronchial hygiene.

This lesson discusses drug control of mucus, focusing on the mucociliary escalator and its importance in airway defense. It covers clinical indications for mucoactive drugs, including conditions like cystic fibrosis and chronic bronchitis. The lesson also identifies specific agents used in mucus control, such as N-Acetylcysteine and Dornase alfa.