Mucociliary Function

Foster, W. Michael

doi:10.1016/b978-0-12-404577-4.00029-1

Cited by 3 publications

(1 citation statement)

References 159 publications

(176 reference statements)

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“…The mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7 (7q31.2) results in defective chloride transport across the apical surface of the epithelial ( 20–22 ). Impaired ion transport, imbalanced water flow in the CF airway surface liquid volume, and airway dehydration prevent adequate cough clearance via the mucociliary escalator ( 23 ). There are also higher concentrations of mucins in the lungs of those with CF and elevated osmotic pressure of the mucus layers, which subsequently triggers thick, dense mucus production and drives muco-inflammatory airway obstruction ( 24–27 ).…”

Section: Cystic Fibrosismentioning

confidence: 99%

Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

2023

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For those born with cystic fibrosis (CF), hyper-concentrated mucus with a dysfunctional structure significantly impacts CF airways, providing a perfect environment for bacterial colonization and subsequent chronic infection. Early treatment with antibiotics limits the prevalence of bacterial pathogens but permanently alters the CF airway microenvironment, resulting in antibiotic resistance and other long-term consequences. With little investment into new traditional antibiotics, safe and effective alternative therapeutic options are urgently needed. One gathering significant traction is bacteriophage (phage) therapy. However, little is known about which phages are effective for respiratory infections, the dynamics involved between phage(s) and the host airway, and associated by-products, including mucus. Work utilizing gut cell models suggest that phages adhere to mucus components, reducing microbial colonization and providing non-host-derived immune protection. Thus, phages retained in the CF mucus layer result from the positive selection that enables them to remain in the mucus layer. Phages bind weakly to mucus components, slowing down the diffusion motion and increasing their chance of encountering bacterial species for subsequent infection. Adherence of phage to mucus could also facilitate phage enrichment and persistence within the microenvironment, resulting in a potent phage phenotype or vice versa. However, how the CF microenvironment responds to phage and impacts phage functionality remains unknown. This review discusses CF associated lung diseases, the impact of CF mucus, and chronic bacterial infection. It then discusses the therapeutic potential of phages, their dynamic relationship with mucus and whether this may enhance or hinder airway bacterial infections in CF.

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Section: Cystic Fibrosismentioning

confidence: 99%

Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

2023

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Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments

Stucki,

Sauer,

Allen

et al. 2024

Regulatory Toxicology and Pharmacology

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Elucidating the Interaction of CF Airway Epithelial Cells and Rhinovirus: Using the Host-Pathogen Relationship to Identify Future Therapeutic Strategies

et al. 2018

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Chronic lung disease remains the primary cause of mortality in cystic fibrosis (CF). Growing evidence suggests respiratory viral infections are often more severe in CF compared to healthy peers and contributes to pulmonary exacerbations (PEx) and deterioration of lung function. Rhinovirus is the most prevalent respiratory virus detected, particularly during exacerbations in children with CF <5 years old. However, even though rhinoviral infections are likely to be one of the factors initiating the onset of CF lung disease, there is no effective targeted treatment. A better understanding of the innate immune responses by CF airway epithelial cells, the primary site of infection for viruses, is needed to identify why viral infections are more severe in CF. The aim of this review is to present the clinical impact of virus infection in both young children and adults with CF, focusing on rhinovirus infection. Previous in vitro and in vivo investigations looking at the mechanisms behind virus infection will also be summarized. The review will finish on the potential of transcriptomics to elucidate the host-pathogen responses by CF airway cells to viral infection and identify novel therapeutic targets.

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Mucociliary Function

Cited by 3 publications

References 159 publications

Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

Pulmonary bacteriophage and cystic fibrosis airway mucus: friends or foes?

Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments

Elucidating the Interaction of CF Airway Epithelial Cells and Rhinovirus: Using the Host-Pathogen Relationship to Identify Future Therapeutic Strategies

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