Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+/- IVS8Tn:T7/9 patient with acute recurrent pancreatitis.

Background: Acute recurrent pancreatitis (ARP) is characterized by episodes of acute pancreatitis in an otherwise normal gland. When no cause of ARP is identifiable, the diagnosis of "idiopathic" ARP is given. Mutations in the cystic fibrosis transmembrane conductance regulator () gene increase the risk of ARP by 3- to 4-times compared to the general population, while cystic fibrosis (CF) patients present with a 40- to 80-times higher risk of developing pancreatitis.

Occurrence, outcomes and predictors of portal hypertension in cystic fibrosis: A longitudinal prospective birth cohort study.

Background: The reported prevalence of portal hypertension (PH) in Cystic Fibrosis is variable, incidence rates rarely provided and the utility of liver function tests (LFT's) early in life to predict PH is questionable. The aims were to (1) determine PH prevalence (P) and incidence rate (IR) and combined mortality transplant (MTX) data in PH vs non-PH patients and (2) to assess association of LFTs in early life with liver disease and PH.

Method: (1) A double centre longitudinal cohort study of 577 CF patients diagnosed by newborn screening (NBS) with annual examinations for PH up to 18.

The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE: the study protocol.

Background: A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE).

Ratiometric sweat secretion optical test in cystic fibrosis, carriers and healthy subjects.

We have simplified the published procedure (5) for measuring sweat rates in individual human sweat glands. Sweat secretion rates were obtained from sweat drops secreted on the forearm by multiple individual glands. We computed a ratio between CFTR-dependent (by intradermal microinjection of a β adrenergic cocktail) and CFTR-independent (by methacoline as cholinergic stimulus) sweat secretion rates.

Ataluren-driven restoration of Shwachman-Bodian-Diamond syndrome protein function in Shwachman-Diamond syndrome bone marrow cells.

Shwachman-Diamond syndrome (SDS) is a rare inherited recessive disease mainly caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, which encodes for the homonymous protein SBDS, whose function still remains to be fully established. SDS affects several organs causing bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, and cognitive disorders. About 15% of SDS patients develop myelodysplastic syndrome (MDS) and are at higher risk of developing acute myeloid leukemia (AML).

Chest computed tomography scores in patients with cystic fibrosis colonized with methicillin-resistant Staphylococcus aureus.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in cystic fibrosis (CF), with increasing incidence in recent years. We examined the association between bacterial colonization in the sputum (MRSA with or without pseudomonas (PA)) and computed tomography (CT) scores in CF patients.

Methods: MRSA patients were divided according to PA status based on at least three consecutive sputum cultures; controls were patients without MRSA (with or without PA), matched for gender and age at CT.

New insights into the Shwachman-Diamond Syndrome-related haematological disorder: hyper-activation of mTOR and STAT3 in leukocytes.

Shwachman-Diamond syndrome (SDS) is an inherited disease caused by mutations of a gene encoding for SBDS protein. So far little is known about SBDS exact function. SDS patients present several hematological disorders, including neutropenia and myelodysplastic syndrome (MDS), with increased risk of leukemic evolution.

Nasal potential difference outcomes support diagnostic decisions in cystic fibrosis.

Background: When cystic fibrosis (CF) is suspected Nasal Potential Difference (NPD) measurements are proposed to support controversial diagnosis: we investigated appropriate outcomes at the CF Centre of Verona.

Subjects/methods: NPD were measured in 196 subjects: 50 non-CF, 65 classical CF (the reference group) and 81 with uncertain CF (case group). Discriminating power was determined by comparison between several outcomes from the CF reference group versus non-CF: basal, amiloride, 0Cl, isoproterenol, ATP, Delta-amiloride, Delta-0Cl, Delta-isoproterenol, Delta-ATP, Delta-isoproterenol+Delta-0Cl, Wilschanski Index (WI) and Sermet score (SS).

Impact of MIF gene promoter polymorphism on F508del cystic fibrosis patients.

Macrophage migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine sustaining the acute response to gram-negative bacteria and a regulatory role for MIF in Cystic Fibrosis has been suggested by the presence of a functional, polymorphic, four-nucleotide repeat in this gene's promoter at position -794, with the 5-repeat allele displaying lower promoter activity. We aimed at assessing the association of this polymorphism with disease severity in a group of Cystic Fibrosis patients homozygous for F508del CFTR gene mutation. Genotype frequencies were determined in 189 Cystic Fibrosis and 134 control subjects; key clinical features of patients were recorded and compared among homozygous 5-allele patients and the other MIF genotypes.

Electrophysiological evaluation of cystic fibrosis conductance transmembrane regulator (CFTR) expression in human monocytes.

Background: Cystic fibrosis is caused by mutations of CFTR gene, a protein kinase A-activated anion channel, and is associated to a persistent and excessive chronic lung inflammation, suggesting functional alterations of immune cells. Leukocytes express detectable levels of CFTR but the molecule has not been fully characterized in these cells.

Methods: Freshly isolated monocytes from healthy individuals and CF patients were assessed by protein expression, single cell electrophysiological and membrane depolarization assays.

Detection of CFTR protein in human leukocytes by flow cytometry.

Leukocytes have previously been shown to express detectable levels of the protein cystic fibrosis transmembrane conductance regulator (CFTR). This study aims to evaluate the application of flow cytometric (FC) analysis to detect CFTR expression, and changes thereof, in these cells. Aliquots (200 μL) of peripheral whole blood from 12 healthy control volunteers (CTRLs), 12 carriers of a CFTR mutation (CFC), and 40 patients with cystic fibrosis (CF) carrying various combinations of CFTR mutations were incubated with specific fluorescent probes recognizing CFTR protein expressed on the plasma membrane of leukocytes.

Challenging the diagnosis of cystic fibrosis in a patient carrying the 186-8T/C allelic variant in the CF transmembrane conductance regulator gene.

Background: This report describe for the first time a clinical case with a CFTR allelic variant 186-8T/C (c.54-8 T/C) in intron 1 of CFTR and underline the importance of applying a combination of genetic and functional tests to establish or exclude a diagnosis of Cystic Fibrosis. In this case the diagnostic algorithm proposed for CF has been successfully applied at our Center and previous CF diagnosis assigned in a different Center was not confirmed.

Hyaluronic acid improves the tolerability of hypertonic saline in the chronic treatment of cystic fibrosis patients: a multicenter, randomized, controlled clinical trial.

Unlabelled: TRIAL DESIGN AND METHODS: Between December 2009 and July 2011, four cystic fibrosis (CF) centers in Italy participated in a randomized, double-blind, controlled clinical trial to test whether 7% hypertonic saline (HS) administered together with 0.1% hyaluronic acid (HA) was better tolerated by patients who previously did not tolerate HS well on its own. Participants were CF patients at least 8 years old, in clinically stable conditions, with forced expiratory volume in 1 sec (FEV1) at least 50% predicted.

Impaired CFTR function in mild cystic fibrosis associated with the S977F/T5TG12complex allele in trans with F508del mutation.

Background: The S977F mutation (c.2930C>T) in the CFTR gene (CFTR/ABCC7) is extremely rare. We describe the case of an adult patient carrying the complex allele S977F/T5TG12 in trans with the F508del mutation.

Further characterization of Shwachman-Diamond syndrome: psychological functioning and quality of life in adult and young patients.

To assess psychosocial functioning and quality of life in a representative group of adult and young patients with Shwachman-Diamond syndrome (SDS), all patients 3 years old and over included in the Italian SDS Registry were investigated using an ad-hoc questionnaire for information about demography, education, socialization, rehabilitation therapy, and standardized questionnaires [SF-36, Child Behavior Check-List (CBCL)] for quality of life and behavior. Results were compared with those of a Cystic Fibrosis (CF) patient group, matched for age and sex. Eighty-one percent of patients answered.

MudPIT analysis of released proteins in Pseudomonas aeruginosa laboratory and clinical strains in relation to pro-inflammatory effects.

Pseudomonas aeruginosa (Pa) is the most common virulent pathogen contributing to the pathogenesis of cystic fibrosis (CF). During bacterial lung colonization, the products of its metabolism are released in the extracellular space contributing to the pathogenic events associated with its presence. To gain insights on the mechanisms involved in the Pa pathogenesis we focused our attention on proteins released by Pa using a MudPIT approach combined with cell biology assays.

Aztreonam inhalation solution for suppressive treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis.

An aerosol form of aztreonam lysinate has recently been developed as a treatment for cystic fibrosis patients suffering from chronic Pseudomonas aeruginosa lung colonization. Local administration means the drug can reach mucus concentrations in the order of hundreds of times the MIC(50) of Pseudomonas associated with severe lung disease in cystic fibrosis, resulting in a significant reduction in airway bacterial density and a parallel improvement in lung function. These advantages are maintained over prolonged periods of treatments.

Defective CFTR expression and function are detectable in blood monocytes: development of a new blood test for cystic fibrosis.

Background: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes.

Absence of a gender gap in survival. An analysis of the Italian registry for cystic fibrosis in the paediatric age.

Background: The existence of gender-related differences since childhood in survival of cystic fibrosis (CF) patients has been recently challenged.

Methods: We evaluated the effect of gender on survival of 2293 CF patients born after 01/01/1988, followed up by 29 CF centres until 31/12/2004 and recorded in the Italian Registry for CF (IRCF).

Results: We observed similar annual mortality rates in females (3.

An interactive computer program can effectively educate potential users of cystic fibrosis carrier tests.

The demand for cystic fibrosis (CF) carrier testing is steadily growing, not only from individuals with raised a priori carrier risk, but also from the general population. This trend will likely exceed the availability of genetic counselors, making it impossible to provide standard face-to-face genetic counseling to all those asking for the test. In order to reduce the time needed to educate individuals on the basics of the disease, its genetic transmission, and carrier testing peculiarities, we developed an educational method based on an interactive computer program (IC).

Whole blood fatty acid analysis with micromethod in cystic fibrosis and pulmonary disease.

Objectives: To assess fatty acid (FA) profiles in whole blood of 90 cystic fibrosis patients (CF) and 30 control subjects (C) and to correlate FA changes to the severity of respiratory disease.

Methods: Whole blood FA were assessed by GC with a micromethod-based analysis.

Results: Saturated and monounsaturated FA are higher, whereas polyunsaturated FA are lower in CF versus C with reduction of total n-6 FA, 22:5n-3 and 22:6n-3 (DHA).

Association between carrier screening and incidence of cystic fibrosis.

Context: A downward trend in cystic fibrosis (CF) birth incidence has been reported in some areas.

Objective: To evaluate the association between carrier screening and CF birth incidence.

Design, Setting, And Participants: In northeastern Italy, CF birth incidence is monitored by means of a long-standing neonatal screening program.

Inconclusive cystic fibrosis neonatal screening results: long-term psychosocial effects on parents.

Aim: Cystic Fibrosis (CF) Newborn Screening occasionally identifies neonates where a CF diagnosis can neither be confirmed nor excluded. To assess how parents of these infants cope with this ambiguous situation.

Methods: Parents of 11 children with Ambiguous Diagnosis (group AD) were compared with parents of 11 children diagnosed with CF through neonatal screening [group Cystic Fibrosis Diagnosis (CFD)] and with parents of 11 Healthy Control children (group HC) matched for gender and age.

Growth and long-term lung function in cystic fibrosis: a longitudinal study of patients diagnosed by neonatal screening.

Objective: So far there is no long-term analysis relating the achievement of growth milestones (such as prepubertal and pubertal take-off and peak velocity) to the course of respiratory function from childhood to adulthood in cystic fibrosis. This study was designed to evaluate linear growth and severity of lung disease, find a correlation between growth and disease severity throughout childhood.

Patients: One hundred sixty-three patients from one center were selected according to: diagnosis by neonatal screening, complete follow-up available (four height measurements/year) until the age of 20, respiratory tests available from the age of 5-6 years until adulthood, lung transplantation, or death.

Azithromycin selectively reduces tumor necrosis factor alpha levels in cystic fibrosis airway epithelial cells.

Azithromycin (AZM) ameliorates lung function in cystic fibrosis (CF) patients. This macrolide has been suggested to have anti-inflammatory properties as well as other effects potentially relevant for therapy of CF. In this study, we utilized three CF (IB3-1, 16HBE14o- AS3, and 2CFSMEo-) and two isogenic non-CF (C38 and 16HBE14o- S1) airway epithelial cell lines to investigate whether AZM could reduce tumor necrosis factor alpha (TNF-alpha) mRNA and protein levels by real-time quantitative PCR analysis and an enzyme-linked immunosorbent assay (ELISA), respectively.