Impact of ambient air pollution on lung function in preterm-born school-aged children.

RATIONALE: Increased outdoor air pollution worsens lung function in children. However, these associations are less well studied in preterm-born individuals. OBJECTIVES: We assessed associations between ambient air pollutants and spirometry measures in preterm-born children. METHODS: The Respiratory Health Outcomes in Neonates study recruited preterm-born children aged 7-12 years who were born at ≤34 week's gestation. We associated four ambient air pollutants (particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), PM10, nitrogen dioxide (NO2) and sulfur dioxide) at time of birth and spirometry assessment and averaged exposure between these two time points with spirometry measures, using linear regression analyses. Gestational age was banded into 23-28, 29-31 and 32-34 week's. Regression models estimated spirometry values against pollutant levels at birth and at the time of spirometry. MEASUREMENTS AND MAIN RESULTS: From 565 preterm-born children, 542 (96%) had satisfactory data. After adjustments for early and current life factors, significant detrimental associations were noted between PM10 at birth and per cent predicted forced vital capacity (%FVC) for the 23-28 and 29-31 week's gestation groups and between current PM2.5 and NO2 exposure and %FVC for the 23-28 week's gestation group. No associations with spirometry were noted for the averaged pollution exposure between birth and spirometry. Predictive models showed 5.9% and 7.4% differences in %FVC between the highest and lowest current pollution exposures for PM2.5 and NO2, respectively, in the 23-28 week group. CONCLUSIONS: Birth and current exposures to road-traffic-associated pollutants detrimentally affected %FVC in preterm-born school-aged children, who already have compromised lung function.

Cystic fibrosis transmembrane conductance regulator modulators for cystic fibrosis: a new dawn?

Cystic fibrosis (CF) is the most common life-limiting inherited condition in Caucasians. It is a multisystem autosomal recessive disorder caused by variants in the gene for cystic fibrosis transmembrane conductance regulator (CFTR) protein, a cell-surface localised chloride channel that regulates absorption and secretion of salt and water across epithelia. Until recently, the treatment for CF was predicated on ameliorating and preventing the downstream symptoms of CFTR dysfunction, primarily recurrent respiratory infections and pancreatic exocrine failure. But a new class of therapy-the CFTR modulators, which treat the basic defect and decrease the complications of CF, leads to significantly improved pulmonary function, decreased respiratory infections and improved nutrition. The newest agent, a combination of elexacaftor, tezacaftor and ivacaftor, will be suitable for approximately 90% of all people with CF and is likely to decrease the morbidity and significantly increase the life expectancy for most people with CF. The major barrier to their widespread introduction has been their cost, with many countries unwilling or unable to fund them. Nevertheless, such is their therapeutic efficacy and their likely potent effect on life expectancy that their advent has wider societal implications for the care of children and adults with CF.

Cystic fibrosis newborn screening: the importance of bloodspot sample quality.

OBJECTIVE: Wales has an immunoreactive trypsin (IRT)-DNA cystic fibrosis (CF) newborn screening (NBS) programme. Most CF NBS false negative cases are due to an IRT concentration below the screening threshold. The accuracy of IRT results is dependent on the quality of the dried bloodspot (DBS) sample. The aim of this study was to determine the cause of false negative cases in CF NBS and their relationship to DBS quality. DESIGN: Longitudinal birth cohort. SETTING: Wales 1996-2016. PATIENTS: Children with CF. INTERVENTIONS: Identification of all CF patients with triangulation of multiple data sources to detect false negative cases. MAIN OUTCOME MEASURES: False negative cases. RESULTS: Over 20 years, 673 952 infants were screened and 239 were diagnosed with CF (incidence 1:2819). The sensitivity of the programme was 0.958, and positive predictive value was 0.476. Eighteen potential false negatives were identified, of whom eight were excluded: four screened outside Wales, two had complex comorbidities, no identified cystic fibrosis transmembrane conductance regulator (CFTR) variants on extended analysis and thus not considered to have CF and two were diagnosed after their 16th birthday. Of the 10 false negatives, 9 had a low DBS IRT and at least one common CFTR variant and thus should have received a sweat test under the programme. DBS cards were available for inspection for five of the nine false negative cases-all were classified as small/insufficient or poor quality. CONCLUSIONS: The majority of false negatives had a low bloodspot IRT, and this was associated with poor quality DBS. The optimal means to improve the sensitivity of our CF NBS programme would be to improve DBS sample quality.

UK trainee-led paediatric governance collaboratives: improving the lives of both trainees and children.

Research is vital to paediatrics; however, many trainees feel there is a deficit in their opportunities, experience and exposure in this area. Three training regions in the UK, the West Midlands, Wales and Peninsula, have recently started region-wide, trainee-led research and governance collaboratives aimed at improving trainee access and education in research, undertaking good quality, multicentre audit, quality improvement and pilot projects in collaboration across the regions and implementing change. We report on the experiences, benefits and challenges of these trainee collaboratives (Paediatric Research Across the Midlands, Wales Research and Education Network and Peninsula Trainee Research Audit and Innovation Network) including a trainee survey looking at how these initiatives have improved skills in conducting multicentre prospective studies, team working skills, leadership, understanding of statistics and manuscripts and presentation skills. We also describe how collaboration with colleagues and participation in projects can benefit trainees in a wider sense of purpose and help to encourage morale, as well as what can be learnt as paediatric training moves forward.