Recombinant growth hormone therapy for cystic fibrosis in children and young adults.
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SUBMITTER: Thaker V
PROVIDER: S-EPMC6517261 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8407505 | biostudies-literature
Project description:BackgroundCystic fibrosis is an inherited condition causing disease most noticeably in the lungs, digestive tract and pancreas. People with cystic fibrosis often have malnutrition and growth delay. Adequate nutritional supplementation does not improve growth optimally and hence an anabolic agent, recombinant growth hormone, has been proposed as a potential intervention.ObjectivesTo evaluate the effectiveness and safety of recombinant human growth hormone therapy in improving lung function, quality of life and clinical status of children and young adults with cystic fibrosis.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of latest search: 15 May 2013.We conducted a search of relevant endocrine journals and proceedings of the Endocrinology Society meetings using Scopus and Proceedings First. Date of latest search: 15 March 2012.Selection criteriaRandomised and quasi-randomised controlled trials of all preparations of recombinant growth hormone compared to either no treatment, or placebo, or each other at any dose (high-dose and low-dose) or route and for any duration, in children or young adults aged up to 25 years diagnosed with cystic fibrosis (by sweat test or genetic testing).Data collection and analysisTwo authors independently screened papers, extracted trial details and assessed their risk of bias.Main resultsFour controlled trials were included in this review (with 161 participants in total), each with an unclear risk of bias. Analysis of data obtained from these trials shows improvement in height for all comparisons, but improvements in weight and lean tissue mass were only reported in the comparison of standard dose recombinant growth hormone versus no treatment. There is moderate improvement in one parameter of pulmonary function tests, functional vital capacity (per cent predicted) when comparing standard dose recombinant growth hormone and no treatment. Little evidence was found for improvement in quality of life. An improvement in fasting blood glucose levels was reported when comparing rhGH to placebo only. Exercise capacity improved in participants receiving standard dose recombinant growth hormone versus no treatment, but not for any other comparison. There is insufficient evidence to conclude any changes in hospitalisations, antibiotic use or significant adverse effects.Authors' conclusionsRecombinant growth hormone therapy is effective in improving the intermediate outcomes in height, weight and lean tissue mass when compared with no treatment. One measure of pulmonary function test showed moderate improvement. No significant changes in quality of life, clinical status or side-effects were observed in this review. Long-term, well-designed randomised controlled trials of recombinant growth hormone therapy in patients with cystic fibrosis are required prior to evaluation of human growth hormone treatment for routine use in patients.
| S-EPMC4465600 | biostudies-literature
Project description:BackgroundChronic rhinosinusitis symptomatology begins in early childhood individuals with cystic fibrosis (CF). Cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to sinus development and disease. Genetic variants of the bitter taste receptor TAS2R38 have been suggested to contribute to sinus disease severity in individuals without CF. Our objective was to explore whether functional TAS2R38 haplotypes and CFTR function are associated with sinus disease or the need for sinus surgery in individuals with CF.MethodsWe conducted a retrospective study using prospectively collected data from the CF Twin-Sibling Study. The function of CFTR was assessed via chloride conductance. Genotyping of the TAS2R38 gene identified patients who were homozygous for the functional haplotype, heterozygous, or homozygous for nonfunctional haplotypes. Clustered multivariate logistic regression was performed, controlling for sex and family relationship.ResultsA total of 1291 patients were evaluated. Patients with ≤1% CFTR function were 1.56 times more likely to require sinus surgery than those with >1% CFTR function (p = 0.049). CFTR function did not correlate significantly with the presence of sinus disease (p = 0.30). In addition, there were no statistically significant differences in diagnosis of sinus disease or need for sinus surgery between patients with functional and nonfunctional TAS2R38 haplotypes.ConclusionCFTR function correlates with need for sinus surgery, whereas TAS2R38 function does not appear to contribute to sinus disease or the need for sinus surgery in patients with CF.
| S-EPMC7266728 | biostudies-literature
Project description:RATIONALE:Yoga has been shown to improve outcomes in patients with asthma but has not been investigated in cystic fibrosis (CF) patients. METHODS:This was a prospective pilot study to evaluate the safety of a standardized yoga program among CF patients aged 12 to 25 years. Participants engaged in a 50-minute yoga session twice weekly for 8 weeks conducted by a certified yoga instructor using a standardized program designed to be safe for health-compromised individuals. Yoga sessions were individual to avoid transmission of infections. Primary outcome was safety and tolerability. Secondary outcome measures included respiratory symptoms, the Cystic Fibrosis Quality of Life instrument (CFQ-R), lung function, Ease of Breathing Score (measure of exercise tolerance), and weight. RESULTS:Eleven participants were enrolled, and 10 completed the study. Adherence was very good; the mean (SD) number of sessions completed was 14.2 (1.3) out of 16 sessions. Eight patients reported 25 adverse events. The most common was cough, reported in 7. Two events were possibly related to study procedures: calf pain and headache. There were no significant changes in dyspnea or pain scales. The mean (SD) CFQ-R respiratory domain score increased from screening to end of study: 67.9 (11.4) to 82.1 (9.9), P=.04. There were no significant changes in the other outcome measures. CONCLUSIONS:In this pilot study, a standardized 8-week yoga program was safe and well tolerated among adolescent and young adult CF patients with mild to moderate lung disease. This study may be helpful to yoga instructors who are interested in working with CF patients. Larger controlled trials are warranted to determine further benefits.
| S-EPMC4653591 | biostudies-literature
Project description:Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7.
| S-EPMC7237337 | biostudies-literature
Project description:BackgroundTo date, no consistent data are available on the possible impact of CFTR modulators on glucose metabolism. The aim of this study was to test the hypothesis that treatment with CFTR modulators is associated with an improvement in the key direct determinants of glucose regulation in children and young adults affected by Cystic Fibrosis (CF).MethodsIn this study, 21 CF patients aged 10-25 underwent oral glucose tolerance test (OGTT) before and after 12-18 months of treatment with Lumacaftor/Ivacaftor or Elexacaftor-Ivacaftor-Tezacaftor. β-cell function (i.e., first and second phase of insulin secretion measured as derivative and proportional control, respectively) and insulin clearance were estimated by OGTT mathematical modelling. Insulin sensitivity was estimated by the Oral Glucose Sensitivity Index (OGIS). The dynamic interplay between β-cell function, insulin clearance and insulin sensitivity was analysed by vector plots of glucose-stimulated insulin bioavailability vs. insulin sensitivity.ResultsNo changes in glucose tolerance occurred after either treatment, whereas a significant improvement in pulmonary function and chronic bacterial infection was observed. Beta cell function and insulin clearance did not change in both treatment groups. Insulin sensitivity worsened in the Lumacaftor/Ivacaftor group. The analysis of vector plots confirmed that glucose regulation was stable in both groups.ConclusionsTreatment of CF patients with CFTR modulators does not significantly ameliorate glucose homeostasis and/or any of its direct determinants.
| S-EPMC9319690 | biostudies-literature
Project description:BackgroundSince recombinant human growth hormone (rhGH) became available in 1985, the spectrum of indications has broadened and the number of treated patients increased. However, long-term health-related quality of life (HRQoL) after childhood rhGH treatment has rarely been documented. We assessed HRQoL and its determinants in young adults treated with rhGH during childhood.Methodology/principal findingsFor this study, we retrospectively identified former rhGH patients in 11 centers of paediatric endocrinology, including university hospitals and private practices. We sent a questionnaire to all patients treated with rhGH for any diagnosis, who were older than 18 years, and who resided in Switzerland at time of the survey. Three hundred participants (58% of 514 eligible) returned the questionnaire. Mean age was 23 years; 56% were women; 43% had isolated growth hormone deficiency, or idiopathic short stature; 43% had associated diseases or syndromes, and 14% had growth hormone deficiency after childhood cancer. Swiss siblings of childhood cancer survivors and the German norm population served as comparison groups. HRQoL was assessed using the Short Form-36. We found that the Physical Component Summary of healthy patients with isolated growth hormone deficiency or idiopathic short stature resembled that of the control group (53.8 vs. 54.9). Patients with associated diseases or syndromes scored slightly lower (52.5), and former cancer patients scored lowest (42.6). The Mental Component Summary was similar for all groups. Lower Physical Component Summary was associated with lower educational level (coeff. -1.9). Final height was not associated with HRQoL.Conclusions/significanceIn conclusion, HRQoL after treatment with rhGH in childhood depended mainly on the underlying indication for rhGH treatment. Patients with isolated growth hormone deficiency/idiopathic short stature or patients with associated diseases or syndromes had HRQoL comparable to peers. Patients with growth hormone deficiency after childhood cancer were at high risk for lower HRQoL. This reflects the general impaired health of this vulnerable group, which needs long-term follow-up.
| S-EPMC4608786 | biostudies-literature
Project description:BackgroundLittle is known about the impact of COVID-19 and the United Kingdom's (UK) national shielding advice on people with cystic fibrosis (CF) and their families. This study explored the experiences and support needs of children and young adults (CYAs) with CF, and parents who have a child with CF, during the COVID-19 pandemic.MethodsCYAs with CF and parents of CYAs with CF completed a UK wide online survey with open and closed questions exploring experiences, information and support needs and decision-making processes. Qualitative thematic content analysis and descriptive quantitative analyses were undertaken.ResultsCYAs aged 10-30 years (n = 99) and parents of CYAs aged 0-34 years (n = 145) responded. Parents (72.7%) and CYAs (50.0%) worried about the virus, and both were vigilant for virus symptoms (82.7% and 79.7%). Over three-quarters of CYAs were worried about their own health if they caught the virus. CYAs worried about feeling more isolated during the virus (64.9%). Qualitative findings reported the following themes: (1) Disruption-caused by isolation, (2) impact on psychological wellbeing, (3) safety of shielding, and (4) healthcare and treatment provision-changes to care, access and support.ConclusionsThe impact of COVID-19 and UK shielding advice to have no contact with anyone outside the household caused disruption to the lives and routines of individuals in relation to work, education, social lives, relationships, CF management routines and support. Parents and CYAs highlighted the need for clear, up-to-date and tailored advice on individualized risks and shielding.
| S-EPMC8441823 | biostudies-literature
Project description:Cystic fibrosis (CF)-related diabetes (CFRD) is thought to result from beta-cell injury due in part to pancreas exocrine damage and lipofibrosis. CFRD pancreata exhibit reduced islet density and altered cellular composition. To investigate a possible etiology, we tested the hypothesis that such changes are present in CF pancreata before the development of lipofibrosis. We evaluated pancreas and islet morphology in tissues from very young CF children (<4 years of age), and adult patients with CF and CFRD. The relative number of beta-cells in young CF tissues was reduced by 50% or more when compared to age-matched controls. Furthermore, young CF tissues displayed significantly smaller insulin-positive areas, lower proportion of beta-cells positive for the proliferation marker Ki67 or the ductal marker CK19 vs. control subjects, and islet inflammatory cell infiltrates, independently of the severity of the exocrine lesion and in the absence of amyloid deposits. CFRD pancreata exhibited greater islet injury with further reduction in islet density, decreased relative beta-cell number, and presence of amyloid deposits. Together, these results strongly suggest that an early deficiency in beta-cell number in infants with CF may contribute to the development of glucose intolerance in the CF pediatric population, and to CFRD, later in life.
| S-EPMC5722914 | biostudies-literature
Project description:Secondhand smoke exposure (SHSe) is a common environmental factor known to increase asthma severity and respiratory infections in children, as well disrupt metabolic signals and host immune responses in patients with cystic fibrosis (CF). This study defines biomarkers and metabolic profiles of SHSe (includes ENDS exposure) in the young CF population and determines how SHSe impacts regulation of infection, inflammation, and respiratory health.
2018-10-10 | ST001079 | MetabolomicsWorkbench