Cystic fibrosis (CF) is a genetic disease resulting in chronic polymicrobial infections of the airways and progressive decline in lung function. To gain insight into the underlying causes of severe lung diseases, we aimed at comparing the airway microbiota detected in sputum of CF patients with stable lung function (S) versus those with a substantial decline in lung function (SD). Microbiota composition was investigated by using culture-based and culture-independent methods, and by performing multivariate and statistical analyses. Culture-based methods identified some microbial species associated with a worse lung function, i.e. Pseudomonas aeruginosa, Rothia mucilaginosa, Streptococcus pneumoniae and Candida albicans, but only the presence of S. pneumoniae and R. mucilaginosa was found to be associated with increased severe decline in forced expiratory volume in 1 second (FEV1). Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis revealed a higher bacterial diversity than that detected by culture-based methods. Molecular signatures with a statistically significant odds ratio for SD status were detected, and classified as Pseudomonas, Burkholderia and Shewanella, while for other Terminal Restriction Fragments (T-RFs) no species assignation was achieved. The analysis of T-RFLP data using ecological biodiversity indices showed reduced Evenness in SD patients compared to S ones, suggesting an impaired ecology of the bacterial community in SD patients. Statistically significant differences of the ecological biodiversity indices among the three sub-groups of FEV1 (normal/mild vs moderate vs severe) were also found, suggesting that the patients with moderate lung disease experienced changes in the airway assembly of taxa. Overall, changes in CF airway microbial community associated with a severe lung function decline were detected, allowing us to define some discriminatory species as well as some discriminatory T-RFs that represent good candidates for the development of predictive biomarkers of substantial decline in lung function.

In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease.

Glargine treatment was well accepted and tolerated. No real efficacy in improving clinical and glycometabolic conditions was demonstrated. Further studies are necessary to test glargine at higher dosage and for a longer follow-up period.

Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance.

Chronic airway infection is a hallmark feature of cystic fibrosis (CF) disease. In the present study, sputum samples from CF patients were collected and characterized by 16S rRNA gene-targeted approach, to assess how lung microbiota composition changes following a severe decline in lung function. In particular, we compared the airway microbiota of two groups of patients with CF, i.e. patients with a substantial decline in their lung function (SD) and patients with a stable lung function (S). The two groups showed a different bacterial composition, with SD patients reporting a more heterogeneous community than the S ones. Pseudomonas was the dominant genus in both S and SD patients followed by Staphylococcus and Prevotella. Other than the classical CF pathogens and the most commonly identified non-classical genera in CF, we found the presence of the unusual anaerobic genus Sneathia. Moreover, the oligotyping analysis revealed the presence of other minor genera described in CF, highlighting the polymicrobial nature of CF infection. Finally, the analysis of correlation and anti-correlation networks showed the presence of antagonism and ecological independence between members of Pseudomonas genus and the rest of CF airways microbiota, with S patients showing a more interconnected community in S patients than in SD ones. This population structure suggests a higher resilience of S microbiota with respect to SD, which in turn may hinder the potential adverse impact of aggressive pathogens (e.g. Pseudomonas). In conclusion, our findings shed a new light on CF airway microbiota ecology, improving current knowledge about its composition and polymicrobial interactions in patients with CF.

Aims: The primary aim was to determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared to controls, and secondarily to evaluate genotype-phenotype correlations among CF subjects found to have AWP. Methods: Fifty-eight patients with CF underwent a hand immersion test in tap water. Twenty-three of their CF carrier relatives and 7 subjects with a negative genetic test for CF were recruited as controls. Secondary analyses explored associations with genotype, pulmonary function, and sweat electrolyte levels in all subjects with and without AWP. Additional information about atopic diathesis, hyperhidrosis of the palms and drug intake were also collected. Results: Thirty-one of the patients with CF (53.4%) exhibited AWP, in contrast to only 2 carriers (8.7%) and none in the control group. No correlation was found between CF genotype and AWP score severity. Twenty-three (39.7%) CF patients reported a history of hyperhidrosis, and in 17 of them (74%) AWP had been provoked. No correlation with history of atopy and lung function was noted. The difference between CF patients with hyperhidrosis and those without was highly significant (p = 0.016). Salt concentrations were significantly higher in patients with AWP. Conclusions: AWP is linked to CF and its diagnosis should lead the patients to a genetic or sweat test for CF. We found a significant association with hyperhidrosis and sweat electrolytes which supports the ‘hyperconcentrated sweat' pathogenetic theory of AWP.

Nutritional failure is present in a minority of Italian patients with CF, particularly during adolescence. Different auxologic indicators should be used for identifying children at risk for or with actual malnutrition.

CF patients show a high prevalence of SIBO, related to a poorer nutritional status. Rifaximin therapy is well tolerated and the results are promising in terms of efficacy in eradicating small intestinal bacterial overgrowth in CF.