• Ciliary function and the integrity of the mucus layer are the two most important determinants of mucociliary clearance (MC).
  • Toxins, dust, microorganisms, and other debris entrapped in the mucus are removed from the respiratory system by the cephalad stroke of cilia.
  • In addition to binding various substances and hindering their way further down into the respiratory tract, tracheobronchial mucus also has directly antibacterial as well as immunological functions.
• for clinical purposes, ciliary function and mucus integrity need to be treated as one unit that determines MC.

• Cilia
  • Cilia in the respiratory tract "sweep" mucus cephalad until it can be expectorated.
  • On the microscopic level, ATPase activity, resulting in adenosine triphosphate (ATP) hydrolysis, provokes conformational changes in the interconnecting dynein arms of ciliary microtubules. ATPase functions as a motor that results in sliding between adjacent microtubules A and B (see Anatomy).
  • The bending or "stroke" of the cilium is explained by the initial activation of dynein in only half the microtubules, with the activation of the other half accounting for the backwards movement of the cilium (1). This is referred to as the effective stroke or principal bend and the recovery stroke or reverse bend, respectively.
  • Ciliary beat frequency is 11–15 Hz.
• Mucus
  • Liquid secretion from submucosal glands is largely under neuronal control, where vagal stimulation causes an increase in glandular secretion (via local ACH release).
  • Substance P and vasoactive intestinal peptide (VIP) are second-line regulatory mechanisms that provoke the upregulation of mucus secretion.
  • On the cellular level, liquid secretion is largely driven by active Cl^- and HCO₃^- secretion, creating a lumen-negative potential difference to pull cations through paracellular tight junctions. This results in an osmotic gradient that drives water movement across the epithelial barrier (2).
  • Mucus contains ~95% water.
  • Tracheal mucus clearance is remarkably rapid with a speed of 4–20 mm per minute. Velocities in the peripheral airways are lower.

Pediatric Considerations

• Cilia
  • Cilia are found in the upper (nasal cavities, sinuses, Eustachian tubes, middle ear) and lower (trachea to terminal bronchioles) airway, decreasing in height from 5 to 7 µm (trachea) to 2 to 3 µm (bronchioles).
  • There are ~100–200 cilia on each ciliated cell, with ~3×10¹² cilia in total.
  • Underneath the outer cell membrane of each cilium, the ciliary axoneme is composed of over 250 proteins forming a "9 + 2" pattern with 9 peripheral microtubular pairs (A and B) surrounding a central pair (1).
  • The peripheral A microtubules have an attached inner and outer dynein arm; all pairs are connected via nexin links.
  • Central and peripheral microtubules are connected via radial spokes to finally form the complex microtubular unit that equals 1 cilium.
• Mucus
  • All ciliated respiratory epithelia are covered by a blanket of viscoelastic mucus that is divided into 2 layers:
    • A deeper, more liquid sol-layer that allows unhindered movement of cilia.
    • A superficial mucous layer to entrap substances.
  • Submucosal glands consist of
    • Secretory tubules that contain serous and mucous cells. Serous cells have apical vesicles containing lysozyme, lactoferrin, IgA, peroxidases, and albumin (2). Mucous cells produce gel-forming mucins or polysaccharides.
    • A collecting duct
    • A ciliated duct that passes through the smooth muscle and lamina propria of the mucosa and finally opens to the airway surface.

• Reduced MC can result from certain conditions or diseases, artificial or mechanical ventilation, and drugs.
  • Conditions and diseases
    • Immotile cilia (Kartagener’s) syndrome; the absence of dynein arms or radial spokes can result in impairment, or complete loss, of ciliary function.
    • Asthma results in inflammation and hypersecretion.
    • COPD and bronchiectasis can result in epithelial damage.
    • Cystic fibrosis; dehydrated and thick mucus is produced as a result of abnormalities in Cl^- ion transport.
    • Wegener's granulomatosis
    • Acute respiratory tract infection as a result of cytotoxins
    • Acute illness such as in intensive care unit (ICU) patients.
    • Extremes of temperature
    • Sleep
    • Immobility
  • Artificial or mechanical ventilation related
    • High fresh gas flow can dry mucus.
    • High airway pressure reduces ciliary beat frequency (3) [C].
    • Lack of airway humidification can dry mucus.
    • Bronchial suctioning can result in epithelial damage.
    • Tracheal intubation (decreased MC when compared with laryngeal mask airway) (4) [B]
  • Drugs
    • Volatile anesthetic agents (halothane, isoflurane, sevoflurane, desflurane) (5) [B] can potentially inhibit Cl^- channels. The MC inhibitory effects of volatile agents last for ~60–90 minutes after cessation of their administration.
    • Morphine; evidence is conflicting.
    • Remifentanil, when compared to morphine, may lower MC.
    • Pentobarbital has an inhibitory ciliary effect.
    • Temazepam, diazepam
    • Ketamine at clinical doses
    • Atropine; Evidence is conflicting.
    • Furosemide
    • Tobacco
    • Alcohol
• Increased MC can also result from certain conditions, ventilatory maneuvers, or drugs.
  • Conditions
    • Exercise
    • Change of posture can have a mucus draining effect
  • Ventilation related
    • Positive end-expiratory airway pressure; studies and evidence are mainly from cystic fibrosis patients.
    • Nasal continuous positive airway pressure; likely has only a short-term effect.
    • Air humidification (e.g., by means of HME devices)
  • Drugs
    • Ketamine at supraclinical doses has been seen during in vitro experiments.
    • Anticholinergic drugs; Evidence is conflicting
    • 2-adrenergic agents; evidence is conflicting. Studies have shown that they may stimulate ciliary beat frequency, but also mucus production. The effect on MC especially in diseased lungs is unclear.
    • Methylxanthines
• Drugs with likely no significant effect on MC
  • Propofol
  • Midazolam
  • Dexmedetomidine
  • Thiopental
  • Fentanyl

• MC is of utmost importance for unhindered gas exchange as a result of the
  • Maintenance of normal pulmonary physiology
  • Prevention of infection
  • Prevention of airway obstruction and atelectasis
  • Preservation of surfactant function
• The rate of perioperative pulmonary complications can be reduced with simple perioperative measures such as airway humidification or the avoidance of potentially detrimental ventilation patterns (see above).
• Laryngeal mask airways may result in reduced MC impairment compared to tracheal intubation (4) [B].
• Smoking has a negative impact on MC and on pulmonary complications in ICU patients.
• Smoking cessation does not appear to have immediate effects on MC function. In fact, compared to nonsmokers, mucus production is ~50% greater in patients who ceased smoking <8 weeks prior to surgery, 25% higher in those who quit >8 weeks prior to surgery and not significantly different to nonsmokers when stopped smoking >6 months prior to surgery.

See link under "additional reading."

• Smoking

Thomas Ledowski , MD, PD, DEAA, FANZCA