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Effects of Different Nasal Saline Irrigation Solutions on the Innate Nasal Proteome in Patients with Chronic Rhinosinusitis with Nasal Polyps

Guy Botera, Medical Student, Flinders University, Darwin, Australia
Authors List
Botera, G., Abdul Baseer, S., Pietris, N., Henshaw, P., Chegeni, N., Chataway, T., Carney, A. S., Flinders University, Adelaide, Australia
 
Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) impairs quality of life and is therapeutically challenging. Nasal saline irrigation (NSI) with topical steroid is a low-cost, evidence-based intervention. Our pilot in healthy volunteers used both isotonic (IsoNa) and low-sodium (LowNa) NSI. It suggested short-term use following prolonged priming upregulates innate immune proteins, potentially enhancing mucosal health. However, the effects of IsoNa versus LowNa NSI on innate protein expression in CRSwNP are unclear, which this study explores. We hypothesised that low-sodium NSI would improve innate immune protein expression, particularly lysozyme. 

​Aims: To investigate the effects of IsoNa versus LowNa NSI on innate immune protein expression in CRSwNP. 

Methods: In a randomized controlled trial, 21 CRSwNP patients were assigned to receive once-daily NSI for 14 days using either IsoNa or LowNa with topical mometasone. Nasal secretions were collected pre and post-treatment, and protein content analyzed via liquid chromatography-tandem mass spectrometry with data-independent acquisition. Differential expression of innate immune proteins was assessed using Spectronaut. 

Results: In 18 analyzable patient samples, 3850 unique proteins were identified, representing, to our knowledge, the most extensive protein profile in nasal mucus. Of these, 54 are key to the nasal mucosa's innate immune system. IsoNa led to broader but mainly down-regulatory changes (83% decreased), despite affecting more proteins overall. Conversely, LowNa resulted in a predominantly upregulatory effect on innate immune proteins (82% increased), with 2 proteins increasing by over 500% and 5 by over 100%, including a 113% increase in lysozyme.
 

Conclusion: Regular NSI use significantly alters the innate immune proteome in CRSwNP. Building on our pilot in healthy volunteers, LowNa NSI demonstrates evidence of improving innate immune secretions in CRSwNP. These findings highlight the potential for tailored NSI formulations to modulate the sinonasal immune environment and guide future therapeutic strategies in Type-2 CRS.

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