ITALIAN CYSTIC FIBROSIS REGISTRY • REPORT 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 Gesu" (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 Gesu") 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: FEV 1 (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 FEV 1 % >= 70% of the predicted value, while the proportion of patients with severe lung disease (FEV 1 % < 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 20112014; 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.