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BackgroundA comparison of the longitudinal progression of lung disease in cystic fibrosis patients identified through newborn screening (NBS) in cohorts located in two different countries has never been performed and was the primary objective of this study.MethodsThe study included 56 patients in Brittany diagnosed through NBS between 1989 and 1994 and 69 similar patients in Wisconsin between 1985 and 1994. The onset and progression of lung disease was radiographically quantified using the Wisconsin Chest X-ray (WCXR) scoring system. A single pediatric pulmonologist blinded to all identifiers scored the films.ResultsGeneralized estimating equation analyses adjusted for age, genotype, sex, pancreatic insufficiency, and meconium ileus showed worse WCXR scores in Brittany patients compared to Wisconsin patients (average score difference=4.48; p

Objectives: 5−10% of CF patients are diagnosed as adults. They often present with non-classical CF and suffer a milder clinical course. We postulate an increased incidence of adult CF diagnoses. We sought to determine if the adult CF, diagnostic characteristics and clinical course differed between 2000–2009 and 1990–1999. Methods: Patients attending CF centres in Northern Ireland from 1990 with a diagnosis of CF after the age of 16 were identified. Comparison of their demographics and biostatistics was made and a F508del homozygous cohort used as a control. Results: Fifty-two patients were identified. There was an increased incidence of individuals diagnosed with CF in adulthood in the latter decade (12 vs 40). Mean age at diagnosis was 30.4(±4.0) yrs in the 90’s and 43.2(±2.7) yrs in the 00’s (p = 0.02). The majority of patients presented with respiratory manifestations in both cohorts. Mean FEV1% predicted at presentation in the 90’s group 71.3% (±7.6) and the 00’s group 76.9% (±4.1) (p = 0.52). Class 1−3 mutations represented 75% of the 90’s group and 50% of the 00’s (p = 0.18), Class 4 mutations 25% of 90’s and 2.5% of 00’s (p = 0.03) and unknown mutations accounted for 0% of 90’s and 50% of 00’s (p = 0.002). A comparison of FEV1 % decline between the late diagnosis group (0.46ml/yr) and F508del homozygous patients (1.64ml/yr) (p = 0.02). Conclusions: Owing to the increased recognition of the heterogeneity of CF, this diagnosis is increasingly being made in adulthood. The majority of patients in both cohorts presented with Bronchiectasis. While having a milder clinical course these patients still suffer a considerable burden of disease and have a declining respiratory status.

NBS is aimed at early pre-symptomatic diagnosis of severe inherited diseases. CF NBS in France is based on IRT/DNA (CF 30 Elucigene)/IRT [1]. Detection of babies carrying one non-CF causing mutation (e.g. R117H) is one of the most negative impacts of DNA analysis [2]. Objective To assess the relevance and feasibility of R117H removal (r). Methods a.Describe the NBS carrying at least one R117H (T5, T7); b.Explain the decision making process of R117Hr (simulation; CF centres' opinion; feasibility; AFDPHE decision). Results In 2002–2012: a.Among 8,420,082 NBS (0.56% screened positive), 6309 were referred for sweat testing (ST). Of these, 1531 had CF and 245 an inconclusive diagnosis (58% R117H). Considering those with at least one R117H and the ST, were identified 365 carriers with only one R117H and a negative (–) ST; 142 carrying 2 CF 30 mutations with at least one R117H all on a T7 background with (–), 30–59 and (+) ST values respectively in 74, 59 and 9 cases; b.With respect to decision making, 1.Simulation of R117Hr would prevent identification of 365 carriers and 12 R117H HZ (377/507; 75%); only 130 infants, carrying a non-R117H mutation would be referred for ST (130/507; 25%). Among them, 62 with (–) ST would be classified as carriers but 68 with ST ≥30 mmol/L would be further investigated. 2.CF teams favoured R117Hr (61%). 3.Elucigene confirmed feasibility and AFDPHE validated R117Hr. Conclusion In France, R117H exclusively found on a T7 background allowed R117Hr to minimize the negative impact of DNA analysis. In those with one CFTR mutation and ST ≥30 mmol/L, the search for other mutations will be required, with R117H included in the second line panel.

International audience; BACKGROUND: French health authorities promoted a study on 553,167 newborns comparing the performances of IRT/DNA and IRT/PAP for CF newborn screening. METHODS: In parallel to IRT/DNA, PAP was assayed in newborns with IRT\textgreater50 mug/L. Provisional PAP cutoffs at 3.0 mug/L when 50\textlessIRT\textless100 mug/L and 1.7 mug/L when IRT\textgreater100 were used. Positive newborns were subjected to sweat test. Optimal cutoffs were established by a non-inferiority method. RESULTS: 95 CF newborns were identified (83 classical forms (ClF), including 9 meconium ileus (MI), and 12 atypical (mild) forms (AF) Of them, IRT/DNA identified 85 (73 ClF including 5 MI and 12 AF). PAP cutoffs at 1.8 mug/L when 50\textless IRT\textless100 mug/L and 0.6 mug/L when IRT\textgreater100 mug/L would identify 82 CF: 77 ClF, including 8 MI, and 5 AF. The number of sweat tests was 314 and 1039 in the IRT/DNA and IRT/PAP strategies, respectively. CONCLUSIONS: Using the optimal cutoffs, the sensitivity of the IRT/PAP strategy would not be inferior to that of IRT/DNA if identification of MF is not required.

Maldigestion in cystic fibrosis (CF) affects approximately 90% of patients. As soon as pancreatic insufficiency is identified, enzyme supplementation is prescribed even with breast fed infants. A pancreatic enzyme preparation developed particularly for infants, Creon ® for children (CfC), contains smaller granules to be administered with a dosing spoon (5000 lipase units per scoop). Patients and methods In a prospective, randomised, multi-centre study, 40 infants and toddlers received both CfC and Creon ® 10000 (C10) for two weeks each in a cross-over design. Dosing of pancreatic enzymes was continued as applied before the study. The primary endpoint was the parents' treatment preference. Secondary endpoints included coefficient of fat absorption (CFA), clinical symptoms and safety parameters. Results 20 parents (51%) from the N =39 intent to treat sample preferred CfC, 9 (23%) preferred C10, and 10 (26%) had no preference The applied doses led to a mean CFA with similar results for both treatments (77.8% vs. 78.7%). Gastrointestinal symptoms were reported on a number of study days, and some children had abnormal results for laboratory parameters of malabsorption. Safety and tolerability of the preparations were good and all these parameters were comparable for both treatments. Conclusion Those parents who had a preference favoured CfC over C10. Both enzyme preparations improved malabsorption to a similar degree, although the applied dosages could have been too low in some children reflected in a suboptimal CFA. These data support the use of CfC for young patients with cystic fibrosis improving the daily care of this cohort detected mainly now through neonatal screening programmes.

Background Newborn screening (NBS) for cystic fibrosis (CF) can lead to the detection of healthy carriers. We report a unique assessment of family testing following the identification of carriers by NBS for over 20years, in an area where CF is frequent. Methods We reviewed all of the carriers identified by NBS between 1991 and 2010 and registered the tests done in those families. Results NBS identified 0.1% of the newborns as carriers, which correspond only to 2.6% of the expected carriers born within the period, and 1/3 of those with an increased IRT level. Of the 195 families, 75.9% requested testing (2.5 tests per family). We identified 183 carriers and five 1-in-4 risk couples. Reassurance about genetic status was provided to 96% of the couples. Conclusions Carriers detected by NBS appeared to be well managed in our area, and cascade testing that informs on genetic status seems relatively active.