Mucolytic treatment of chronic rhinosinusitis in a murine model of primary ciliary dyskinesia

Frontiers in Molecular Biosciences

Molecular Biosciences

Julia S. Kimbell¹  Amy J. Ferguson²  Barbara R. Grubb²  Troy D. Rogers²  Weining Yin²  Hannah L. Golliher²  Alessandra Livraghi-Butrico²  Adam J. Kimple³  Lawrence E. Ostrowski⁴ 

[1]Department of Otolaryngology—Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

[2]Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

[3]Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

[4]Department of Otolaryngology—Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

[5]Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

[6]Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States

关键词: chronic rhinosinusitis;    mucus;    primary ciliary dyskinesia;    nasal;    computed tomography;    sinus;    CT;    PCD;   

DOI  :  10.3389/fmolb.2023.1221796

 received in 2023-05-12, accepted in 2023-07-03,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Genetic defects in motile cilia cause primary ciliary dyskinesia (PCD), a rare disease with no specific therapeutics. Individuals with PCD often have impaired fertility and laterality defects and universally suffer from upper and lower airway diseases. Chronic rhinosinusitis is a universal feature of PCD, and mucus accumulation and subsequent infections of the sinonasal cavity cause significant morbidity in individuals with PCD. Despite this, there are no approved treatments that specifically target mucus.Objective: The goals of this study were to determine whether computed tomography (CT) imaging could be used to quantify mucus accumulation and whether the use of a mucolytic agent to reduce disulfide cross-links present in mucins would improve the effectiveness of nasal lavage at removing mucus in a murine model of PCD.Methods: Adult mice with a deletion of the axonemal dynein Dnaic1 were imaged using CT scanning to characterize mucus accumulation. The animals were then treated by nasal lavage with saline, with/without the disulfide-reducing agent tris(2-carboxyethyl)phosphine. Post-treatment CT scans were used to quantify improvement in the sinonasal cavity.Results: Mucus accumulation in the nasal cavity was readily quantified by CT. Compared to sham-treated control animals, nasal lavage with/without a mucolytic agent resulted in a significant reduction of accumulated mucus (p < 0.01). Treatment with the mucolytic agent showed a greater reduction of accumulated mucus than treatment with saline alone.Conclusion: The results suggest that inclusion of a mucolytic agent may increase the effectiveness of nasal lavage at reducing mucus burden in PCD.

【 授权许可】

Unknown   
Copyright © 2023 Yin, Golliher, Ferguson, Kimbell, Livraghi-Butrico, Rogers, Grubb, Kimple and Ostrowski.