Prebiotics for people with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease; the importance of growth and nutritional status is well established given their implications for lung function and overall survivability. Furthermore, it has been established that intestinal microbial imbalance and inflammation are present in people with CF. Oral prebiotics are commercially available substrates that are selectively utilised by host intestinal micro-organisms and may improve both intestinal and overall health. OBJECTIVES: To evaluate the benefits and harms of prebiotics for improving health outcomes in children and adults with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 19 October 2022. We also searched PubMed and online trials registries. Date of last search: 13 January 2023. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs assessing the efficacy of prebiotics in children and adults with CF. We planned to only include the first treatment period from cross-over RCTs, regardless of washout period. DATA COLLECTION AND ANALYSIS: We did not identify any relevant trials. MAIN RESULTS: We did not identify any relevant trials for inclusion in this review. AUTHORS' CONCLUSIONS: This review did not find any evidence for the use of prebiotics in people with CF. Until such evidence is available, it is reasonable for clinicians to follow any local guidelines and to discuss the use of dietary prebiotics with their patients. Large and robust RCTs assessing the dietary prebiotics of inulin or galacto-oligosaccharides or fructo-oligosaccharides, or any combination of these, are needed. Such studies should be of at least 12 months in duration and assess outcomes such as growth and nutrition, gastrointestinal symptoms, pulmonary exacerbations, lung function, inflammatory biomarkers, hospitalisations, intestinal microbial profiling, and faecal short-chain fatty acids. Trials should include both children and adults and aim to be adequately powered to allow for subgroup analysis by age.

Postprandial changes in gastrointestinal function and transit in cystic fibrosis assessed by Magnetic Resonance Imaging.

BACKGROUND: Cystic fibrosis (CF) is a multi-system genetic disorder affecting >72,000 people worldwide. Most CF patients experience gastrointestinal symptoms and can develop complications. However, the mechanisms of CF gut disease are not well understood. We evaluated gut function and transit in CF using magnetic resonance imaging (MRI). We hypothesised oro-caecal transit time (OCTT) is longer in CF; with lower small bowel water content (SBWC). METHODS: Twelve CF patients aged 12-40 years and 12 age and sex-matched controls underwent serial MRIs over 1 day with standardised meals. The primary endpoint was OCTT, assessed by the appearance of a food bolus in the caecum. Other measures included corrected SBWC and corrected colonic volume (both area under the curve, AUC), gastric half-emptying time and gastrointestinal symptoms. RESULTS: OCTT was longer in CF (CF 330 mins [270, >360] vs. controls 210 mins [173, 315], p = 0.04), with no difference in gastric half-emptying times. Corrected SBWC was higher in CF (CF 62 L.min/m2 [36, 80] vs. controls 34 L.min/m2 [28, 41], p = 0.021); minimal postprandial decrease between T240 and T300 (CF 13 mL/m2 [-13, 57] vs. controls 102 mL/m2 [67, 108], p = 0.002) suggests impaired ileal emptying. Corrected colonic volumes were higher in CF (CF 186 L.min/m2 [167, 206] vs. controls 123 L.min/m2 [89, 146], p = 0.012). There were no differences in gastrointestinal symptoms. CONCLUSIONS: MRI provides novel insights into CF pathophysiology. Sub-clinical ileal obstruction may be more prevalent than previously thought. Gastrointestinal MRI shows promise as an investigational tool in CF.

Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic review.

INTRODUCTION: Cystic fibrosis (CF) is a multisystem disorder. Treatment is complex and evidence for treatment decisions may be absent. Characterising gaps in the research evidence will highlight treatment uncertainties and help prioritise research questions. We systematically identified the evidence gaps for treatment decisions in CF. METHODS: We searched for systematic reviews and guidelines on treatment interventions in CF. Two researchers identified eligible reviews with arbitration from a third. Using a structured framework, we extracted and characterised evidence gaps. RESULTS: There were 73 reviews and 21 guidelines that met our inclusion criteria. From these, we identified 148 evidence gaps across a range of treatment areas. We found 111 evidence gaps through systematic reviews and a further 37 from guidelines. The reason for an evidence gap could only be reliably characterised for systematic reviews. In most cases, there was more than one explanation-most commonly few or no trials (97/111 evidence gaps). Other important factors leading to evidence gaps were small sample size (49/111), inadequate duration of follow-up (38/111) or intervention (37/111) and factors relating to outcomes (35/111). Evidence gaps from both systematic reviews and guidelines fell into the following categories: Respiratory (91); Gastrointestinal (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1). CONCLUSIONS: We have compiled an up-to-date list of treatment uncertainties in CF and the reasons for these uncertainties. These can be used as a resource to aid researchers and funders when planning future trials. PROSPERO REGISTRATION NUMBER: Pre-results; CRD42015030111.

Growth and nutrition in children with ataxia telangiectasia.

BACKGROUND: Ataxia telangiectasia (A-T) is a rare multisystem disease with high early mortality from lung disease and cancer. Nutritional failure adversely impacts outcomes in many respiratory diseases. Several factors influence nutrition in children with A-T. We hypothesised that children with A-T have progressive growth failure and that early gastrostomy tube feeding (percutaneous endoscopic gastrostomy, PEG) is a favourable management option with good nutritional outcomes. METHODS: Data were collected prospectively on weight, height and body mass index (BMI) at the national paediatric A-T clinic. Adequacy and safety of oral intake was assessed. Nutritional advice was given at each multidisciplinary review. RESULTS: 101 children (51 girls) had 222 measurements (32 once, 32 twice, 24 thrice) between 2009 and 2016. Median (IQR) age was 9.3 (6.4 to 13.1) years. Mean (SD) weight, height and BMI Z-scores were respectively -1 (1.6), -1.2 (1.2) and -0.4 (1.4). 35/101 children had weight Z-scores below -2 on at least one occasion. Weight, height and BMI Z-scores declined over time. Decline was most obvious after 8 years of age. 14/101 (14%) children had a PEG, with longitudinal data available for 12. In a nested case control study, there was a trend for improvement in weight in those with a PEG (p=0.10). CONCLUSIONS: Patients with A-T decline in growth over time. There is an urgent need for new strategies, including an understanding of why growth falters. We suggest early proactive consideration of PEG from age 8 years onwards to prevent progressive growth failure.

Intravenous antibiotics for pulmonary exacerbations in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. Intravenous antibiotics are commonly used in the treatment of acute deteriorations in symptoms (pulmonary exacerbations); however, recently the assumption that exacerbations are due to increases in bacterial burden has been questioned. OBJECTIVES: To establish if intravenous antibiotics for the treatment of pulmonary exacerbations in people with cystic fibrosis improve short- and long-term clinical outcomes. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews and ongoing trials registers.Date of last search of Cochrane trials register: 27 July 2015. SELECTION CRITERIA: Randomised controlled trials and the first treatment cycle of cross-over studies comparing intravenous antibiotics (given alone or in an antibiotic combination) with placebo, inhaled or oral antibiotics for people with cystic fibrosis experiencing a pulmonary exacerbation. DATA COLLECTION AND ANALYSIS: The authors assessed studies for eligibility and risk of bias and extracted data. MAIN RESULTS: We included 40 studies involving 1717 participants. The quality of the included studies was largely poor and, with a few exceptions, these comprised of mainly small, inadequately reported studies.When comparing treatment with a single antibiotic to a combined antibiotic regimen, those participants receiving a combination of antibiotics experienced a greater improvement in lung function when considered as a whole group across a number of different measurements of lung function, but with very low quality evidence. When limited to the four placebo-controlled studies (n = 214), no difference was observed, again with very low quality evidence. With regard to the review's remaining primary outcomes, there was no effect upon time to next exacerbation and no studies in any comparison reported on quality of life. There were no effects on the secondary outcomes weight or adverse effects. When comparing specific antibiotic combinations there were no significant differences between groups on any measure. In the comparisons between intravenous and nebulised antibiotic or oral antibiotic (low quality evidence), there were no significant differences between groups on any measure. No studies in any comparison reported on quality of life. AUTHORS' CONCLUSIONS: The quality of evidence comparing intravenous antibiotics with placebo is poor. No specific antibiotic combination can be considered to be superior to any other, and neither is there evidence showing that the intravenous route is superior to the inhaled or oral routes. There remains a need to understand host-bacteria interactions and in particular to understand why many people fail to fully respond to treatment.

Rate of improvement of CF life expectancy exceeds that of general population--observational death registration study.

BACKGROUND: It is unclear why cystic fibrosis (CF) survival has improved. We wished to quantify increases in CF median age of death in the context of general population survival improvement. METHOD: Death registration data analysis (US, England & Wales (E&W)-1972-2009). RESULTS: CF median age of death is higher in US than E&W and greater for males, opposite to that of death from all causes. CF median age of death has increased by 0.543 life years per year (E&W, US combined (95% confidence interval 0.506, 0.582)). The difference in median age at death between those dying from all causes and CF decreased in both territories. CF median age of death for males is greater than for females in both territories. This gap has not narrowed. CONCLUSION: The median age of death of people with CF is improving more rapidly than that of the general population in US and E&W.

From pipeline to patient: new developments in cystic fibrosis therapeutics.

INTRODUCTION: Cystic fibrosis (CF) is an inherited rare disease characterised by recurrent pulmonary infection, pancreatic malabsorption and a number of other multisystem effects. In the past few years new drugs specifically designed to treat CF have entered the pipeline, and some are now used in clinical practice. AREAS COVERED: Clinical trial results from CF trials reported or ongoing within the last 3 years are discussed. A literature and trials registry search of trials and meta-analyses involving patients with CF was conducted, from which the most exciting developments were selected. EXPERT OPINION: Drugs to address the basic defect in CF have finally come to market, albeit for a limited number of patients with a specific genotype. Traditional areas of CF therapeutics continue to be developed, with modest success, including drugs to modulate the airway surface liquid, new pancreatic supplements, antibiotics and new treatments for endocrine complications of CF.

Percutaneous lines for delivering intravenous antibiotics in people with cystic fibrosis.

BACKGROUND: Percutaneous long lines (long intravenous lines) and short intravenous lines (also termed cannulae) are both used to deliver intravenous antibiotics in cystic fibrosis to treat respiratory exacerbations of the disease. The perceived advantage of a long intravenous line is a greater duration of line function, which has to be balanced against a technically more challenging insertion procedure, and the possibility of more discomfort on insertion. OBJECTIVES: To compare long intravenous lines with short intravenous lines in people with cystic fibrosis receiving intravenous antibiotics, in terms of lifespan of the line, ease of insertion, complication rates of the line and patient satisfaction. This will help patients and clinicians choose between devices. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 26 August 2010. SELECTION CRITERIA: Randomised studies comparing long intravenous lines lines with short intravenous lines or comparing different types of long intravenous lines. DATA COLLECTION AND ANALYSIS: We identified two studies, one comparing long intravenous lines with short intravenous lines, and one comparing two different types of long intravenous lines. MAIN RESULTS: Two studies (67 participants) were included in the review. Based on the published reports, both studies had potential for bias in several domains. There is some evidence that long intravenous lines are superior to short intravenous lines. One study of 20 participants found that the lifespan of a long intravenous line is longer than that of a short intravenous line, and that participants preferred the long intravenous lines to short intravenous lines. A further study of 47 participants found no difference in lifespan, or participant preference when comparing two different long intravenous lines (the Hydrocath and Vygon EC). Neither study was powered to detect differences in serious complications of the devices. AUTHORS' CONCLUSIONS: There is some evidence to support the use of long intravenous lines rather than short intravenous lines, in terms of lifespan of the line and patient satisfaction. There is no evidence to suggest that any one type of long intravenous line is superior, and currently choice of line should be determined by operator and patient preference. There are numerous devices available which are used in cystic fibrosis. Further research is required to identify clinically important differences between these devices.