Acid-base disturbances in dehydrated patients with cystic fibrosis : four case reports with review of literature

Most episodes of vomiting, reduced intake and diarrhoea in children can be evaluated and treated without additional tests. However, when the degree of clinical dehydration is not in line with the patient's medical history, other diagnoses should be suspected. In the presence of a hyponatraemic hypochloraemic metabolic alkalosis, cystic fibrosis (CF) should be included in the differential diagnosis, especially if there is failure to thrive even in the absence of respiratory symptoms. Furthermore, young patients diagnosed with CF have a higher risk for an acute electrolyte decompensation caused by increased salt and fluid losses. We present 4 paediatric cases to raise the awareness of electrolyte disturbances in CF patients

A comprehensive study of three different portable XRF scanners to assess the soil geochemistry of an extensive sample dataset

The assessment of soil elemental concentrations nowadays mainly occurs through conventional laboratory analyses. However, proximal soil sensing (PSS) techniques such as X-ray fluorescence (XRF) spectrometry are proving to reduce analysis time and costs, and thus offer a worthy alternative to laboratory analyses. Moreover, XRF scanners are non-destructive and can be directly employed in the field. Although the use of XRF for soil elemental analysis is becoming widely accepted, most previous studies were limited to one scanner, a few samples, a few elements, or a non-diverse sample database. Here, an extensive and diverse soil database was used to compare the performance of three different XRF scanners with results obtained through conventional laboratory analyses. Scanners were used in benchtop mode with built-in soil calibrations to measure the concentrations of 15 elements. Although in many samples Cu, S, P, and Mg concentrations were up to 6, 12, 13, and 5 times overestimated by XRF, and empirical recalibration is recommended, all scanners produced acceptable results, even for lighter elements. Unexpectedly, XRF performance did not seem to depend on soil characteristics such as CaCO3 content. While performances will be worse when expanding to the field, our results show that XRF can easily be applied by non-experts to measure soil elemental concentrations reliably in widely different environments

Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis

Cystic fibrosis (CF) has entered the era of variant-specific therapy, tailored to the genetic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CFTR modulators, the first variant-specific therapy available, have transformed the management of CF.The latest standards of care from the European CF Society (2018) did not include guidance on variant-specific therapy, as CFTR modulators were becoming established as a novel therapy. We have produced interim standards to guide healthcare professionals in the provision of variant-specific therapy for people with CF.Here we provide evidence-based guidance covering the spectrum of care, established using evidence from systematic reviews and expert opinion. Statements were reviewed by key stakeholders using Delphi methodology, with agreement (≥80%) achieved for all statements after one round of consultation. Issues around accessibility are discussed and there is clear consensus that all eligible people with CF should have access to variant-specific therapy

Working towards an optimal nutritional status in people with cystic fibrosis

Nutritional intake is a demand-led process. Via intake of energy and nutrients our body aims to maintain homeostasis through a complex of internal and external systems. The region of homeostasis is threatened on a daily basis by environmental, lifestyle and biological factors. Nutritional science focuses on the ability to determine the requirements for energy and nutrients and the extent to which the demand has been met. Nutrition requirements vary in health and disease. Many disciplines are needed to understand how energy and nutrients are made available to the body so they can be metabolized and used for functioning, growth and development. Cystic Fibrosis is an example that challenges homeostasis through different complex systems. Since the first report on Cystic Fibrosis in 1938, a body of literature in the field of nutrition, aiming to improve the nutritional status in pwCF, has developed. However, optimizing the nutritional status of pwCF is still challenging. Current guidelines on nutrition in CF were published in 2016, compiled with recommendations that are mostly based on expert opinions. In this thesis, several domains in the CF nutrition therapy are addressed. As the first subject, literature was reviewed on assessment of the nutritional status, namely the use of growth charts and evaluation of body composition, and on the nutritional therapy, namely protein intake and digestibility and the use of pancreatic enzyme replacement therapy. The persistent association between FEV1pp and BMI has led to continuous strategies to improve BMI or maintain a BMI in target range. As a consequence, the appropriate classification of the patients’ nutritional status requires national and ethnic appropriate growth charts when evaluating nutritional interventions or using BMI z-scores as an outcome parameter in research. Especially, in the first years of life as nutrition therapy is considered an important adjunct to pulmonary therapy. Measurement of body composition should receive more attention in clinics and research as it is suggested to be a more sensitive parameter for the evaluation of nutritional status and predictor for deterioration of pulmonary function. Despite this recommendation, more research is needed in the use of bio-electrical impedance technique. This method requires reference ranges and a consensus on the used frequencies and equations. Current and future nutritional therapy should focus on improving body composition. This requires a multidisciplinary approach. As nutrition is a demand-led process, pwCF have to tackle obstacles: a sufficient intake of nutrients and achieving an adequate digestion.   Currently there is no protein recommendation according to age, disease stage or pancreatic function. As amino acids are mainly absorbed in the proximal part of the small intestine, pH in the small intestine, pancreatic enzyme activity and timing of administration of pancreatic enzymes might play a crucial role, independently of the dosage. The lack of evidence on adequate use of pancreatic enzyme supplementation feeds the necessity for research on timing and dosing. Especially in infants and young children as they have the highest requirement for protein expressed per kg body weight. A second subject focused on the sodium status in pwCF. In a first phase a literature review was performed to discuss current evidence on prevalence, pathophysiology and clinical impact of sodium deficiency in pwCF. Also, the available methods to assess the sodium status and the necessity of sodium supplementation were discussed. A high prevalence of sodium deficiency was observed in infants, especially in infants living in an arid climate. A hyponatremic, hypochloremic metabolic alkalosis with or without hypokalemia was diagnosed in 42% of the infants. However, metabolic alkalosis was also observed in adult CF patients. A risk for a decrease in serum sodium was also observed as a consequence of physical activity. The presence of sodium depletion is associated with a worse body weight or weight loss. Therefore, European nutrition guidelines recommended to routinely evaluate the sodium status in pwCF by measuring fractional sodium (FENa) excretion or urinary sodium: creatinine ratio (UNa+/Ucreat). FENa is the gold standard however, this method requires a paired blood and urine samples. UNa+/Ucreat has only been studied in 50 samples of 10 infants. Therefore in a second phase a retrospective study was performed to evaluate urinary salt parameters as a surrogate for the FENa in a large group of children and adults with CF. Based on our results UNa+/Ucreat appears to be surrogate marker for FENa and age-related thresholds are associated with a FENa of 0.5%. In people with an established CF diagnosis, the prevalence of electrolyte disturbances is expected to decrease due to highly effective CFTR-function targeting therapies. In this case the ratio can be used to select individuals who are still in need for an increased intake of sodium. The third subject of this thesis focused on enteral nutrition as nutrition therapy. Tube feeding has been used as a nutritional intervention since the early 1980’s in CF. Small retrospective studies have shown improvements in weight and some suggested an improvement in pulmonary function. Despite the absence of large-scale clinical trials, enteral tube feeding has been considered an appropriate way to deliver nutrients when nutritional demands cannot be met. Studies on the long-term use of enteral tube feeding (ETF) are scarce and equivocal on the effect of ETF on pulmonary function. In a first phase the data of the Belgian CF Registry were used to compare individuals with ETF with controls over a period of 6 years before the start of ETF to up to 6 years after the start of ETF. A low prevalence of ETF was observed between 2000 and 2013, 1.8 – 5.3%. In pwCF and ETF a low BMI was already reported at start of ETF and six years before ETF initiation. In the first two years there was a rapid increase in BMI observed. However, BMI did not reach the 50th percentile and it remained significantly lower than that of controls. We observed a decrease in the rate of pulmonary decline after ETF was started concurrent with a decrease in admission to the hospital. In a second phase a multicenter retrospective study was conducted to explore the long-term effect of ETF on nutritional status, growth velocity and pulmonary function. Also, the timing of ETF initiation was compared with the recommendation in the European nutrition guidelines. Anthropometric parameters were described over a period of 8 years, 3 years before and 5 years after the start of ETF. Based on the guidelines, in 60% of the patients the start of ETF was too late as 3 years before the start of ETF they already had a height z-score 1.3 two years after the start of ETF. This was especially seen in younger patients. Concurrent, a significant increase in growth velocity was seen after ETF was started. These data support considering ETF at an early age if nutrition-demands are not met. The improvement in height was not observed in the registry study. In a fourth subject of this thesis the impact of a multidisciplinary approach to improve the nutritional status was studied. A 3-week intervention study in the resident rehabilitation center “Zeepreventorium” resulted in an improvement in BMI and body composition in children and adults. An improvement in FEV1pp was observed in children and adults. An increase in weight was observed despite a lower kcal intake compared to the theoretical energy requirements. The change in BMI was positively correlated with a higher energy intake and a higher protein intake (g/kg). However, it was also negatively correlated to the number of steps. The change in FFMI was weakly correlated to protein intake and with total energy expenditure. This small study showed that a multi-factorial approach in a residential 3-weekprogram might improve BMI and also FEV1pp. In a fifth and final subject of this thesis, diurnal and nocturnal glycemic patterns, measured by CGM, were studied in children and adults with CF not previously diagnosed with diabetes. CGM-derived indices of glycemic control were also studied in relation to pulmonary function and nutritional status. This was in response to the reported insidious character of cystic fibrosis related diabetes and the absence of clinical relevant CGM indices in the pre-diabetes state. A retrospective analysis of CGM data of pwCF with an impaired OGGT and/or increased HbA1c was conducted. As previously reported in literature CGM patterns are disturbed despite a normal OGTT at 2-hours. Our study is the first to report diurnal and nocturnal glycemic patterns in children and adults with CF and an impaired OGTT and/or increased HbA1c. In our adult cohort, an adversely association was found between CGM indices especially reflecting the glucose metabolism during nighttime and concurrent FEV1pp. Despite a similar glucose profile, this association was not found in the pediatric cohort. Based on the results of our study and the available literature it can be suggested that age related cut-offs for CGM indices are needed. But in a first step a consensus is warranted on the appropriate CGM indices to study clinical deterioration as a consequence of subtle changes in the glucose metabolism

Clinical effects of probiotics in cystic fibrosis patients : a systematic review

Cystic fibrosis (CF) is characterised by a build-up of thick, intransient mucus linings of the digestive and respiratory mucosa, which disrupts digestive system functioning and microbiota composition. In view of the potential for probiotics to enhance microbiota composition in other contexts, this study investigated the current evidence for probiotics as an adjunct to usual therapy for CF. Electronic clinical databases were interrogated for human randomised, controlled, intervention trials (1985–2015) testing the effects of probiotics on clinical endpoints in CF were reviewed. From 191 articles identified in initial searches, six studies met the critical inclusion criteria, and were reviewed in detail. These studies varied in size (n = 22 to 61) but were generally small and showed substantial diversity in protocol, specific probiotic species used and range of clinical outcomes measured. Probiotic administration showed beneficial effects on fecal calprotectin levels, pulmonary exacerbation risk, and quality of life indicators. In one study, such changes were associated with variations in gut microbiota composition. Despite encouraging preliminary results, the limited number of small and highly varied studies to date do not justify the addition of probiotics as an adjunct to current CF treatment protocols. Importantly, very minimal adverse effects of probiotics have been reported

Nutrition and pancreatic enzyme intake in patients with cystic fibrosis with distal intestinal obstruction syndrome

Background: The etiology of distal intestinal obstruction syndrome (DIOS) remains unclear. Food intake and pancreatic enzyme replacement therapy (PERT) are often blamed for its occurrence. This study evaluates the nutrition intake and PERT of patients with cystic fibrosis (CF) at a first episode of DIOS. Methods: All patients with CF perform annually a 3-day intake diary to evaluate their caloric, protein, fat, dietary fiber, liquid, and PERT intake. Patients diagnosed with a first episode of DIOS (n = 12) retrospectively completed an intake diary of the 3 days preceding the DIOS episode supervised by an expert dietitian. Results were compared with those of 1 year before and also with 36 CF controls matched for age, sex, genotype, and disease severity. All were pancreatic insufficient. Results: A first DIOS episode was diagnosed in 12 patients with CF. Only the absolute median fat intake (P = .015) and pancreatic enzyme intake (P = .035) were higher at the time of the DIOS attack in comparison to the preceding year. This could result from the difference in data collection or from the recommendations to increase fat intake and concomitant enzyme intake, since this trend was also found in the control group. The significant difference disappears when enzyme intake is expressed as units of lipase/g of fat. No other significant dietary differences were found. Conclusions: This study provides no indications for a potential role of nutrition factors or pancreatic enzymes in the first occurrence of DIOS