[Italian Cystic Fibrosis Registry (ICFR). Report 2021-2022]. / Registro Italiano Fibrosi Cistica (RIFC). Rapporto 2021-2022.

INTRODUCTION: Italian Cystic Fibrosis Registry (ICFR) collects data of patients with cystic fibrosis (CF) through the collaboration with Italian CF referral and support Centres (Italian law 548/93). It aims at analysing medium and long-term clinical and epidemiological trends, identifying healthcare needs at regional and national levels, contributing to healthcare programmes, and resource allocation. Italian data are also compared at international level through the collaboration with the European CF Registry for sharing epidemiological data on general aspects like CF epidemiology and specific topics such as the use of CFTR modulators. OBJECTIVES: The purpose of this Report is to provide updated demographic and clinical data of the Italian FC population for the years 2021 and 2022, to contribute essential information for the implementation of projects aimed at improving the management of patients affected by this disease. DESIGN: Analyses and results presented in this Report pertain to patients currently under care at Italian National Referral and Support Centres for Cystic Fibrosis and Paediatric Hospital 'Bambino Gesù' in the 2021-2022 period. Data were submitted by clinical Centres through a dedicated web-based software and underwent dual quality control (QC) measures: automated quantitative QC within the software and secondary QC at the European level before the integration into the European Cystic Fibrosis Registry. These measures ensure data completeness, accuracy, and longitudinal consistency with European core data. SETTING AND PARTICIPANTS: A total of 27 CF Centres, including referral and support centres, as well as 'Bambino Gesù' Children's Hospital CF centre, submitted their data to ICFR for the years 2021-2022. Althourgh CF Centres in Verona and Messina do not use the ICFR software, their data are centrally collected and subsequently forwarded to the European Registry. Data from service centres in Treviso and Rovereto are transmitted via the Verona CF Centre. Data from Sardinia Centre are currently unavailable. RESULTS: The results section provides a comprehensive overview of various aspects of CF epidemiology and patient characteristics. 1.Demography: in 2021 and 2022, 5,977 and 6,077 CF patients were respectively included in the ICFR, with median ages of 23.3 and 23.7 years. The prevalence rates were 10.1 and 10.3 per 100,000 residents in Italy for the respective years, with males comprising 51.6% on average. The distribution by age showed a higher frequency among patients aged 7 to 35 years; adult patients constituted 63.5% on average in both years. 2. Diagnosis: most CF patients were diagnosed before the age of two (mean value 57.9%), with a significant percentage diagnosed in adult age (35.4% in 2021 and 25.6% in 2022). 3.New diagnoses: there were 113 new diagnoses in 2021 and 121 in 2022, with estimated incidences of 1 in 9,097 living births in 2021 and 1 in 6,232 in 2022. 4. Genetics: genetic analyses were conducted on 99.9% of patients, revealing CFTR gene mutations in over 98% of cases. The F508del mutation was the most common (44% of alleles in 2021), with 18% of patients having at least one "residual function" mutation. Gating mutations were present in 3.4% of Italian patients, while 20% had at least one-stop codon mutation. 5.Lung function: lung function, measured by percent predicted (pp)FEV1 (Forced Expiratory Volume in the first second) progressively declined before adulthood, with the majority of paediatric patients (92.8% in 2021 and 93.8% in 2022) maintaining a ppFEV1≥70%. 6.Nutrition: critical periods for nutrition were identified as the first 6 months of life and adolescence, with higher prevalence of malnourished male adolescents compared to females. Suboptimal BMI values were more common in adult females (28.7% in 2021 and 26.9% in 2022) compared to males (14.2% in 2021 and 12.6% in 2022). 7. Complications: CF-related liver disease without cirrhosis was prevalent in patients under 18 years (21.9% in 2021 and 21.2 in 2022), while CF-related diabetes was most frequent in adults (24.2%). 8.Transplantation: over the two-year period, 28 patients underwent double-lung transplantation, with median ages of 29.1 in 2021 and 35.3 in 2022, respectively. Median waiting times ranged from 9.4 to 11.6 months. 9.Microbiology: chronic Pseudomonas aeruginosa infection affected 37.2% of adult patients in 2021 and 36.0% in 2022, compared to 7.4% and 6.5% in paediatric patients. Staphylococcus aureus infection rates were 34.6% and 42.2% in 2021 among adults and 34.4% and 36.7% in 2022 among paediatric patients. 10. Mortality: a total of 34 patients died during the 2021-22 period (19 females, 15 males), with median ages at death of 43.7 years in 2021 and 46 years in 2022 (excluding transplanted patients). CONCLUSIONS: The present Report is an update of the data published in the past years and summarizes the main epidemiological and clinical data regarding Italian CF subjects in the years 2021 and 2022. The number of patients registered in 2021 was 5,977, while in 2022 was 6,077. The population coverage estimates for 2022 to be around 97%. In 2020, 60.5% of patients were older than 18 years, in 2022 adult patients account for 63.5% of the Italian CF population. Over the years, therefore, an increase in the median age of Italian CF patients has been observed, reaching 23.7 years in 2022. The absolute number of new diagnoses per year remains substantially unchanged over the years (a total of 234 in the period under review). The median age at diagnosis in 2022 was 2.5 months, 62.6% of subjects are really diagnosed within the first year of life and almost 90% of them are diagnosed through neonatal screening. In 2022, almost all patients underwent genetic analysis (99.9%). Data collected confirm the great variability among Italian CF patients. As regards respiratory function, what is reported in previous reports is here confirmed, with an ever-increasing percentage of subjects under the age of 18 having normal respiratory function, moreover, less than 1% of paediatric patients has a severe lung function (ppFEV1<40). The marked improvement in this indicator in the adult population seems to be mainly due to the introduction from 2021 in Italy of therapy with highly effective CFTR modulators. At the same time, the close positive correlation between nutritional status and respiratory function is confirmed for the adult population. As regards chronic infection by Pseudomonas aeruginosa, in 2022, a reduction in the percentage of chronic infection is observed both among adults (36% vs 38.8% in 2020) and in paediatric patients (6.5% vs 7.6% in 2020). The most frequent complication in both paediatric and adult populations is liver disease (respectively, in 24.2% and 41.3% of subjects). In the two-year period, 34 patients died; their median age at death was between 43 and 46 years (transplant patients excluded); only two patients under the age of 18 died in the period 2021 and 2022, confirming once again that mortality in paediatric age is a rare event. The data presented in this Report shows how the register can be a national and international point of reference for CF patients and the scientific community, a tool for describing the Italian CF population over the years, and a starting point for planning epidemiological studies and clinical studies.

Residual feed intake is related to metabolic and inflammatory response during the preweaning period in Italian Simmental calves.

Residual Feed Intake (RFI) is defined as the difference between measured and predicted intake. Understanding its biological regulators could benefit farm profit margins. The most-efficient animals (M-Eff) have observed intake smaller than predicted resulting in negative RFI, whereas the least-efficient (L-Eff) animals have positive RFI. Hence, this observational study aimed at retrospectively comparing the blood immunometabolic profile in calves with divergent RFI during the preweaning period. Twenty-two Italian Simmental calves were monitored from birth through 60 d of age. Calves received 3 L of colostrum from their respective dams. From 2 to 53 d of age, calves were fed a milk replacer twice daily, whereas from 54 to 60 d (i.e., weaning) calves were stepped down to only one meal in the morning. Calves had ad libitum access to concentrate and intakes were recorded daily. The measurement of BW and blood samples were performed at 0, 1, 7, 14, 21, 28, 35, 45, 54, and 60 d of age. Calves were ranked and categorized as M-Eff or L-Eff according to the median RFI value. Median RFI was -0.06 and 0.04 kg of DMI/d for M-Eff and L-Eff, respectively. No evidence for group differences was noted for colostrum and plasma IgG concentrations. Although growth rate was not different, as expected, (0.67 kg/d [95% CI = 0.57-0.76] for both L-Eff and M-Eff) throughout the entire preweaning period (0-60 d), starter intake was greater in L-Eff compared with M-Eff calves (+36%). Overall, M-Eff calves had a greater gain-to-feed ratio compared with L-Eff calves (+16%). Plasma ceruloplasmin, myeloperoxidase, and reactive oxygen metabolites concentrations were greater in L-Eff compared with M-Eff calves. Compared with L-Eff, M-Eff calves had an overall greater plasma concentration of globulin, and γ-glutamyl transferase (indicating a better colostrum uptake) and Zn at 1 d. Retinol and urea were overall greater in L-Eff. The improved efficiency in nutrient utilization observed in M-Eff was paired with a lower grade of oxidative stress and systemic inflammation. L-Eff may have had greater energy expenditure to support the activation of the immune system.

Phenotypic and Genomic Characterization of the Comune di Sicilia Goat: Towards the Conservation of an Endangered Local Breed.

The Comune di Sicilia, a local goat breed from Sicily (Italy), is currently undergoing recognition as a distinct breed. This study aims to characterize the population both phenotypically and genomically to advance its recognition process. A total of 78 subjects from two locations were enrolled, and their phenotypic data, including qualitative traits and morphometric measurements of adult animals, were recorded and statistically analyzed. The goats were genotyped using the Illumina 50 k Goat SNPchip, comparing them with 473 goats from 15 Italian breeds. Population structure, phylogenetic relationships, admixture, and genomic inbreeding were analyzed. Additionally, subjects with different morphological traits were compared using FST and runs of homozygosity, leading to the identification of potential candidate genes associated with anotia and wattle presence in goats. The Comune di Sicilia breed exhibited distinctive genomic and phenotypic features, setting it apart from other breeds in the same region. However, moderate variability, possibly influenced by selection practices, was also observed. To ensure the breed's preservation and prevent excessive inbreeding, a comprehensive approach considering both morphology and genomic background is recommended. This study contributes valuable insights into the genetic peculiarities of the Comune di Sicilia goat, supporting its recognition as a unique and valuable breed.

Effect of olive cake supplementation on faecal microbiota profile of Holstein and Modicana dairy cattle.

The present study aimed to investigate the effect of olive cake supplementation on faecal microbiota of Holstein (n = 16) and Modicana (n = 16) dairy cows. Although no difference in richness was detected, within breeds and between the two dietary treatment, the PERMANOVA analysis applied to the beta diversity allowed to discriminate samples according to breeds (p < 0.001) and treatment (p < 0.001). In Holstein cows, the olive cake supplementation led to the increase of Pseudobutyrivibrio and Christensenellaceae_R7-group genera (p < 0.05) recognized as health-promoting or associated with feed efficiency. Differently, no difference was detected between control and treated groups for Modicana suggesting a high adaptive capacity to diet changes. In addition, the higher prevalence of Firmicutes phyla in the Modicana microbiota reflected its better capacity to digest the fibrous sources. Our study supports the suitability of olive cake as a feed supplement for cows and could help validating a sustainable livestock system in the Mediterranean area, characterized by a relevant oil production and by a native breeds reared with extensive systems.

Whole cottonseed inclusion in starter feeds improves performance, inflammometabolic profile, and rumination behavior in Holstein dairy calves.

The high energy, protein, and fiber contents of whole cottonseed make it a potential candidate for the inclusion in calf starters to promote the rumen development. This study aimed at assessing whether the inclusion of whole cottonseed in the starter would affect performance, metabolic profile, and rumination time in Holstein dairy calves. From 2 to 55 d of age, 12 heifer calves were fed a constant amount of milk replacer twice daily (8 L/d), whereas from 56 to 65 d (weaning) milk replacer was gradually reduced (from 4 to 1 L/d) and fed in a single meal. Calves were blocked by birth body weight and % Brix of colostrum received and randomly assigned to 1 out of 2 dietary treatments: (1) control starter (CTR); (2) starter with 8% inclusion of whole cottonseed (WCS). Treatments were fed for ad libitum intake. From d 56, TMR and hay were offered ad libitum. At 0, 2, 7, 21, 65, and 80 d, BW was measured and blood samples were collected. Feed intake and rumination time were automatically recorded. Compared with CTR, WCS calves were heavier at weaning and after weaning, and consumed more starter from 59 to 72 d. In the immediate postweaning (from 66 to 72 d of age), rumination time increased more in WCS calves. Overall, WCS calves had greater plasma glucose, ß-carotene, and retinol concentrations, whereas ceruloplasmin and myeloperoxidase were lower. Calves in the WCS group had greater glucose concentration at 21 and 65 d and lower urea at 65 d (weaning). Plasma ß-carotene concentration was greater at 65 and 80 d in calves of the WCS group compared with CTR calves. At 80 d, WCS calves had lower plasma alkaline phosphatase and greater ß-hydroxybutyrate, paraoxonase, and tocopherol. These results suggest that inclusion of WCS in the calf starter might be beneficial for rumen development, leading to greater feed intake and BW. Moreover, WCS inclusion was associated with lower oxidative stress and inflammation, improved energy metabolism and liver functionality, and likely quicker rumen development, as might be indicated by the higher plasma ß-hydroxybutyrate and rumination time. These changes occurred mainly after weaning, when no differences in starter intake and average daily gain were detected, suggesting a better efficiency of nutrient utilization at this age.

Changes of acute-phase proteins, glucose, and lipid metabolism during pregnancy in lactating dairy cows.

The study aimed to evaluate the effects of different stages of lactation (0 to >  300 d) and pregnancy (0 to >  180 d) on serum amyloid A (SAA), C-reactive protein (CRP), glucose, total cholesterol (TCho), and triglyceride (TG) concentrations in dairy cows of different breeds. Thus, 40 healthy multiparous cows (10 Holstein, 10 Simmental, 10 Brown, and 10 Modicana) were randomly selected, and blood samples were collected once every 60 d for 1 year. Overall, SAA and CRP serum concentrations progressively increased and became more variable along the lactation, peaking at >  240-300 d, and then decreased in the last period ( >  300 d). Along pregnancy, SAA and CRP initially increased, with the highest concentrations at >  60-120 d, and then decreased until the last phase of pregnancy ( >  180 d). However, lactation and gestation phases did not significantly affect SAA and CRP when all the cows were analyzed together. A significant and positive correlation was observed between SAA and CRP both along lactation ( r = 0.89 ; p < 0.0001 ) and pregnancy ( r = 0.91 ; p < 0.0001 ). Breeds only showed differences in CRP levels along gestation ( p = 0.0102 ), due to a peak registered at 0-60 d in Holstein cows. In pregnant cows, glucose was positively correlated with SAA ( r = 0.43 ; p = 0.0017 ) and CRP ( r = 0.42 ; p = 0.0019 ). Hence, these significant and positive relationships reflect the physiological adaptations of the dairy cows along both gestational and lactational dynamics, suggesting that these proteins may also be involved in non-pathological processes. In this perspective, this study established that the obtained response markedly varies among healthy individuals along lactation and gestation and thus that the physiological range of acute-phase proteins (APPs) is wide; this makes it difficult to use these proteins as a marker of different physiological reproductive and productive periods.

[Italian Cystic Fibrosis Registry (ICFR). Report 2019-2020]. / Registro italiano Fibrosi Cistica (RIFC). Rapporto 2019-2020.

INTRODUCTION: Italian cystic fibrosis registry (ICFR) collects data from cystic fibrosis (CF) patients through the collaboration with Italian CF referral and support Centres (Italian law 548/93). ICFR contributes: • to the analysis of medium and long term clinical and epidemiological trends of the disease; • to the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources; • to the comparison of the Italian data with international ones. This latter is based on the collaboration with the European CF registry and, due the COVID-19 pandemic emergency, with important global projects. OBJECTIVES: The purpose of this Report is to update the demographic and clinical data of the Italian FC population in the years 2019 and 2020, contributing to the information necessary to implement projects to improve the management of patients affected by this disease. DESIGN: Analyses and results described in the present Report are referred to patients currently followed at the Italian National Referral and Support Centres for Cystic Fibrosis in the 2019-2020 period. Data were sent by clinical Centres through a dedicated web-based software. Data undergo a double quality control (QC): the first is automatically performed by the software (quantitative QC), the second is performed at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their longitudinal consistency with the European core data. SETTING AND PARTICIPANTS: A total of 29 CF Centres (referral and support centres and 'Bambino Gesù' Children's Hospital CF centre) sent to ICFR their data referred referred to years 2019-2020. CF Centres of Verona, Messina, and Palermo (this latter only for 2019) do not use the ICFR software; however, their data are firstly collected in a centralized manner, then sent to the European Registry. Data from support centres of Treviso and Rovereto are sent through the Verona CF Center. Finally, data from Sardinia Centre are still missing. RESULTS: The present Report has been organized into 10 sections. 1. Demography: in 2019, 5,585 CF patients were registered in the ICFR and 5,801 in 2020; median age was 21.6 years in 2019 and 22.4 years in 2020. Prevalence was 9.36/100,000 and 9.79/100,000 residents in Italy in 2019 and in 2020, respectively. Male percentage was 51.5% in 2019 and 2020 and CF distribution by age range showed higher frequency in patients aged 7 to 35 years. Adult patients (aged more than 18 years) were 59.5% on average in both years. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (median value 68.5%); a significant percentage of patients (12.9% in 2019 and 13.4% in 2020) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 136 in 2019 and 96 in 2020. Estimated incidence was 1/5.568 living births in 2019 and 1/7.369 in 2020. 4. Genetics: 99.9% of patients underwent genetic analyses and in 98.2% of these patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. The F508del mutation was the most frequent (identified in 44.7% allele; 2019 data). Furthermore, on average 17.3% of patients had at least one 'residual function' mutation. At least one gating mutation is present in 3.3% of Italian patients. Finally, 20.5% of patients had at least one stop codon mutation (class 1). 5. Lung function: percent predicted FEV1 (Forced Expiratory Volume in the first second) progressively declined before adult age, in accordance with the natural history of the disease. The majority of paediatric patients (6-17 years of age), i.e., 86.7% in 2019 and 90.5% in 2020, had percent predicted FEV1 >=70%; whereas paediatric patients with a FEV1% >=40% are less than 2% in the study period. 6. Nutrition: the two most critical periods are the first 6 months of life and adolescence. Prevalence of malnourished adolescent males (12-17 years of age) is higher than the prevalence observed in females. Increasing percentages of female patients with a suboptimal BMI value (33.5% and 31.4%, respectively, in 2019 and 2020) are observed in adult age. 7. Complications: in 2019, CF-related liver disease without cirrhosis was the main complication both in patients aged less than 18 years (20.3% on average) and in adults (37.5%). CF-related diabetes was also frequent in CF adults (23.4%). 8. Transplantation: in 2019-2020, 64 patients received a double-lung transplantation. Median and range of age were 33 years (12.29-57.46) in 2017 and 32.9 (16.5-53.6) years in 2020. Median waiting times for lung transplantation in the two-year period ranged from 6 to 8 months. 9. Microbiology: percentage of adult patients with chronic Pseudomonas aeruginosa infection was 41.6% in 2019 and 38.8% in 2020 vs 14.3% in 2019 and 7.6% in 2020 in paediatric age. Staphylococcus aureus infection is present in 31.1% and 35.9% of adult patients in 2019 and in 33.5% and 34.7% of paediatric patients in 2020. 10. Mortality: a total of 51 patients died in the 2019-2020 period (28 females and 23 males); median age at death was 35.7 years in 2019 and 39 years in 2020 (transplanted patients are not included). CONCLUSIONS: The present report shows that the Italian CF population is growing (4,159 in 2010 vs 5,801 in 2020). Median age of patients increased in the 2010-2020 period (17 years in 2010 vs 22.4 years in 2020). Prevalence of adult patients is increasing (in 2020, 60.5% of patients is more than 18 years old). About 68.5% of new patients is diagnosed within the second year of life and median age at death (transplanted patients not included) increased in 2020 up to 39 years (in 2018 this value was 35.8). Some statistical differences between 2019 and 2020 are mainly due to the absence of about 200 patients not included in 2019 data by a participating centre for a technical problem.

Disease characterization of people with cystic fibrosis and a minimal function mutation: Data from the Italian registry.

BACKGROUND: People with cystic fibrosis (pwCF) and a minimal function (MF) mutation are poorly characterized. The aim of this study was to evaluate the disease characteristics of adult and pediatric pwCF with a genotype including an MF mutation on the basis of 2018 data from the Italian CF Registry (ICFR). METHODS: This cross-sectional, descriptive analysis of CF disease characteristics included all of the pwCF with at least one MF mutation or two F508del (F) mutations, and at least one 2018 entry in the ICFR. Data concerning the disease characteristics of pwCF with an F/F genotype are provided for reference. FINDINGS: A total of 5501 pwCF had at least one entry in the 2018 ICFR, including 2867 whose genotype included an MF mutation; in particular, 1432 had an MF/F genotype and 1148 the F/F genotype. The most frequent F/MF genotypes were F/N1303K (n = 247, 8.6%) and F/G542X (n = 193, 6.7%). The MF/no-F patients generally had a milder phenotype (a later diagnosis, lower sweat chloride levels, better nutrition, better lung function [starting from adolescence], and a lower prevalence of chronic infections and CF-related complications) than the MF/F or F/F patients. INTERPRETATION: The findings of this descriptive analysis highlight the disease characteristics of pwCF with an MF-including genotype in Italy. The considered clinical outcomes of the pwCF with an F/MF genotype were not generally different from those of pwCF with an F/F genotype, but the patients with an MF/no-F genotype generally had a milder phenotype.

[Italian Cystic Fibrosis Registry (ICFR). Report 2017-2018]. / Registro italiano Fibrosi Cistica (RIFC). Rapporto 2017-2018.

INTRODUCTION: On the 15th of November 2020, the National Centre for Rare Diseases of the Italian National Health Institute, clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, Children's Hospital "Bambino Gesù", Italian Cystic Fibrosis Society, Italian League for Cystic Fibrosis renewed the agreement about CF data flow for a 3-year period. The possibility to access data by third parties is among the most important innovation introduced within the agreement. OBJECTIVES: Aim of the present Report is to improve the know-how of cystic fibrosis (CF) through a better characterization of Italian patients. Furthermore, the present Report aims at improving the care of CF patient. In particular, this Report should contribute to the following objectives: • to analyse the medium- and long-term clinical and epidemiological trends of the disease; • to identify the main healthcare needs at regional and national level, in order to contribute to the healthcare programmes and to the distribution of resources; • to compare Italian data with international ones. DESIGN: Analyses and results described in the present Report are referred to patients currently followed at the Italian National Referral and Support Centres for Cystic Fibrosis in the 2017-2018 period. Data were sent by clinical Centres through a new-committed software. Data underwent a double quality control (QC): the first is automatically performed by the software (quantitative QC), the second is performed at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their consistency with the European core data. SETTING AND PARTICIPANTS: The present Report has been organized into 10 sections. 1. Demography: in the ICFR, 5,565 CF patients were registered in 2017 and 5,501 in 2018; median age was 21.4 years in 2017 and 21.2 years in 2018. Prevalence was 9.20/100,000 residents in Italy in 2017 and in 2018. Male percentage was 51.65% in 2017 and 2018, CF distribution by age range showed higher frequency in patients aged 7 to 35 years. Adult patients (aged more than 18 years) were 56.4% on average in 2017 and 2018. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (median value 66.4%); a significant percentage of patients (21.6% in 2017 and 18.3% in 2018) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 162 in 2017 and 142 in 2018. Estimated incidence was 1/5.214 living births in 2017 and 1/5.442 in 2018. 4. Genetics: 99.8% of patients underwent genetic analyses and in 97.1% of these patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. The F508del mutation was the most frequent (44.6% in 2018). Furthermore, 16.3% of patients in 2017 and 16.9% of patients in 2018 had at least one 'residual function' mutation. At least one gating mutation is present in 3.3% of Italian patients. Finally, 20.5% of patients had at least one stop codon mutation (class 1). 5. Lung function: percent predicted FEV1 (Forced Expiratory Volume in the first second) progressively declined before adult age, in accordance with the natural history of the disease. The majority of paediatric patients (6-17 years of age), i.e., 86.70% in 2017 and 90.50% in 2018, had percent predicted FEV1 ≥70%; whereas paediatric patients with a FEV1% ≤40% are less than 2% in the 2017-2018 period. 6. Nutrition: the two most critical periods are the first 6 months of life and adolescence. Prevalence of malnourished adolescent males (12-17 years of age) is higher than the prevalence observed in females. Increasing percentages of adult female patients with a suboptimal BMI value (39.1% and 36.1%, respectively, in 2017 and 2018) are observed. 7. in 2018, CF-related liver disease without cirrhosis was the main complication both in patients aged less than 18 years (17.0% on average) and in adults (31.5%). CF-related diabetes was also frequent in CF adults (23.4%). 8. Transplantation: in 2017-2018, 83 patients received a double-lung transplantation. Median and range of age were 29.3 years (11.8-60.2) in 2017 and 29.1 (7.8-45.6) years in 2018. Median waiting times for lung transplantation in the two considered years were 8.6 and 7.7, respectively. 9. Microbiology: percentage of adult patients with chronic Pseudomonas aeruginosa infection was 51.3% in 2017 and 46.3% in 2018 vs 15.6% in 2017 and 10.2% in 2018 in paediatric age. Staphylococcus aureus infection is present in 53.4% and 53.5% of adult patients in 2017 and in 41.6% and 37.5% of paediatric patients in 2018. 10. Mortality: a total of 89 patients died in the 2017-2018 period (49 females); median age at death was 33.9 years in 2017 and 35.8 years in 2018 (transplanted patients are not included). CONCLUSIONS: The present report shows that the Italian CF population is growing (4,159 in 2010 vs 5,501 in 2018; +1,342). Quality of data collected has been improved by the drastic reduction of missing data, thanks to the new software for data collection. Median age of patients increased in the 2010-2018 period (17 years in 2010 vs 21.2 years in 2018). Paediatric death is a very rare event. A very low percentage of paediatric population was characterized by severe lung disease (FEV1% <40). Prevalence of adult patients is increasing (56.4% in 2018). Age at diagnosis is decreasing (4.2 months in 2017 vs 3.8 months in 2018). Median age at death (transplanted patients not included) was 33.9 in 2017 and 35.8 in 2018. RIFC is completely compliant with the GDPR (UE 2016/679 regulation) and its role in national and international CF communities is confirmed.

Perinatal outcomes in women with cystic fibrosis: Data from the Italian Cystic Fibrosis Registry.

INTRODUCTION: Data from the Italian Cystic Fibrosis Registry concerning pregnancies in the period 2010-2015 were used to investigate the association between the preconception clinical status and perinatal outcomes of women with cystic fibrosis (CF). MATERIAL AND METHODS: The assessed clinical variables were genotype, age at the time of conception, body mass index (BMI) and the percentage of predicted forced expiratory volume in the first second (ppFEV1 ). The analyzed outcomes were gestational age, birthweight and the frequency of cesarean deliveries. A generalized linear mixed model (GLIMMIX) was used to evaluate the association between type of delivery and age at the time of becoming pregnant, BMI, ppFEV1 and gestational age. Robust multivariable regression was used to evaluate the relation between gestational age and age at the time of becoming pregnant, BMI and ppFEV1 . Multivariable linear regression was performed to verify association between birthweight and BMI, and ppFEV1 . RESULTS: Complete information concerning mother and child was available for 56 completed pregnancies. Median age at the time of conception was 30.8 years (range: 18.7-42.3); median BMI was 21.5 kg/m2 (range: 16.5-26.8); and median ppFEV1 was 73.9 (range: 30-128). In all, 31 women (55.36%) had a genotype consisting of two CF-causing variants. Eight were homozygous for the F508del mutation (14.28% of the total). The median duration of pregnancy was 37 weeks (range: 31-41) and the frequency of prematurity (<37 weeks of gestational age) was 28.30%. Median birthweight was 2910 g (range: 1300-3650). The overall frequency of cesarean sections was 63.64%. A low preconception ppFEV1 was associated with prematurity (p = 0.014), and birthweight was positively related to ppFEV1 (p = 0.04). There was no association between the clinical variables or gestational age and the type of delivery. CONCLUSIONS: Maternal preconceptional respiratory function correlates with the duration of pregnancy and the birthweight of newborns. Cesarean deliveries are also frequent among young women with CF with normal respiratory function.

The Diagnosis of Cystic Fibrosis in Adult Age. Data from the Italian Registry.

Cystic Fibrosis (CF) registries are an essential resource of epidemiological and clinical data. Although the median age at diagnosis is usually reported in the first months of life, a minority of individuals is diagnosed during adulthood. The aim of this study was to describe demographic, genetic, and clinical characteristics of this subgroup of the Italian CF population by using data from the Italian CF Registry (ICFR). Patients ≥18 years at diagnosis were selected and clinical data at diagnosis were analyzed from the 2012-2018 ICFR data (Cohort A). Subjects with diagnosis ≥18 years were selected from 2018 ICFR dataset (Cohort B) to describe their clinical status. In 2012-18 the incidence of late diagnosis was 18.2%, whereas, in 2018, the prevalence of patients diagnosed ≥18 years was 12.54%. The median age of late diagnosis was 36.2 years, ranging from 19.0 to 68.3. The male patients were diagnosed because of infertility in the 45.9% of cases. Median sweat chloride value (SCL) was 69 mmol/L (range 9-150). F508del mutation accounted for 28.3% of alleles. A wide variability in respiratory function was present with a median percent predicted Forced Expiratory Volume in the first second (ppFEV1) of 90.8% (range 20-147%). Low prevalence of pancreatic insufficiency (25%) and of Pseudomonas aeruginosa (Pa) infection (17%) suggest a mild CF phenotype in the majority of patients. The assessment of the clinical status in the 2018 dataset and the comparison between genders showed a greater nutritional and respiratory impairment in females. Further studies are needed to clarify the importance of a true diagnostic delay or of late onset of CF symptoms.

Cystic fibrosis with non-G551D gating mutations in Italy: Epidemiology and clinical characteristics.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) gating mutations (GMs) result in CFTR that is present at the cell surface but nonfunctional. Patients with the G551D mutation, the most prevalent worldwide, have been well studied. Italian GM patients have mainly non-G551D mutations. We studied their epidemiology and clinical characteristics in the period spanning the pre/post ivacaftor introduction to the Italian market. METHODS: Data from the Italian CF Registry were used to describe patients with GMs and compare them with F508del homozygous (F/F) patients. RESULTS: In total, 186 patients with GMs (median [range] age, 21.96 [0.13-63.38] years) were identified among the 5552 patients included in the study (3.3%). They had lower sweat chloride values at diagnosis than the F/F and a lower ratio of males. In the GM group, examining the data of the years 2012 and 2017 and comparing with F/F, lung infection by Staphylococcus aureus and diabetes became less prevalent, and better FEV1 and nutritional status were observed in 2017. The cross-sectional evaluation year-by-year from 2012 to 2017 of the GM group showed improving trends in lung function and body mass index, and the decreasing prevalence of diabetes compared with F/F. Longitudinal evaluation of GM patients showed improvement in percent predicted (pp)FEV1 and nutrition in the 2012-2017 period. These variations correspond to the introduction of treatment with the CFTR potentiator ivacaftor (2014/2015). CONCLUSIONS: Italian patients with GMs are few and are characterized by milder phenotypes than F/F patients. Improved outcomes are likely influenced by treatment with ivacaftor.

The Italian External Quality Assessment Program for Cystic Fibrosis Sweat Chloride Test: Does Active Participation Improve the Quality?

(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 Sanità (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-after receiving the EQA results-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.

[Italian Cystic Fibrosis Registry (ICFR). Report 2015-2016]. / Registro italiano Fibrosi Cistica (RIFC). Rapporto 2015-2016.

INTRODUCTION: On the 27th of October 2017 the National Center for Rare Diseases of the Italian National Health Institute (NHI), clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, Paediatric Hospital "Bambino Gesù", Italian Cystic Fibrosis Society, and the Italian League for Cystic Fibrosis renewed the agreement about FC data flow for a 3 years period. The possibility to access data by third parties is among the most important new introduced within the agreement. OBJECTIVES: Aim of the present report is to improve the know-how on cystic fibrosis (CF) through a better characterization of Italian patients. Furthermore, the present Report aims at improving the care of CF patient. In particular, the Report should contribute to the following objectives: * to analize medium- and long-term clinical and epidemiological trends of the disesase; * to identify the main health care needs at regional and national level in order to contribute to the healthcare programmes and to the distribution of resources; * to compare Italian data with international ones. DESIGN: Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral and Support Centers for Cystic Fibrosis in the period 2015-2016. Data were sent by Centres by means of a specific software (Camilla, Ibis Informatica). Data underwent to a double quality control (QC): the first by NHI and the second at a European level (before the inclusion of the italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and the accuracy of data as well as their consistency with European core data. Finally, in 2017, an additional CQ was performed to further reduce the number of missing data and consequently improve the precision and the consistency in the nomenclature adopted for genetic mutations. SETTING AND PARTICIPANTS: A total of 29 different CF Centres (referral, support, and Paediatric Hospital "Bambino Gesù") sent their data referred to 2015-2016 years to ICFR . Data regarding Sardinia (Southern Italy) are missing and those from Treviso (Veneto Region, Northern Italy) and Rovereto (Trentino-Alto Adige Region, Northern Italy) are sent through Verona CF Centre. RESULTS: The present Report has been organized into 10 sections. 1. Demography: estimated CF patients is 5,204 in 2015 and 5,362 in 2016; median age is 20.6 and 21.0, respectively. Prevalence is 8.6/100,000 residents in Italy in 2015 and 8.8 in 2016. Male percentage is 51.6% on average for 2015 and 2016; CF distribution showed higher frequency in patients aged from 7 to 35 years. The mean of patients aged more than 18 years is 56.5% on average in 2015 and 2016. 2. Diagnoses: most of the CF patients were diagnosed before 2 years of age (median value: 68%); a significant percentage of patients (median value: 13%) was diagnosed in adult age. 3. New diagnoses: new diagnoses were 169 in 2015 and 153 in 2016. Estimated incidence in 2015 was 1/4,176 living births in 2015 and 1/5,510 in 2016. 4. Genetics: 99.5% of patients underwent genetic analyses and in 96% of patients a mutation in Cystic Fibrosis Transmembrane Regulator (CFTR) gene was identified. [delta]508F was the most frequent mutation (44,7% in 2016). Furthermore, 16.0% and 3.4% of patients was characterized by the presence of at least one "residual function" mutation and gating, respectively. Finally, 21% of patients was a stop codons (class 1 mutation) carrier. 5. Lung function: FEV1 (forced expiratory volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. FEV1% values in patients between 6 and 17 years of age is ≥70%; patients with a FEV1% value of 40% are less than 2% in the period 2015-2016. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years is constant in 2015-2016 and is always more than the prevalence observed in female. An increasing percentage of female patient with a suboptimal BMI value (35.5%) is observed among patients aged more than 18 years 7. COMPLICATIONS: it was estimated that, in 2016, hepatopathies without cirrhosis (17.7%) is the principal complications in patients aged less than 18 years; in patients aged more than 18 years the principal complication was due to hepatopathies without cirrhosis (29.5%) and diabetes (23.3%). 8. Transplantation: in 2015-2016, 74 patients were bipulmunary transplanted; age was comprised between 8 and 52 years, median age at transplantation was 29,6 years. Median waiting times for transplantation is estimated in 17 months (24 months in 2015 and 14 months in 2016). 9. Microbiology: analyses were referred to test performed in 2016. Percentage of adult patients with chronic Pseudomonas aeruginosa infection is 52.1% compared to 15.2% of paediatric patients; Staphylococcus aureus infection is present in 53.2% of adult patients and 52.8% of paediatric ones; Burkholderia Cepacia complex is present almost exclusively in adult patients (4.3%); Nontuberculous mycobacteria is present in 1.2% and 0.4% of adult and paediatric patients, respectively; Stenotrophomonas maltophilia infection is present in the 6.1% of adult patients and 4.9 of paediatric patients. 10. Mortality: 102 patients (49 males and 53 females; median age 36.9 years in 2015 and 36.5 in 2016) died in 2015-2016 (transplanted patients are not included). CONCLUSIONS: The present Report shows that Italian CF population is growing (median age) and paediatric mortality is decreasing. A very low percentage of paediatric population is characterized by complication of pulmonary function; adult patients are characterized by an increase of age at death (more than 36 years of age in 2016).

Patients with cystic fibrosis having a residual function mutation: Data from the Italian registry.

BACKGROUND: CFTR mutations permitting residual function (RF) of the CFTR protein are disease-causing. These mutations are associated with a pneumopathy that is delayed in onset and is slower in progression than are more common forms of cystic fibrosis (CF), although the disease may become severe in some patients. RF mutations are among the most frequent in Italy, thus encouraging investigation of their prevalence and associated phenotypes. METHODS: Data from the Italian Registry were used to compare patients with at least one RF mutation with those homozygous for F508del. RESULTS: A total of 806 patients bearing at least one RF mutation were identified among 5204 registered patients (15.5%). The RF patients were older than the F508del homozygotes (median age 26.0 years vs 19.8 years, respectively), with a higher median age at diagnosis (6.3 years vs 0.2 years, respectively) and a lower median sweat chloride value (76.0 mmol/L vs 100.0 mmol/L, respectively). In the RF group, lung infections and comorbidities were less prevalent than those in the F508del homozygotes, while better FEV1 and nutritional status were observed at all ages. Within the RF group, RF/F508del subjects showed more severe pneumopathy than did patients with RF/other mutations. In particular, the 3849 + 10kbC → T/F508del subjects had worse FEV1 and a higher prevalence of lung infections than did patients with other genotypes. CONCLUSIONS: Patients with RF mutations are numerous in Italy and have a milder disease phenotype than do F508del homozygotes. Inside the RF group, F508del heterozygotes and, in particular, 3849 + 10kbC → T/F508del patients showed more severe pneumopathy.

[Italian Cystic Fibrosis Registry. Report 2011-2014]. / Registro italiano Fibrosi Cistica. Rapporto 2011-2014.

INTRODUCTION: The Italian Cystic Fibrosis Registry (ICFR) is based on a new agreement about the data flow towards the Registry signed on October, 4th 2016 by the Centre for Rare Diseases of the Italian National Institute of Health (NIH), the clinicians of the Italian National Referral and Support Centres for Cystic Fibrosis, the Paediatric Hospital "Bambino Gesù" (Rome), the Italian Cystic Fibrosis Society, and the Italian League for Cystic Fibrosis. OBJECTIVES: The aim of the present Report is to improve the knowledge on cystic fibrosis (CF) through the epidemiological description of Italian patients. The members of the Scientific and Technical Committee have to write a report on data collected by ICFR, in order to contribute to achieve the aims of ICFR itself, i.e., to improve the care of CF patients. In particular, the Report should contribute to the following objectives: - to analyze the medium and long-term clinical and epidemiological trends of the disease; - to identify the main healthcare needs at regional and national level in order to contribute to the healthcare programmes and to the distribution of resources; - to compare Italian data with the international ones. DESIGN: Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral and Support Centres for Cystic Fibrosis in the period 2011-2014. Data were sent by Centres by means of a specific software (Camilla, Ibis Informatica) and has undergone a double quality control (QC): the first by NIH and the second at a European level (before the inclusion of the Italian data within the European Cystic Fibrosis Registry). These QCs assure the completeness and accuracy of data as well as their consistency with European core data. SETTING AND PARTICIPANTS: A total of 29 different CF centres (referral, support, and Paediatric Hospital "Bambino Gesù") sent their data to ICFR; data referred to the period 2011-2014. Data regarding Sardinia Region (Southern Italy) are missing; data from Molise (Southern Italy) CF centre refer only to 2014. RESULTS: The present Report has been organized into 10 sections. 1. Demography - number of Italian patients with cystic fibrosis (CF) in 2014 was 4,981 and their median age was 20.4 years; estimated 2014 CF prevalence was 8.2/100,000 residents in Italy; on average, 52.1% of the patients were male and CF distribution showed higher frequency in patients aged from 7 to 35 years. On average, 53.7% of CF patients are aged more than 18 years. 2. Diagnoses - most of the CF patients were diagnosed before two years of age (around 66%); a significant proportion of patients (on average, 12%) was diagnosed in adult age. 3. New diagnoses - new diagnoses were 187 in 2011, 200 in 2012, 160 in 2013, and 135 in 2014. Estimated incidence was 1/4,052 live births in 2011; 1/4,313 in 2012; 1/5,189 in 2013 and 1/8,243 in 2014. 4. Genetics - 99.5% of patients was studied at the molecular level, with identification of 90.1% of Cystic Fibrosis Transmembrane Regulator CFTR mutations; [delta]508F was the most frequent mutation (44.8% in 2014). 5. Lung function - FEV1 (Forced Expiratory Volume in the first second) scores progressively decreased shortly before the start of adult age, in accordance with the natural history of the disease. Most of the patients between 6 and 17 years of age reported a FEV1 % ≥ 70% of the predicted value, while the proportion of patients with severe lung disease (FEV1 % <40% of the predicted value) is <2% over the period 2011-2014. 6. Nutrition - most critical periods come out during the first 6 months of life and during adolescence. Prevalence of malnourished male aged 12-17 years decreases over the period 2011-2014; an increasing percentage of patient (both male and female) with a suboptimal body mass index value is observed among patients aged more than 18 years 7. Complications - the presence of missing data represents an obstacle in the correct evaluation of prevalence value of complications related to Italian patients within ICFR. Nevertheless, it was estimated that, in 2014, the principal complication in patients aged <18 years was hepatopathies (15%), while in patients aged more than 18 years the principal complications were due to hepatopathies (25%) and diabetes (22%). 8. Transplantation - during the period 2011-2014, 135 patients ageed between 7 and 53 years received a double lung transplant; median age at transplantation was 32.5 years. Median duration of waiting list for transplantation is estimated in 11 months. 9. Microbiology - analyses were referred to test performed in 2014. Prevalence of adult patients with Pseudomonas aeruginosa chronic infection is 49.4% compared to 14.5% of paediatric patients; Staphylococcus aureus chronic infection is present in 48% of adult patients and 45.6% of paediatric patients; Burkholderia Cepacia complex is present almost exclusively in adult patients (4.9%); Nontuberculous mycobacteria is present in 0.9% and 0.3% of adult and paediatric patients, respectively; Stenotrophomonas maltophilia infection is present in 4.6% of patients (both adults and paediatric). 10. Mortality - RIFC data show that 176 patients (median age 32 years; 81 males and 95 females) died in the period 2011-2014. CONCLUSIONS: The present Report shows that CF population is growing (median age), so paediatric mortality is decreasing. A very low percentage of paediatric population is characterized by complication of pulmonary functions; adult patients are characterized by an increase of age at death (more than 30 years of age). ICFR Report may represent an important tool to analyze clinical and epidemiological trends of the disease as well as to identify the main healthcare needs at regional and national level to contribute to the healthcare programmes and to the distribution of the resources.

Italian external quality assessment program for cystic fibrosis sweat chloride test: a 2015 and 2016 results comparison.

BACKGROUND: Diagnostic testing in cystic fibrosis (CF) is based on the sweat chloride test (SCT) in the context of appropriate signs and symptoms of disease and results of the gene mutation analysis. In 2014 the Istituto Superiore di Sanità (ISS) established a pilot Italian external quality assessment program for CF sweat chloride test (Italian EQA-SCT). In 2015 this activity was recognized as a third party service carried out by the ISS. The aim of the paper is to compare 2015 and 2016 results and experiences. METHODS: The scheme is prospective; enrollment is voluntary and the payment of a fee is required. Participants are registered and identified by a specific Identification Number (ID) through a dedicated web-facility. Assessment covers analysis, interpretation and reporting of results. RESULTS: Thirteen and fifteen laboratories, participated in the 2015 and 2016 round respectively. Seven laboratories participated constantly from 2014, eleven participated both in 2015 and 2016 and four participated in 2016 for the first time. Variability in scores of chloride titration and heterogeneity in interpretation/reporting results were detected in both rounds. A total of 18 critical errors in chloride titration were made by eight different participants. Four laboratories made errors in chloride titration in 2015 but drastically improved their performance in 2016. In 2016 poor performance criteria were established and adopted. CONCLUSIONS: Even though results show variability in performance of laboratories, constant and mandatory participation may contribute to the improvement of performance and quality reached by laboratory.

[Italian Cystic Fibrosis Register - Report 2010]. / Registro italiano fibrosi cistica - Rapporto 2010.

UNLABELLED: The Italian National CF Registry (INCFR) is based on the official agreement between the clinicians of the Italian National Referral Centers for Cystic Fibrosis and the researchers of the Istituto Superiore di Sanità (National Center for Rare Diseases; National Center for Epidemiology, Surveillance and Health Care Promotion). OBJECTIVES The main aim of INCFR is to contribute to the improvement in CF patients health care and clinical management through: i. the estimates of CF prevalence and incidence in Italy; ii. the analyses of medium and long term clinical and epidemiological trends of the disesase; iii. the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources. MATERIALS AND METHODS Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral Centers for Cystic Fibrosis in 2010. Data were sent by Centers by means of a specific software (Camilla, Ibis Informatica). The Italian National Referral Centers for Cystic Fibrosis sent a total of 5,271 individual records; 1,112 records were excluded from the analyses due to restricted inclusion criteria. The total number of patients included in INCFR for analyses is 4,159. RESULTS INCFR database includes all prevalent cases at 1th January 2010 as well as all new diagnoses done in 2010. The present Report has been organized into 9 sections. 1. Demography: estimated 2010 CF prevalence was 7/100,000 residents in Italy; 52% of the patients were male, CF distribution showed higher frequency in patients aged 7 to 35 years. In 2010, 48.9% of the patients were more than 18 years old. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (66.7%); a significant percentage of patients (11.4%) was diagnosed in adult-age. 3. New diagnoses (2010): new diagnoses were 168. Sixty-five percent of them was diagnosed before the second year of age and 17%in adulthood. No differences were observed between male and female. Incidence at birth was estimated 1/4,854 living births. 4. GENETICS: in 95.9% of patients, 2 (or more) CFTR mutations were identified. [delta]508F mutation was the most frequent (45.1%). 5. Respiratory function: analyses were performed on 2,966 out of 3,341 patients aged 7 years or older. FEV1 (Forced Expiratory Volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Fourteen per cent of the patients within 2-18 years resulted malnourished. From 18 years onwards, optimal BodyMass Index (BMI) values were detected in 36.5%of males and in 28%of females. BMI also improved during age. 7. Transplantation: in 2010, 20 patients (10 males and 10 females) were bi-pulmunary transplanted; age was comprised between 11 and 46 years, median age at transplantation was 27.5 years. Eleven out of the 20 patients resulted still alive on the 31th December 2010. 8. Microbiology: analyses were performed on 3.272 patients (887 did not report these data) and were exclusively referred to tests performed in 2010. A percentage of 34 patients, younger than 18 years of age, was characterized by the presence of Pseudomonas aeruginosa compared to 61.8% of the older patients. Prevalence of Burkholderia Cepacia was 0.8% in patients aged up to 17 years; in patients aged more than 17 years, prevalence was 6.8%. Staphylococcus aureus meticillino sensitive prevalence was not correlated with patients' age. 9. MORTALITY: 34 patients aged from 0 to 45 years died in 2010 (16 males and 18 females). Respiratory insufficiency was the main cause of death (73.5%). CONCLUSIONS The report aims at being an instrument for CF community, with particular attention to the needs of patients and their families. Information collected within INCFR are an important starting point for further studies from health care perspectives. Finally, INCFR represents an important tool to foster research and innovative treatment for CF, as the rareness of the disease is a constraint to clinical trials and other studies set-up. A significant subset of data are regularly sent to the European Registry of Cystic Fibrosis.

The Italian pilot external quality assessment program for cystic fibrosis sweat test.

OBJECTIVES: Sweat chloride test is the gold standard test for cystic fibrosis (CF) diagnosis. In 2014 the Istituto Superiore di Sanità established the Italian pilot external quality assessment program for CF sweat test (IEQA-ST). DESIGN AND METHODS: Ten laboratories, included among the 33 Italian CF Referral Centers, were selected and enrolled on the basis of their attitude to perform sweat test (ST) analysis by using methods recommended by the Italian Guidelines. They received three different sweat-like samples (normal, borderline and pathologic chloride concentration), with mock clinical indications, for analysis according to routine procedures. Assessment, performed by a panel of experts, covered analytical performance, interpretation and reporting of results; categories of "poor" and "satisfactory" performance were not defined. All data were managed through a web utility. RESULTS: The program identified important areas of interest and, in some case, of concern. It is important to underline that results are referred to a small proportion, i.e. about 30%, of Italian laboratories performing CF ST in the context of the Referral Centers. CONCLUSIONS: Data collected highlight the importance of participation in EQA programs as it may improve laboratory/clinical performance; our study represents a model for the setting up of a large-scale EQA scheme for ST.