CF is characterized by a progressive decline in lung function. Interpreting the significance of changes in % FEV1 over time requires a more indepth comprehension of the airway microbiome in patients with a substantialdecline in lung function, and the assessment of whether a pathogen is only a marker of the disease severity or an independent contributor to the lung function loss. In theproject FFC#8/2012, potential biomarkers related to FEV1 decline have been already identified and a large set of metagenomic data were produced.The specific aims of this project are to perform bioinformatics analysis of airway metagenomes sequenced and to identify additional biomarkers (in terms of both opportunistic non-culturable pathogens and gene functions) related to the serious decline in lung function; to set-up diagnostic tools based on the already and the newly identified biomarkers for the identification of substantial decliners in lung function.In this way we think that a more personalized antibiotic strategy could be applied to CF patients.