Lactulose-rhamnose intestinal permeability in children with cystic fibrosis

The lactulose-rhamnose intestinal permeability test was performed in 10 cystic fibrosis (CF) children. Urine was collected for 5 h after oral intake of the test solution. A single thin-layer chromatography followed by densitometry was used for the measurement of lactulose and rhamnose concentrations in the urine specimens. The excretion of each molecule was expressed as the percentage of the orally administered dose excreted and the lactulose-rhamnose ratio was the ratio of the percentage quantities of each probe molecule excreted. The mean lactulose-rhamnose excretion ratio in CF patients and controls was 0.16 and 0.038, respectively (p less than 0.001). The mean 5-h lactulose excretion was 2% and 0.28% in CF patients and control subjects, respectively (p less than 0.001). The mean 5-h rhamnose excretion was 12.8% and 7.6% in CF patients and control subjects (p less than 0.05). We conclude that CF patients have an increased intestinal permeability to lactulose and rhamnose. Further studies are needed in order to elucidate the mechanisms involved as well as the eventual nutritional implications.     

Effects of cisapride in patients with cystic fibrosis and distal intestinal obstruction syndrome

In a double-blind, placebo-controlled, crossover trial, we investigated the effects of the prokinetic drug cisapride in patients with cystic fibrosis and chronic recurrent distal intestinal obstruction syndrome (DIOS). After a baseline period, 17 patients (12.9 to 34.9 years; 12 boys) received, in random order, cisapride (7.5 to 10 mg) and placebo three times daily by mouth, each for 6 months. Gastrointestinal symptoms (flatulence, abdominal pain, fullness, abdominal distension, nausea, anorexia, heartburn, diarrhea, vomiting and regurgitation) were scored three times monthly and physical examinations assessed. At baseline and at each 6-month period, assessment included food intake for 7 days, 3-day stool collection, pulmonary function tests, and abdominal radiographs. During cisapride therapy compared with placebo, there were significant reductions in flatulence (p less than 0.005), fullness, and nausea (p less than 0.05). Patients with the worst symptom scores benefited most from cisapride. With cisapride, 12 patients felt better and three worse (p less than 0.05); physicians judged 11 patients improved and two worse (p less than 0.05). No side effects were noted. There were no significant differences between cisapride and placebo periods in nutritional status, x-ray scores, pulmonary function, food intake (fat, protein, calories), stool size and consistency, and fecal losses of fat, bile acids, chymotrypsin, and calories. For acute episodes of DIOS, intestinal lavage was needed 6 times in 4 patients during treatment with cisapride, and 11 times in 6 patients receiving placebo. In comparison with unselected patients with cystic fibrosis and pancreatic insufficiency who were receiving enzyme supplements and who had no distal intestinal obstruction, fecal fat losses (percentage of intake) were almost twice as high in the study group with DIOS (31.2 +/- 20.6% vs 16.2 +/- 17.6%; p less than 0.01). We conclude that in the dosage used, long-term treatment with cisapride appears to improve chronic abdominal symptoms in patients with cystic fibrosis and DIOS, but fails to abolish the need for intestinal lavage. Cisapride treatment had no effect on digestion and nutritional status of cystic fibrosis patients with pancreatic insufficiency.     

Small intestinal permeability and orocaecal transit time in cystic fibrosis.

Cellobiose and mannitol were used as probe molecules to measure intestinal permeability in 36 children with cystic fibrosis, and 25 age matched controls. Orocaecal transit was also evaluated for each subject using the lactulose/hydrogen breath test. There was a fourfold increase in permeability to disaccharide (cellobiose) in patients with cystic fibrosis, but permeability to the monosaccharide (mannitol) was similar to controls. The orocaecal transit time of lactulose was prolonged in patients with cystic fibrosis, but was unrelated to the percentage excretion of cellobiose or mannitol in cystic fibrosis patients or control subjects.     

Improved survival among young patients with cystic fibrosis

OBJECTIVE: To investigate age-specific trends in survival among US patients with cystic fibrosis between 1985 and 1999 and to assess whether survival in female patients with cystic fibrosis has improved relative to survival in male patients. STUDY DESIGN: A retrospective cohort study of 31,012 subjects in the US Cystic Fibrosis Foundation National Patient Registry. Trends in survival outcome were evaluated by the Cox model. RESULTS: Between 1985 and 1999, mortality fell 61% (95% CI, 36-76) for patients age 2 to 5 years, 70% (60-88) for patients age 6 to 10 years, and 45% (32-66) for patients age 11 to 15 years. Improvements in mortality rates among patients older than 15 years were smaller. Female patients had poorer survival rates than male patients in the age range 2 to 20 years, and this gender gap did not narrow throughout time. CONCLUSIONS: Survival rates of US patients with cystic fibrosis have improved remarkably since 1985. However, most of the improvement was limited to patients 2 to 15 years old. Although both genders benefitted from this trend, female patients have had consistently poorer survival rates than male patients in the age range 2 to 20 years. Further studies are needed to clarify why adult patients with cystic fibrosis had little improvement in survival rates.     

Intestinal inflammation in cystic fibrosis

BACKGROUND—There is controversy about whether the inflammatory response observed in the cystic fibrosis (CF) lung occurs secondary to bacterial infection or is caused by a dysregulation of the inflammatory response associated with the basic cellular defect of CF.AIMS—To study the inflammatory response in the gastrointestinal tract of children with CF; and to investigate whether there is increased inflammation in the gastrointestinal tract of CF children with fibrosing colonopathy.METHODS—Whole gut lavage was performed on 21 pancreatic insufficient children with CF, who were clinically well, five children with CF and fibrosing colonopathy, and 12 controls. Intestinal outputs of plasma derived proteins (albumin, α₁ antitrypsin, IgG), secretory immunoglobulins (IgA and IgM), cellular constituents (eosinophil cationic protein and neutrophil elastase), and cytokines (interleukin 8 and interleukin 1β) were measured.RESULTS—Compared to controls, the 21 CF patients, with no intestinal complications, had increased intestinal outputs of albumin, IgG, IgM, eosinophil cationic protein, neutrophil elastase, interleukin 1β, and interleukin 8. Similar values were obtained for the CF patients with fibrosing colonopathy.CONCLUSIONS—These data suggest that there is immune activation in the gastrointestinal mucosa of children with cystic fibrosis, which may result from the basic cellular defect. Fibrosing colonopathy does not appear to be associated with increased inflammation.     

Effect of elective antibiotic therapy on resting energy expenditure and inflammation in cystic fibrosis

Cystic fibrosis (CF) patients often present with malnutrition which may partly be due to increased resting energy expenditure (REE) secondary to inflammation. Both REE and tumour necrosis factor-alpha (TNF-α), as other markers of inflammation, are elevated during respiratory exacerbations and decrease after antibiotic treatment. However, the effect of antibiotic therapy on REE and inflammation in patients without respiratory exacerbation is not known. The aim of our study was to determine the effect of such an elective antibiotic therapy on REE, TNF-α, and other serum markers of inflammation. Twelve CF patients 5F/7M, age 15.9 ± 6.1 years, weight for height ratio 89 ± 8% without clinically obvious exacerbation and treated by intravenous antibiotics were studied. Both before (D0) and after (D14) treatment, pulmonary function tests were performed. REE was measured by indirect calorimetry and blood taken to measure inflammation parameters. Body weight increased by 1.1 kg from D0 to D14 (P < 0.001), composed of 0.3 kg fat mass and 0.8 kg fat-free mass (FFM). The forced expiratory volume at 1 s increased from 43 ± 15% of predicted at D0 to 51 ± 15% of predicted at D14 (P < 0.01). Mean REE was 41.1 ± 7.6 kcal/kg FFM per day at D0 and did not change significantly at D14 (40.6 ± 8.5 kcal/kg FFM per day). Serum markers of inflammation decreased from D0 to D14: C-reactive protein 17 ± 17 mg/l to 4 ± 7 mg/l (P < 0.05), elastase 62 ± 29 μg/l to 45 ± 18 μg/l (P < 0.02), orosomucoid acid 1.25 ± 0.11 g/l to 0.80 ± 0.15 g/l (P < 0.001), and TNF-α 37 ± 14 pg/ml to 29 ± 6 pg/ml (P = 0.05). Individual values showed a correlation between changes in REE and in TNF-α (P < 0.02). Conclusion The contribution of inflammation to energy expenditure is possible but appears to be minimal in cystic fibrosis patients treated by antibiotics on a regular basis in the absence of clinically obvious exacerbation. Received: 6 August 1998 and in revised form: 23 November 1998 / Accepted: 23 November 1998     

Bacterial infections and inflammation in the lungs of cystic fibrosis patients

The aim of this review is to describe the role of respiratory epithelial cells in processes that contribute to the pathogenesis of lung disease in patients with cystic fibrosis.     

Pancreatic enzyme therapy and clinical outcomes in patients with cystic fibrosis

OBJECTIVE: To assess the relationship between pancreatic enzyme therapy (PET) and the clinical outcomes of growth, abdominal pain, constipation, gassiness, and number of stools in cystic fibrosis (CF). STUDY DESIGN: Patients (n = 1215) >4 weeks of age from 33 Cystic Fibrosis Foundation accredited sites who had a sweat chloride >60 mmol/L or two CF-causing mutations were enrolled using a proportionate sampling strategy in a nonblinded study. Patients submitted a stool sample and completed a questionnaire. The study coordinator also completed a questionnaire for each patient. Enzyme dosing and growth, abdominal pain, gassiness, constipation, and number of stools were compared. RESULTS: Of the 1215 enrolled patients, 1131 (93.1%) were prescribed PET. Only 14.9% had pancreatic function assessed before enrolling in this study. Stool elastase-1 analysis identified 1074 (89%) patients as pancreatic insufficient (PI). There was no association between PET and the outcomes: growth, abdominal pain, gassiness, constipation, and number of stools. CONCLUSION: PET dose is not correlated with growth or gastrointestinal symptoms. More sensitive outcome measures of the effectiveness of PET in patients with CF are needed to guide treatment of PI.     

Disaccharidase activities in small intestinal mucosa in patients with cystic fibrosis.

The disaccharidase activities in small intestinal biopsies were related to the morphology of the mucosa and the ages of 63 patients with cystic fibrosis and 177 healthy control subjects of Caucasian origin. In patients with CF and in the healthy control subjects under 5 years of age with normal intestinal mucosa, no low lactase activity was found. In those patients with CF who were over 5 years of age, one group had high and one group had low lactase activity, as occurs in healthy Caucasian control subjects of the same age. This finding supports the view that in patients with CF, lactase deficiency is not related to the disease entity. In patients with or without CF who had the same degree of mucosal atrophy, the decrease of disaccharidase activities followed the same pattern, indicating that enzyme activities are affected to the same extent by the damage of the mucosa. In patients with CF with pancreatic insufficiency, the disaccharidase activities were significantly (P less than 0.001) higher when compared to those in control subjects of the same age and ethnic group, although the increase was not uniform in all patients with cystic fibrosis.     

Intestinal inflammation in cystic fibrosis.

BACKGROUND: There is controversy about whether the inflammatory response observed in the cystic fibrosis (CF) lung occurs secondary to bacterial infection or is caused by a dysregulation of the inflammatory response associated with the basic cellular defect of CF. AIMS: To study the inflammatory response in the gastrointestinal tract of children with CF; and to investigate whether there is increased inflammation in the gastrointestinal tract of CF children with fibrosing colonopathy. METHODS: Whole gut lavage was performed on 21 pancreatic insufficient children with CF, who were clinically well, five children with CF and fibrosing colonopathy, and 12 controls. Intestinal outputs of plasma derived proteins (albumin, alpha(1) antitrypsin, IgG), secretory immunoglobulins (IgA and IgM), cellular constituents (eosinophil cationic protein and neutrophil elastase), and cytokines (interleukin 8 and interleukin 1beta) were measured. RESULTS: Compared to controls, the 21 CF patients, with no intestinal complications, had increased intestinal outputs of albumin, IgG, IgM, eosinophil cationic protein, neutrophil elastase, interleukin 1beta, and interleukin 8. Similar values were obtained for the CF patients with fibrosing colonopathy. CONCLUSIONS: These data suggest that there is immune activation in the gastrointestinal mucosa of children with cystic fibrosis, which may result from the basic cellular defect. Fibrosing colonopathy does not appear to be associated with increased inflammation.     

Pancreatitis in young children with cystic fibrosis.

Five young children with cystic fibrosis and abdominal pain were found to have pancreatitis. Diagnosis was delayed in four patients because of the belief that pancreatitis occurs only in older patients with cystic fibrosis. In one patient pancreatitis was diagnosed before cystic fibrosis and diagnosis of cystic fibrosis was delayed. Pancreatitis should be considered as a possible cause of abdominal pain in pancreatic-sufficient children with cystic fibrosis and cystic fibrosis should be considered as a possible cause of pancreatitis, even in the young child.     

Silastic catheters for home antibiotic therapy in patients with cystic fibrosis

Repeated 14-day courses of intravenous antibiotic therapy for patients with cystic fibrosis (CF), who have been colonized with Pseudomonas aeruginosa (PA), is one currently accepted treatment. Conventional intravenous cannulas for antibiotic delivery often have a short line life leading to frequent venipunctures. Therefore we used silastic catheters as a peripheral venous access. Silastic catheters (15 cm, 0.6 mm diameter) were inserted 10 cm into a cubital vein in 15 patients with CF (age 5–32 years) for 20 antibiotic courses. After the antibiotic infusion the catheter was flushed with 200 U heparin (2 ml Vetren). In all patients the antibiotic therapy was delivered as a home therapy. In 15 antibiotic courses the silastic catheter could be continuously used for 14 days. One patient with methicillin resistant Staphylococcus aureus received antibiotic therapy for 54 consecutive days using the same silastic catheter. The catheter had to be removed in four courses: once because of thrombophlebitis with local inflammation, once because of burning pain during infusion and occlusion twice. In one case the patient removed his catheter because of technical problems. No other serious side effects occurred. Ten patients had previously received intravenous antibiotics at least once. The median line life of the last used conventional peripheral cannula of all patients was 4 days versus 14 days with the use of the silastic catheter (P < 0.005). All patients preferred the silastic catheter to other venous access. Conclusion Because of the long line life and easy handling, silastic catheters may be an alternative venous access to perform home antibiotic therapy in patients with CF. Received: 9 May 1996 / Accepted: 24 September 1996