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PubMed2006

A morphometric study of mucins and small airway plugging in cystic fibrosis.

RATIONALE: Little knowledge exists on structural changes and plugging in small airways in cystic fibrosis. OBJECTIVE: To characterise the extent of plugging and contribution of secreted mucins to the plugs. METHODS: Small airways in patients with cystic fibrosis at transplantation (n = 18) were compared with control non-smokers (n = 10). Tissue sections were stained with Alcian blue (AB)/periodic acid-Schiff (PAS), for mucins MUC5B and MUC5AC, and for neutrophils and its chemoattractant interleukin (IL) 8. Epidermal growth factor receptor (EGFR) and its ligand pro-transforming growth factor alpha were also identified using immunohistochemical staining. Epithelial and luminal contents were assessed morphometrically. RESULTS: Plugs occupying >50% of total luminal volume were found in 147 of 231 (63.6%) airways in patients with cystic fibrosis, but only in 1 of 39 (2.6%) airways in controls. In the epithelium of patients with cystic fibrosis, AB/PAS, MUC5B, and MUC5AC-stained volume densities were increased 10-fold (p < 0.01), indicating increased mucin production. In airway lumens, staining for mucins was also increased in cystic fibrosis, indicating increased mucin secretion. In the epithelium of patients with cystic fibrosis, neutrophil numbers were markedly increased and were inversely correlated with volume densities of mucous glycoconjugates (r = -0.66, p < 0.005). IL8 staining was increased in the epithelium of patients with cystic fibrosis and colocalised with mucins. Staining for EGFR and for pro-transforming growth factor alpha were increased in the epithelium of patients with cystic fibrosis; positive correlations were found between EGFR-stained volume density and both AB/PAS and IL8-stained volume densities. CONCLUSIONS: Most of the small airways are plugged in cystic fibrosis at the time of transplantation. Mucins contribute to airway plugging. Recruited neutrophils may be involved in mucin secretion in the plugs. Increased expression of EGFR and its ligand suggests roles in mucin synthesis and neutrophil recruitment.

Adult↗

PubMed1990

Excessive faecal losses of vitamin A (retinol) in cystic fibrosis.

Vitamin A (retinol) deficiency is a recognised complication of cystic fibrosis and is presumed to be a consequence of an impairment in the digestion and absorption of dietary fats. The dietary intake of fat and retinol was assessed from a seven day weighed food intake in 11 subjects with cystic fibrosis and 12 matched controls. Faecal excretion of retinol and fat were measured from three day stool collections. There was little difference between the two groups in the intake of fat or retinol equivalents. When studied the subjects with cystic fibrosis were clinically stable and the apparent absorption of fat was not significantly different to that in the controls. There was a significant increase in the faecal losses of retinol in cystic fibrosis, which was unrelated to the degree of fat in the stool. In cystic fibrosis the median retinol recovered in the stool was 40% of the intake, compared with 1.8% in the controls. It is concluded that there is a specific defect in the handling of retinol by the gastrointestinal tract in cystic fibrosis, which may be unrelated to the digestion and absorption of dietary fat.

Adolescent↗

PubMed2005

Inhaled bronchodilators for cystic fibrosis.

BACKGROUND: Recurrent wheeze and breathlessness are common in people with cystic fibrosis, and bronchodilators are commonly prescribed. Despite their wide-scale and often long-term use, there is limited objective evidence about their efficacy in cystic fibrosis. OBJECTIVES: To evaluate the effectiveness of inhaled bronchodilators in children and adults with cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic databases searches, and handsearches of relevant journals and abstract books of conference proceedings. Latest search of the Group's Trials Register: August 2005 SELECTION CRITERIA: Randomised or quasi-randomised trials comparing inhaled bronchodilators to placebo or another inhaled bronchodilator in people with CF, diagnosed clinically and by sweat or genetic testing and at all stages and severity of lung disease. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed trial quality. If data were missing, the primary author was contacted where possible. The data were subgrouped into classes of bronchodilator and for each class into short-term effects (less than one week) and long-term effects (greater or equal to one week). MAIN RESULTS: The search identified 43 references. Fourteen trials, with a total of 257 participants, were suitable for inclusion. The trials were all cross-over in design; in this case a meta-analysis was not possible. There were varied conclusions from the different trials, reflecting their heterogeneity. Compared to placebo, short-acting beta-2 agonists increased forced expiratory volume at one second (FEV(1)) in the short term in three out of five trials, and in the long-term increased peak expiratory flow rate in individuals who had been shown to have bronchial hyperreactivity or bronchodilator responsiveness or both. Compared to placebo, long-acting beta-2 agonists increased FEV(1) and forced expiratory flow between 25% and 75% of expiratory flow (FEF 25-75%) in the short term in participants known to have bronchodilator responsiveness, but produced inconsistent results in long-term trials. Short acting-anticholinergics had no consistent effect on lung function tests in either the short or the long term. We found no published trials of fenoterol, formoterol or tiotropium and the use of these agents in cystic fibrosis cannot be supported. AUTHORS' CONCLUSIONS: It was not possible to determine fully the effectiveness of inhaled bronchodilators in cystic fibrosis as a meta-analysis was not possible. However, both short and long-acting beta-2 agonists can be beneficial both in the short and long term in individuals with demonstrable bronchodilator responsiveness or bronchial hyperrresponsiveness.

Adrenergic beta-Agonists↗

PubMed2005

A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice.

BACKGROUND & AIMS: Cystic fibrosis transmembrane regulator (CFTR) gene mutations are associated with pancreatic insufficiency and pancreatitis. Chronic pancreatitis, including cystic fibrosis-related disease, may exist as a continuum between acute and chronic disease and may manifest as recurrent pain. We hypothesized that cftr(m1UNC) (-/-) mice, which have no evidence of chronic pancreatitis, are susceptible to developing acute pancreatitis. METHODS: We used a cerulein hyperstimulation model of acute pancreatitis and measured histological changes, tissue edema, neutrophil infiltration, inflammatory mediators' mRNA expression, apoptosis markers, and pancreatic trypsin and serum lipase activities. Additionally, we quantitated in vivo pancreatic secretion and pancreatic digestive enzymes. RESULTS: Multiple proinflammatory cytokine genes were constitutively overexpressed in cftr (-/-) pancreas compared with wild-type mice. During acute pancreatitis, cftr (-/-) mice developed more severe acute pancreatitis than wild-type, as indicated by greater pancreatic edema, neutrophil infiltration, mRNA expression of multiple inflammatory mediators, and less apoptotic cell death. In contrast to wild-type mice, cftr (-/-) mice had blunted increases in pancreatic trypsin and serum lipase activities, but similar percentages of pancreatic trypsinogen activation. Finally, cftr (-/-) mice had less in vivo pancreatic secretion in response to cholecystokinin octapeptide and reduced pancreatic digestive enzyme protein and mRNA levels, thus suggesting mild pancreatic insufficiency. CONCLUSIONS: A baseline proinflammatory state and an antiapoptotic phenotype may sensitize cftr (-/-) mice to developing more severe acute pancreatitis with an exuberant pancreatic inflammatory response. Cftr (-/-) mice have mild pancreatic insufficiency, which partially explains the blunted increase of pancreatic and serum digestive enzymes during acute pancreatitis. These findings may explain the susceptibility to acute pancreatitis in persons with classic and nonclassic cystic fibrosis.

Acute Disease↗

PubMed1984

[Pregnancy and delivery in cystic fibrosis].

The authors report about the course of pregnancy and delivery in two patients with cystic fibrosis. Epidemiology and clinical symptoms of cystic fibrosis, possible problems anticipated during pregnancy, delivery and puerperium in patients with cystic fibrosis, and questions concerning therapeutic abortion and contraceptive counseling are discussed. Important premises to the management of pregnancy and delivery in cystic fibrosis have to be: (1) adequate pre- and postpartal diagnosis and therapy of pulmonary and/or cardiac disease, (2) careful management of nutrition, control of pancreatic insufficiency and electrolyte balance, (3) exclusion of maternal diabetes mellitus, (4) sonographic measurements to supervise the development of the fetus, (5) adequate management of delivery, (6) monitoring of puerperium with regard to maternal cystic fibrosis, (7) exclusion of cystic fibrosis in the newborn.

Adult↗

PubMed2004

Association of cystic fibrosis with abnormalities in fatty acid metabolism.

BACKGROUND: Patients with cystic fibrosis have altered levels of plasma fatty acids. We previously demonstrated that arachidonic acid levels are increased and docosahexaenoic acid levels are decreased in affected tissues from cystic fibrosis-knockout mice. In this study we determined whether humans with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have a similar fatty acid defect in tissues expressing CFTR. METHODS: Fatty acids from nasal- and rectal-biopsy specimens, nasal epithelial scrapings, and plasma were analyzed from 38 subjects with cystic fibrosis and compared with results in 13 obligate heterozygotes, 24 healthy controls, 11 subjects with inflammatory bowel disease, 9 subjects with upper respiratory tract infection, and 16 subjects with asthma. RESULTS: The ratio of arachidonic to docosahexaenoic acid was increased in mucosal and submucosal nasal-biopsy specimens (P<0.001) and rectal-biopsy specimens (P=0.009) from subjects with cystic fibrosis and pancreatic sufficiency and subjects with cystic fibrosis and pancreatic insufficiency, as compared with values in healthy control subjects. In nasal tissue, this change reflected an increase in arachidonic acid levels and a decrease in docosahexaenoic acid levels. In cells from nasal mucosa, the ratio of arachidonic to docosahexaenoic acid was increased in subjects with cystic fibrosis (P<0.001), as compared with healthy controls, with values in obligate heterozygotes intermediate between these two groups (P<0.001). The ratio was not increased in subjects with inflammatory bowel disease. Subjects with asthma and those with upper respiratory tract infection had values intermediate between those in subjects with cystic fibrosis and those in healthy control subjects. CONCLUSIONS: These data indicate that alterations in fatty acids similar to those in cystic fibrosis-knockout mice are present in CFTR-expressing tissue from subjects with cystic fibrosis.

Arachidonic Acid↗

PubMed1999

Differential function of the two nucleotide binding domains on cystic fibrosis transmembrane conductance regulator.

The genetic disease cystic fibrosis is caused by defects in the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR). CFTR belongs to the family of ABC transporters. In contrast to most other members of this family which transport substrates actively across a membrane, the main function of CFTR is to regulate passive flux of substrates across the plasma membrane. Chloride channel activity of CFTR is dependent on protein phosphorylation and presence of nucleoside triphosphates. From electrophysiological studies of CFTR detailed models of its regulation by phosphorylation and nucleotide interaction have evolved. These investigations provide ample evidence that ATP hydrolysis is crucial for CFTR gating. It becomes apparent that the two nucleotide binding domains on CFTR not only diverge strongly in sequence, but also in function. Based on previous models and taking into account new data from pre-steady-state experiments, a refined model for the action of nucleotides at two nucleotide binding domains was recently proposed.

ATP-Binding Cassette Transporters↗

PubMed2000

Severe allergic bronchopulmonary aspergillosis in an infant with cystic fibrosis and her asthmatic father.

An infant with cystic fibrosis and her asthmatic father were diagnosed as suffering from allergic bronchopulmonary aspergillosis (ABPA). Cystic fibrosis was diagnosed in the infant at 6 weeks of age, and gene mutations were W1282X/G542X. She was diagnosed definitively as suffering from ABPA at age 3.5 years, but had suggestive symptoms from age 11 months. This may be the youngest age described to date for ABPA. The child responded well to systemic steroid therapy, but remained steroid-dependent over the next 4 years. Treatment with itraconazole enabled a marked reduction in steroid dosage. The father was an asthmatic, and a heterozygote for the cystic fibrosis transmembrane regulator (CFTR) mutation W1282X. He had a normal sweat test, atopy, and moderate reversible airway obstruction. There was no proven exposure to Aspergillus in the home environment. The importance of considering the diagnosis of ABPA even in infancy, the therapeutic dilemmas, and the possible role of abnormal CFTR function in the development of ABPA are discussed.

Adult↗

PubMed2000

Enteral tube feeding for cystic fibrosis.

BACKGROUND: Enteral tube feeding is routinely used in many cystic fibrosis centres when weight for height percentage is less than 85%, when there has been weight loss for greater than a two month period or when there has been no weight gain for two to three months (under five years old) or for six months (over five years old). OBJECTIVES: To examine the evidence that in patients with cystic fibrosis supplemental enteral tube feeding improves nutritional status, respiratory function, and quality of life without significant adverse effects. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialised register and contacted the companies which market enteral feeds and reviewed their databases. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised controlled trials comparing supplemental enteral tube feeding for one month or longer with no specific intervention in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: There are no trials included in this review. MAIN RESULTS: There are no trials included in this review. REVIEWER'S CONCLUSIONS: Supplemental enteral tube feeding is widely used throughout the world to improve nutritional status in patients with cystic fibrosis. The methods mostly used, nasogastric or gastrostomy feeding, are invasive, expensive, and may have a negative effect on self esteem and body image. Reported use of enteral tube feeding suggests that it results in nutritional and respiratory improvement and it is disappointing that their efficacy has not been fully assessed by randomised controlled trials. With the more frequent recommendations to use enteral tube feeding as an early rather than a late intervention, this systematic review identifies the need for a multi-centre randomised controlled trial assessing both efficacy and possible adverse effects of enteral tube feeding in cystic fibrosis.

Cystic Fibrosis↗

PubMed1995

Normal energy expenditure in the infant with presymptomatic cystic fibrosis.

To investigate whether a fundamental lesion in energy metabolism is a feature of cystic fibrosis, we measured total energy expenditure using the doubly labeled water technique in 19 infants with presymptomatic cystic fibrosis (0.8 to 6.6 months of age) identified through newborn screening. Total energy expenditure data collected in a cohort of healthy infants by the same method were used for comparison. Energy balance studies were additionally performed in 10 of the infants with cystic fibrosis. Total energy expenditure levels in infants with cystic fibrosis, expressed as either kilocalories per day or kilocalories per kilogram of fat free mass per day, did not differ from control levels. When expressed on the basis of body weight (in kilocalories per kilogram per day), expenditure levels in infants with cystic fibrosis were greater (p < 0.05) than control levels. No differences in expenditure were observed between those infants who were homozygous (n = 10) for the delta F508 mutation and the heterozygous infants (n = 7), regardless of how expenditure was expressed. Assessment of energy balance indicated that infants with cystic fibrosis grow at a normal rate for metabolizable energy intakes similar to those reported for healthy infants. We conclude that there are no differences in energy expenditure between infants with presymptomatic cystic fibrosis and healthy infants, once differences in body composition are taken into account. This finding indicates that the primary cystic fibrosis defect is not an energy-requiring one.

Anthropometry↗

PubMed1976

Surface enzymes in cultured fibroblasts from cystic fibrosis patients.

Membrane function was examined in cultured cells from cystic fibrosis patients by assaying several enzymes on intact skin fibroblasts attached to culture dishes. This technique required few cells and minimized disruption of cellular organization. Comparison of enzyme activities of intact and broken cells showed that 12% of total glucose-6-phosphate dehydrogenase, a cytoplasmic enzyme, was measurable using intact cells, while all adenosine monophosphatase was measurable using intact cells. Alkaline paranitrophenylphosphatase activity was divided between the cell surface and interior. Substrate competition experiments indicated that substrate specificities for adenosine monophosphatase and paranitrophenylphosphatase activities were different. Adenosine monophosphatase activities of 2 control and 2 cystic fibrosis strains fluctuated similarly during the cell culture cycle. The apparent Km values relative to adenosine monophosphate were similar in all strains. A chromatographic fraction of serum from a cystic fibrosis patient that was inhibitory to oyster ciliary activity had no effect on adenosine monophosphatase activity of normal fibroblasts. Furthermore, fractions of media from cystic fibrosis homozygote and heterozygote fibroblast cultures were not inhibitory to adenosine monophosphatase activities of intact normal fibroblasts or of part iculate fractions prepared from them. In light of previous studies that showed that factors from cystic fibrosis serum of culture medium disrupted specific membrane activities, it is proposed that the cystic fibrosis factor interacts with the plasma membrane, interfering most conspicuously with the protein functions that are sensitive to changes in their membrane environment.

4-Nitrophenylphosphatase↗

PubMedDate not supplied

Exercise response and rehabilitation in cystic fibrosis.

Exercise testing can be performed safely in cystic fibrosis patients, and provides a simple and reproducible index of overall health in the disease. A wide variability in exercise capacity of cystic fibrosis patients is found, but, in general, exercise is limited by the degree of lung disease and, to a lesser extent, by compromised nutritional status. Based on the results of exercise tests, patients can then be supplied with individualised exercise prescriptions. Exercise training can be expected to improve the exercise capacity of the majority of cystic fibrosis patients, but pulmonary function generally remains unchanged. Whether exercise rehabilitation will improve the long term prognosis for patients with cystic fibrosis is currently not known.

Adolescent↗

PubMed1994

Desensitisation of neutrophil responses by systemic interleukin 8 in cystic fibrosis.

BACKGROUND: Inflammation associated with neutrophil infiltration is a commonly observed feature of children with cystic fibrosis. Production of the major neutrophil chemotactic cytokine interleukin 8 (IL-8) is potentially of great importance in the pathology of cystic fibrosis. Concentrations of IL-8 in both sputum and bronchoalveolar lavage fluid have been found to be higher in children with cystic fibrosis than in controls. The IL-8 induced chemotactic response and numbers of IL-8 receptors on peripheral neutrophils obtained from children with cystic fibrosis have been compared with a control group of children. METHODS: Cells were isolated from 18 patients with cystic fibrosis (aged 4-20 years) and 13 controls (aged 5-12 years) by dextran centrifugation followed by separation on Lymphoprep. Chemotaxis was assayed using multiwell microchemotaxis chambers and 5 microns polycarbonate filters. Filters were fixed and stained with Haema-Gurr for counting. Results were expressed as numbers of neutrophils per high power field (HPF). RESULTS: At the optimum concentration (1 x 10(-8) mol/l) the number of cells migrating were similar for controls (150 (12)/HPF) and for the cystic fibrosis group (140 (14)/HPF)). At lower concentrations the numbers of neutrophils migrating were lower for the cystic fibrosis group. Scatchard analysis of 125I-labelled IL-8 binding revealed lower numbers of receptors on neutrophils from patients with cystic fibrosis (22,000 per cell) than from controls (75,000 per cell). CONCLUSIONS: Reduced responsiveness to IL-8 of neutrophils from patients with cystic fibrosis is associated with receptor desensitisation as a result of exposure to high systemic levels of IL-8.

Adolescent↗

PubMed2000

Oral calorie supplements for cystic fibrosis.

BACKGROUND: Poor nutrition occurs frequently in children and adults with cystic fibrosis and is associated with a number of other adverse outcomes. Oral calorie supplements are used to try and increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns that they may lead to a reduction in the amount of food eaten and no overall improvement in energy intake. OBJECTIVES: To examine the evidence that in patients with cystic fibrosis, oral calorie supplements increase daily calorie intake, improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess possible adverse effects associated with use of oral calorie supplements. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. The companies which market oral calorie supplements were also contacted. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: indices of nutrition and growth, anthropometric measures of body composition, calorie intake (total, from oral calorie supplements and from food), nutrient intake, eating behaviour, quality of life, specific adverse effects, lung function and mortality. MAIN RESULTS: Two trials which reported results from a total of 29 patients were suitable for inclusion in the review. From the data provided in the published reports only one item (change in weight) could be extracted from one trial for inclusion in the review. This showed no difference between intervention and comparison group. REVIEWER'S CONCLUSIONS: Oral calorie supplements are very widely used around the world in an attempt to improve nutritional status in patients with cystic fibrosis, at some considerable cost. It is therefore very disappointing that their effectiveness has not been assessed by adequate clinical trials. No conclusions can be made about the use of oral calorie supplements in cystic fibrosis from the information currently available and clinicians must balance potential benefits against possible adverse effects of treatment in making decisions about individual patients. This systematic review has clearly identified the need for a well designed, adequately-powered, multicentre, randomised controlled trial assessing the effectiveness and possible adverse effects of oral calorie supplements in cystic fibrosis.

Adult↗

PubMed1997

Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis.

BACKGROUND: Arthritis is a well recognised complication of cystic fibrosis. The cause of this arthritis is not yet clear but it is likely to be an immunological reaction to one of the many bacterial antigens to which the lungs are exposed. One such group, the heat shock proteins, (hsp), was investigated. These are immunodominant antigens of a wide variety of infectious microorganisms and have varying amino acid chain sequences, some of which are similar to those found in human tissues. METHODS: Antibodies to human hsp 27 and hsp 90 in the serum of patients with cystic fibrosis, with and without arthritis, and in normal age and sex matched healthy controls were measured. The severity of the cystic fibrosis was assessed by lung function tests and chest radiographs. The nature of the organisms colonising the lungs was determined by bacteriological examination of sputum. RESULTS: Higher mean titres of serum IgG anti-human hsp 27 and hsp 90 antibodies were found in 50 patients with cystic fibrosis than in healthy controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07); hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These antibodies were higher in patients in whom the lungs were colonised with Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17 to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57) versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with arthritis had higher anti-hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the 42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). CONCLUSIONS: These findings suggest that the arthritis associated with cystic fibrosis, despite being seronegative for rheumatoid factor, was associated with more severe lung disease and with a greater inflammatory response to heat shock proteins.

Adolescent↗

PubMed1994

Therapeutic approaches to cystic fibrosis: memorandum from a joint WHO/ICF(M)A meeting.

Cystic fibrosis is one of the commonest genetic diseases among Caucasians and represents an important cause of suffering and death among children and adults. In the past two decades marked prolongation of the life of patients with cystic fibrosis has been achieved as the result of improved case-finding and an extensive regimen of therapies. More recently, a variety of new approaches to therapy have been developed or proposed as the result of advances in cell physiology and molecular biology. This article summarizes the presentations and discussions made at a joint WHO/ICF(M)A (International Cystic Fibrosis (Mucoviscidosis) Association) meeting, held in Washington, DC, on 14 October 1992, and reviews the current status of possible therapies for cystic fibrosis and their implications for treatment in various countries of the world.

Adolescent↗

PubMed1994

Lipid levels in adults with cystic fibrosis.

OBJECTIVE: To examine the hypothesis that an energy-dense, high-fat diet, which is necessary to maintain weight in adults with cystic fibrosis, does not result in high serum cholesterol levels. DESIGN: Dietary, anthropometric, and biochemical data were correlated. SETTING: A cystic fibrosis center in Pittsburgh, Pa. SUBJECTS: Thirty-one adults with cystic fibrosis, 50 obligate carriers of the cystic fibrosis gene, and 26 controls who did not have cystic fibrosis. MAIN OUTCOME MEASURES: Adults with cystic fibrosis had a lower mean serum cholesterol level and higher mean intakes of energy and fat than controls. STATISTICAL ANALYSES PERFORMED: Student's t test was used to determine the statistical significance between two means. Univariate correlation coefficients were determined to measure the relative intensity of association between two variables. RESULTS: Mean total serum cholesterol levels in men with cystic fibrosis was 3.1 mmol/L vs 4.7 mmol/L in male controls (P < .001). Mean total serum cholesterol levels in women with cystic fibrosis was 3.2 mmol/L vs 4.3 mmol/L in female controls (P < .001). Three adults with cystic fibrosis and no signs of pancreatic insufficiency had serum cholesterol levels in the high normal range. Carriers had serum lipid levels in the same range as the controls. CONCLUSIONS/APPLICATIONS: The findings indicate that a high-energy, high-fat diet does not raise serum lipid levels in those patients with cystic fibrosis and pancreatic insufficiency. However, those individuals with cystic fibrosis and normal pancreatic function may be at the same risk as the general population for developing high serum lipid levels. They should have their serum lipid levels monitored and be given appropriate dietary recommendations.

Adult↗

PubMed2006

Adenosine regulation of cystic fibrosis transmembrane conductance regulator through prostenoids in airway epithelia.

Cystic fibrosis is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, leading to altered ion transport, chronic infection, and excessive inflammation. Here we investigated regulation of CFTR in airway cell monolayers by adenosine, adenosine receptors, and arachidonic acid. Our studies demonstrate that the A2B adenosine receptor is expressed at high levels relative to the other adenosine receptor subtypes, with a characteristic low-affinity profile for adenosine-stimulated CFTR Cl- currents in both Calu-3 cells and CFBE41o- airway cell monolayers stably transduced with wild-type CFTR. The levels of adenosine found in sputum from patients with cystic fibrosis with moderate to severe lung disease stimulated apical prostaglandin release in Calu-3 and CFBE41o- cells, implicating adenosine regulation of phospholipase A2 (PLA2) activity. A2B adenosine receptor and arachidonic acid stimulation produced CFTR-dependent currents in airway monolayers and increased cAMP levels that were sensitive to cyclooxygenase inhibition. Arachidonic acid demonstrated dual regulation of CFTR, stimulating CFTR and Cl- currents in intact airway monolayers, and potently inhibiting PKA-activated Cl- currents in excised membrane patches. Cl- currents produced by arachidonic acid were sensitive to inhibition of PKA, cyclooxygenase, and 5-lipoxygenase. Together, the results provide a converging mechanism to link regulation of CFTR and airway cell inflammation through adenosine and adenosine receptors.

Adenosine↗