Cystic Fibrosis and Fertility

In the last 20 years, the prognosis of cystic fibrosis (CF) has slightly increased and nowadays more than 50% of CF patients are adults. An obvious consequence of this deep change is the increasing question about fertility in both males and females

Efficacy of advanced hybrid closed loop systems in cystic fibrosis related diabetes: a pilot study

Background and aimsCystic fibrosis related diabetes (CFRD) is correlated with worsening of nutritional status and greater deterioration of lung function. The role of new technologies for the treatment of CFRD is little explored. The aim of the study was to evaluate the efficacy of Advanced Hybrid Closed Loop (AHCL) systems on glycemic control in CF patients.MethodsA single-center retrospective study on CFRD patients using AHCL systems was performed. Glycated hemoglobin (HbA1c) values and Continuous Glucose Monitoring (CGM) metrics were collected at T0 (AHCL placement), T1 (1-month), T2 (6-months) and T3 (1-year) to evaluate glycemic control.Results10 patients were included in the study. Data showed a reduction of HbA1c value (7.31 ± 0.34 to 6.35 ± 1.00; p=0.03), glycemic variability (p=0.05) and insulin requirement (p=0.03). The study population reached American Diabetes Association (ADA) recommended glycemic targets at 1-year. An increase in the Time in Range (TIR) and a reduction in time in hyperglycemia were also observed, although not statistically significant.ConclusionsIn patients with CFRD, the use of AHCL leads to an improvement in glycemic control in terms of HbA1c and glycemic variability. The increase in TIR and the reduction of time in hyperglycemia, although not statistically significant, are extremely encouraging from a clinical point of view. Further studies with a larger population and a longer follow-up are needed. The results of this study demonstrate the importance of proposing the use of AHCL even in CF patients, who could benefit from glycemic improvement also in terms of nutritional status and respiratory function

Evaluation of specific immune response in early P. aeruginosa infection in cystic fibrosis patients

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Pharmacokinetics of high-dose extended-infusion meropenem during pulmonary exacerbation in adult cystic fibrosis patients: a case series

This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography. Six adult CF patients with a median age of 47 years were included in the study. MEM showed a high Vd (mean 45.98 L, standard deviation [SD] \ub134.45). A minimal PK/PD target of 40% T > minimum inhibitory concentration (MIC) with respect to the MEM MIC of P. aeruginosa strains isolated from sputum during exacerbation was achieved in 5/6 patients (83%). MEM failed to achieve this target only in one patient, whose strain showed the highest MEM MIC in our cohort (8 mg/L). In all patients, MEM was well tolerated, and no adverse events were reported. In conclusion, high-dose, extended-infusion MEM during pulmonary exacerbation showed a high Vd in six adult CF patients with high median age, and was well tolerated

The role of small intestinal bacterial overgrowth in cystic fibrosis: a randomized case-controlled clinical trial with rifaximin

Background: Scientific literature shows a high prevalence of Small Intestinal Bacterial Overgrowth (SIBO) in patients with Cystic Fibrosis (CF). The role of SIBO in nutritional status and gastrointestinal symptoms in CF is not known. Our aim was to study epidemiology and clinical impact of SIBO while assessing the efficacy of rifaximin in eradicating SIBO in CF patients. Methods: Symptoms questionnaire and Glucose Breath Test (GBT) were given to 79 CF patients (median age 19.6 years; 9.2\u201336.9). Subjects with a positive GBT were enrolled in a randomized controlled trial and received rifaximin 1200 mg for 14 days or no treatment. Questionnaire and GBT were repeated 1 month after the end of treatment or 45 days after the first negative GBT. Results: Out of 79 patients, 25 were affected by SIBO (31.6%) with a significant correlation with lower BMI, SDS-BMI (p < 0.05) and serum albumin levels (p < 0.05), independently from pancreas insufficiency. Twenty-three patients took part in the randomized trial, 13 patients (56.5%) in rifaximin group and 10 patients (43.5%) in control group. Eradication rate of SIBO was 9/10 (90%) in rifaximin group and 2/6 (33.3%) in control group (p < 0.05). In the rifaximin group, gastrointestinal symptom improvement was observed in 4/5 patients aged 64 14 years and in 0/5 patients aged > 14 years (p < 0.05); in 2/6 patients in the control group. Conclusions: 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 C

Rheological Properties of Cystic Fibrosis Bronchial Secretion and in Vitro Drug Permeation Study: The Effect of Sodium Bicarbonate

Background: Cystic fibrosis (CF) is characterized by a thick, sticky mucus responsible for both airway obstruction and resistance to drug diffusion, reducing the effectiveness of drug delivery to the lung. Studies of drug-mucus interaction may be a crucial step in therapeutic management of CF. In the present research, the effect of a saline solution of sodium bicarbonate (100 mM) on sputum viscosity and the permeation properties of ketoprofen lysinate (Klys) from a previously developed dry powder inhaler were evaluated. Methods: Rheological measurements were performed using an ARES rotational rheometer (Rheometrics, Inc.) with a parallel plate geometry. The gel fraction, separated from the liquid phase of various sputum samples from CF patients was loaded onto the plate. The elastic (G') and the viscous (G") moduli, tan δ (ratio of G" to G') and η∗ (complex viscosity) were evaluated as frequency-dependent parameters. Drug permeation across CF sputum from dry powders was studied by means of Franz-type vertical diffusion cells. The experiments were conducted on untreated sputum and on sputum treated with bicarbonate. Results: Rheological studies showed that the elastic modulus (G') was always greater than the viscous modulus (G") and the viscosity decreased with increasing frequency, as for pseudo-plastic fluids. Bicarbonate caused a downward shift of both the elastic and viscous moduli, with a reduction in complex viscosity. As to drug permeation, the untreated sputum slowed down drug dissolution and permeation compared to buffer permeability (control). Permeation studies across CF sputum treated with bicarbonate showed higher Klys dissolution/permeation than untreated sputum. Conclusions: The interesting results confirm the previously reported bicarbonate. effectiveness in CF; this weak base seems to act by decreasing high viscosity of the CF bronchial secretion and, potentially, resulting in better mucus clearance and in fighting pulmonary infections