Retention of airway secretions in patients on invasive mechanical ventilation constitutes a common problem associated with several complications. Therefore, secretion management represents a great challenge for respiratory therapists, nurses, and physicians, particularly in the patient with underlying airways disorders. This chapter discusses management of airway secretions in mechanically ventilated patients, focusing on physiology of mucus production, clearance, and the most common treatments, both pharmacologic and nonpharmacologic, to enhance removal of retained secretions. Although adequate humidification of the inspired gas plays a primary role on mucus clearance, the reader is referred to Chapter 51 for a comprehensive discussion of this topic.
The lungs are exposed daily to 10,000 to 12,000 L of inhaled air, which potentially carries pathogens and noxious particles. Nevertheless, airways are efficiently protected by the airway lining fluid, which constitutes a physical barrier and a medium with antimicrobial and immunomodulatory properties. The airway lining fluid is a biphasic layer formed by a gel-phase (mucus), mainly consisting of water (97%), with proteins, lipids, electrolytes, and cellular debris making up the remaining 3% of its weight. By contrast, the inner layer is a low-viscosity sol-phase that mainly provides lubrication for continuous ciliary beating.
The main components of mucus are mucins. These are large (up to 3 × 106 Daltons per monomer) heavily glycosylated proteins that provide a tangled network necessary to entrap any particles inhaled during ventilation. Two different types of mucins have been identified: (a) cell-tethered and (b) secreted mucins. Cell-tethered mucins present several functions in cellular adhesion, pathogen binding, and cellular transduction. We focus on secreted mucins, because detailed description of membrane-bound mucins goes beyond the scope of this chapter.
Four genes coding for airway-secreted mucins have been identified and map to chromosome 11p15.51 and 12q12.2 As depicted in Table 52-1, the genes can be found in different organs; MUC5AC and MUC5B are the ones most commonly expressed in human airways.3,4 Mucin genes comprise a single large central domain (approximately 10 kb) that encodes for serine-rich, threonine-rich, and proline-rich regions, which are the sites of O-linked glycosylation of mucins. Importantly, linked glycans present an extraordinary diversity5 among species and even within species; this feature provides the highly efficient binding capability between mucus and almost any particle and/or pathogen deposited on the airways. The 5′ and 3′ genomic regions encode for the von Willebrand factor-like proteic regions, rich in cysteine,6 which allow the disulfide bonds between mucin monomers to form the ultimate polymeric structure.
Table 52-1: Genes Coding for Secreted Mucins in the Airways ||Download (.pdf)
Table 52-1: Genes Coding for Secreted Mucins in the Airways
|Gene||Chromosomal Locus||Tissue Distribution||Airways Predominant Distribution|
|MUC2||11p15||Lung, conjunctiva, middle ear, stomach, small intestine, colon, nasopharynx, prostate|
- Surface goblet cell
- Duct of submucosal glands
|MUC5AC||11p15||Lung, conjunctiva, middle ear, stomach, gallbladder, nasopharynx||Surface goblet cell...|