Background: Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is an innate defence protein that acts as an anti-microbial agent and regulates airway surface liquid volume through inhibition of the epithelial sodium channel (ENaC). SPLUNC1 levels were found to be reduced in airway secretions of adults with cystic fibrosis (CF). The potential of SPLUNC1 as a biomarker in children with CF is unknown.
Methods: We quantified SPLUNC1, interleukin-8 (IL-8) and neutrophil elastase (NE) in sputum of CF children treated with either intravenous antibiotics or oral antibiotics for a pulmonary exacerbation (PEx)s, and in participants of a prospective cohort of CF children with preserved lung function on spirometry, followed over a period of two years.
Results: Sputum SPLUNC1 levels were significantly lower before compared to after intravenous and oral antibiotic therapy for PEx. In the longitudinal cohort, SPLUNC1 levels were found to be decreased at PEx visits compared to both previous and subsequent stable visits. Higher SPLUNC1 levels at stable visits were associated with longer PEx-free time (hazard ratio 0.85, p = 0.04). SPLUNC1 at PEx visits did not correlate with IL-8 or NE levels in sputum or forced expiratory volume in one second (FEV) but did correlate with the lung clearance index (LCI) (r=-0.53, p < 0.001).
Conclusion: SPLUNC1 demonstrates promising clinometric properties as a biomarker of PEx in children with CF.
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Article Synopsis
- Orai1 is a calcium channel that plays a key role in regulating inflammation and store-operated calcium entry (SOCE), whereas SPLUNC1 is a gene modifier related to asthma that inhibits Orai1's function.
- In asthma models, researchers found that inhaling α6 peptidomimetics, derived from SPLUNC1, could lower Orai1 levels and reduce immune cell responses linked to inflammation.
- The study revealed that α6 effectively decreased eosinophil and neutrophil counts in mice exposed to allergens, suggesting it could be a promising new treatment for asthma.
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