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Effective Mucus Clearance Is Essential for Respiratory Health
Open accessAbstract
Studies of the pathogenesis of cystic fibrosis (CF) and primary ciliary dyskinesia (PCD), as well as novel genetic mouse models, vividly illustrate that effective "mucus clearance" is a critical innate airway defense mechanism.Modern physics, physical chemistry, biochemistry, and cell and systems biology are revealing the structure of the mucus clearance apparatus and elucidating key parameters underlying its efficient function.New paradigms are evolving to describe the interaction of the near-cell surface environment with overlying mucus, the dominant role of adequate hydration for effective mucus clearance, the role of nucleotide and nucleoside signaling to regulate airway surface hydration, the physiochemical basis of mucus adhesion, and the pathophysiologic consequences of impaired mucus clearance.The recent success of hypertonic saline to restore surface hydration and improve mucus clearance in CF suggests that novel therapeutic strategies will be similarly efficacious in other airway diseases, including chronic obstructive pulmonary disease (COPD).
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“Low humidity in the respiratory tract leads to impaired mucociliary function and increases the risk of both upper and lower respiratory tract infections [6].”
From Investigating the case of human nose shape and climate adaptation (2017) · cites this paper as [6]
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Even-Tzur, N., Kloog, Y., Wolf, M., & Elad, D. (2008) · Biophysical Journal · doi:10.1529/biophysj.107.127142 · Cited by 62
“These results are in good accordance with the outcomes of a study in which the airway surface liquid of normal human airway epithelial cells was doubled in cultures subjected to rotational WSS that characterize tidal breathing (18,23).”
ResultAlterations in Mucus Barrier Function and Matrix Structure Induced by Guluronate Oligomers
Nordgård, C. T., Nonstad, U., Olderøy, M. Ø., Espevik, T., & Draget, K. I. (2014) · Biomacromolecules · doi:10.1021/bm500464b · Cited by 61
Structure and function relationships of mucociliary clearance in human and rat airways
Roth, D., Sahin, A. T., Ling, F., Tepho, N., Senger, C. N., Quiroz, E. J., Calvert, B. A., van der Does, A. M., Güney, T. G., Glasl, S., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57667-z · Cited by 68
Nanomedicine strategies to target coronavirus
Heinrich, M. A., Martina, B. E. E., & Prakash, J. (2020) · Nano Today · doi:10.1016/j.nantod.2020.100961 · Cited by 60
The Effect of CFTR Modulators on Airway Infection in Cystic Fibrosis
Harvey, C., Weldon, S., Elborn, J. S., Downey, D. G., & Taggart, C. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073513 · Cited by 61
“The gene codes for the cystic fibrosis transmembrane regulator protein (CFTR) [4,5], a 1480 amino acid cyclic-AMP (c-AMP) activated transmembrane protein that controls the secretion of chloride (Cl−) and bicarbonate (HCO3) ions across epithelial barriers, thereby regulating the composition of mucosal fluids [6,7].”
BackgroundFunctionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion
Chen, E. Y. T., Wang, Y.-C., Chen, C., & Chin, W. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015434 · Cited by 57
“As a result, the poorly hydrated, highly viscous and less transportable mucus appears to accumulate within airway passages [24,29].”
Londino, J. D., Lazrak, A., Collawn, J. F., Bebok, Z. M., Harrod, K. S., & Matalon, S. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00244.2017 · Cited by 57
Nebulised delivery of RNA formulations to the lungs: From aerosol to cytosol
Neary, M. T., Mulder, L. M., Kowalski, P. S., MacLoughlin, R. J., Crean, A. M., & Ryan, K. B. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.12.012 · Cited by 63
Laube, B., Afshar-Mohajer, N., Koehler, K., Chen, G., Lazarus, P., Collaco, J., & McGrath-Morrow, S. (2017) · Inhalation Toxicology · doi:10.1080/08958378.2017.1336585 · Cited by 53
Aspiration syndromes and associated lung injury: incidence, pathophysiology and management
Kosutova, P., & Mikolka, P. (2021) · Physiological Research · doi:10.33549//physiolres.934767 · Cited by 52
“…in asthma, COPD, sleep apnea of the obstructive type, atypical lung infections and cystic fibrosis (CF) where along with an acid reflux the coordination of breathing and swallowing (Miller et al. 2005) and clearance of microorganisms from the lower airways (Randell and Boucher 2006) are reduced.”
An inhaled bioadhesive hydrogel to shield non-human primates from SARS-CoV-2 infection
Mei, X., Li, J., Wang, Z., Zhu, D., Huang, K., Hu, S., Popowski, K. D., & Cheng, K. (2023) · Nature Materials · doi:10.1038/s41563-023-01475-7 · Cited by 53
“14 and 15).”
BackgroundMultifaceted activity ofN-acetyl- l -cysteine in chronic obstructive pulmonary disease
Calzetta, L., Matera, M. G., Rogliani, P., & Cazzola, M. (2018) · Expert Review of Respiratory Medicine · doi:10.1080/17476348.2018.1495562 · Cited by 51
“This condition, together with the inability of soluble antimicrobial factors and neutrophils to penetrate thick mucus to kill bacteria, makes viscous mucus an environment that likely enhances biofilm growth [13,19].”
BackgroundInhaled protein/peptide-based therapies for respiratory disease
Fellner, R. C., Terryah, S. T., & Tarran, R. (2016) · Molecular and Cellular Pediatrics · doi:10.1186/s40348-016-0044-8 · Cited by 48
“Both CF and COPD airways exhibit increased neutrophil elastase (NE) activity, which has the potential to damage the lung and also to cleave and activate ENaC, exacerbating mucus dehydration and further reducing mucociliary clearance [24, 40, 45, 50].”
BackgroundUPPER AIRWAY MUCUS DEPOSITION IN LUNG TISSUE OF BURN TRAUMA VICTIMS
Cox, R. A., Mlcak, R. P., Chinkes, D. L., Jacob, S., Enkhbaatar, P., Jaso, J. M., Parish, L. P., Traber, D. L., Jeschke, M. G., Herndon, D. N., et al. (2008) · Shock · doi:10.1097/shk.0b013e31814541dd · Cited by 48
“and smoke inhalation injury but also of patients with asthma, COPD, and cystic fibrosis (15, 16).”
BackgroundGoto, D. M., Lança, M., Obuti, C. A., Barbosa, C. M. G., Saldiva, P. H. N., Zanetta, D. M. T., Lorenzi‐Filho, G., Santos, U. D. P., & Nakagawa, N. K. (2011) · Environmental Research · doi:10.1016/j.envres.2011.03.006 · Cited by 47
“Mucociliary clearance occurs from the nose to the lower airways and is a critical innate respiratory defense mechanism that removes particles and microorganisms from the respiratory system (Lioté et al., 1989; Nakagawa et al., 2000; Randell and Boucher, 2006).”
BackgroundGeiser, M., Stoeger, T., Casaulta, M., Chen, S., Semmler‐Behnke, M., Bolle, I., Takenaka, S., Kreyling, W. G., & Schulz, H. (2014) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-11-19 · Cited by 47
“Potential mechanisms discussed are changes in the breathing pattern, which result in increased particle deposition in CF patients [13], or alterations of mucociliary and/or macrophage-mediated particle clearance [14,15].”
BackgroundOhar, J. A., Donohue, J. F., & Spangenthal, S. (2019) · Chronic Obstructive Pulmonary Diseases Journal of the COPD Foundation · doi:10.15326/jcopdf.6.4.2019.0139 · Cited by 46
Muco-ciliary clearance: A review of modelling techniques
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“One paradigm is that defects in mucus clearance produce static mucus that provide a nidus for microbial colonization and resultant inflammatory responses [5].”
BackgroundProbing mucin interaction behavior of magnetic nanoparticles
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Regulation of Neuregulin 1β1–Induced MUC5AC and MUC5B Expression in Human Airway Epithelium
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17β-Estradiol Inhibits Phosphorylation of Stromal Interaction Molecule 1 (STIM1) Protein
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“Characteristics of COPD include abnormal ion transport, goblet cell hyperplasia, and mucus dehydration (45).”
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“The lower layer, known as the periciliary liquid layer (PCL), is a polyanionic low friction gel layer (41) thought to promote efficient ciliary beating.”
BackgroundAspiration syndromes and associated lung injury: incidence, pathophysiology and management
Košútová, P., & Mikolka, P. (2021) · Physiological Research · doi:10.33549/physiolres.934767 · Cited by 42
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Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction
Livraghi-Butrico, A., Grubb, B. R., Kelly, E. J., Wilkinson, K. J., Yang, H., Geiser, M., Randell, S. H., Boucher, R. C., & O’Neal, W. K. (2012) · Physiological Genomics · doi:10.1152/physiolgenomics.00185.2011 · Cited by 38
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Cigarette whole smoke solutions disturb mucin homeostasis in a human in vitro airway tissue model
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Mucus hypersecretion in COPD: should we only rely on symptoms?
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Metadata
- Authors
- Randell, S. H., & Boucher, R. C.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- American Journal of Respiratory Cell and Molecular Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07-01
- Volume
- 35
- Issue
- 1
- Pages
- 20-28
- ISSN
- 1044-1549 (ISSN-L)
- 1535-4989
- PMC
- PMC2658694
- OpenAlex
- W2104048715
- Cited by
- 335
- References
- 67
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 17 · 2023: 25 · 2022: 11 · 2021: 21 · 2020: 13 · 2019: 23 · 2018: 16 · 2017: 14 · 2016: 17 · 2015: 11 · 2014: 30 · 2013: 24 · 2012: 24
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Respiratory Cell and Molecular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory and Cough-Related Research
- Keywords
- mucus clearance, cystic fibrosis, primary ciliary dyskinesia, mucus adhesion, nucleotide signaling, hypertonic saline, airway defense, chronic obstructive pulmonary disease
- MeSH terms
- Animals, Body Water, Humans, Inflammation, Mucociliary Clearance, Respiratory System, Immunity, Mucosal
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