Salivary Cytokines and Airways Disease Severity in Patients with Cystic Fibrosis.

Alice Castaldo,Renato Liguori,Giuseppe Castaldo,Monica Gelzo,Valeria Raia,Paola Iacotucci,Vincenzo Carnovale,Marika Comegna,Roberta Cimino,Gaetano Corso

doi:10.3390/diagnostics10040222

Abstract

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-α and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-α was significantly lower in patients with NP. A decreasing trend of TNF-α in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-α levels.

Highlights

Cystic fibrosis (CF) is an autosomal recessive life-limiting disorder due to mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR)
We found a significant increase of IL-6, IL-8, and TNF-α in saliva from CF patients as compared to the controls
Our preliminary study suggests that resting saliva could represent a valid non-invasive matrix for the investigation of CF-related airway disease

Summary

Introduction

Cystic fibrosis (CF) is an autosomal recessive life-limiting disorder due to mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The mutated protein causes a variable defect in the transport of sodium and chloride through epithelial cells of the respiratory, biliary, gastrointestinal, and reproductive tracts, giving rise to secretions of thick mucus [1]. Diagnostics 2020, 10, 222 and upper airways are typically involved [2,3]. From the first months of life, infection and inflammation trigger lung disease [6]. Patients with CF may have chronic recurrent sinusitis, hypertrophy of the inferior turbinates (NTH), and nasal polyposis (NP) with nasal airway obstruction [7]. Sinonasal symptoms are frequently underestimated in CF patients due to the severity of other clinical issues [8]

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