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Objective We evaluated the prevalence, Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene profile, clinical data, management and outcome for infants with a CFTR-related metabolic syndrome/CF Screen Positive, Inconclusive Diagnosis (CRMS/CFSPID) designation from six Italian centres. Methods All newborn bloodspot screening (NBS) positive infants born from January 2011 to August 2018 with a CF diagnosis or a CRMS/CFSPID designation were enrolled. Data on sweat testing, genetics, clinical course and management were collected. Results We enrolled 257 CF patientsand 336 infants with a CRMS/CFSPID designation (CF: CRMS/CFSPID ratio of 1:1.30).Blood immuno-reactive trypsinogen (IRT) was significantly lower in CRMS/CFSPID infants and the F508del variant accounted for only 20% of alleles. Children with CRMS/CFSPID showed a milder clinical course, pancreatic sufficiency compared to CF infants. Varied practice across centres was identified regarding sweat testing, chest radiograph (8-100%) and salt supplementation (11-90%). Eighteen (5.3%) CRMS/CFSPID infants converted or were reclassified to diagnosis of CF. Four infants (1.3%) developed a clinical feature consistent with a CFTR-related disorder (1.2%). Twenty-seven were re-classified as healthy carriers (8.0%) and 16 as healthy infants (4.8%). Conclusions We have identified considerable variability in the evaluation and management of infants with an inconclusive diagnosis following NBS across six Italian centres. CRMS/CFSPID is more regularly seen in this population compared to countries with higher prevalence of F508del.Conversion to a CF diagnosis was recorded in 18 (5.3%) of CRMS/CFSPID infants and in 16 was as a result of increasing sweat chloride concentration.

(1) Background: Diagnostic testing for cystic fibrosis (CF) is based on a sweat chloride test (SCT) considering the appropriate signs and symptoms of the disease and results of a gene mutation analysis. In 2014, the Istituto Superiore di Sanit&agrave, (ISS) established a pilot Italian external quality assessment program for CF SCT (Italian EQA-SCT), which is now a third party service carried out by the ISS. (2) Methods: The ongoing scheme is prospective, enrollment is voluntary, and the payment of a fee is required. Results are shared through a dedicated web-facility. Assessment covers the analysis, interpretation, and reporting of results. (3) Results: Thirteen, fifteen, sixteen, and fifteen different laboratories, respectively, participated from 2015 to 2016 and from 2018 to 2019 in the Italian EQA-SCT scheme. Eleven different laboratories participated each year in all four rounds of the Italian EQA-SCT. (4) Conclusions: The overall results obtained from the laboratories participating constantly clearly show that their qualitative and quantitative performance improved significantly. This is due to the opportunity&mdash, after receiving the EQA results&mdash, to constantly review their performance and address any inconsistencies. We firmly believe that participation in the EQA program will improve the quality of participating laboratories and that EQA participation should become mandatory as a fundamental requirement for laboratory accreditation.

Background Recurrent (RP) and chronic pancreatitis (CP) may complicate Cystic Fibrosis (CF). It is still unknown if mutations in genes involved in the intrapancreatic activation of trypsin (IPAT) or in the pancreatic secretion pathway (PSP) may enhance the risk for RP/CP in patients with CF. Methods We enrolled: 48 patients affected by CF complicated by RP/CP and, as controls 35 patients with CF without pancreatitis and 80 unrelated healthy subjects. We tested a panel of 8 genes involved in the IPAT, i.e. PRSS1, PRSS2, SPINK1, CTRC, CASR, CFTR, CTSB and KRT8 and 23 additional genes implicated in the PSP. Results We found 14/48 patients (29.2%) with mutations in genes involved in IPAT in the group of CF patients with RP/CP, while mutations in such genes were found in 2/35 (5.7%) patients with CF without pancreatitis and in 3/80 (3.8%) healthy subjects (p

Background: In 2001 Liou published a 5-year survival model using CFF Registry data. Aims: To evaluate its validity in predicting survival in Italian CF patients. Methods: In a retrospective study on 945 patients, the 9 variables selected by Liou were analyzed, vital status on December 2008 recorded and observed and expected deaths compared. To develop a new model, patients were randomly divided into a derivation (n = 475) and a validation sample (n = 470). Results: A significant difference was found between observed and expected deaths based on Liou's model (62 vs 94), with a 34% reduction in mortality (p < 0.05). A new model (based on FEV1, Staphylococcus aureus and Burkholderia cepacia complex infection, number of pulmonary exacerbations/year) was generated, that correctly predicted survival in the validation sample (31 observed vs 29 expected deaths, p = 0.660). Conclusions: The Liou model did not adequately predict 5-year survival in our CF population that, compared to the one in which it was originally tested, could benefit from 10. years of improvement in treatments and practice patterns. A new generated model, based on only four variables, was more accurate in predicting 5-year survival in Italian CF patients

Background Cystic Fibrosis diagnosis is confirmed using sweat test. The aim of our study was to evaluate current techniques and methodologies in use at Italian CF Care Centres. Methods A series of questions related to the performance of the sweat test was collected by all CF Care Centres in Italy. Answers were compared with UK and NCCLS guidelines. Results 39/41 Centres replied to the questionnaire. A good adherence to guidelines was registered for storing samples before analysis in 90.9%, while performing CF diagnosis by at least two sweat tests, and chloride analysis were reported respectively in 100% and 75.7% of Centres. Some inconsistencies were registered for minimum acceptable sweat quantity and time to collect sweat inadequate in respectively 42.5% and 24.2% of Centres, while performing quality control procedures and referring to an external quality assessment scheme were found inadequate in respectively 54.6% and 100%. 57.6% didn't provide any appropriate analytical ranges and only 15.1% of Centres offered proper information to patients/parents. A report form, including sweat quantity, reference ranges and interpretation, was adequate only for 9.4 up to 41.4% of CF Centres. Conclusions Our study showed areas of inconsistencies in sweat testing current practices in Italy and highlights the need for evidence based national guidelines to improve practice and management strategies.