Investigation of cystic fibrosis airway microbiome in patients showing a severe decline in lung function and not respondin to conventional antimicrobial therapy

Objectives: The objectives of the present project are to assess the composition of airways microbiota in CF patients with a severe decline in lung function and not responding to antimicrobial therapy, and to discover new opportunistic (nonculturable) pathogens involved in pulmonary disease. Targeted antibiotic therapy against other members of the polymicrobial community can contribute to resolve pulmonary disease in CF patients. Methods: Three groups of CF patients were investigated: 1. normal lung function/mild decline (FEV1, >70% of predicted), 2. moderate lung dysfunction (FEV1, 40 to 69% of predicted) and 3. severe lung dysfunction (FEV1 <40% predicted). Within each group, “non-responder” CF patients who have showed a severe decline in lung function (FEV1 5% in the last year) and did not respond to antimicrobial therapy, and “stable CF patients” (having had no change in pulmonary function or a rate decline in FEV1 equal to average value in the last year) has been enrolled. Composition of CF microbiota was investigated by using advanced culture-base methods and the molecular profiling method of Terminal Restriction Fragment Length Polymorphism (T-RFLP). Conclusion: Our preliminary findings suggest that combining culture-dependent and culture-independent approaches provides a more comprehensive perspective of CF microbiology than either approach alone. The results obtained will set the basis to identify new targets for treatment and management of bacterial infections in CF patients. This work was supported by the Italian Cystic Fibrosis Foundation (grant FFC#8/2012).