Cystic Fibrosis (CF) lung disease is characterized by high levels of cytokines and chemokines in the airways, producing chronic inflammation. Non-invasive biomarkers, which are also specific for the inflammatory and immune responses, are urgently needed to identify exacerbations and evaluate therapeutic efficacy. The aim of this study is to evaluate the association of sputum and exhaled breath condensate (EBC) biomarker changes with clinical exacerbation and response to therapy. We studied the simultaneous presence and concentration of twelve cytokines and growth factors (EGF, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, MCP-1, TNF-α and VEGF) by a multi-parametric biochip array in sputum and EBC of 24 CF patients before, after 6 and 15 days of therapy, and 15 days after the end of treatment for an acute exacerbation. Correlations with functional respiratory tests (FEV₁, FVC) and the systemic marker C-reactive protein (CRP) were looked for. In sputum, before therapy, VEGF and IL-1β levels positively correlated with the respiratory function and CRP. Sputum IL-1α, IL-1β IL-4, IL-10, TNF-α, and VEGF significantly decreased, while EGF increased, during therapy. IL-8 and IL-4 levels negatively correlated with the respiratory function at 15 and 30 days from the start of therapy, respectively. IL-4, IL-6, IL-10 and TNF-α positively correlated with CRP during therapy. Although some EBC biomarkers correlated with respiratory function and CRP, no significant associations with these clinical parameters were found. Sputum IL-1β and VEGF might be considered biomarkers of an acute exacerbation in CF patients. A panel of sputum cytokines and growth factors may better describe the response to intravenous antibiotic treatment of CF than one single systemic marker.

Aspergillus fumigatus is frequently recovered from respiratory secretions of cystic fibrosis (CF) patients. Azole resistance has been increasingly reported. To assess the prevalence of azole resistance in A. fumigatus isolates from patients followed by two CF centers of northern Italy. 423 isolates (220 patients) were screened for azole resistance. Resistance was confirmed with the EUCAST method and cyp51A gene sequencing. Microsatellite genotyping was performed and results were compared with those of environmental resistant isolates. No resistance was detected in one center, while 8.2% of the patients of the other center harbored resistant isolates. The TR₃₄/L98H alteration in the cyp51A gene, present in seven cases, resulted associated with poor in-vitro activity of all tested azoles. The environmental origin of the resistance seems to be probable since azole resistance was found also in naïve patients and an identical microsatellite genotype in clinical and environmental isolates was observed.

Vitamin A is a fundamental micronutrient that regulates various cellular patterns. Vitamin A deficiency (VAT) is a worldwide problem and the primary cause of nocturnal blindness especially in low income countries. Cystic fibrosis (CF) is a known risk factor of VAD because of liposoluble vitamin malabsorption due to pancreatic insufficiency. We describe a case of a 9-year-old girl who experienced recurrent episodes of nocturnal blindness due to profound VAD. This little girl is paradigmatic for the explanation of the key role of the gut–liver axis in vitamin A metabolism. She presents with meconium ileus at birth, requiring intestinal resection that led to a transient intestinal failure with parenteral nutrition need. In addition, she suffered from cholestatic liver disease due to CF and intestinal failure-associated liver disease. The interaction of pancreatic function, intestinal absorption and liver storage is fundamental for the correct metabolism of vitamin A.