Jürg Barben

The expansion and performance of national newborn screening programmes for cystic fibrosis in Europe

BACKGROUND Newborn screening (NBS) for cystic fibrosis (CF) is a well-established public health strategy with international standards. The aim of this study was to provide an update on NBS for CF in Europe and assess performance against the standards. METHODS Questionnaires were sent to key workers in each European country. RESULTS In 2016, there were 17 national programmes, 4 countries with regional programmes and 25 countries not screening in Europe. All national programmes employed different protocols, with IRT-DNA the most common strategy. Five countries were not using DNA analysis. In addition, the processing and structure of programmes varied considerably. Most programmes were achieving the ECFS standards with respect to timeliness, but were less successful with respect to sensitivity and specificity. CONCLUSIONS There has been a steady increase in national CF NBS programmes across Europe with variable strategies and outcomes that reflect the different approaches.

Sweat test in patients with glucose-6-phosphate-1-dehydrogenase deficiency

Background: A false-positive sweat test in patients with deficiency of glucose-6-phosphate-1-dehydrogenase (EC 1.1.1.49; G6PD) is repeatedly reported. Methods: Sweat chloride or conductivity was measured in 11 patients with G6PD deficiency. Results: Mean (SD) chloride level (n = 8, median age 9.2 years, range 1.9–48.5) was 18.8 (9.6 mmol/l) and, mean (SD) sodium level was 26.0 (10.0 mmol/l), respectively, and mean (SD) conductivity (n = 3, median age 6.6 years, range 1.9–40.5) was 34.3 (6.5 mmol/l). Conclusion: In sweat of 11 patients with G6PD deficiency we did not find any abnormality. The reason for alleged false-positive sweat test in patients with G6PD deficiency is not known and we were unable to identify any original reference. It appears that tables of putative false-positive sweat tests in several disease states have been directly “copied and pasted” from one paper or textbook to another without verifying the original literature, a phenomenon one can call “chain citation”.

ECFS best practice guidelines: the 2018 revision

Developments in managing CF continue to drive dramatic improvements in survival. As newborn screening rolls-out across Europe, CF centres are increasingly caring for cohorts of patients who have minimal lung disease on diagnosis. With the introduction of mutation-specific therapies and the prospect of truly personalised medicine, patients have the potential to enjoy good quality of life in adulthood with ever-increasing life expectancy. The landmark Standards of Care published in 2005 set out what high quality CF care is and how it can be delivered throughout Europe. This underwent a fundamental re-write in 2014, resulting in three documents; center framework, quality management and best practice guidelines. This document is a revision of the latter, updating standards for best practice in key aspects of CF care, in the context of a fast-moving and dynamic field. In continuing to give a broad overview of the standards expected for newborn screening, diagnosis, preventative treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support, this consensus on best practice is expected to prove useful to clinical teams both in countries where CF care is developing and those with established CF centres. The document is an ECFS product and endorsed by the CF Network in ERN LUNG and CF Europe.

Hypertonic saline for acute viral bronchiolitis: take the evidence with a grain of salt.

Fifty years ago, Reynolds and Cook [1] wrote, “Oxygen is vitally important in bronchiolitis and there is little convincing evidence that any other therapy is consistently or even occasionally useful.” Their claim is once again supported by the new trial on hypertonic saline published in this issue of the European Respiratory Journal ( ERJ ) [2]. Acute viral bronchiolitis (AVB) is the most common lower respiratory tract infection in infancy. It is caused by respiratory viruses, typically by respiratory syncytial virus [3]. Although only 1–2% of children are hospitalised, AVB accounts for a large proportion of paediatric emergency visits and hospitalisations during winter months [4]. An effective treatment would reduce the number of hospitalisations, hospital length of stay (LOS) and their corresponding health costs. Over the past half century, no therapy for AVB has shown a convincing effect, though many have been tested. Among those treatments ruled out are β2-agonists, anticholinergics, inhaled or oral corticosteroids and chest physiotherapy [5–8]. Adrenaline might slightly improve short-term outcomes in outpatients but does not seem to reduce LOS in in-patients [9]. Current management recommendations and guidelines thus focus on supportive treatment with supplemental oxygen, fluid management, nasal douche with normal saline and/or nasal decongestants and respiratory support as needed, and avoiding unnecessary handling [10–14]. Recently, studies have investigated the effectiveness of nebulised hypertonic saline. The first results looked promising [15–18]. A Cochrane review, which included papers indexed in medical databases until May 2013 [15–25], concluded that nebulised 3% hypertonic saline may reduce LOS among infants with nonsevere acute bronchiolitis, and improves clinical severity scores among in- and outpatients [26]. Unfortunately, the studies included in …

Measurement of Bronchial Responsiveness in Children

Bronchial hyperresponsiveness (BHR) is considered to be a complex system of various interactions between airway inflammation, airway smooth muscle function, and airway mechanics. Because BHR is still considered to be a key feature of asthma, measures of BHR are widely used for diagnosis and monitoring of asthma in clinical practice and for research. Bronchial provocation tests (BPT) provide additional and useful information, which is not always picked up by non-invasive markers of airway inflammation. Direct airway challenge tests (e.g. methacholine, histamine) cause airway narrowing by acting ‘directly’ on their respective receptors on bronchial smooth muscles. Indirect challenge tests (e.g. exercise, hypertonic saline, cold air, mannitol, adenosine monophosphate) induce airflow limitation by an action on cells other than smooth muscle cells, with a variety of cells, mediators and receptors being involved in this process. Due to the closer association with inflammation, indirect challenges seem to be more specific for current clinically relevant asthma, and changes in BHR after treatment with inhaled steroids are observed within days to weeks.While there are standardized protocols for BPT in adults and older children, BPT in preschool children and infants are still in the research domain.

Cystic fibrosis screen positive, inconclusive diagnosis.

Purpose of review A challenging sequelae of newborn bloodspot screening (NBS) for cystic fibrosis (CF) has been the identification of infants with an unclear diagnosis after a positive NBS result, which leads to uncertainty for healthcare professionals and families. This review describes the classification, frequency, clinical outcome and early management of these infants. Recent findings In the US, infants with an inconclusive diagnosis after NBS are labelled ‘CF transmembrane conductance regulator (CFTR)-related metabolic syndrome’ (CRMS), and in Europe ‘CF screen positive, inconclusive diagnosis’ (CFSPID). According to recent studies, the majority of CRMS/CFSPID infants will remain well and have no long-term health implications. CRMS/CFSPID infants are at risk of developing CFTR-related disorder or atypical CF, with clinical features of CF but normal or intermediate sweat chloride values. Summary The frequency of CRMS/CFSPID is more than anticipated, relating to the increased use of screening algorithms that employ extended gene sequencing. The terms CRMS and CFSPID are interchangeable and there has been an international effort to harmonise the designation to CRMS/CFSPID. With clearer designation criteria, long-term data will be collected on outcomes that will guide management strategies.

Pulmonary Function Test Abnormalities in Pediatric Inflammatory Bowel Disease

Background: Pulmonary involvement in adult patients with inflammatory bowel disease (IBD) seems more common than previously appreciated. Its prevalence and development over time in pediatric IBD patients are largely unknown. Objectives: The aim was to study lung function including fraction of exhaled nitric oxide (FeNO) and transfer capacity for carbon monoxide (TLCO) in pediatric IBD patients and to describe the longitudinal development in a subset of patients with lung function abnormalities. Methods: Sixty-six measurements were made in 48 IBD patients (30 patients with Crohns disease and 18 with ulcerative colitis) and 108 matched controls. Patients with abnormal TLCO or elevated residual volume/total lung capacity (RV/TLC) ratios were invited for a follow-up. Statistical comparisons were made by nonparametric tests and ANOVA. Results: TLCO was decreased in IBD patients [median: 88% predicted (interquartile range, IQR, 22) vs. 99% predicted (IQR 19) in controls]. RV/TLC ratios were mildly elevated in patients with ulcerative colitis [32% (IQR 9) vs. 27% (IQR 8) in controls], and maximum expiratory flows at 50 and 25% of vital capacity were mildly reduced in patients with Crohns disease. FeNO and disease activity did not correlate with lung function abnormalities. Abnormalities did not consistently persist over a median follow-up period of 34 months. Conclusions: This study supports evidence that variable and fluctuating pulmonary involvement also occurs in pediatric IBD patients. Its clinical significance is unclear.

Key paediatric messages from Amsterdam.

The Paediatric Assembly of the European Respiratory Society (ERS) maintained its high profile at the 2015 ERS International Congress in Amsterdam. There were symposia on preschool wheeze, respiratory sounds and cystic fibrosis; an educational skills workshop on paediatric respiratory resuscitation; a hot topic session on risk factors and early origins of respiratory diseases; a meet the expert session on paediatric lung function test reference values; and the annual paediatric grand round. In this report the Chairs of the Paediatric Assemblys Groups highlight the key messages from the abstracts presented at the Congress. Paediatric highlights of the 2015 ERS International Congress http://ow.ly/10iBsz

Prevalence and reasons for smoking in adolescent Swiss childhood cancer survivors.

Smoking harms health, particularly that of childhood cancer survivors, who face risk of pulmonary and cardiovascular diseases because of chemotherapy and radiotherapy to the chest. This nationwide study assessed smoking habits and reasons for smoking in adolescent survivors and healthy peers.

Die Cystische Fibrose im Wandel der Zeit

Am Beispiel der haufigsten Erbkrankheit beim Menschen, der Cystischen Fibrose (CF), lasst sich gut nachvollziehen, was die Schweiz fur die steigenden Ausgaben im Gesundheitswesen erhalt. In den letzten 30 Jahren haben medizinische Fortschritte Lebenserwartung und Lebensqualitat von CF-Betroffenen drastisch verbessert, was nicht nur fur die Betroffenen, sondern fur die ganze Gesellschaft positive Auswirkungen hat.