Nutritional status is strongly associated with pulmonary function and survival in cystic fibrosis patients. Attainment of a normal growth pattern in childhood and maintenance of adequate nutritional ...status in adulthood represent major goals of multidisciplinary cystic fibrosis centers. International guidelines on energy intake requirements, pancreatic enzyme-replacement therapy and fat-soluble vitamin supplementation are of utmost importance in daily practice. The present review summarizes the most up-to-date information on early nutritional management in newly diagnosed patients and evaluates the benefits of aggressive nutritional support, assessment of nutritional status, recommendations for nutrition-related management in pancreatic-insufficient patients and the possible therapeutic impact of fat intake modulation upon inflammatory status.
Abstract Specialised CF care has led to a dramatic improvement in survival in CF: in the last four decades, well above what was seen in the general population over the same period. With the ...implementation of newborn screening in many European countries, centres are increasingly caring for a cohort of patients who have minimal lung disease at diagnosis and therefore have the potential to enjoy an excellent quality of life and an even greater life expectancy than was seen previously. To allow high quality care to be delivered throughout Europe, a landmark document was published in 2005 that sets standards of care. Our current document builds on this work, setting standards for best practice in key aspects of CF care. The objective of our document is to give a broad overview of the standards expected for screening, diagnosis, pre-emptive treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support. For comprehensive details of clinical care of CF, references to the most up to date European Consensus Statements, Guidelines or Position Papers are provided in Table 1 . We hope that this best practice document will be useful to clinical teams both in countries where CF care is developing and those with established CF centres.
Pulmonary neuroendocrine (NE) cells represent a small population in the airway epithelium, but despite this, hyperplasia of NE cells is associated with several lung diseases, such as congenital ...diaphragmatic hernia and bronchopulmonary dysplasia. The molecular mechanisms causing the development of NE cell hyperplasia remains poorly understood. Previously, we showed that the SOX21 modulates the SOX2-initiated differentiation of epithelial cells in the airways. Here, we show that precursor NE cells start to develop in the SOX2 + SOX21 + airway region and that SOX21 suppresses the differentiation of airway progenitors to precursor NE cells. During development, clusters of NE cells start to form and NE cells mature by expressing neuropeptide proteins, such as CGRP. Deficiency in SOX2 resulted in decreased clustering, while deficiency in SOX21 increased both the numbers of NE ASCL1 + precursor cells early in development, and the number of mature cell clusters at E18.5. In addition, at the end of gestation (E18.5), a number of NE cells in
Sox2
heterozygous mice, did not yet express CGRP suggesting a delay in maturation. In conclusion, SOX2 and SOX21 function in the initiation, migration and maturation of NE cells.
Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterized by the herniation of abdominal organs into the chest cavity. The high mortality and morbidity of CDH patients are ...primarily caused by the associated pulmonary hypertension (PH), characterized by the thickening of the vascular media and adventitia. The media consist of heterogeneous populations of vascular smooth muscle cells (VSMC), ranging from synthetic to the characteristic contractile cells. VSMCs are influenced by developmental and environmental cues and may play a role in the development of the structural changes observed in CDH patients. Therefore, we hypothesized that the distribution of the VSMC populations may already be different at the origin of CDH development.
We analyzed the protein expression of specific markers associated with synthetic and contractile VSMC phenotypes in human lungs at different developmental stages. Next, we compared lungs of premature and term CDH patients, as well as patients with lung hypoplasia due to renal agenesis or PROM, with age-matched controls.
Synthetic and contractile VSMCs are distributed in a temporal and spatial specific pattern along the proximodistal axis of the lung. CDH patients have more abundant contractile VSMCs which are also more distally distributed. This different distribution pattern is already observed from 19weeks of gestation onwards.
Our data suggest that the more extensive distribution of contractile VSMCs is associated with an early maturation of the pulmonary vasculature, contrasting the concept that CDH might be the result of delayed maturation of the epithelium.
► Vascular smooth muscle cells (VSMC) vary morphologically from synthetic to contractile cells ► Congenital Diaphragmatic Hernia (CDH) patients suffer from pulmonary hypertension (PH) ► PH shows thickening of adventitia, VSMC layer and vascular neo-muscularization ► CDH lungs contain more synthetic VSMCs than controls ► We show that VSMCs are phenotypically different at the onset of CDH.
Congenital diaphragmatic hernia is a structural birth defect of the diaphragm, with lung hypoplasia and persistent pulmonary hypertension. Aside from vascular defects, the lungs show a disturbed ...balance of differentiated airway epithelial cells. The Sry related HMG box protein SOX2 is an important transcription factor for proper differentiation of the lung epithelium. The transcriptional activity of SOX2 depends on interaction with other proteins and the identification of SOX2-associating factors may reveal important complexes involved in the disturbed differentiation in CDH. To identify SOX2-associating proteins, we purified SOX2 complexes from embryonic mouse lungs at 18.5 days of gestation. Mass spectrometry analysis of SOX2-associated proteins identified several potential candidates, among which were the Chromodomain Helicase DNA binding protein 4 (CHD4), Cut-Like Homeobox1 (CUX1), and the Forkhead box proteins FOXP2 and FOXP4. We analyzed the expression patterns of FOXP2, FOXP4, CHD4, and CUX1 in lung during development and showed co-localization with SOX2. Co-immunoprecipitations validated the interactions of these four transcription factors with SOX2, and large-scale chromatin immunoprecipitation (ChIP) data indicated that SOX2 and CHD4 bound to unique sites in the genome, but also co-occupied identical regions, suggesting that these complexes could be involved in co-regulation of genes involved in the respiratory system.
L’état nutritionnel est étroitement corrélé à la fonction respiratoire et à la survie des patients atteints de mucoviscidose. La généralisation du dépistage néonatal en France depuis 2002 permet de ...débuter dès les premières semaines de vie la prise en charge nutritionnelle préventive, voire un support nutritionnel ayant pour objectif un statut nutritionnel identique à la population générale et ceci tout au long de la vie du patient. Cette mise au point qui s’appuie sur des recommandations internationales décrit l’approche diététique, les modalités de prescription des extraits pancréatiques et des vitamines liposolubles ainsi que la prise en charge nutritionnelle en cas de dénutrition débutante ou confirmée.
Nutritional status has a strong association with respiratory function and survival. Implementation of the French nationwide newborn screening program since 2002 allows an early preventive nutritional approach and nutritional support if indicated, aiming at maintaining a nutritional status similar to healthy peers during the patient's life. This review relies on international recommendations and describes the dietetic approach, pancreatic enzymes and fat-soluble vitamins supplementation and also nutritional support in case of moderate or severe malnutrition.
Abstract Complete or incomplete intestinal obstruction by viscid faecal material in the terminal ileum and proximal colon – distal intestinal obstruction syndrome (DIOS) – is a common complication in ...cystic fibrosis. Estimates of prevalence range from 5 to 12 episodes per 1000 patients per year in children, with higher rates reported in adults. DIOS is mainly seen in patients with pancreatic insufficiency, positive history of meconium ileus and previous episodes of DIOS. DIOS is being described with increasing frequency following organ transplantation. Diagnosis is based on suggestive symptoms with a right lower quadrant mass confirmed on X-ray. The main differential is chronic constipation. Treatment consists of rehydration combined with stool softening laxatives or gut lavage with balanced electrolyte solutions. Rapid fluid shifts have been described following osmotic agents. Avoiding dehydration and optimizing pancreatic enzyme dosage may reduce the chance of further episodes. Prophylactic laxative therapy is widely used, but is not evidence-based.
Over the past two decades there has been considerable progress with the evaluation and management of infants with an inconclusive diagnosis following Newborn Screening (NBS) for cystic Fibrosis (CF). ...In addition, we have an increasing amount of evidence on which to base guidance on the management of these infants and, importantly, we have a consistent designation being used across the globe of CRMS/CFSPID. There is still work to be undertaken and research questions to answer, but these infants now receive more consistent and appropriate care pathways than previously.
It is clear that the majority of these infants remain healthy, do not convert to a diagnosis of CF in childhood, and advice on management should reflect this. However, it is also clear that some will convert to a CF diagnosis and monitoring of these infants should facilitate their early recognition. Those infants that do not convert to a CF diagnosis have some potential of developing a CFTR-RD later in life. At present, it is not possible to quantify this risk, but families need to be provided with clear information of what to look out for. This paper contains a number of changes from previous guidance in light of developing evidence, but the major change is the recommendation of a detailed assessment of the child with CRMS/CFSPID in the sixth year of age, including respiratory function assessment and imaging. With these data, the CF team can discuss future care arrangements with the family and come to a shared decision on the best way forward, which may include discharge to primary care with appropriate information. Information is key for these families, and we recommend consideration of a further appointment when the individual is a young adult to directly communicate the implications of the CRMS/CFSPID designation.
Abstract 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.
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