Abstract
MicroRNAs are small non-coding RNAs that regulate immune response and inflammation. We assumed that miRNAs may be involved in the immune response during cystic fibrosis pulmonary exacerbations (CFPE) and that altered expression profile in the airways and blood may underlie clinical outcomes in CF pediatric patients. Methods: We included 30 pediatric patients diagnosed with cystic fibrosis. The biologic material (blood, sputum, exhaled breath condensate) was collected during pulmonary exacerbation and in stable condition. The miRNA expression profile from blood and sputum (n = 6) was done using the next-generation sequencing. For validation, selected four miRNAs were analyzed by qPCR in exosomes from sputum supernatant and exhaled breath condensate (n = 24). NGS analysis was done in Base Space, correlations of gene expression with clinical data were done in Statistica. Results: The miRNA profiling showed that four miRNAs (miR-223, miR-451a, miR-27b-3p, miR-486-5p) were significantly altered during pulmonary exacerbation in CF patients in sputum but did not differ significantly in blood. MiRNA differently expressed in exhaled breath condensate (EBC) and sputum showed correlation with clinical parameters in CFPE. Conclusion: MiRNA expression profile changes in the airways during pulmonary exacerbation in CF pediatric patients. We suggest that miRNA alterations during CFPE are restricted to the airways and strongly correlate with clinical outcome.
Highlights
Cystic fibrosis (CF) is a common autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Taking into account that miRNAs are regulators of immune inflammatory responses and that enhanced chronic inflammation plays a significant role in pulmonary exacerbations in cystic fibrosis, we aimed to investigate if miRNA expression differs between exacerbation and stable period of disease and if altered expression profile in the airways may underlie clinical outcome in CF pediatric patients
Clinical characteristics of the patients based on biologic material are given in Tables 1 and 2
Summary
Cystic fibrosis (CF) is a common autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Common pulmonary symptoms include deposition of thick mucus that leads to severe airflow obstruction, chronic inflammation and chronic airway infection [2]. Lung disease is characterized by intermittent episodes of acute worsening of respiratory symptoms, pulmonary exacerbations (CFPE) [3] that cause lung function decline and contribute to disease progression, poor quality of life and shortened life expectancy in CF patients. Pulmonary exacerbations do not usually result from increased bacterial density within the airways [5,6], and more severe symptoms are caused by chronic enhanced airway inflammation that may even precede infection. Chronic inflammation in the airways leads to airway epithelium damage and activates repair processes contributing to remodeling and subepithelial fibrosis that further impair lung function. Current CFPEs are the leading cause of morbidity and mortality [7,8], indicating the need for biomarker discovery
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