Aleksandra Lisowska

The changing face of the exocrine pancreas in cystic fibrosis: pancreatic sufficiency, pancreatitis and genotype.

TABLE. No caption available 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.

Faecal elastase-1 test is superior to faecal lipase test in the assessment of exocrine pancreatic function in cystic fibrosis.

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.

Small intestine bacterial overgrowth does not correspond to intestinal inflammation in cystic fibrosis

Abstract Introduction. 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. Material and methods. 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. Results. Fecal calprotectin concentrations in CF patients (range: 1.8–302.5; median 80.0 mg/L) were significantly higher (p < 0.00001) 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. Conclusions. 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.

Oral antibiotic therapy improves fat absorption in cystic fibrosis patients with small intestine bacterial overgrowth.

BACKGROUND The aim of the present study was to assess the influence of antibiotic therapy on fat assimilation in cystic fibrosis (CF) patients with small intestine bacterial overgrowth (SIBO). MATERIALS AND METHODS Twenty six pancreatic insufficient CF patients with bronchopulmonary exacerbation and diagnosed SIBO (positive hydrogen-methane breath test) entered the study. (13)C mixed triglyceride breath test was performed before and after antibiotic therapy. Sixteen subjects were treated intravenously (ceftazidime and amikacin), ten patients orally (ciprofloxacin). RESULTS Cumulative percentage dose recovery changed significantly in the subgroup receiving antibiotics orally [median (mean±SEM): 3.6% (4.5±1.3%) vs. 7.2 (6.9±1.6%); p=0.019]. In the subgroup with intravenous drug administration, the tendency towards improvement was noted [2.7 (4.3±1.5%) vs. 5.2 (5.7±0.8%); p=0.109]. CONCLUSIONS Antibiotic therapy applied in CF patients with SIBO in the course of pulmonary exacerbation results in a significant improvement of fat digestion and absorption.

Green tea extract decreases starch digestion and absorption from a test meal in humans: a randomized, placebo-controlled crossover study

Green tea is known worldwide for its beneficial effects on human health. However, objective data evaluating this influence in humans is scarce. The aim of the study was to assess the impact of green tea extract (GTE) on starch digestion and absorption. The study comprised of 28 healthy volunteers, aged 19 to 28 years. In all subjects, a starch 13C breath test was performed twice. Subjects randomly ingested naturally 13C-abundant cornflakes during the GTE test (GTE 4 g) or placebo test. The cumulative percentage dose recovery (CPDR) was significantly lower for the GTE test than for the placebo test (median [interquartile range]: 11.4% [5.5–15.5] vs. 16.1% [12.7–19.5]; p = 0.003). Likewise, CPDR expressed per hour was considerably lower in each point of the measurement. In conclusion, a single dose of green tea extract taken with a test meal decreases starch digestion and absorption.

Serum lipase after secretin stimulation detects mild pancreatic involvement in cystic fibrosis.

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.

Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

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<0.0028) and in patients with at least one mild mutation (P<0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable.

Chronic pouchitis is not related to small intestine bacterial overgrowth.

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.

Lactose malabsorption is a risk factor for decreased bone mineral density in pancreatic insufficient cystic fibrosis patients.

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<0.028 and P<0.043, respectively). The abnormal BMD was stated more frequently in patients with the C/C genotype (P<0.042) and with LM (P<0.007). BMD, daily calcium intake and serum vitamin D concentration were significantly lower in LM subjects than in the other patients (P<0.037, P<0.000004 and P<0.0038, respectively). In logistic regression analysis, the relationship between examined parameters and BMD, was found to be statistically significant (P<0.001). However, only standardized body weight and LM were documented to influence BMD (P<0.025 and P<0.044, respectively). In conclusion, LM seems to be an independent risk factor for decreased BMD in CF patients.

Comparison of fecal pyruvate kinase isoform M2 and calprotectin in acute diarrhea in hospitalized children

Fecal concentrations of pyruvate kinase isoform M2 (M2-PK) and calprotectin (FC) serve as biomarkers of inflammation of gastrointestinal mucosa. The value of M2-PK in discriminating between patients with viral and bacterial acute diarrhea (AD) is currently unknown. We analyzed M2-PK and FC concentrations in fifty hospitalized children with AD (29 of which were caused by rotavirus and 21 by Salmonella enteritidis) as well as 32 healthy subjects. There was no difference in the areas under the receiver operating characteristic curves plotted for the two tests in differentiating rotaviral from bacterial AD. The sensitivity and specificity of M2-PK at optimal cut-off (20 U/g) were 75.9% and 71.4%, respectively. M2-PK and FC had similar values in distinguishing between children with AD caused by rotavirus and Salmonella enteritidis. The performance of both tests in hospitalized patients did not meet the needs of everyday clinical practice. Moreover, no advantage of fecal tests over the measurement of CRP was documented.