Low prevalence of glucose intolerance in racially mixed children with cystic fibrosis

Alves C, Lima DS, Cardeal M, Santana A. Low prevalence of glucose intolerance in racially mixed children with cystic fibrosis. Objective: To evaluate glucose tolerance in racially mixed Brazilian youth with cystic fibrosis (CF). Methods: Cross‐sectional study conducted between August and September 2007, at a reference service for CF, evaluating: glycated hemoglobin (HbA1c), blood glucose, and insulin levels, before and 2 h after a glucose overload. Results: There were 46 patients aged between 6 yr and 16 yr and 2 months (median: 9 yr and 10 months) of whom 64% were boys. Of these, 26% were Whites; 54.4% Mulattoes; and 19.6% Blacks. HbA1c was normal in all patients. Only one participant (12‐yr old) had glucose intolerance. Insulin levels ranged from 1 to 23 µIU/mL (median: 4.5 µIU/mL) at baseline and from 3.2 to 192.1 µIU/mL (median: 11 µIU/mL) after a glucose overload. Insulin resistance evaluated by the HOMA index, stratified by sex and age, was present in three patients. The ΔF508 mutation was present in only 4.3% of the sample, all of them being heterozygous. Conclusions: The low prevalence of carbohydrate intolerance in this population is probably a result of their young age. Another possibility is the low frequency of the ΔF508 mutation. Although not conclusive, these data suggest that in addition to age, the genotype:phenotype ratio may influence the development of glucose intolerance in patients with CF.     

Oral glucose tolerance testing in cystic fibrosis: Correlations with clinical parameters and glycosylated haemoglobin determinations

In 48 patients (age 2–28 years) with documented cystic fibrosis, glucose tolerance was evaluated by means of an oral glucose tolerance test (OGTT) and repeated glycosylated haemoglobin (HbA1C) measurements. An impaired OGTT was found in 15 patients. Their degree of undernutrition and severity of lung and liver involvement were no different from those with normal glucose tolerance. The mean peak insulin concentration as well as the integrated insulin concentration during the OGTT were comparable with patients with normal glucose tolerance (GT) and those with an impaired tolerance (GI). The mean time to attain peak insulin levels was significantly delayed in the GI group. (117 min vs 86 minP<0.01). On initial testing, elevated HbA1C levels were found in 22 patients. Mean HbA1C levels in the GI group were higher than in the GT group *8.2% vs 7.5%P<0.01). The HbA1C levels at the moment of OGT testing were positively correlated with the glycaemic response during the OGTT. The repeated HbA1C measurements 1 year later were no different from the initial mean HbA1C values in both groups. Two GI patients with initial HbA1C levels of 7.5% and 11% respectively developed diabetes mellitus several months after testing. The need for serial HbA1C determinations in cystic fibrosis is questioned.     

Hyperglycaemia and insulinopenia in a neonate with cystic fibrosis

Abnormal glucose tolerance is a frequent late complication of cystic fibrosis (CF), but the prevalence of CF-related diabetes mellitus (CFRD) in children less than 10 y old is less than 2%. The youngest child with CFRD reported to date was 6 mo of age. Insulinopenia is the primary cause of abnormal glucose tolerance/CFRD, but it is unknown whether it may begin in the neonatal period. We describe a case of a neonate with CF who presented with hyperglycaemia in the diabetic range and marked insulinopenia. Insulinopenia and impaired glucose tolerance were permanent findings at 6 and 15 mo of age. CONCLUSION: This case suggests that abnormal glucose tolerance/diabetes may occur much earlier in the course of CF, even during neonatal age. Careful follow-up and further studies in CF infants could reveal that the real incidence of glucose intolerance and diabetes in this age group has been underestimated.     

Does probiotic supplementation affect pulmonary exacerbation and intestinal inflammation in cystic fibrosis: a systematic review of randomized clinical trials

Background:Patients with cystic fibrosis (CF) usually have abnormal intestinal microbiota due to massive exposure to antibiotics.Probiotics could modify the gut microbiota and hence may affect CF management.So the aim of present systematic review was evaluation of the efficacy and safety of probiotic supplementation for the management of cystic fibrosis.Data sources:We searched PubMed,Science Direct,Google Scholar,Springer Cochrane Library Databases until January 2016 for randomized controlled trials (RCTs) performed in pediatric or adult populations related to the study aim.Key words were selected based on Mesh terms.Based on the Critical Appraisal Skills Programme checklist,eligibility of included articles was evaluated.Results:Five studies included in this review represent 188 participants with a follow up period ranging from 1 month to 6 months.The results of the included studies supporting the use of probiotics in management of pulmonary exacerbation and intestinal calprotectin in patients with cystic fibrosis.However the level of evidence was limited.Conclusion:The lack of high quality RCTs makes it impossible to support a general recommendation about the use of probiotics in the treatment of CF pulmonary exacerbation and intestinal inflammation.     

Carnitine metabolites in infants with cystic fibrosis: a prospective study

Acylcarnitine is low in cord blood in patients with cystic fibrosis, suggesting that fatty acid metabolism is disturbed in utcro. Carnitine metabolites (total, free, short- and long-chain acylcarnitine) were measured prospectively in 23 newly diagnosed infants with cystic fibrosis treated with a carnitine-containing, predigested formula for 6–12 months. Total ( p < 0.002), free ( p < 0.004), and long-chain (p < 0.001) plasma concentrations of carnitines were significantly less than controls (n = 48) at diagnosis. Total and free concentrations were corrected with nutritional management, whereas short-and long-chain acylcarnitines remained unchanged. By three years of age all plasma concentrations of carnitine metabolites were significantly less than controls despite a carnitine-containing diet. Urinary carnitine metabolites were increased at diagnosis and follow-up. The physiological significance of these observations in cystic fibrosis is unknown, but could be compatible with disturbed regulatory control with resultant increased utilization.     

Metabolic alkalosis with hypoelectrolytemia in infants with cystic fibrosis

BACKGROUND: Infants with cystic fibrosis (CF) can develop episodes of hyponatremic hypochloremic dehydration with metabolic alkalosis when they sweat excessively, which is not caused by sweating in normal infants. We investigated the incidence of the metabolic alkalosis with hypoelectrolytemia in CF infants, the possible risk factors for its occurrence and the importance of the manifestation in the diagnosis of CF. METHODS: In order to evaluate the incidence and the risk factors for the development of this sweat-related metabolic disorder in CF, we reviewed the records of all children diagnosed as having CF before the age of 12 months in a 10-year period. Data analysis included medical history data, clinical features, biochemical parameters (blood pH, serum bicarbonate, sodium, chloride and potassium levels), sweat chloride test values, as well as genetic analysis data. RESULTS: The prevalence of metabolic alkalosis in association with low serum electrolyte concentrations (hyponatremia, hypochloremia, and hypokalemia) in infant CF population in our region was 16.5%. We found no season predilection in its occurrence. Early infant age, breast-feeding, delayed CF diagnosis, heat exhaustion and the presence of severe CF transmembrane conductance regulator mutations are predisposed factors for the development of metabolic alkalosis with hypoelectrolytemia. CONCLUSIONS: The results from our study suggest that metabolic alkalosis with hypoelectrolytemia is a relatively common manifestation of CF in infancy. The possibility of CF should be seriously considered in any infant with this metabolic disorder.     

Efficacy and safety of acarbose in patients with cystic fibrosis and impaired glucose tolerance

Impaired glucose tolerance (IGT) is an increasingly frequent complication of cystic fibrosis (CF). In CF patients, a fast postprandial rise in plasma glucose is typically followed by a delayed but prolonged insulin response. Patients may develop symptoms of both hyper- and hypoglycaemia. The α-glucosidase inhibitor, acarbose, delays the hydrolysis and subsequent absorption of ingested carbohydrates. The aim of this study was to investigate the efficacy of acarbose in CF patients with IGT. During a 2-week inpatient period for treatment of Pseudomonas infection, 12 CF patients with IGT were studied in a double-blinded, randomized crossover trial. Each patient received acarbose (50 mg t.i.d.) for 5 days and placebo for 5 days (days 3–8 and days 10–14, respectively). Glucose, insulin and C-peptide responses to a standardized nutritional load were measured at baseline and at the end of each study period (Days 2, 8 and 14). Treatment with acarbose was associated with significant reductions in the mean value, mean peak values and the area under the curve of plasma glucose, insulin and C-peptide, compared to respective baseline values and placebo. Gastro-intestinal disturbances were recorded in 67% of patients during therapy with acarbose. Conclusion Acarbose has a positive therapeutic effect on glucose tolerance in cystic fibrosis patients, as shown by attenuation of postprandial plasma glucose increase and a significant decrease in insulin secretion response. However, acarbose treatment was associated with adverse gastro-intestinal effects that may prevent patients from accepting long-term therapy. Received: 1 December 1997 / Accepted in revised form: 15 September 1998     

Unrecognised infection in a cystic fibrosis patient

We report a 17-year-old Malay boy with cystic fibrosis who over a 14-month period experienced worsening respiratory symptoms and deteriorating lung function. Burkholderia pseudomallei was eventually isolated from his sputum. He improved clinically following treatment for meliodosis and his lung function returned to normal.     

Home intravenous antibiotic treatment of patients with cystic fibrosis

We report one-year's experience of home iv antibiotic treatment in 31 patients with cystic fibrosis chronically colonized with Pseudomonas aeruginosa. The patients were aged 4-67 years and had a mild to severe disease as indicated by a Shwachman score of 46-95 (mean 77). Ninety-two courses of iv antibiotic therapy were given (mean 3.0 per patient). The mean duration of the courses was 15.4 days. The entire antibiotic course, except for the first dose, was administered at home in 70% of the courses. Most patients (94%) were given a combined treatment of a beta-lactam and an aminoglycoside, administered by the patients themselves or their parents. One inserted venous cannula could be used for the whole treatment period in 30% of the courses. There were no complications. The clinical and bacteriological outcome was good to excellent in 89% of the courses, with temporary eradication or semi-quantitative decrease of Pseudomonas growth in sputum. Lung function (forced expiratory volume at 1 s) and blood gases improved significantly (p less than 0.001) and p less than 0.01, respectively). Most patients were able to attend work or school as usual, and 96% of the patients preferred this type of treatment to hospitalization. Apart from the psychosocial advantages, the economical savings were substantial. In comparison to traditional treatments in hospital (21 patients, 41 courses) home iv antibiotic treatment was safe and effective.     

Longitudinal evaluation of glucose tolerance and insulin secretion in non-diabetic children and adolescents with cystic fibrosis: results of a two-year follow-up

Thirty-two patients with cystic fibrosis and repeatedly normal fasting blood glucose underwent oral glucose tests and islet-cell antibody assessments on two occasions approximately two years apart. Fourteen patients underwent two iv glucose tolerance tests also. Although in the group as a whole mean glucose areas in response to the oral test remained substantially unmodified over the two-year period, the prevalence of glucose tolerance abnormalities increased from 37.5 to 50%. Insulin output in response to both oral and iv tolerance tests decreased over time. Worsening of insulin secretion and/or of glucose tolerance was never accompanied by deteriorating clinical status. Islet-cell antibodies were detected in no patients, even in those who developed a diabetic glucose tolerance. These results support, on a longitudinal basis, the view of a progressive impairment of B-cell function in cystic fibrosis, which may precede the onset of metabolic abnormalities and is not triggered by autoimmunity.     

Comparison of a positive expiratory pressure (PEP) mask with postural drainage in patients with cystic fibrosis

The use of a positive expiratory pressure (PEP) mask was compared with postural drainage in the treatment of 10 patients with cystic fibrosis. The patients were allocated randomly in a crossover fashion to the two regimens and evaluated initially by a physiotherapist and over a 4 week treatment period by use of a diary card. There was no significant difference in sputum production or change in lung function between each technique as assessed by the physiotherapist. Diary card evaluation also failed to demonstrate a difference in sputum production, symptom score or peak expiratory flow rate between the 4 week treatment periods. It was concluded that PEP mask therapy is an acceptable and effective alternative to postural drainage in interval therapy of patients with cystic fibrosis, although the patients have tended to revert to postural drainage during acute exacerbations.     

Cascade carrier-testing in cystic fibrosis

It is good medical practice to offer carrier tests and counselling to the relatives of those affected by recessive disorders. Many are concerned about their own chances of having affected offspring. Cystic fibrosis carrier tests have been feasible since the discovery of the gene in 1989. It was generally agreed that although population screening was not practical, testing should be offered to relatives and their partners. There is evidence that such offers have not always been made and relatives have sometimes found it difficult to be tested. An active cascade programme of the counselling and testing of cystic fibrosis patients' relatives and their partners has operated from Royal Manchester Children's Hospital since 1993. The service operates with dedicated staff, backed up by a specialist cystic fibrosis molecular genetics laboratory and a specialist genetic counselling service. The main target groups are couples or individuals of child-bearing age. There is discouragement of the testing of young children and of grandparents beyond reproductive age, although, if parents or individuals are insistent, testing is often performed, after counselling. An audit of users has shown satisfaction, very few feeling that they were pressured into having the tests. The experience of other centres with cascade-testing in cystic fibrosis is summarised. Cascades can start whenever a sufferer or carrier is identified, although care should be exercised in instituting active cascades in the extended families of newborns identified as carriers in neonatal screening programmes.     

Liver and intestinal transplantation in a child with cystic fibrosis: a case report

Cystic fibrosis (CF) is an inherited disorder that presents as a multisystem disease with meconium ileus being the presenting symptom in 20% of patients. Approximately half of these patients present with complicated meconium ileus mandating early surgical intervention, potentially resulting in short gut syndrome. Although liver transplantation in children with CF has been described, this is the first report of a combined liver and small bowel transplant in a recipient with CF. A 7-month-old boy with CF presented with short bowel syndrome following extensive small bowel resection for meconium ileus and progressive cholestatic liver failure from intravenous hyperalimentation. He underwent combined liver and small intestinal transplant. He was discharged home three weeks post-transplant on enteral feeds with supplemental intravenous fluid. He has had routine protocol small bowel allograft biopsies with no documented rejection episodes. He has been treated for minor respiratory infections without major sequelae. Improvements in pulmonary therapy have impacted on the survival in the CF population to the point where the need for multiorgan transplantation will be increased in the future. Extrapolating from the excellent experience of liver transplantation in children with CF, early liver and small intestinal multivisceral transplantation, if indicated, can be performed safely in children with CF.     

Neutrophil chemotaxis in acutely infected and clinically stable cystic fibrosis patients*

Abstract Purpose : The aim of the present study was to evaluate the role of neutrophil chemotaxis in cystic fibrosis (CF) and to also determine whether an acute bacterial infection and the nutritional status of a child can affect neutrophil chemotaxis.
Methods : Twelve acutely infected and 12 clinically stable CF patients and 10 healthy age-matched controls were studied. Neutrophil chemotaxis and random migration were investigated in vitro in the peripheral blood of subjects by the Boyden chamber method and the results were expressed as chemotactic index (CI). The nutritional status of the cases was evaluated as body mass index (BMI).
Results : The CI values in the acutely infected group were found to be significantly lower than the clinically stable and healthy control groups ( P <0.05 and P <0.005, respectively). There was no significant difference between the clinically stable CF group and the healthy control group ( P >0.1). No significant correlation was detected between the CI and BMI of the two groups of CF patients ( P >0.05).
Conclusions : The present study confirms that neutrophil chemotaxis and random migration are normal in clinically stable CF patients. The decreased CI in the acutely infected patients indicates the possible role of infection itself on neutrophil chemotaxis.     

Peak inspiratory flows in children with cystic fibrosis

OBJECTIVE: To show that in children with moderately severe cystic fibrosis lung disease: (i). inspiratory flow may be reduced; and (ii). peak inspiratory flow may be predicted from height, expiratory flow analysis or body mass index. METHODS: All children attending the Royal Children's Hospital, Melbourne, between May and July, 2001 who had cystic fibrosis, were aged > 5 years, were able to perform spirometry reproducibly and who had a forced expiratory volume in 1 s < 60% predicted were prospectively enrolled. Height, weight, peak inspiratory flow, forced expiratory volume in 1 s and forced vital capacity were recorded. Linear regression analysis was performed. RESULTS: The age range was 9.4-19.9 years. Sixteen boys and 11 girls were studied. All children had a peak inspiratory flow > 0.5 L/s. There was a significant relationship between peak inspiratory flow and forced vital capacity (R2 = 0.50) especially in boys (R2 = 0.65). In boys, peak inspiratory flow was significantly related to forced expiratory volume in 1 s (R2 = 0.47). There was no relationship between peak inspiratory flow and predicted values of expiratory flow, age, height, weight or body mass index. Logistic regression was used to predict the probability that peak inspiratory flow was < 2.0 L/s for a given forced vital capacity. If the forced vital capacity is > 2.5 L, peak inspiratory flow is likely to be > 2.0 L/s. CONCLUSIONS: In children with significant cystic fibrosis lung disease, peak inspiratory flow is likely to be > 0.5 L/s, which is required to activate dry powder inhalers. If the forced vital capacity is < 2.5 L, the peak inspiratory flow may be < 2.0 L/s, and a metered dose inhaler and spacer should be considered. Further studies that investigate the relationship between expiratory flow and peak inspiratory flow against an internal resistance are needed.     

Myocardial fibrosis — a rare complication in patients with cystic fibrosis

We report a 10-month-old male infant who was admitted to our hospital with a history of failure to thrive and bulky stools. On examination, he was dystrophic and had a protruding abdomen, but he was well oxygenated and his lungs were clear on auscultation. A tachycardia of 145 beats per min and radiological evidence of cardiomegaly indicated involvement of the heart, but an ECG failed to show signs of myocarditis or cardiac hypertrophy. An elevated sweat chloride concentration of 141 mEq/l confirmed the diagnosis of cystic fibrosis (CF). Molecular analysis revealed heterozygosity for the common mutation delta F₅₀₈. He died unexpectedly of a sudden cardiac arrest 2 days later. Autopsy revealed scattered myocardial necrosis and fibrosis. Some 50 documented cases of myocardial fibrosis in infants with CF have been reported. Suggested causes such as malnourishment and hypovitaminosis remain speculative as systematic studies have yet to be done.     

Nebulized gentamicin in children and adolescents with cystic fibrosis

A study of 29 children and adolescents with cystic fibrosis over 2 years showed some evidence of benefit from the twice daily inhalation of 20 mg nebulized gentamicin when compared to the inhalation of a nebulized saline mixture. Clinical symptoms, deterioration in pulmonary function, antibiotic usage, days in hospital and development of Pseudomonas aeruginosa in the sputum were recorded. There was no significant difference in antibiotic usage, days in hospital or clinical symptoms between the two regimes. Those subjects with P. aeruginosa in sputum showed significantly less deterioration in lung function over 2 years while using gentamicin aerosol. There was no difference in progress between the two treatment regimes for those subjects with P.aeruginosa in sputum at the beginning of the study, nor was there any difference in the number developing P. aeruginosa in sputum.