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.     

Gene transfer to the tracheobronchial tree: implications for fetal gene therapy for cystic fibrosis

Gene transfer to the tracheobronchial tree has been an active area of investigation since the discovery of the genetic defect in the cystic fibrosis transmembrane conductance regulator over two decades ago. Cystic fibrosis (CF) is the most common lethal monogeneic disorder for which there is no cure short of lung transplantation. The ultimate goal of gene therapy in CF is to achieve efficient gene transfer at a level and distribution in target tracheobronchial epithelial cells and submucosal gland cells, which results in the genotypic and phenotypic correction of CF. This article reviews the current challenges and limitations of postnatal gene therapy to the tracheobronchial tree, and the potential advantages of fetal gene therapy for CF. We review recent work with novel viral vectors to achieve extremely efficient gene transfer in target cells in the respiratory epithelium and submucosal glands in models that are representative of the developing human fetal trachea. Finally, we will examine the prospects for, limitations of, and regulatory challenges facing the translation of fetal gene therapy from research to clinical application.     

Feeding behavior problems in children with cystic fibrosis in the UK: prevalence and comparison with healthy controls

BACKGROUND: Feeding behavior problems contribute to inadequate dietary intake for many patients with cystic fibrosis (CF). However, to establish effective intervention programs, more needs to be known about the occurrence and distribution of these difficulties. The aims of this study were to establish the prevalence and range of disruptive child behaviors (DCB) in patients with CF and the inappropriate parental responses (IPR) during mealtimes and to compare the results with those of healthy children. METHODS: In study A, parents of 108 patients (aged 1-7 years) completed a Behavioural Paediatric Feeding Assessment Scale comprising two domains: DCBs and IPRs during mealtimes. Parents rated the frequency of the behaviors and responses and identified those they considered problematic. In study B, data from the CF group (n = 69, aged 1-12 years) were compared with 69 age- and sex-matched control subjects. RESULTS: Parents of children with CF aged 5 to 8 years recorded significantly more DCBs than those in all other age ranges. These parents also reported significantly more IPRs than did parents of children aged 9 to 12 years and 13 to 17 years. Parents of children with CF reported significantly more DCBs and IPRs than did those of the control subjects. There were significantly more problematic DCBs and IPRs in the CF group than in the control group for children aged 5 to 8 years and 9 to 12 years but not for those aged 1 to 4 years. CONCLUSIONS: Parents of children with CF report more feeding behavior problems than do those of healthy control subjects. The high prevalence of feeding behavior problems in older children suggests that preventative and reactive interventions must continue throughout childhood and vary according to the child's developmental abilities.     

Growth hormone therapy improves growth in children with cystic fibrosis related liver disease

Growth impairment in cystic fibrosis (CF) is worsened by liver disease. Children with CF have serum levels of insulin-like growth factor-I (IGF-I) that are lower than expected for their normal growth hormone (GH) production. In children with CF-related liver disease (CFLD), response to endogenous GH is further reduced. We present our experience with two young children with CFLD given recombinant human GH (rhGH). The first patient was a 5 year-old female with CFLD and poor growth who responded well for 1 1/2 years to rhGH therapy during her initial course and without a significant increase in serum IGF-I, but with a substantial increase in IGF-I concentration when the GH dose was increased. The second patient was a 5 month-old male with advanced liver disease who had transient improved growth and liver function following rhGH. These patients suggest that rhGH is safe and may be effective in children with CFLD.     

Assessment of hypoxia in children with cystic fibrosis

Hypoxia during sleep and exercise may occur in an important number of patients with cystic fibrosis (CF). Despite its recognition, no clear definition for hypoxia in CF exists, and nor do guidelines for commencing oxygen therapy. CF patients with hypoxia may have increased pulmonary artery pressure, reduced exercise ability, and skeletal muscle strength, and most importantly of all worse sleep quality, and a worse quality of life. Laboratory and rodent evidence exists to suggest that hypoxia may contribute to the decline in lung function in CF by upregulating lung inflammation, and encouraging growth of Pseudomonas aeruginosa, the most important pathogen associated with CF lung disease. The effects of hypoxia in childhood CF need to be fully studied, and a potential expanded role for oxygen as therapy in CF may be worthy of exploration.     

Ibuprofen in children with cystic fibrosis: pharmacokinetics and adverse effects

Antiinflammatory therapy with ibuprofen has been proposed to retard the progression of lund disease in cystic fibrosis (CF). The pharmacokinetics and toxicity of ibuprofen were investigated in a randomized, double-blind, placebo-controlled, 3-month dose-escalation study in 19 children with CF, 6 to 12 years of age. The subjects received orally and twice daily 300 mg of drug during the first month, 400 mg in the second month, and 600 mg in the third month. Ibuprofen pharmacokinetics and evaluation for adverse effects were performed at the beginning and end of each month. The dose of ibuprofen was increased if peak plasma concentration (Cmax) was less than 50 micrograms/ml. To preserve the blind nature of the study, the dose in matched subjects taking placebo was also increased. The subjects randomly assigned to receive ibuprofen (n = 13) completed 26 months of treatment; placebo subjects (n = 5) completed 12 months. With dose escalation, Cmax and the area under the concentration-time curve from zero to infinity significantly increased (p less than 0.01). The pharmacokinetics of ibuprofen in 13 children with CF who received 13.4 +/- 4.1 mg/kg (mean +/- SD) were compared with those in four healthy children who received a similar dose. Peak plasma concentration (48 +/- 17 micrograms/ml) was decreased by 27% (p = 0.06), the area under the concentration-time curve (6.1 +/- 1.7 mg.min/ml) was decreased by 46% (p less than 0.001), apparent total clearance (2.3 +/- 0.6 ml/min.kg-1) was increased by 77% (p less than 0.01), and apparent volume of distribution during terminal phase (291 +/- 91 ml/kg) was increased by 84% (p = 0.01) in the children with CF. Time to Cmax (66 +/- 20 minutes) and elimination half-life (92 +/- 27 minutes) were not significantly different. No subjects were withdrawn from the study because of side effects. No adverse effects could be attributed to ibuprofen. Thus ibuprofen administration has no significant toxic effects, but Cmax will need to be monitored for effective dosing in patients with CF.     

Exercise and physical activity in children with cystic fibrosis

Regular exercise and habitual physical activity are important for patients with cystic fibrosis (CF). Research has demonstrated the benefits of aerobic, anaerobic, and strength exercise training programs for health and quality of life, however, the CF patient is faced with unique barriers and challenges to participation. Recently, increased levels of habitual physical activity have been shown to slow the decline in lung function in patients with CF, and regular participation in a variety of activities may result in greater adherence in the long term. Research is now available to justify the incorporation of exercise into the routine care of patients with CF. This paper provides the background and rationale for the implementation of exercise and habitual physical activity recommendations by the health care team. Education of health care providers regarding the importance of exercise and habitual physical activity for patients with CF is needed in order for exercise and physical activity to be incorporated as key components of clinical practice and into the lives of patients with CF.     

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.     

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.     

Late effect of nocturnal mist tent therapy related to the severity of airway obstruction in children with cystic fibrosis

To evaluate the long-term effect of nocturnal mist tent therapy on the progression of airway obstruction in children with cystic fibrosis (CF) of varying severity, two matched groups each consisting of 24 children with CF were studied during 18 months on mist tent therapy and 18 months of therapy. The progression in airway obstruction was measured by change in serial measurements of maximal midexpiratory flow (MMEF), from which a regression equation of MMEF against time was obtained for each individual. Changes in MMEF value with or without therapy were compared in patients matched for severity of disease as indicated by initial MMEF values. For the group as a whole no differences were found in the progression of the airway obstruction whether the patients received mist tent therapy or not. This therapy failed to benefit any of the groups of children with CF who had early, moderate, or advanced airway obstruction as judged from their initial MMEF value. It is concluded that nocturnal mist tent therapy neither decreases airway obstruction nor prevents its progression in children with CF.     

Pulmonary infections in cystic fibrosis: pathogenesis and therapy

Infections of airways and lung in patients with cystic fibrosis determine quality of life and prognosis. Despite overall improvement of management of infections the underlying causes leading to infection early in life remain an enigma. As a consequence of infection various morphologic alterations arise. The most prominent are development of bronchiectases afflicting more than 70% of patients at age two. The spectrum of bacterial involvement has undergone significant changes. In contrast to earlier reports Pseudomonas aeruginosa at present is the most commonly encountered pathogen. Mucoid forms are typical for cystic fibrosis and are rarely seen in other conditions. Pseudomonas cannot be eradicated once it is established. Antipseudomonas chemotherapy leads to a diminution of bacteria from 10(8)/ml sputum to 10(6) at best. However, clinical results are convincing. Thus regular antispeudomonas treatment has been advocated by one CF-centre. Apart from conventional chemotherapy alternative approaches of treatment such as vaccination or immunoregulation need to be explored in greater detail.     

Care for Amish and Mennonite children with cystic fibrosis: a case series

Background  

Published articles have described a lack of willingness to allow preventative measures, as well as other types of modern therapies, as an obstacle to providing medical care for Amish and Mennonite populations.