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Background Patients with cystic fibrosis (CF) are exposed to overlapping cardiovascular risk factors. We hypothesized that CF is characterized by increased arterial stiffness and greater intima-media thickness (IMT). Methods This cross-sectional study assessed the digital volume pulse arterial stiffness index (SIDVP) using photopletysmography, measured intima-media complex thickness (IMT) at the common carotid artery, and obtained an extended set of clinical and atherosclerosis-related laboratory parameters. Results Fifty-five patients with moderate-to-severe CF (mean age 26.3±8.6 years, BMI 20.3±3.1 kg/m2, FEV1 62±26%) and 51 healthy controls (25.1±4.4 years, BMI 21.7±3.0 kg/m2) entered the study. SIDVP was greater in pancreatic insufficient (PI), but not pancreatic sufficient (PS) CF patients compared with control (7.3±1.8 m/s vs 6.0±1.2 m/s; p=7.1 × 10−5). IMT was increased in PS (but not PI) participants relative to control (552±69 µm vs 456±95 µm, p=0.0011). SIDVP was also greater in PI than in PS patients (7.3±1.8 m/s vs 6.3±1.7 m/s, p=0.0232) and IMT was higher in PS compared with PI (552±69 µm vs 453±82 µm, p=0.0002). SIDVP independently associated with age, PI, the lack of liver cirrhosis, and with Pseudomonas aeruginosa colonization. PS was the only independent correlate of IMT in CF. Conclusions PI patients are at risk of developing general arterial stiffness. PS may relate to carotid IMT thickening, which underscores the need for further study that could lead to reconsideration of dietary guidance in PS CF.

The optimal type of exercise that simultaneously decreases body weight and preserves bone health in people with obesity is unknown. This parallel randomized trial aimed to compare the effect of endurance and endurance-strength training on bone mineral density (BMD) and content (BMC) in abdominally obese postmenopausal women. A total of 101 women were recruited and randomly assigned to endurance or endurance-strength training groups. Participants trained for 60 min per day, three times per week for 12 weeks. The endurance exercises were performed at an intensity of 50–75% of the maximum heart rate, whereas the strength exercises were at 50–60% of the one-repetition maximum. Pre- and post-intervention BMD and BMC of the total body, lumbar spine, and femoral neck and physical capacity were measured. There were no differences among the densitometric parameters in the endurance group, but a significant increase in whole-body BMD in the endurance-strength group was found. Moreover, there was a significant difference between the groups in the changes in the lumbar spine BMC. Furthermore, both training programs significantly improved physical capacity with no differences between groups. Endurance training was more effective in maintaining BMC at the lumbar spine. However, both groups did not differ in effect on BMD. Further studies with a long-term follow-up should be considered to confirm these findings. The study was registered with the German Clinical Trials Register within the number DRKS00019832, and the date of registration was 26 February 2020 (retrospective registration).

The primary objective of the study is to compare the effect of endurance and endurance‑strength training on endothelial function in women with abdominal obesity. The secondary objectives include the assessment of the effect of both types of training on anthropometric, densitometric and biochemical parameters. In total, at least 100 women will be recruited for the study. The study population will be randomly divided into two groups according to the type of training: endurance and endurance‑strength training. During the 3-month of intervention, both groups will be performed three times a week training of an equal exercise volume and duration of 60 minutes. Before and after the intervention selected anthropometric and densitometric parameters will be measured and body composition will be analysed. In addition, biochemical parameters related to glucose and insulin homeostasis, lipid metabolism, antioxidant status, oxidative stress, inflammatory markers and endothelial function will be assessed.

Background The interest in cystic fibrosis (CF) dyslipidaemia as a potential risk factor for cardiovascular disease is increasing with patients' survival. This study aimed to investigate CF dyslipidaemia, its clinical correlates and links to oxidized low-density lipoprotein (oxLDL), adiponectin, and apolipoprotein E (APOE). Methods This cross-sectional study assessed clinical characteristics of CF, as well as the serum lipid profile, oxLDL, adiponectin, and APOE. Results In total, 108 CF subjects were enrolled in this study, with a median age of 22 years, BMI of 20.5 kg/m2, FEV1% of 61%, of which 81% were pancreatic insufficient (PI). Healthy subjects (HS; n = 51) were in similar age. Hypocholesterolaemia occurred in 31% of CF subjects and in no HS. Hypertriglyceridaemia concerned 21% of patients (HS: 8%, p = .04), and low HDL-C 45% (HS: 6%, p Conclusions CF dyslipidaemia is highly prevalent and heterogenous. The lipid profile weakly associates with the clinical characteristics of CF as well as oxLDL, adiponectin, and APOE. Further research is needed, especially regarding HDL function in CF, the causes of hypertriglyceridaemia, and the value of essential fatty acid supplementation for CF dyslipidaemia.

Limited data suggested that inclusion of a strength component into endurance exercises might intensify the beneficial effect of training. However, the available data is limited. Therefore, we aimed to compare the effect of endurance and endurance-strength training on anthropometric parameters, endothelial function, arterial stiffness, antioxidant status, and inflammatory markers in abdominally obese women without serious comorbidities. A total of 101 women were recruited and randomly divided into endurance (n = 52) and endurance-strength (n = 49) groups. During the three-month intervention, both groups performed supervised sixty-minute training three times a week. All studied parameters were measured pre- and post-intervention period. In total, 85 women completed the study. Both training significantly decreased anthropometric parameters. Besides, endurance training decreased endothelial nitric oxide synthase, central aortic systolic pressure, pulse wave velocity, glutathione (GSH), total antioxidant status (TAS), interleukin (IL) 8, matrix metalloproteinase (MMP) 9, and tumor necrosis factor alpha, while endurance-strength training decreased MMP-2 concentrations, and increased IL-6, monocyte chemoattractant protein-1, and MMP-9 levels. We observed significant differences between groups for GSH, TAS, and MMP-9 levels. In summary, endurance and endurance-strength training did not differ in the impact on endothelial function and arterial stiffness. However, endurance training significantly depleted the antioxidant defense, simultaneously reducing MMP-9 levels. The study was retrospectively registered with the German Clinical Trials Register within the number DRKS00019832.

Background: Several factors could lead to lipid disturbances observed in cystic fibrosis (CF). This study aimed to assess sterol homeostasis in CF and define potential exogenous and endogenous determinants of lipid dysregulation. Methods: The study involved 55 CF patients and 45 healthy subjects (HS). Sterol concentrations (μg/dL) were measured by gas chromatography/mass spectrometry. CF was characterised by lung function, pancreatic status, liver disease and diabetes coexistence, Pseudomonas aeruginosa colonisation and BMI. CFTR genotypes were classified as severe or other. Results: Campesterol and β-sitosterol concentrations were lower (p = 0.0028 and p &lt, 0.0001, respectively) and lathosterol levels (reflecting endogenous cholesterol biosynthesis) were higher (p = 0.0016) in CF patients than in HS. Campesterol and β-sitosterol concentrations were lower in patients with a severe CFTR genotype, pancreatic insufficiency and lower pancreatic enzyme dose (lipase units/gram of fat). In multiple regression analyses, β-sitosterol and campesterol concentrations were predicted by genotype and pancreatic insufficiency, whereas cholesterol and its fractions were predicted by phytosterol concentrations, age, dose of pancreatic enzymes, nutritional status and genotype. Conclusions: Independent determinants of lipid status suggest that malabsorption and pancreatic enzyme supplementation play a significant role in sterol abnormalities. The measurement of campesterol and β-sitosterol concentrations in CF patients may serve for the assessment of the effectiveness of pancreatic enzyme replacement therapy and/or compliance, but further research is required.

We hypothezied that telomere length is considerably altered in cystic fibrosis (CF) patients compared to healthy subjects (HS), and that leukocyte telomere length variation reflects the severity of CF. Relative telomere length (RTL) was assessed by qPCR in 70 children aged 5–10 (34 CF, 36 HS) and 114 adults aged 18–45 (53 CF, 61 HS). Telomere length was similar in CF and HS (median (interquartile range): 0.799 (0.686–0.950) vs. 0.831 (0.707–0.986), p = 0.5283) both in children and adults. In adults, women had longer telomeres than men (0.805 (0.715–0.931) vs. 0.703 (0.574–0.790), p = 0.0002). Patients treated with inhaled corticosteroids had a shorter RTL compared to those without steroid therapy (0.765 (0.664–0.910) vs. 0.943 (0.813–1.191), p = 0.0007) and this finding remained significant after adjusting for gender, age, BMI, and child/adult status (p = 0.0003). Shorter telomeres were independently associated with the presence of comorbidities (0.763 (0.643–0.905) vs. 0.950 (0.783–1.130), p = 0.0006) and antibiotic treatment at the moment of blood sampling (0.762 (0.648–0.908) vs. 0.832 (0.748–1.129), p = 0.0172). RTL correlated with number of multiple-day hospitalizations (rho = −0.251, p = 0.0239), as well as number of hospitalization days (rho = −0.279, p = 0.0113). Leukocyte RTL in children and adults with CF was not shorter than in healthy controls, and did not seem to have any potential as a predictor of CF survival. However, it inversely associated with the investigated clinical characteristics.

Preliminary evidence suggests that conjugated linoleic acid (CLA) may reduce body weight and affect body composition. The present study assessed the effect of CLA supplementation on body fat composition in overweight and obese women, while also evaluating the liver safety of CLA use. Seventy-four obese or overweight women were randomly assigned to receive 3 g/day CLA or placebo for 12 weeks. Body composition (dual-energy X-ray absorptiometry) and liver function (13C-methacetin breath test and serum liver enzymes) were assessed before and after the trial. Patients receiving CLA experienced a significant reduction of total body fat expressed as mass (p = 0.0007) and percentage (p = 0.0006), android adipose tissue (p = 0.0002), gynoid adipose tissue (p = 0.0028), and visceral adipose tissue (p = 4.2 &times, 10&minus, 9) as well as a significant increase in lean body mass to height (p = 6.1 &times, 11) when compared to those receiving a placebo. The maximum momentary 13C recovery changes and end-point values were significantly higher in the CLA group when compared to the placebo group (p = 0.0385 and p = 0.0076, respectively). There were no significant changes in alanine aminotransferase, asparagine aminotransferase, and gamma-glutamyl transpeptidase activities between the groups. In conclusion, CLA supplementation was well tolerated and safe for the liver, which shows beneficial effects on fat composition in overweight and obese women.

Purpose As life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics. Methods Serum sVCAM-1 and sP-selectin levels were measured using ELISA. CF was characterized using: forced expiratory volume in 1 s, exocrine pancreatic and CF-related liver disease status, Pseudomonas aeruginosa colonization, serum high-sensitivity C-reactive protein, and body mass index (BMI). CFTR genotypes were classified as severe (classes I and II) or other. Results 108 CF patients and 51 healthy subjects volunteered for the study. In the CF group BMI was lower (median [IQR]: 20.5 kg/m2 [18.4–22.2] vs. 21.6 kg/m2 [19.9–23.4], p = 0.02) and hsCRP levels were higher (3.6 mg/L [1.1–7.1] vs. 0.5 mg/dL [0.3–1.0], p

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency.

Background: The aim of the study was to compare serum lactoferrin concentrations in metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) women. Methods: Three hundred (101 MHO and 199 MUHO) women were recruited to the study. Basic anthropometric parameters and blood pressure were measured. Body mass index (BMI) was calculated. Fat mass and visceral adipose tissue mass were assessed using dual X-ray absorptiometry scan. Fasting glucose, insulin, lipid profile, high sensitivity C-reactive protein (hs-CRP) and lactoferrin levels were determined. Results: Lactoferrin levels did not differ between MHO and MUHO subjects (median (interquartile range): 1639 (1055&ndash, 2396) vs. 1622 (1009&ndash, 23345) ng/mL). However, in the total population insulin (r = 0.131, p = 0.0234) and hs-CRP (r = 0.165, p = 0.0045) levels were correlated with lactoferrin concentrations. In addition, a weak positive association between serum lactoferrin concentrations and anthropometric parameters was also detected, and predominantly referred to MHO group (body weight: r = 0.231, p = 0.0201, BMI: r = 0.286, p = 0.0037, waist circumference: r = 0.258, p = 0.0092). In addition, serum lactoferrin concentrations were negatively correlated with fasting glucose (r = &minus, 0.250, p = 0.0115) and HDL-C levels (r = &minus, 0.203, p = 0.0411) in MHO subjects. Conclusions: Lactoferrin levels did not differ between MHO and MUHO women. However, some mild correlations between lactoferrin concentrations and anthropometric and metabolic parameters were observed mostly in MHO subjects.

Background At present, fecal elastase-1 ELISA determination is the most sensitive and specific tubeless pancreatic function test available. However, the results are not available the same day in routine clinical practice. This prospective study aims at evaluating the sensitivity and specificity of the Elastase-1 Quick™ Test by comparing the results with the ELISA test. Methods The study was composed of three groups: the screening-diagnosed cystic fibrosis (CF) patients (n=28), the screened, but non-CF subjects (n=36) and non-screened CF patients (n=62). Pancreatic status (normal vs abnormal) was evaluated using the Pancreas Elastase-1 Quick™ Test. Fecal elastase-1 concentration was determined with a commercially available ELISA kit, used as reference. The cut-off for abnormal results was set at Results The Pancreatic Elastase-1 Quick Test™ showed the following sensitivities and specificities in the studied groups: 92.8% and 96.6% in all subjects, 90.5% and 100% in screening samples, and 92.8 and 90.5% in CF patients. Conclusion Pancreatic Elastase-1 Quick Test™ proves to be a rapid and reliable option to qualitatively evaluate pancreatic function for diagnostic purposes in a clinical setting of CF care.

Background. Conjugated linoleic acid (CLA) reduces body weight (BW), body fat mass (BFM), and in- creases or maintains lean body mass in animals. However, the results concerning the eff ect of CLA on weight reduction in humans are contradictory. The present study aimed to evaluate the eff ect of CLA supplementa- tion on the BW and anthropometric parameters (waist and hip circumferences) in overweight and obese adult women. Material and methods. A total of 74 subjects (BMI: 28-42 kg/m 2 ) were included in a double blind, placebo- controlled trial. Subjects were randomized into two groups, those supplemented with either 3.0 g/d CLA or with placebo (sunfl ower oil) for 12 weeks. Results. CLA signifi cantly decreased the hip circumferences compared to placebo (p = 0.016209), but had no eff ect on body weight, BMI, or waist circumference. The number of subjects with a reduction in hip circum- ference in the CLA group was signifi cantly larger compared to that in the placebo group (p = 0.0017; NNT = 2.65; CI (6.27-1.685)). Conclusions. In conclusion, our fi ndings do not support the hypothesis that 12 weeks CLA supplementation, as dosed in the present study, is eff ective for body weight reduction in overweight and obese women. How- ever, its local action in decreasing the hip circumference seems to be encouraging and suggests that CLA may represent an attractive dietary supplement.

Alagille syndrome (AGS) is often associated with symptoms of maldigestion, such as steatorrhea, hypotrophy and growth retardation. Exocrine pancreatic insufficiency was proposed as the underlying cause. We aimed to assess the exocrine pancreatic function with the use of different methods in AGS patients. Concentrations of fecal elastase-1 (FE1) and fecal lipase (FL) activities were measured in 33 children with AGS. The C-mixed triglyceride breath test (MTBT) in a subgroup comprising 15 patients. In all patients studied, FE1 concentrations and FL activities were normal. Abnormal MTBT results were documented in 4 (26.7%) patients. The FE1 and FL levels in MTBT-positive and MTBT-negative children did not differ. The results of this research do not confirm the presence of exocrine pancreatic dysfunction in AGS patients. Routine screening for exocrine pancreatic insufficiency of this group of patients is not necessary.

Purpose A lower parasympathetic activity was described in patients with the gastroesophageal reflux disease. We aimed to determine whether gastroesophageal reflux (GER) episodes are associated with a short-term parasympathetic tone variability in children. Methods In order to address this question we performed simultaneous 24-h esophageal multichannel intraluminal impedance-pH and electrocardiographic monitoring in 16 children (age range 6–18 years), including 8 with asthma and 2 with gastroesophageal reflux disease. After describing duration, height, and acidity of 483 GER episodes we also measured parasympathetic-related heart rate variability parameters in 4 time periods: preceding, containing, following GER, and in-between GERs (control). High frequency (HF) power and root-mean square differences of successive R–R intervals (r-MSSD) were assessed in 2.5-min and 1-min periods, respectively. Results We did not identify the searched short-term parasympathetic tone changes. Conclusions In conclusion, GER episodes and their characteristics were not associated with short-term variability of parasympathetic activity in children.

OBJECTIVES New tools are needed in cystic fibrosis (CF) diagnostics in pancreatic-sufficient CF (PS-CF) patients. Secretin-enhanced magnetic resonance cholangiopancreatography (SE-MRCP) allows for improved assessment of the width of the pancreatic duct. METHODS Sixteen PS-CF patients and 17 healthy volunteers underwent SE-MRCP. The width of the pancreatic duct in the head, the body, and the tail of the pancreas was measured at the baseline and 1, 2, 3, 5, and 10 minutes after secretin administration. RESULTS The width of the pancreatic duct in the head of the pancreas did not differ between the groups at the baseline; after 10 minutes of secretin stimulation, it was smaller in PS-CF patients (median, 1.4 mm [first-third quartile, 1.3-2.0] vs 2.2 mm [1.7-2.4], P = 0.008). The area under the curve for discrimination between the 2 groups using this parameter was 0.77 (95% confidence interval, 0.60-0.93). CONCLUSIONS The SE-MRCP identified differences in the width of the pancreatic duct between PS-CF and healthy volunteers. Further improvements of the method are needed to augment its clinical utility.

BACKGROUND Ursodeoxycholic acid (UDCA) supplementation is recommended for cystic fibrosis (CF) patients with associated liver disease. However, its effect on fat digestion and absorption is not known. MATERIALS AND METHODS In 23 patients with mild liver involvement, a C-mixed triglyceride breath test was performed on UDCA supplementation (with and without pancreatic enzymes - standard and increased dose) and after 1 month of UDCA withdrawal. Cumulative percentage dose recovery [CPDR; median (interquartile range)] has been considered to reflect lipid digestion and absorption. RESULTS The enzyme supplementation resulted in a significant CPDR improvement [0% (0-0) vs. 4.6% (0.4-6.0); P

As decreased bone mineral density (BMD) is a common problem in cystic fibrosis (CF) and milk products may have pivotal dietary role affecting BMD, we aimed to assess the potential influence of adult-type hypolactasia (ATH) and lactose malabsorption (LM) on BMD in adolescent and young adult patients. In 95 CF pancreatic-insufficient patients aged 10–25 years (without liver cirrhosis, steatosis and cholestasis, diabetes mellitus, systemic glucocorticoid therapy), lumbar BMD, the nutritional status, pulmonary function, vitamin D3 concentration, calcium intake and single-nucleotide polymorphism upstream of the lactase gene were assessed. In subjects with the −13910 C/C genotype predisposing to ATH, the presence of LM was determined with the use of a hydrogen–methane breath test (BT). BMD and calcium intake were significantly lower in patients with the C/C genotype (P

Background Most methods used for the assessment of severe steatorrhea in cystic fibrosis (CF) are sensitive. In fact, the tests show their usefulness in a borderline zone of the results. Yet, the existing data related to acid steatocrit (AS) are still contradictory. Therefore, in the present study we have aimed to assess CF patients without or with mild steatorhea (

Previously published studies have indicated that gastroesophageal reflux (GER) disease is common in pediatric patients with cystic fibrosis. The aim of the present study was to get insight into the incidence of GER and to characterize the nature of reflux episodes in children with cystic fibrosis. This was a multicenter, prospective study of children with cystic fibrosis older than 18 months. Forty four consecutive patients (22 boys, mean age 10.4 ± 3.6, range 3.0–17.8 years) were enrolled into the study. All patients underwent 24 h pH-impedance monitoring. GER were classified according to the widely recognized criteria as an acid, weakly acid, weakly alkaline, or proximal. The pH-impedance trace was considered abnormal when acid exposure was >6 %. GER was diagnosed in 24/44 (54.5 %) children. A total of 1585 (median 35, range 7–128) reflux episodes were detected; 1199 (75.6 %) were acidic, 382 (24.1 %) weakly acidic, and 4 (0.3 %) weakly alkaline. Six hundred and ninety-one (43.6 %) reflux episodes reached the proximal esophagus. In 14/44 patients typical GER symptoms were present. We conclude that the incidence of GER in children with cystic fibrosis is very high. In the majority of patients typical GER symptoms are absent. Therefore, diagnostic procedures should be considered, regardless of lacking symptoms. Although acid reflux episodes predominate in children with cystic fibrosis, classical pH-metry may not constitute a sufficient diagnostic method in this population because of a relatively high number of proximal reflux episodes. Such episodes also indicate an increased risk for aspiration. The pH-impedance diagnostic measurement is advocated when suspecting GER in children with cystic fibrosis.

The etiology of altered blood fatty acid (FA) composition in cystic fibrosis (CF) is understood only partially. We aimed to investigate the determinants of serum glycerophospholipids’ FAs in CF with regard to the highest number of FAs and in the largest cohort to date. The study comprised 172 CF patients and 30 healthy subjects (HS). We assessed Fas’ profile (gas chromatography/mass spectrometry), CF transmembrane conductance regulator (CFTR) genotype, spirometry, fecal elastase-1, body height and weight Z-scores, liver disease, diabetes and colonization by Pseudomonas aeruginosa. The amounts of saturated FAs (C14:0, C16:0) and monounsaturated FAs (C16:1n-7, C18:1n-9, C20:1n-9, C20:3n-9) were significantly higher in CF patients than in HS. C18:3n-6, C20:3n-6 and C22:4n-6 levels were also higher in CF, but C18:2n-6, C20:2n-6 and C20:4n-6, as well as C22:6n-3, were lower. In a multiple regression analysis, levels of seven FAs were predicted by various sets of factors that included age, genotype, forced expiratory volume in one second, pancreatic status and diabetes. FA composition abnormalities are highly prevalent in CF patients. They seem to be caused by both metabolic disturbances and independent clinical risk factors. Further research into the influence of CFTR mutations on fat metabolism and desaturases’ activity is warranted.

Background: Restorative ileal pouch-anal anastomosis (IPAA) potentially may lead to upper gastrointestinal tract motility disturbances. In addition, a bacterial etiology of IPAA complication—pouchitis—has been suggested. The oro-anal transit time is significantly reduced in this patient group. Therefore, we investigated the hypothesis if IPAA constitutes a significant risk for small intestine bacterial overgrowth (SIBO). Methods: Twenty-eight patients age 23–71 years with IPAA operated due to ulcerative colitis without subjective symptoms of pouchitis were evaluated as outpatients according to the prescheduled follow-up after operation and included in the study. The modified Pouchitis Disease Activity Index (PDAI) was determined in all IPAA patients, including clinical, endoscopic, and histopathological (Moskowitz criteria) parameters. In addition, anorectal manometry was performed. The presence of SIBO was determined with the use of a glucose breath test (GBT). Results: In 1 subject (3.6%) an abnormal GBT result was recorded consistent with SIBO. In addition, 2 borderline values (7.1%) were documented. Both patients with SIBO as subjects with borderline values presented with low PDAI values. All patients with PDAI >7 had normal GBT results. In patients with SIBO the maximal tolerated rectal volume was significantly higher than in subjects without SIBO (P < 0.007). Similarly, the PDAI value was significantly lower (P < 0.014). Conclusions: Asymptomatic chronic pouchitis is not related to SIBO. However, excessive colonization of the small intestine does occur in some IPAA patients and needs to be kept in the differential diagnosis. (Inflamm Bowel Dis 2008)

In 105 pancreatic insufficient CF patients (steatorrhea and low fecal elastase-1 concentrations), the effectiveness of pancreatic enzyme therapy (PET) has been assessed (fecal fat losses and coefficient of fat reabsorption). Eight unresponsive subjects were checked for PET compliance with fecal chymotrypsin assay. Three patients were documented to be non-compliant. Unresponsive patients should undergo evaluation for PET compliance.

Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with −13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (P

INTRODUCTION High prevalence of elevated serum pancreatic enzymes in children with cholestasis with normal fecal elastase-1 concentrations has been documented. However, this state is related predominantly to biliary atresia. Therefore, we aimed to assess pancreatic damage by measuring serum pancreatic enzymes in patients with progressive familial intrahepatic cholestasis type 2 (PFIC type 2). MATERIALS AND METHODS Twenty PFIC type 2 patients with normal serum bilirubin and bile acid concentrations were included in the study. Thirty pancreatic insufficient cystic fibrosis (PI-CF) patients, thirty patients with acute pancreatitis (AP) and thirty healthy subjects (HS) served for the purpose of comparison. In all subjects, serum lipase and elastase-1 levels were measured. RESULTS In all but one PFIC type 2 patients and all HS normal lipase activities were found. Serum elastase-1 concentrations were normal in all PFIC type 2 patients and HS. The enzyme levels were very similar in both groups studied. Lipase activities in PFIC type 2 patients were significantly higher than in PI-CF patients (p < 0.00001) and lower than in patients with AP (p < 0.00001). Serum elastase-1 levels in PFIC type 2 patients were significantly lower than in patients with AP (p < 0.00001) and not different from those in PI-CF patients. In conclusion. serum pancreatic enzymes in patients with PFIC type 2 are normal. No pancreatic damage in these patients could be detected.

Small intestine bacterial overgrowth (SIBO) has been reported in cystic fibrosis (CF) patients. However, the potential link to intestinal inflammation has not been studied so far. Therefore, we aimed to assess whether SIBO correlates with intestinal inflammation in CF patients.As a preliminary study, we assessed whether calprotectin is detectable in sputum expectorated by 10 CF patients. Since significant immunoreactivity was documented, in the major study we have included exclusively CF subjects not expectorating sputum for at least two weeks. Fecal calprotectin was measured in 25 CF patients and 30 healthy subjects (HS). All CF subjects were tested for the presence of SIBO using the hydrogen-methane breath test (BT). According to obtained results CF patients were divided into SIBO positive and negative subgroups. Subsequently, the intensity of intestinal inflammation in both subgroups was compared.Fecal calprotectin concentrations in CF patients (range: 1.8-302.5; median 80.0 mg/L) were significantly higher (p0.00001) than in HS (not detectable-15.5; 2.5 mg/L). Calprotectin levels were abnormal in 21 (84%) studied CF subjects and none of HS. Abnormal BT results were found in 10 (40.0%) of CF patients. Calprotectin concentrations in SIBO positive and negative patients did not differ.Gastrointestinal inflammation is a frequent finding in cystic fibrosis patients. However, small intestine bacterial overgrowth does not seem to be the major or at least not the only determinant of intestinal inflammation. Indirect measures of intestinal inflammation in CF patients may give false positive results.

Background: The coexistence of cystic fibrosis (CF) and celiac disease (CD) has been reported. To our knowledge there is no study directly comparing the incidence of CD in CF patients to that in the general population at the same time. There is no published data on genetic predisposition to CD in CF patients either. Therefore, in the present study we aimed to assess the genetic predisposition to CD and its incidence in CF patients comparing it to data from the general population. Patients and methods: Two hundred eighty-two CF patients were enrolled in the study. In 230 CF patients the genetic predisposition to CD (the presence of HLA-DQ2/ DQ8) was assessed. In all CF patients, serological screening for CD was conducted. In patients with positive antiendomysial antibodies (EMA) gastroduenoscopy was offered. Intestinal histology was classified according to modified Marsh criteria. The results of serological CD screening in 3235 Polish schoolchildren and HLA-DQ typing in 200 healthy subjects (HS) were used for comparison. Results: Positive EMA was found in 2.84 % of the studied CF patients. The incidence of proven CD was 2.13 %. The incidence of CD as well as positive serological screening were significantly more frequent in the CF group than in the general population. The frequency of CD-related HLA-DQ alleles in CF and HS did not differ. Conclusions: Genetic predisposition to celiac disease in cystic fibrosis patients is similar to that of the general population. However, our results suggest that cystic fibrosis is a risk factor for celiac disease development.

Introduction: Hydrogen breath test (BT) is commonly used as a diagnostic tool for the detec tion of small intestine bacterial overgrowth (SIBO). It was reported that colonic methane pro duction is far more frequent in cystic fibrosis (CF) patients than in other subjects. Therefore, measuring exclusively hydrogen in the diagnostic breath test for diagnosing SIBO might be of limited value. We aimed to assess the usefulness of combined measurement of hydrogen and methane expiration for the diagnosis of SIBO in CF. Material and Methods: The study com prised 62 CF patients aged 5 to 18 years. Three-hundred-ninety subjects assessed due to gas trointestinal symptoms for the presence of SIBO served as a comparative group. In all subjects hydrogen/methane BT using glucose was performed. A positive BT was defined as fasting hy drogen ≥ 20 ppm or fasting methane ≥ 10 ppm or a rise of ≥ 12 ppm hydrogen or ≥ 6 ppm methane over baseline during the test. Results: In 23 (37.1%) CF patients and in 52 (13.3%) subjects from the comparative group abnormal BT results were found. In seven (11.3%) CF patients and 29 (7.4%) of the other subjects studied methane measurement allowed diagnosis of SIBO. Con clusions: Small intestine bacterial overgrowth is frequent in cystic fibrosis. For its detection in cystic fibrosis and other gastrointestinal patients, combined hydrogen and methane measure ment instead of hydrogen breath test should be applied. Without the additional measurement of methane a significant percentage of SIBO will be missed.

(Table is included in full-text article.)Cystic fibrosis (CF) is the most frequent cause of exocrine pancreatic insufficiency in childhood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes CFTR protein that functions as cyclic AMP-dependent chloride channel allowing the passage of anions and secondarily water into the lumen of pancreatic ducts. Luminal chlorides are exchanged for bicarbonates. The lack of CFTR channel or its disrupted function (being the consequence of CFTR gene mutations) results in reduced volume of more acidic secretion. It has been suggested that such a situation leads to the precipitation of highly concentrated protein-containing secretion with obstruction and organ damage. The intensity of this process determines the progression of the disease. Steatorrhea is the significant symptom of classical form of CF. Residual pancreatic secretion in a subset of patients, however, allows for normal lipid digestion and absorption. Previous cross-sectional clinical studies estimated that about 85-90% of CF patients in preschool, school and older age are pancreatic insufficient. More frequent detection of mild and nonclassic forms of CF leads to higher frequency of pancreatic sufficiency (PS). The potential decline of exocrine pancreatic function, however, should be always considered. All PS patients with at least one severe or unknown CFTR mutation should be longitudinally assessed for the progression of pancreatic dysfunction. Recurrent acute and chronic pancreatitis is not a rare clinical condition in PS patients with PS: it might be the presenting symptom, even preceding CF diagnosis by several years. Potential appearance of this complication in individuals with pancreatic insufficiency demands elucidation.

BACKGROUND AND AIMS Direct tests are characterized by the highest sensitivity and specificity. However, their practical use, especially in children, is limited. Among the indirect tests, the highest sensitivity and specificity was documented for faecal elastase-1 test, yet the value of faecal lipase test in cystic fibrosis (CF) has not been defined. Therefore, the aim of the present study was to compare the sensitivity and the specificity of the faecal lipase test to the faecal elastase-1 test in the assessment of exocrine pancreatic function in children with CF. METHODS The study comprised 90 CF patients and 95 healthy subjects (HS). In all subjects, faecal elastase-1 concentrations (ELISA) and lipase activities (ELISA) were measured. The presence of pancreatic insufficiency was documented by the determination of faecal fat excretion in 78 pancreatic insufficient and by the secretin-cholecystokinin test in 12 CF patients without steatorrhoea. Sensitivity and specificity of the faecal elastase-1 test and faecal lipase test were analysed and, in 50 HS, sample-to-sample and day-to-day variations were determined. RESULTS With cut-off levels providing the same specificity for both tests (95.8%), the sensitivity of the faecal elastase-1 test (91.1%) was significantly higher (p < 0.0036) than that of the faecal lipase test (76.7%). Sample-to-sample (mean +/- SEM: 13.2 +/- 1.2% vs 23.4 +/- 2.2%) and day-to-day variations (mean +/- SEM: 16.3 +/- 1.2% vs 32.5 +/- 2.6%) were significantly lower (p < 0.0001) for elastase-1 than for lipase measurements. CONCLUSION Among indirect tests, faecal elastase-1 test is superior to faecal lipase test in the assessment of exocrine pancreatic function in cystic fibrosis.

Introduction: Despite routine oral supplementation, levels of 25-OHD in CF patients are often unsatisfactory. Although the aetiology is multi-factorial, reduced skin exposure to sunlight is a contributory cause but there is no consensus as to when 25-OHD levels should be estimated. We therefore compared the variation in 25-OHD levels and monthly UK sunshine in our CF-patients, and also looked at any intra-patient variability in relation to the month in which testing was performed. Methods and Results: We compared 711 25-OHD estimations taken between 2004– 2010 from 240 adult CF patients (mean age 28 years, 173 [72%] receiving vitamin D supplementation, 133 male) with average monthly sunshine data obtained from the UK Meteorological Office. A positive correlation was observed between the average 25-OHD levels and average monthly UK sunshine (2004–2010) (Pearson’s coefficient r = 0.54, P 5 estimations of 25-OHD during the study period: same-patient variability expressed as the inter quartile difference (IQR), dependent upon the month of testing (Table 2).

Antibiotic therapy in the cystic fibrosis (CF) mouse model has been shown to result in reduced bacterial load of the intestine and significant body mass gain. The effect was suggested to be linked to the improvement of intestinal digestion and absorption. Therefore, we aimed to assess the influence of routinely applied antibiotic therapy in CF patients on fat assimilation. Twenty-four CF patients aged 6 to 30 years entered the study. Inclusion criteria comprised confirmed exocrine pancreatic insufficiency and bronchopulmonary exacerbation demanding antibiotic therapy. Exclusion criteria comprised: antibiotic therapy six weeks prior to the test, liver cirrhosis, diabetes mellitus, oxygen dependency, the use of systemic corticosteroids. In all enrolled CF subjects, (13)C-labelled mixed triglyceride breath test ((13)C MTG-BT) was performed to assess lipid digestion and absorption, before and after antibiotic therapy. Sixteen subjects were treated intravenously with ceftazidime and amikacin, eight patients orally with ciprofloxacin. Cumulative percentage dose recovery (CPDR) was considered to reflect digestion and absorption of lipids. The values are expressed as means (medians). The values of CPDR before and after antibiotic therapy did not differ in the whole studied group [4.6(3.3) % vs. 5.7(5.3) %, p = 0.100] as well as in the subgroup receiving them intravenously [4.6(3.2) % vs. 5.7(5.3) %, p = 0.327] or in that with oral drug administration [4.6(3.4) % vs. 5.7(5.4) %, p = 0.167]. In conclusion, antibiotic therapy applied routinely in the course of pulmonary exacerbation in CF patients does not seem to result in an improvement of fat digestion and absorption.

BACKGROUND: The assessment of severe pancreatic insufficiency in cystic fibrosis (CF) is not a diagnostic problem. However, identification of mild cases remains a challenge. The aim of this study was to assess the ability of serum lipase after secretin stimulation to identify mild pancreatic insufficiency in patients with CF. MATERIAL AND METHODS: Thirty patients with CF and pancreatic insufficiency (CF-PI) and 30 patients with CF and pancreatic sufficiency (CF-PS) were studied. Thirty healthy subjects with no known gastrointestinal disease served as controls. In all subjects, fecal fat excretion, fecal elastase-1 (E1) concentration and basal and secretin-stimulated serum lipase concentration were measured. RESULTS: All patients with CF-PI and 3 with CF-PS had abnormally low fecal E1 concentrations. The remaining 27 CF-PS patients and all controls had normal values. Basal and post-stimulation lipase levels were extremely low in patients with CF-PI. Mean basal and poststimulation serum lipase concentrations were significantly higher in CF-PS who had normal fecal E1 concentrations but were still below those of controls (P < 0.001). Among the 27 CF-PS patients with normal fecal elastase, high basal and poststimulation lipase values were found in 6 and 17 patients respectively. CONCLUSION: In patients with CF-PS who have normal fecal elastase-1 concentration, the measurement of basal or secretin-stimulated lipase levels might be helpful in identifying the progression of the destructive process in the pancreas.

The available data on the incidence of lactose malabsorption are contradictory. Potential bias in random selection is a major drawback of studies performed to-date. Moreover, molecular analysis of polymorphism -13910 C>T upstream of the lactase (LCT) gene (NM_005915.4:c.1917+326C>T; rs4988235) has not been reported in those studies. Therefore, in this study we aimed to assess genetic predisposition and clinical manifestation of adult-type hypolactasia (ATH). In two-hundred randomly chosen healthy subjects (HS) aged from 18 to 20 years, the presence of -13910 C>T polymorphic variants upstream of the LCT gene was assessed. In a subgroup of subjects with genotype predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted to determine the current state of lactase activity. In addition, clinical symptoms typical for lactose malabsorption were assessed using the questionnaire method. Sixty-three out of 200 (31.5 %) HS had -13910 C/C genotype. Thus, genetically determined lactase persistence is expected in the remaining 137 (68.5 %) subjects. Thirteen out of 53 (24.5 %) HS having -13910 C/C genotype were proved to be lactose intolerant. Recalculating the data for the entire studied population it implies the incidence of lactose malabsorption in 7.7 % of subjects. Only three out of 13 (23.1 %) subjects with abnormal BT results, reported clinical symptoms related to lactose consumption. Significantly lower than previously reported incidence of clinically detectable lactose malabsorption in young healthy adults in Poland has been documented. The -13910 C/C genotype upstream of the LCT gene indicates a predisposition to ATH, but definitely does not define the current ability to tolerate lactose.

Background & Aims: Although indirect methods of assessment of the exocrine pancreatic function have become the standard of care in the monitoring of pancreatic status, it still remains a current clinical challenge. Our aim was to compare the width of the pancreatic duct in pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) patients using secretin-enhanced magnetic resonance cholangiopancreatography (SE-MRCP). Methods: Thirty-seven CF patients were enrolled for this cross-sectional study, including 21 PI and 16 PS, all of whom underwent SE-MRCP. Measurement of the diameter of the pancreatic duct was performed in the head, body, and the tail of the pancreas at the baseline and after 1, 2, 3, 5, and 10 minutes after secretin administration. Results: The diameter of the pancreatic duct in the head of the pancreas after 5 and 10 minutes of secretin injection was greater in PI than in PS patients (median = 2.0 mm [interquartile range: 1.6-3.0] vs. 2.0 mm [1.0-2.0] and 2.0 mm [1.4-2.0] vs 1.0 mm [1.0-2.0], p=0.047 and p=0.040, respectively). Areas under ROC curves for discriminating between PI and PS patients were 0.693 (95% CI 0.521-0.866) and 0.698 (95% CI 0.528-0.868), respectively. No other differences in the width of the duct were identified at the baseline or during SE-MRCP. Conclusions: The measurement of the diameter of the pancreatic duct during secretin stimulation does not allow for differentiating between PS and PI status in CF patients. Abbreviations: CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane conductance regulator; ELISA: enzyme-linked immunosorbent assay; ERCP: endoscopic retrograde cholangiopancreatography; E1: elastase-1; MRI: magnetic resonance imaging; PI: pancreatic insufficient; PS: pancreatic sufficient; SCT gene: secretin gene; SE-MRCP: secretin-enhanced magnetic resonance cholangiopancreatography; T: tesla; TR: repetition time; TE: echo time.