This project follows the FFC#8/2012 and FFC#10/2014 projects. Researchers will continue the analysis of the airway microbiome dynamics in cystic fibrosis (CF) patients exploring “severe decliners” (SD) and “stable” (S) patients for an additional 18 months and a total of a two-year period. The aim is to identify bacterial taxa and microbial gene functions related to severe decline in lung function and to individuate new potential biomarkers (in terms of both opportunistic non-culturable pathogens and novel genes potentially involved in pulmonary disease) for the early detection of lung function decline. Real-Time PCR protocols will be developed for the direct translation of the biomarkers to the clinical practice. The ability to analyze the entire microbiome and to identify biomarkers can provide a set of tools for future approaches to personalized medicine in CF.