Physiology and pathophysiology of mucus and mucolytic use in critically ill patients

Airway mucus is a highly specialised secretory fluid which functions as a physical and immunological barrier to pathogens whilst lubricating the airways and humifying atmospheric air. Dysfunction is common during critical illness and is characterised by changes in production rate, chemical composition, physical properties, and inflammatory phenotype. Mucociliary clearance, which is determined in part by mucus characteristics and in part by ciliary function, is also dysfunctional in critical illness via disease related and iatrogenic mechanisms. The consequences of mucus dysfunction are potentially devastating, contributing to prolonged ventilator dependency, increased risk of secondary pneumonia, and worsened lung injury. Mucolytic therapies are designed to decrease viscosity, improve expectoration/suctioning, and thereby promote mucus removal. Mucolytics, including hypertonic saline, dornase alfa/rhDNase, nebulised heparin, carbocisteine/N-Acetyl cysteine, are commonly used in critically ill patients. This review summarises the physiology and pathophysiology of mucus and the existing evidence for the use of mucolytics in critically ill patients and speculates on journey to individualised mucolytic therapy.

Key Points

1. Mucus Composition and Function: Airway mucus consists of water, proteins, lipids, carbohydrates, and electrolytes, providing protection against infections while maintaining airway hydration. Mucin glycoproteins (MUC5AC and MUC5B) form the mucus gel layer, crucial for mucociliary clearance.
2. Mucus Dysfunction in Critical Illness: Factors such as infection, dehydration, mechanical ventilation, and inflammatory cell accumulation alter mucus composition, leading to impaired clearance, airway obstruction, and secondary infections.
3. Mechanical Ventilation and Mucus Abnormalities: Ventilation induces mucus hypersecretion and alters mucociliary transport, increasing MUC5AC production and reducing mucus clearance, leading to airway plugging and prolonged ventilator dependency.
4. Impact of Hyperoxia and Inflammation on Mucus Clearance: High oxygen exposure in ICU settings reduces cilia length, impairs ciliary function, and increases mucus viscosity, further worsening secretion clearance.
5. Mucolytic Therapies in the ICU: Hypertonic saline, dornase alfa, nebulized heparin, and carbocisteine are commonly used to reduce mucus viscosity and facilitate clearance, but strong evidence for their efficacy in mechanically ventilated patients is lacking.
6. Challenges in Mucolytic Therapy Selection: ICU mucolytic use is often driven by clinical experience rather than evidence-based guidelines, with only 4% of ICUs following standardized prescribing protocols.
7. Individualized Approaches to Mucolytic Therapy: Future strategies should incorporate mucus phenotyping and personalized therapy based on rheological assessments, patient-specific factors, and real-time mucus composition analysis.
8. Hypertonic Saline in Critical Care: HTS enhances mucus hydration and reduces viscosity but has mixed clinical efficacy. Studies show its effectiveness in cystic fibrosis, but its role in ICU patients remains uncertain.
9. Dornase Alfa for Airway Clearance: Dornase alfa breaks down DNA-rich mucus in conditions such as cystic fibrosis and ARDS, with emerging interest in its use in COVID-19-related lung injury. However, its high cost and limited ICU data restrict widespread adoption.
10. Future Directions in Mucolytic Therapy: Advances in AI-driven diagnostics and real-time mucus analysis could help refine mucolytic selection, improving patient outcomes through targeted interventions.

ACCESS FULL ARTICLE HERE

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.