Does the Nutritional Intake and Diet Quality of Children With Chronic Kidney Disease Differ From Healthy Controls? A Comprehensive Evaluation.

OBJECTIVE: Children with chronic kidney disease (CKD) experience many obstacles to achieving optimal dietary intake. Dietary intake patterns remain unexplored or poorly described. This study compares nutritional intake and diet quality of Australian children with CKD to controls. METHODS: A food frequency questionnaire captured intake data and was compared to controls. Nutritional intake was determined using individualized nutrient reference values, and diet quality described using the Australian Guide to Healthy Eating and the Australian Child and Adolescent Recommended Food Score. RESULTS: Children with CKD (n = 36) and controls (n = 82) were studied. Children with CKD had lower weight and height z scores, but higher body mass index (P < .0001 for all parameters). Children with CKD had adequate energy intake, and excessive protein and sodium intake (336% and 569%). They were significantly less likely to meet requirements for vitamin A (P < .001), thiamine (P = .006), folate (P = .01), vitamin C (P = .008), calcium (P < .0001), iron (P = .01), magnesium (P = .0009), and potassium (P = .002). No child met recommended vegetable intake; however, less than half of children with CKD met fruit (44%), grains (31%), and dairy serves (31%). They were also less likely to meet recommended fruit and dairy serves (P = .04 and P = .01, respectively). Non-core foods provided 36% of energy, and although comparable to controls, was contributed more by takeaway foods (P = .01). CONCLUSION: Children with CKD have reduced nutritional intake of key nutrients and consume more takeaways than controls. Attention to increasing core foods, limiting sodium intake, and managing restrictions while promoting nutrient density appears necessary.

Body composition and body mass index measures from 8 to 18 years old in children with cystic fibrosis.

BACKGROUND: Historically, body mass index (BMI) >50th percentile has represented optimal nutritional status in children with cystic fibrosis (CF) due to its positive association with lung function. Body composition parameters including fat-free mass index (FFMI) have been suggested as a more physiological nutrition benchmark. AIMS: (1) describe changes in body composition with age and gender; (2) assess the correlation between measures of nutritional status (FFMI-z, FMI-z, BMI-z) and lung function (forced expiratory volume in one second predicted; FEV1pp). METHODS: This retrospective, mixed cross-sectional and serial measures study consisted of children with CF (8 to 18 years) attending Sydney Children's Hospital (2007-2020). FFMI and fat mass index (FMI) were taken from biennial dual energy x-ray absorptiometry (DXA) scans. Z-scores were derived using Well's reference population [1]. Repeated measures correlation analyses assessed correlations between FFMI-z, FMI-z, and BMI-z with FEV1pp. RESULTS: 339 DXA reports were analysed from 137 patients. There were slight downwards trends in BMI-z and FMI-z, and an upwards trend in FFMI-z with increasing age and across both genders. Females had higher FMI-z and FFMI-z than males from 12.5 years. There was a weak, positive correlation between FEV1pp and BMI-z (r = 0.14, p = 0.04), and FFMI-z (r = 0.25, p<0.001). FMI-z had no correlation with FEV1pp (r=-0.06, p = 0.41). CONCLUSION: Deficits in FFMI exist despite increasing trends with age. FFMI-z and BMI-z had a weak, positive correlation with FEV1pp. In contemporary cohorts, nutritional status (reflected by surrogate markers such as FFMI and BMI) may be less influential upon lung function than in previous decades. [1]: Wells, J.C., et al. Body-composition reference data for simple and reference techniques and a 4-component model: a new UK reference child. Am. J. Clin. Nutr.96, 1316-1326 (2012).

Diet and the gut-lung axis in cystic fibrosis - direct & indirect links.

Cystic fibrosis (CF) is a multisystem, autosomal, recessive disease primarily affecting the lungs, pancreas, gastrointestinal tract, and liver. Whilst there is increasing evidence of a microbial 'gut-lung axis' in chronic respiratory conditions, there has been limited analysis of such a concept in CF. We performed a comprehensive dietary and microbiota analysis to explore the interactions between diet, gastrointestinal microbiota, respiratory microbiota, and clinical outcomes in children with CF. Our results demonstrate significant alterations in intestinal inflammation and respiratory and gastrointestinal microbiota when compared to age and gender matched children without CF. We identified correlations between the gastrointestinal and respiratory microbiota, lung function, CF pulmonary exacerbations and anthropometrics, supporting the concept of an altered gut-lung axis in children with CF. We also identified significant differences in dietary quality with CF children consuming greater relative proportions of total, saturated and trans fats, and less relative proportions of carbohydrates, wholegrains, fiber, insoluble fiber, starch, and resistant starch. Our findings position the CF diet as a potential modulator in gastrointestinal inflammation and the proposed gut-lung axial relationship in CF. The dietary intake of wholegrains, fiber and resistant starch may be protective against intestinal inflammation and should be explored as potential therapeutic adjuvants for children with CF.

Gastroenterology services for patients with Cystic Fibrosis across Australia and New Zealand: a multi-stakeholder assessment of patients' and professionals' perspectives.

Introduction: Gastrointestinal (GI) symptoms are common in individuals with Cystic Fibrosis (CF). International research has highlighted that GI care for this group of patients is lacking. Gastroenterology services to CF clinics across Australasia are yet to be examined. This study aimed to describe the current service delivery model and identify areas for improvement that may lead to positive patient outcomes. Materials and methods: CF clinicians (dietitians, clinical nurse consultants, respiratory consultants), gastroenterologists (GE), and patients or their carers from Australia and New Zealand (NZ) were surveyed online to gather their opinions on CF gastroenterology services provided in their region. Data were analysed using descriptive statistics (frequencies and percentages). Likert scale questions were analysed by grouping responses 1-5 and 6-10, presented alongside the median and interquartile range (IQR). Mann-Whitney U and chi-square tests were used to look at differences between stakeholder groups. Results: One hundred and fifty-six health professionals and 172 patients or their carers completed the survey. Results showed that the current GI model of care is predominantly a publicly funded service delivered outside of CF clinic time. GE are largely not integrated into the CF team and report a lack of training opportunities. There is a higher level of dissatisfaction with the current service model in NZ than Australia. Discussion: No stakeholder group deemed the current CF gastroenterology service model as adequate, leaving opportunity for transformations in this field. Ideally this study will invigorate the need for promotion and integration of GI services that would ultimately benefit the whole CF community.

Dietary intake in children on the autism spectrum is altered and linked to differences in autistic traits and sensory processing styles.

Diets of children and adolescents on the autism spectrum often differ when compared to their non-autistic peers. Most dietary studies have been limited by small sample sizes and rarely assess the heterogeneity of autism. Addressing this gap, this study compared the anthropometrics, dietary composition, dietary quality, and food variety of 154 Australian children and adolescents on the spectrum and 213 non-autistic children (71 siblings and 142 unrelated controls). Beyond the case-control approach, within-group comparisons assessed the influence of autism clinical presentations and sensory processing styles on body mass index (BMI) and measures of dietary intake among those on the spectrum. In this word first study of diet that included between-group comparisons with non-autistic peers (siblings and an unrelated comparison group) and within-autism group comparisons, we found that children on the spectrum consumed limited variety and lower quality of food and non-autistic siblings also ate comparably higher levels of energy-dense, nutrient poor food, and less diary. This may be due to autistic traits influencing family's diets or shared sensory sensitivities driving dietary intake. Within the autism group, higher autistic traits were associated with lower BMIs and a specific dietary pattern higher in simple carbohydrates and lower in unprocessed protein. Contrastingly, greater sensitivity to sensory stimuli was associated with a healthier diet. Increased age was linked to more varied diets but also diets higher in saturated fats and energy-dense, nutrient poor foods. Overall, this research highlights that potential mediators of dietary intake, such as familial influences, autistic traits, sensory processing styles, age and sex, need to be considered when assessing diet in the autistic population. LAY SUMMARY: In this study of dietary differences linked to autism, children, and teenagers on the spectrum ate fewer different foods and were less likely to eat recommended amounts of fruits and vegetables when compared to non-autistic siblings and unrelated children and teenagers. There were also family differences, in that those on the spectrum and their siblings ate more unhealthy foods and less dairy. Among those on the spectrum, dietary differences were linked to age, sex, autistic traits and sensory processing styles.

Evaluating the Dietary Intake of Children With Esophageal Atresia: A Prospective, Controlled, Observational Study.

OBJECTIVES: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. METHODS: This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. RESULTS: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. CONCLUSIONS: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.

Evaluating the Dietary Intakes of Energy, Macronutrients, Sugar, Fiber, and Micronutrients in Children With Celiac Disease.

OBJECTIVES: Children with celiac disease (CD) follow a lifelong gluten-free diet. This restrictive diet may be associated with nutritional compromise. Our objectives were, therefore, to evaluate the dietary composition (energy, macronutrients and micronutrients, and fiber) in children with CD compared with healthy controls (HC) and relationship between dietary composition and socioeconomic status. METHODS: This cross-sectional, case-control study recruited children with CD ages 2 to 18 years and HC matched for age, sex, and socioeconomic status. Clinical, sociodemographic, and dietary information were collected. A false discovery rate correction was applied to the P-value for multiple comparisons (q-value). RESULTS: Sixty-five CD children were matched with 65 HC (mean [SD] age: 10.2 [3.6] vs 10.1 [3.7] years, P = 0.96). Compared with HC, CD children had higher intakes of energy (2413.2 [489.9] vs 2190.8 (593.5) kcal/day, P = 0.02), total fat (818.1 ±â€Š180.9 vs 714.3 ±â€Š212.2 kcal/day, q = 0.018), and subtypes of fat (saturated, polyunsaturated, and monounsaturated). There were no differences in other macronutrients, sugar, micronutrients, or fiber between CD and HC, and no difference in dietary intake among CD between socioeconomic disadvantage versus advantage. Children with CD had lower weight z-scores (-0.06 [1.05] vs 0.47 [0.96], P = 0.003) and body mass index (BMI) z-scores (-0.02 [0.88] vs 0.41 [1.09], P = 0.02) than HC. CONCLUSIONS: Children with CD had higher calorie and fat intake compared with HC. Despite this, CD children had lower weight and BMI z-scores compared with HC.

Evaluating the Alimentary and Respiratory Tracts in Health and disease (EARTH) research programme: a protocol for prospective, longitudinal, controlled, observational studies in children with chronic disease at an Australian tertiary paediatric hospital.

INTRODUCTION: Chronic gastrointestinal and respiratory conditions of childhood can have long-lasting physical, psychosocial and economic effects on children and their families. Alterations in diet and intestinal and respiratory microbiomes may have important implications for physical and psychosocial health. Diet influences the intestinal microbiome and should be considered when exploring disease-specific alterations. The concepts of gut-brain and gut-lung axes provide novel perspectives for examining chronic childhood disease(s). We established the 'Evaluating the Alimentary and Respiratory Tracts in Health and disease' (EARTH) research programme to provide a structured, holistic evaluation of children with chronic gastrointestinal and/or respiratory conditions. METHODS AND ANALYSIS: The EARTH programme provides a framework for a series of prospective, longitudinal, controlled, observational studies (comprised of individual substudies), conducted at an Australian tertiary paediatric hospital (the methodology is applicable to other settings). Children with a chronic gastrointestinal and/or respiratory condition will be compared with age and gender matched healthy controls (HC) across a 12-month period. The following will be collected at baseline, 6 and 12 months: (i) stool, (ii) oropharyngeal swab/sputum, (iii) semi-quantitative food frequency questionnaire, (iv) details of disease symptomatology, (v) health-related quality of life and (vi) psychosocial factors. Data on the intestinal and respiratory microbiomes and diet will be compared between children with a condition and HC. Correlations between dietary intake (energy, macro-nutrients and micro-nutrients), intestinal and respiratory microbiomes within each group will be explored. Data on disease symptomatology, quality of life and psychosocial factors will be compared between condition and HC cohorts.Results will be hypothesis-generating and direct future focussed studies. There is future potential for direct translation into clinical care, as diet is a highly modifiable factor. ETHICS AND DISSEMINATION: Ethics approval: Sydney Children's Hospitals Network Human Research Ethics Committee (HREC/18/SCHN/26). Results will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04071314.

Micronutrient intake in children with cystic fibrosis in Sydney, Australia.

BACKGROUND: Children with CF have been reported to consume significantly more energy-dense, nutrient-poor foods than controls where there are now concerns of inadequate micronutrient intake. There are no current or comprehensive dietary studies assessing micronutrient intake in CF children. OBJECTIVES: To evaluate micronutrient intake in children with CF compared to recommended dietary intakes (RDIs). METHODS: Dietary intake of 13 micronutrients was measured in CF children aged 2-18 years and age- and sex-matched controls using a validated food frequency questionnaire (The Australian Child and Adolescent Eating Survey). RESULTS: CF children (n = 82) consumed significantly more energy than controls (n = 82) [3142(2531-3822) kcal vs 2216(1660-2941) kcal; p < .001]. Absolute intake in CF children was significantly higher in all micronutrients except vitamin C and folate, however energy-adjusted intake was significantly lower for all micronutrients except vitamin A, sodium, calcium and phosphorous. Energy-adjusted intake in primary school CF children was significantly less than controls in 8/13 micronutrients. Overall, median intakes exceeded the RDIs for all micronutrients however CF children fell short of the RDIs for folate (26.8%), iron (15.9%) and calcium (9.8%). In pre-school, 50% of CF children and 91.7% of controls did not meet the iron RDI. High school CF and control children failed to meet RDIs for 7/13 and 9/13 micronutrients respectively. CONCLUSION: Increased intake of most micronutrients in CF children was largely attributed to higher energy consumption. However, micronutrient density of the diet declined with increasing age, where high school children failed to meet RDIs for most key micronutrients.

Dietary intake of energy-dense, nutrient-poor and nutrient-dense food sources in children with cystic fibrosis.

BACKGROUND: Prescription of a high-energy, high-fat diet is a mainstay of nutrition management in cystic fibrosis (CF). However, families may be relying on energy-dense, nutrient-poor (EDNP) foods rather than nutrient-dense (ND) foods to meet dietary targets. We aimed to evaluate the relative contribution of EDNP and ND foods to the usual diets of children with CF and identify sociodemographic factors associated with higher EDNP intakes. METHODS: This is a cross-sectional comparison of children with CF aged 2-18 years and age- and gender-matched controls. Dietary intake was assessed using the Australian Child and Adolescent Eating Survey (ACAES) food frequency questionnaire. RESULTS: Children with CF (n = 80: 37 males; mean age 9.3 years) consumed significantly more EDNP foods than controls (mean age 9.8 years) in terms of both total energy (median [IQR]: 1301 kcal/day (843-1860) vs. 686 kcal/day (480-1032); p < 0.0001), and as a proportion of energy intake (median [IQR]: 44% (34-51) vs. 31% (24-43); p < 0.0001). Although children with CF met their estimated energy requirements (median [IQR]: 158% (124-187) vs. 112% (90-137); p < 0.0001) and their diets were high in fat (median [IQR]: 38% (35-41) vs. 34% (32-36); p < 0.0001), this was largely attributable to EDNP foods. High EDNP intakes (≥10 serves/day) were associated with socioeconomic disadvantage (p = 0.01) and rural residential location (p = 0.03). DISCUSSION: The energy- and fat-dense CF diet is primarily achieved by overconsumption of EDNP foods, rather than ND sources. This dietary pattern may not be optimal for the future health of children with CF, who are now expected to survive well into adulthood.

Age-related levels of fecal M2-pyruvate kinase in children with cystic fibrosis and healthy children 0 to 10years old.

BACKGROUND: The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. METHODS: M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used. RESULTS: M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) (P=0.998) or HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6; 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively; P=0.001). CONCLUSIONS: Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.

Age-dependent variation of fecal calprotectin in cystic fibrosis and healthy children.

BACKGROUND: Fecal calprotectin may be used as a non-invasive method to assess the effect of novel therapies on the gut in cystic fibrosis (CF). METHOD: Stools from CF patients and healthy controls (HC) (0-10years old) were prospectively collected for evaluation of temporal trends. RESULTS: 130 CF samples (64 subjects) and 114 HC samples (101 subjects) were collected. Overall, fecal calprotectin levels were different in CF patients and HC from 0 to 10years (P=0.0002). Fecal calprotectin in CF was significantly lower than HC from 0 to 1years (P=0.03) and demonstrated an upward trajectory until 4years. From >4 to 10years calprotectin was consistently higher in CF patients compared with HC (P=0.007). CONCLUSIONS: Fecal calprotectin levels in children with CF and HC were age-dependent and had distinct trajectories. Careful interpretation of calprotectin is required if used in drug trials for CF, particularly in children less than 4years old.

High ambient temperature and risk of intestinal obstruction in cystic fibrosis.

AIMS: Distal intestinal obstruction syndrome (DIOS) and constipation in cystic fibrosis (CF) are conditions associated with impaction and/or obstruction by abnormally viscid mucofaecal material within the intestinal lumen. Dehydration has been proposed as a risk factor for DIOS and constipation in CF. The study primarily aimed to determine whether warmer ambient temperature and lower rainfall are risk factors for DIOS and constipation in CF. METHODS: Hospitalisations for DIOS (incomplete or complete) and/or constipation were retrospectively identified (2000-2012). Genotype, phenotype, temperatures and rainfall data (for the week preceding and season of hospitalisation) were collected. RESULTS: Twenty-seven DIOS (59.3% incomplete; 40.7% complete) and 44 constipation admissions were identified. All admitted patients were pancreatic insufficient. Meconium ileus was significantly more likely in DIOS than constipation (64.7% vs. 33.3%; P = 0.038) and in complete than incomplete DIOS (100% vs. 57.1%; P = 0.04). The maximum temperature of the week before DIOS admission (mean (standard deviation) = 28.0 (5.8) °C) was significantly higher than the maximum temperature of the season of admission (25.2 (3.4) °C; P = 0.002). Similarly, the maximum temperature of the week before hospitalisation for constipation (mean (standard deviation) = 27.9 (6.3) °C) was significantly warmer compared with the season of admission (24.0 (4.1) °C; P < 0.0001). There were no significant differences between levels of rainfall during the week before hospitalisation and the season of admission for both DIOS and constipation. CONCLUSIONS: Relatively high ambient temperature may play a role in the pathogenesis of DIOS and constipation in CF.

Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency.

AIM: Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). METHODS: A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. RESULTS AND CONCLUSIONS: Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the 'unlikely' PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000-40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy.

Fecal Human ß-Defensin 2 in Children with Cystic Fibrosis: Is There a Diminished Intestinal Innate Immune Response?

BACKGROUND: Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human ß-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown. AIM: To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim. METHODS: Feces from children with CF and HC were collected for analysis. RESULTS: Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7-77.2) versus 43.4 (26.5-71.9) ng/g; P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8-143.8) versus 19.5 (19.5-35.1) mg/kg; P < 0.0001). There was no difference in fecal HBD-2 levels between CF subjects with fecal calprotectin ≥50 mg/kg and <50 mg/kg (50.5 (19.6-80.2) versus 43.0 (19.0-70.4); P = 0.7). There was no correlation between fecal HBD-2 and calprotectin in CF (r = 0.14; P = 0.4). CONCLUSION: Fecal HBD-2 levels were not increased in children with CF, in inflamed or noninflamed states. The lack of HBD-2 induction and upregulation under inflammatory conditions may suggest a diminished intestinal innate immune response in CF.

Elevated fecal M2-pyruvate kinase in children with cystic fibrosis: a clue to the increased risk of intestinal malignancy in adulthood?

BACKGROUND AND AIM: Adult patients with cystic fibrosis (CF) have an increased risk of gastrointestinal malignancies. We hypothesized that increased intestinal cell turnover beginning in childhood may explain the increased risk of malignancy in early adulthood. Therefore, we aimed to measure fecal M2-pyruvate kinase (M2-PK), a biomarker of intestinal cell turnover, in children with CF. To assess whether the increased cell turnover is secondary to intestinal inflammation, the secondary aims were to measure fecal calprotectin and evaluate its association with fecal M2-PK. METHODS: Fecal samples, for M2-PK and calprotectin measurements, were prospectively collected from children with CF and healthy controls (HC). RESULTS: Thirty-three children with CF (mean [standard deviation] 7.3 [3.8] years old; 29 pancreatic insufficient [PI]) were enrolled and compared with 33 age-matched HC. Fecal M2-PK in CF patients (median [interquartile range, IQR]: 4.7 [1.5-9.7]) was greater than HC (1.0 [1.0-1.0] U/mL; P < 0.0001), and higher in PI (median [IQR]: 5.1 [1.8-13.7]) than pancreatic sufficient patients (1.0 [1.0-1.0] U/mL; P = 0.002). Fecal calprotectin was significantly elevated in CF than HC (median [IQR] 61.3 [43.8-143.8] vs 19.5 [19.5-35.1] mg/kg; P < 0.0001). However, there was no correlation between fecal M2-PK and fecal calprotectin levels among subjects with CF (r = 0.29; P = 0.1). CONCLUSION: Increased intestinal cell turnover is present in children with PI CF. The lack of relationship between fecal M2-PK and calprotectin suggests that contributing factor(s) other than inflammation may be present.

Intestinal inflammation and impact on growth in children with cystic fibrosis.

OBJECTIVE: The aim of the study was to evaluate and compare faecal markers of intestinal inflammation in children with cystic fibrosis (CF), and determine whether intestinal inflammation adversely affects the nutritional phenotype. METHODS: Faecal samples for markers of intestinal inflammation, calprotectin, S100A12, and osteoprotegerin, were collected from children with CF, healthy controls (HCs), and Crohn disease (CD). Associations between inflammatory markers and clinical and nutritional indices were determined in subjects with CF. RESULTS: Twenty-eight children with CF (mean [standard deviation (SD)] 8.4 [3.3] years old, 22 pancreatic insufficient [PI]), 47 HC, and 30 CD were recruited. Mean (SD) faecal calprotectin in CF (94.3 [100.6] mg/kg) was greater than HC (26.7 [15.4] mg/kg, P < 0.0001), but lower than CD (2133 [2781] mg/kg, P = 0.0003). Abnormal faecal calprotectin was found in subjects only with PI (17/22 (77%), P = 0.001). There was no difference in faecal mean (SD) S100A12 (0.8 [0.9] vs 1.5 [2.2] mg/kg, P = 0.14) and osteoprotegerin concentrations (72.7 [52.2] vs 62.5 [0.0] pg/mL, P = 0.2) between CF and HC. Patients with CD had significantly elevated S100A12 and osteoprotegerin compared with CF and HC. Faecal calprotectin inversely correlated with both weight (r = -0.5, P = 0.003) and height z scores (r = -0.6, P = 0.002) in CF. CONCLUSIONS: The pattern of intestinal inflammation in CF is unique and distinct from inflammatory bowel disease, with elevated faecal calprotectin but normal faecal S100A12 and osteoprotegerin concentrations. The severity of intestinal inflammation, based on faecal calprotectin, significantly correlates with poor growth.

Cystic fibrosis related diabetes: potential pitfalls in the transition from paediatric to adult care.

One of the major complications of Cystic Fibrosis (CF) is CF-Related Diabetes (CFRD), which increases in incidence with age, from 1-2% below the age of 10 years to ∼20% of adolescents and 40-50% of adults. Multiple guidelines have been published over the last few years for the diagnosis and management of CFRD, from the American Diabetes Association (ADA) / US Cystic Fibrosis Foundation, International Society for Pediatric and Adolescent Diabetes (ISPAD) and the Thoracic Society of Australia and New Zealand-Australian Diabetes Society. However, little is published about the particular issues involved in transition of patients with CFRD from paediatric to adult care, nor the issues concerning the development of CFRD during the transition period. This document seeks to provide assistance to physicians, dieticians, nurses, diabetes educators, CF patients and their families by outlining the issues surrounding CFRD during transition from paediatric to adult care.

Fat-soluble vitamin deficiency in children and adolescents with cystic fibrosis.

AIMS: Determine the prevalence of fat-soluble vitamin deficiency in children with cystic fibrosis (CF) aged ≤18 years in New South Wales (NSW), Australia, from 2007 to 2010. METHODS: A retrospective analysis of fat-soluble vitamin levels in children aged ≤18 years who lived in NSW and attended any of the three paediatric CF centres from 2007 to 2010. An audit of demographic and clinical data during the first vitamin level measurement of the study period was performed. RESULTS: Deficiency of one or more fat-soluble vitamins was present in 240/530 children (45%) on their first vitamin level test in the study period. The prevalence of vitamins D and E deficiency fell from 22.11% in 2007 to 15.54% in 2010, and 20.22% to 13.89%, respectively. The prevalence of vitamin A deficiency increased from 11.17% to 13.13%. Low vitamin K was present in 29% in 2007, and prevalence of prolonged prothrombin time increased from 19.21% to 22.62%. Fat-soluble vitamin deficiency is present in 10%-35% of children with pancreatic insufficiency, but only a very small proportion of children who are pancreatic-sufficient. CONCLUSIONS: This is one of few studies of fat-soluble vitamin deficiency in children with CF in Australia. Fat-soluble vitamin testing is essential to identify deficiency in pancreatic-insufficient children who may be non-compliant to supplementation or require a higher supplement dose, and pancreatic-sufficient children who may be progressing to insufficiency. Testing of vitamin K-dependent factors needs consideration. Further studies are needed to monitor rates of vitamin deficiency in the CF community.

Fecal biomarkers of intestinal health and disease in children.

The identification of various fecal biomarkers has provided insight into the intestinal milieu. Most of these markers are associated with the innate immune system of the gut, apart from the more novel M2-pyruvate kinase. The innate immunity of the gut plays a role in maintaining a fine balance between tolerance to commensal bacteria and immune response to potential pathogens. It is a complex system, which comprises of multiple elements, including antimicrobial peptides (e.g., defensins, cathelicidins, lactoferrin, and osteoprotegerin), inflammatory proteins (e.g., calprotectin and S100A12), and microbial products (e.g., short-chain fatty acids). Dysfunction of any component can lead to the development of intestinal disease, and different diseases have been associated with different fecal levels of these biomarkers. Each fecal biomarker provides information on specific biological and disease processes. Therefore, stool quantification of these biomarkers provides a non-invasive method to define potential pathways behind the pathogenesis of diseases and can assist in the assessment and diagnosis of various gastrointestinal conditions. The abovementioned fecal biomarkers and their role in intestinal health and disease will be reviewed in this paper with a pediatric focus.