Ryan J. Marsh
Persistent intestinal abnormalities and symptoms in cystic fibrosis: The underpinning mechanisms impacting gut health and motility. Protocol for a systematic review.
Marsh, Ryan J.; Ng, Christabella; Major, Giles; Rivett, Damian W.; Smyth, Alan R.; Gast, Christopher van der
CHRISTABELLA NG Christabella.Ng1@nottingham.ac.uk
Clinical Research Fellow
GILES MAJOR Giles.Major@nottingham.ac.uk
Clinical Associate Professor
Damian W. Rivett
ALAN SMYTH email@example.com
Professor of Child Health
Christopher van der Gast
Background Patients with cystic fibrosis (CF) are characterised by abnormalities of the intestinal tract relating to gut motility and physiological issues, with daily symptoms of disease including abdominal pain, flatulence, bloating, and constipation. With improvements in respiratory outcomes, a shift in disease manifestations has highlighted the prevalence of the gastrointestinal-related problems associated with CF, yet most therapies currently in clinical use for the gut symptoms of CF have been repurposed from other disease indications and have not been developed with a knowledge of the mechanisms underpinning gastrointestinal disease in CF. Increased attention towards the role of intestinal inflammation and microbial dysbiosis in the CF population warrants a comprehensive knowledge of these aspects alongside the increased luminal fat content, dysmotility, and small intestinal bacterial overgrowth (SIBO) resultant of the primary consequences of CFTR dysfunction (disrupted fluid secretion and pancreatic insufficiency), and how they contribute towards the intestinal complications of CF disease. Methods and Study Design We will conduct a systematic review to comprehensively address our current understanding of the primary consequences of CFTR dysfunction, and their subsequent secondary effects that contribute towards the disruption of gut motility, health, and associated symptoms in the CF intestine. Databases searched will include PubMed, CINAHL, MEDLINE and the Cochrane library from 1939 until a specified date of last search, alongside clinical trial databases for ongoing studies. Search strategies will include various terminology that relates to the primary mechanistic defects of CF, postulated secondary effects of such defects, and symptoms experienced in patients. A full search strategy is outlined in Appendix B. One reviewer will apply an inclusion criterion to obtained abstracts. Following agreement from a second reviewer, full-text articles will be sought, and data will be extracted from relevant articles. Disagreements will be resolved with a third reviewer. The quality of data will be assessed by the GRADE criteria. Data will be used to present a narrative, and where possible, quantitative synthesis. Discussion This systematic review will discuss our current understanding of the underpinning mechanisms of the persisting abnormalities in gut health and motility within CF, addressing potential intricate relationships that further contribute to disease progression within the intestinal tract. Furthermore, we will identify current gaps in the literature to propose directions for future research. A comprehensive understanding of these aspects in relation to intestinal abnormalities will aid future clinical directions.
|APA6 Citation||Marsh, R. J., Ng, C., Major, G., Rivett, D. W., Smyth, A. R., & Gast, C. V. D. Persistent intestinal abnormalities and symptoms in cystic fibrosis: The underpinning mechanisms impacting gut health and motility. Protocol for a systematic review|
|Additional Information||This is a medRxiv preprint.|
Persistent intestinal abnormalities
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