Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency, leading to fat malabsorption, malnutrition and abdominal discomfort. Until recently, no specific tool was available for assessing gastro-intestinal related quality of life (GI QOL) in patients with CF. As the Horizon2020 project MyCyFAPP aims to improve GI QOL by using a newly designed mobile application, a sensitive and reliable outcome measure was needed. We aimed to study the applicability of the existing child-specific Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Scales and Module (PedsQL GI) in children with CF. A multicenter, prospective observational study was performed in 6 European centers to validate the PedsQL GI in children with CF during 3 months. In total, 248 children and their parents were included. Within-patient variability of PedsQL GI was low (24.11), and there was reasonable agreement between children and parents (ICC 0.681). Nine of 14 subscales were informative (no ceiling effect). The PedsQL GI and the median scores for 4 subscales were significantly lower in patients compared to healthy controls. Positive associations were found between PedsQL GI and age (OR = 1.044, p = 0.004) and between PedsQL GI and BMI z-score (OR = 1.127, p = 0.036). PedsQL GI correlated with most CFQ-R subscales (r 0.268 to 0.623) and with a Visual Analogue Scale (r = 0.20). PedsQL GI is a valid and applicable instrument to assess GI QOL in children with CF. Future research efforts should examine the responsiveness of the CF PedsQL GI to change in the context of clinical interventions and trials.

Obstructive sleep apnea (OSA) affects approximately 1-3% of pediatric population and is associated with significant morbidity. As adenotonsillar hypertrophy (ATH) is its primary cause in children, elective adenotonsillectomy is the first treatment of choice. Noninvasive ventilation (NIV) has been increasingly considered as an option, mainly for children with complex diseases, ineligible or waiting for surgeries, or after surgery failure. To describe the experience in the management of children with complex OSA, and to evidence the feasibility and advantages of NIV. This was a retrospective cohort study of 68 children on NIV, in whom complex OSA was the main indication for ventilation, in a Pediatric Respiratory Unit at a University Hospital between January 1997 and March 2012. Demographic and clinical data were collected on the underlying diagnosis, therapeutic interventions prior to NIV, NIV related issues and outcome. Forty (59%) children were male, median age at starting NIV was 6 years and 7 months, with interquartile range (IQR) of 15-171 months. Twenty-two (32%) were infants and 25 (37%) adolescents. The most common diagnosis was congenital malformations and genetic disorders in 34 (50%) patients. Nine patients had cerebral palsy, 8 were post treatment for central nervous system tumors and 6 had inborn errors of metabolism. Three children had ATH and three obesity. The majority of patients (76%) had exclusively obstructive OSA and started CPAP. Ten patients had minor complications. Twenty-two patients stopped NIV due to clinical improvement, 8 were non-compliant and 8 patients died. NIV median duration was 21.5 months (IQR: 7-72). NIV is feasible and well tolerated by children with OSA associated with complex disorders, and has been shown to have few complications even in infants and toddlers.

The Burkholderia cepacia complex (Bcc) is a heterogeneous group of bacteria comprising around 20 related species. These bacteria are important opportunistic pathogens, especially in cystic fibrosis (CF) patients, and are associated with a worse prognosis and decreased life expectancy. The taxonomic position of 20 Bcc isolates retrieved from CF patients receiving care at Hospital Santa Maria (HSM), in Lisbon, from 1995 to 2006, was re-examined in the present work. These isolates, formerly classified as Burkholderia cepacia (taxon K), are here reclassified as Burkholderia contaminans, including the former B. cepacia IST408, which was the focus of previous studies regarding the biosynthesis of the exopolysaccharide ‘cepacian’. The CF population examined has been previously described as having an exceptionally high representation of B. cepacia, presumably due to a contamination arising from saline solutions for nasal application. Twenty-one additional isolates, obtained from a chronically infected patient, from 2006 to 2010, were also identified as B. contaminans. This study also provides insight into the potential clinical impact of B. contaminans, a species that is rarely associated with CF infections. Isolates belonging to this species were shown to be involved in chronic and transient respiratory infections, and were associated with severe lung function deterioration and with a case of death with cepacia syndrome. However, since the patients were co-infected with Burkholderia cenocepacia and other non-Burkholderia bacteria, the role played by B. contaminans is unclear. Nevertheless, B. contaminans isolates were found to prevail over B. cenocepacia isolates during co-infection of at least one chronically infected patient.

Newborn screening (NBS) for cystic fibrosis (CF) has been shown to be advantageous for children with CF, and has thus been included in most NBS programs using various algorithms. With this study, we intend to establish the most appropriate algorithm for CF-NBS in the Portuguese population, to determine the incidence, and to contribute to elucidating the genetic epidemiology of CF in Portugal. This was a nationwide three-year pilot study including 255,000 newborns (NB) that were also screened for congenital hypothyroidism (CH) and 24 other metabolic disorders included in the Portuguese screening program. Most samples were collected in local health centers spread all over the country, between the 3rd and 6th days of life. The algorithm tested includes immunoreactive trypsinogen (IRT) determination, pancreatitis associated protein (PAP) as a second tier, and genetic study for cases referred to specialized clinical centers. Thirty-four CF cases were confirmed positive, thus indicating an incidence of 1:7500 NB. The p.F508del mutation was found in 79% of the alleles. According to the results presented here, CF-NBS is recommended to be included in the Portuguese NBS panel with a small adjustment regarding the PAP cut-off, which we expect to contribute to the improvement of the CF-NBS performance. According to our results, this algorithm is a valuable alternative for CF-NBS in populations with stringent rules for genetic studies.

A major challenge in Cystic Fibrosis research is applying mutation‐specific therapy to individual patients with diverse and rare CFTR genotypes. Read‐through agents are currently the most promising approach for Class I mutations that introduce premature termination codons (PTCs) into CFTR mRNA. However, variations in degradation of PTC containing transcripts by nonsense mediated decay (NMD) might lower read‐through efficacy. Allele specific quantitative real time (qRT‐)PCR was used to measure variations in CFTR mRNA abundance for several PTC mutations in respiratory cells and intestinal organoids. The majority of PTC mutations were associated with reduced levels of relative mRNA transcript abundance (∼33% and 26% of total CFTR mRNA in respiratory cells and intestinal organoids, respectively, compared to >50% for non‐PTC causing mutations). These levels were generally not affected by PTC mutation type or position, but there could be 2‐fold variations between individuals bearing the same genotype. Most PTC mutations in CFTR are subject to similar levels of NMD, which reduce but do not abolish PTC bearing mRNAs. Measurement of individual NMD levels in intestinal organoids and HNE cells might therefore be useful in predicting efficacy of PTC read‐through in the context of personalized CFTR modulator therapy. This article is protected by copyright. All rights reserved