Abstract
Elexacaftor/Tezacaftor/Ivacaftor (ETI) has led to improved lung function, life expectancy, and body mass index for people with Cystic Fibrosis (CF). The aim of this systematic review was to evaluate the impact that ETI has had on body composition in people with CF. A systematic review was performed using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials. Quality assessment using the Joanna Briggs Institute critical appraisal tools were performed. Results were summarised narratively. Five observational cohort studies involving a total of 185 participants were reviewed. Three studies showed an increase in fat mass (7.0–8.6 kg, 13.2–14.3 kg, and 13.4–15.5 kg). Two studies reported an increase in fat-free mass (49.4–50.1 kg, 52.5–55 kg), while one reported a decrease (50.5–48.9 kg). Two studies found an increase in fat mass index (4.1–6.3 kgm/2 and 4.7–5.4 kg/m2) and fat-free mass index (17.4–17.7 kg/m2 and 18.1–18.8 kg/m2). Two studies observed an increase in percentage body fat mass (12.1–15.4% and 23.1–27.6%). Four studies were classified as low quality, while one was considered medium quality. This review suggest that commencing ETI results in changes in body composition. Firm conclusions about the type and distribution of change in body composition cannot be made due to limited studies, high heterogeneity, and methodical weaknesses. It highlights the necessity for higher quality and longer-term studies to explore the impact that ETI is having on body composition.
This is a preview of subscription content, access via your institution
Access options
Access through your institution
Change institution
Buy or subscribe
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Learn more
Buy this article
Purchase on SpringerLink
Instant access to full article PDF
Buy now
Prices may be subject to local taxes which are calculated during checkout
Additional access options:
Log in
Learn about institutional subscriptions
Read our FAQs
Contact customer support
Fig. 1
Data availability
All data used in this article can be found dolling the search strategy detailed in this article.
References
Cutting GR. Modifier genetics: cystic fibrosis. Annu Rev Genom Hum Genet. 2005;6:237–60.
CASGoogle Scholar
Litvin M, Yoon JC, Leey Casella J, Blackman SM, Brennan AL. Energy balance and obesity in individuals with cystic fibrosis. J Cyst Fibro. 2019;18:S38–S47.
Google Scholar
Milla CE. Nutrition and Lung Disease in Cystic Fibrosis. Clin Chest Med. 2007;28:319–30.
PubMedGoogle Scholar
World Health Organisation. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. 2000. https://iris.who.int/handle/10665/42330. Accessed 28th January 2025.
Romero-Corral A, Somers VK, Sierra-Johnson J, Thomas RJ, Bailey KR, Collazo-Clavell MD, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes. 2010; 32:959–66.
National Institute for Health and Care Excellence. Weight management: lifestyle services for overweight or obese children and young people. PH47. https://www.nice.org.uk/guidance/ph47. Accessed 17/12/24.
Davis LL, Nolan MZ. The influence of obesity on care of adults with cardiovascular Disease. Nurs Clin North Am. 2021; 56:511–25.
Calella P, Valerio G, Brodlie M, Donini LM, Siervo MD. Cystic fibrosis, body composition, and health outcomes: a systematic review. Nutrition. 2018;55-56:131–9.
PubMedGoogle Scholar
Ionescu AA, Evans WD, Pettit RJ, Nixon LS, Stone MD, Shale DJ. Hidden depletion of fat-free mass and bone mineral density in adults with cystic fibrosis. Chest. 2003;124:2220–8.
PubMedGoogle Scholar
Ackermans LLGC, Rabou J, Basrai M, Schweinlin A, Bischoff SC, Cussenot O, et al. Screening, diagnosis, and monitoring of sarcopenia: When to use which tool? Clin Nutr Espen. 2022;48:36–44.
PubMedGoogle Scholar
Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:16–31.
PubMedGoogle Scholar
Coutinho T, Goel K, Corrêa De Sá D, Kragelund C, Kanaya AM, Zeller M, et al. Central Obesity and Survival in Subjects With Coronary Artery Disease. J Am Coll Cardiol. 2011;57:1877–86.
PubMedGoogle Scholar
Patel CJ, Rehkopf DH, Leppert JT, Bortz WM, Cullen MR, Chertow GM, et al. Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States National Health and Nutrition Examination Survey. Int J Epidemiol. 2013;42:1795–810.
PubMedPubMed CentralGoogle Scholar
Piché M, Poirier P, Lemieux I, Despres J. Overview of Epidemiology and Contribution of Obesity and Body Fat Distribution to Cardiovascular Disease: An Update. Prog Cardiovasc Dis. 2018;61:103–13.
PubMedGoogle Scholar
Shuster A, Patlas M, Pinthus JH, Mourtzakis M. The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. Br J Radio. 2012;85:1–10.
CASGoogle Scholar
De Lorenzo A, Gobbo VD, Premrov MG, Bigioni M, Galvano F, Di Renzo LD, et al. Normal-weight obese syndrome: early inflammation? Am J Clin Nutr. 2007;85:40–5.
PubMedGoogle Scholar
Alvarez JA, Ziegler TR, Millson EC, Stecenko AA. Body composition and lung function in cystic fibrosis and their association with adiposity and normal-weight obesity. Nutrition. 2016;32:447–52.
PubMedGoogle Scholar
Scully KJ, Jay LT, Freedman S, Sawicki GS, Uluer A, Finkelstein JS, et al. The Relationship between Body Composition, Dietary Intake, Physical Activity, and Pulmonary Status in Adolescents and Adults with Cystic Fibrosis. Nutrients. 2022;14:310–21.
CASPubMedPubMed CentralGoogle Scholar
Bellissimo MP, Zhang I, Ivie EA, Phong HT, Tangpricha V, Hunt WR, et al. Visceral adipose tissue is associated with poor diet quality and higher fasting glucose in adults with cystic fibrosis. J Cyst Fibro. 2019;18:430–5.
CASGoogle Scholar
Willett W, Hu F. Anthropometric Measures and Body Composition. In: Nutritional Epidemiology. 3rd edn (online edn - 2013) Oxford Academic. pp 213–40. https://doi.org/10.1093/acprof:oso/9780199754038.003.0009, Accessed 30 Dec. 2024.
Lee SY, Gallagher D. Assessment methods in human body composition. Curr Opin Clin Nutr Metab Care. 2008;11:566–72.
PubMedPubMed CentralGoogle Scholar
Bosy-Westphal A, Jensen B, Braun W, Pourhassan M, Gallagher D, Muller MJ. Quantification of whole-body and segmental skeletal muscle mass using phase-sensitive 8-electrode medical bioelectrical impedance devices. Eur J Clin Nutr. 2017;71:1061–7.
CASPubMedPubMed CentralGoogle Scholar
Cannon T, Choi J. Development of a Segmental Bioelectrical Impedance Spectroscopy Device for Body Composition Measurement. Sensors. 2019;19:4825–942.
PubMedPubMed CentralGoogle Scholar
Lopez-Gonzalez D, Wells JCK, Clark P. Body Composition Assessment in Mexican Children and Adolescents. Part 2: Cross-Validation of Three Bio-Electrical Impedance Methods against Dual X-ray Absorptiometry for Total-Body and Regional Body Composition. Nutrients. 2022;14:965–72.
PubMedPubMed CentralGoogle Scholar
Vanitallie TB, Yang MU, Heymsfield SB, Funk RC, Boileau RA. Height-normalized indices of the body’s fat-free mass and fat mass: potentially useful indicators of nutritional status. Am J Clin Nutr. 1990;52:953–9.
CASPubMedGoogle Scholar
Cederholm T, Barazzoni R, Austin P, Ballmer P, Biolo G, Bischoff SC, et al. ESPEN guidelines on definitions and terminology of clinical nutrition. Clin Nutr. 2017;36:49–64.
CASPubMedGoogle Scholar
Csontos ÁA, Molnár A, Piri Z, Pálfi E, Miheller P. Malnutrition risk questionnaire combined with body composition measurement in malnutrition screening in inflammatory bowel disease. Rev Esp Enferm Dig. 2017;109:26–32.
CASPubMedGoogle Scholar
Jouneau S, Kerjouan M, Rousseau C, Lederlin M, Llamas-Guttierez F, De Latour B, et al. What are the best indicators to assess malnutrition in idiopathic pulmonary fibrosis patients? A cross-sectional study in a referral center. Nutrition. 2019;62:115–21.
PubMedGoogle Scholar
Rondel AL, Langius JA, de van der Schueren MA, Kruizenga HM. The new ESPEN diagnostic criteria for malnutrition predict overall survival in hospitalised patients. Clin Nutr. 2018;37:163–8.
CASPubMedGoogle Scholar
Muscaritoli M, Anker SD, Argilés J, Aversa Z, Bauer JM, Biolo G, et al. Consensus definition of sarcopenia, cachexia, and pre-cachexia: Joint document elaborated by Special Interest Groups (SIG) “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics. Clin Nutr. 2010;29:154–9.
CASPubMedGoogle Scholar
Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394:1940–8.
CASPubMedPubMed CentralGoogle Scholar
Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D, et al. Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019;381:1809–19.
CASPubMedPubMed CentralGoogle Scholar
Gushue C, Eisner M, Bai S, Johnson T, Holtzlander M, McCoy K, et al. Impact of Elexacaftor–Tezacaftor–Ivacaftor on lung disease in cystic fibrosis. Pediatr Pulmonol. 2023;58:2308–16.
PubMedGoogle Scholar
Wang A, Lee M, Keller A, Jian S, Lowe K, Finklea JD, et al. Sex differences in outcomes of people with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor. J Cys Fibro. 2024;23:91–8.
CASGoogle Scholar
Daines CL, Tullis E, Costa S, Linnemann RW, Mall MA, McKone EF, et al. Long-term safety, and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least oneF508delallele: 144-week interim results from a 192-week open-label extension study. Eur Respir J. 2023;62:2202029.
CASPubMedPubMed CentralGoogle Scholar
Cystic Fibrosis Trust. Annual Data Report. 2021. www.cysticfibrosis.org.uk/sites/default/files/2022-10/CFT_2021-Annual-Data-Report-WEB.pdf. Accessed 25 January 2025.
Lopez A, Daly C, Vega-Hernandez G, MacGregor G, Rubin JL. Elexacaftor/tezacaftor/ivacaftor projected survival and long-term health outcomes in people with cystic fibrosis homozygous for F508del. J Cyst Fibro. 2023;22:607–14.
CASGoogle Scholar
Sasse L, Simon A, Rückes-Nilges C, Nährlich L. P319 Effects of elexacaftor/tezacaftor/ivacaftor on nutrition parameters and resting energy expenditure in people with cystic fibrosis. J Cyst Fibro. 2023;22:S162.
Google Scholar
Munce D, Lim M, Akong K. Persistent recovery of pancreatic function in patients with cystic fibrosis after ivacaftor. Pediatr Pulmonol. 2020;55:3381–3.
PubMedGoogle Scholar
Stastna N, Pokojova E. Case report of two adults with F508del/3849+10 kb C > T genotype regaining exocrine pancreatic function following treatment with elexacaftor/tezacaftor/ivacaftor. J Cyst Fibro. 2023;23:744–5.
Google Scholar
Mainz JG, Lester K, Elnazir B, Williamson M, McKone E, Cox D, et al. Reduction in abdominal symptoms (CFAbd-Score), faecal M2-pyruvate-kinase and Calprotectin over one year of treatment with Elexacaftor-Tezacaftor-Ivacaftor in people with CF aged ≥12 years – The RECOVER study. J Cyst Fibro. 2024;23:474–80.
CASGoogle Scholar
Caley LR, de Goffau MC, Jones AM, Whitehouse JL, Barrett J, White H, et al. EPS5.01 Change in gut microbiota following elexacaftor/tezacaftor/ivacaftor (ETI) therapy: preliminary analysis. J Cyst Fibro. 2023;22:S49.
Google Scholar
Bailey J, Krick S, Fontaine KR. The Changing Landscape of Nutrition in Cystic Fibrosis: The Emergence of Overweight and Obesity. Nutrients. 2022;14:1216–34.
CASPubMedPubMed CentralGoogle Scholar
Cystic Fibrosis Trust. Annual Data Report. 2023. www.cysticfibrosis.org.uk/sites/default/files/2024-11/CFT_2023_Annual_Data_Report_Oct2024%201.pdf. Accessed 28 January 2025.
Page MJ, Mckenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Rev. 2021;10:89–100.
PubMedPubMed CentralGoogle Scholar
Cochrane. Data collection form: intervention review - RCTs and non-RCTs 2019. https://training.cochrane.org/. Accessed 19 April 2023.
Grancini V, Gramegna A, Zazzeron L, Alicandro G, Porcaro LL, Piedepalumbo F, et al. Effects of elexacaftor / tezacaftor / ivacaftor triple combination therapy on glycaemic control and body composition in patients with cystic fibrosis-related diabetes. Diab Metab. 2023;49:101466.
CASGoogle Scholar
Gur M, Bar-Yoseph R, Hanna M, Abboud D, Keidar Z, Palchan T, et al. Effect of Trikafta on bone density, body composition and exercise capacity in CF: A pilot study. Pediatr Pulmonol. 2022;58:577–84.
PubMedPubMed CentralGoogle Scholar
Knott-Torcal C, Sebastián-Valles F, Girón Moreno RM, Martín-Adán JC, Jiménez-Díaz J, Marazuela M, et al. A prospective study to assess the impact of a novel CFTR therapy combination on body composition in patients with cystic fibrosis with F508del mutation. Clin Nutr. 2023;42:2468–74.
CASPubMedGoogle Scholar
Proud D, Duckers J. Weight a minute: Exploring the effect on weight and body composition after the initiation of elexacaftor/tezacaftor/ivacaftor in adults with CF. J Cyst Fibros. 2023;22:847–50.
CASPubMedGoogle Scholar
Granados A, Chan CL, Moheet A, Vigers T, Arbeláez AM, Larson Ode K. The impact of elexacaftor/tezacaftor/ivacaftor on body composition in a small cohort of youth with cystic fibrosis. Pediatr Pulmonol. 2023;58:1805–11.
PubMedGoogle Scholar
Purcell SA, Oliveira CLP, Mackenzie M, Robson P, Lewis JD, Prado CM. Body Composition and Prostate Cancer Risk: A Systematic Review of Observational Studies. Adv Nutr. 2022;13:1118–30.
PubMedGoogle Scholar
Prado CM, Batsis JA, Donini LM, Gonzalez MC, Siervo M. Sarcopenic obesity in older adults: a clinical overview. Nat Rev Endocrinol. 2024;20:261–77.
PubMedGoogle Scholar
Di Vincenzo O, Marra M, Scalfi L. Bioelectrical impedance phase angle in sport: A systematic review. J Int Soc Sports Nutr. 2019;16:49–60.
PubMedPubMed CentralGoogle Scholar
Rinaldi S, Gilliland J, O’Connor C, Chesworth B, Madill J. Is phase angle an appropriate indicator of malnutrition in different disease states? A systematic review. Clin Nutr Espen. 2019;29:1–4.
PubMedGoogle Scholar
Hirose S, Nakajima T, Nozawa N, Katayanagi S, Ishizaka H, Mizushima Y, et al. Phase angle as an indicator of sarcopenia, malnutrition, and cachexia in inpatients with cardiovascular diseases. J Clin Med. 2020;9:2554–70.
PubMedPubMed CentralGoogle Scholar
Franco LP, Morais CC, Cominetti C. Normal-weight obesity syndrome: diagnosis, prevalence, and clinical implications. Nutr Rev. 2016;74:558–70.
PubMedGoogle Scholar
Fitch AK, Bays HE. Obesity definition, diagnosis, bias, standard operating procedures, and telehealth: An Obesity Medicine Association Clinical Practice Statement 2022. Obes Pillars. 2022;1:100004.
PubMedPubMed CentralGoogle Scholar
Greaney C, Doyle A, Drummond N, King S, Hollander-Kraaijeveld F, Robinson K, et al. What do people with cystic fibrosis eat? Diet quality, macronutrient, and micronutrient intakes (compared to recommended guidelines) in adults with cystic fibrosis–A systematic review. J Cyst Fibros. 2023;22:1036–47.
CASPubMedGoogle Scholar
Wilschanski M, Munck A, Carrion E, Cipolli M, Collins S, Colombo C, et al. ESPEN-ESPGHAN-ECFS guideline on nutrition care for cystic fibrosis. Clin Nutr. 2024;43:413–45.
CASPubMedGoogle Scholar
Download references
Acknowledgements
Laura Kinsey was funded as part of an Applied Research Collaboration for Greater Manchester (ARC-GM) pre-doctoral fellowship.
Funding
LK was funded as part of an Applied Research Collaboration for Greater Manchester (ARC-GM) pre-doctoral fellowship.
Author information
Authors and Affiliations
Manchester Adult Cystic Fibrosis Centre, Manchester University NHS Foundation Trust, Wythenshawe Hospital, Manchester, M23 9LT, United Kingdom
Laura Kinsey, Hannah Winterbottom, Lydia Hudson & Andrew M. Jones
Intestinal Failure Unit, Salford Royal Infirmary, Northern Care Alliance Foundation Trust, Manchester, United Kingdom
Simon Lal & Sorrel Burden
School of Health Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Oxford Road, Manchester, M13 6PL, United Kingdom
Sorrel Burden
Authors
Laura Kinsey
View author publications
You can also search for this author inPubMedGoogle Scholar
2. Hannah Winterbottom
View author publications
You can also search for this author inPubMedGoogle Scholar
3. Lydia Hudson
View author publications
You can also search for this author inPubMedGoogle Scholar
4. Simon Lal
View author publications
You can also search for this author inPubMedGoogle Scholar
5. Andrew M. Jones
View author publications
You can also search for this author inPubMedGoogle Scholar
6. Sorrel Burden
View author publications
You can also search for this author inPubMedGoogle Scholar
Contributions
LK developed the search strategy, conducted the search. LK and HW undertook the study selection. LK undertook the data extract and HW checked data extraction. LK and LH conducted the risk of bias assessment. LK conducted data synthesis and collated results. SL and SB provided expert opinion on body composition and systematic reviews. AMJ provided expert opinion on Cystic Fibrosis. LK wrote the first draft of the manuscript. All authors provided feedback and approved the final manuscript.
Corresponding author
Correspondence to Laura Kinsey.
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Supplemental material 1
Supplemental material 2
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Reprints and permissions
About this article
Check for updates. Verify currency and authenticity via CrossMark
Cite this article
Kinsey, L., Winterbottom, H., Hudson, L. et al. A systematic review of the impact of Elexacaftor/Tezacaftor/Ivacaftor on body composition in people with cystic fibrosis. Eur J Clin Nutr (2025). https://doi.org/10.1038/s41430-025-01589-y
Download citation
Received:21 August 2024
Revised:29 January 2025
Accepted:18 February 2025
Published:22 March 2025
DOI:https://doi.org/10.1038/s41430-025-01589-y
Share this article
Anyone you share the following link with will be able to read this content:
Get shareable link
Sorry, a shareable link is not currently available for this article.
Copy to clipboard
Provided by the Springer Nature SharedIt content-sharing initiative