{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T16:33:54Z","timestamp":1788453234676,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Introduction: Malnutrition has always been a problem in CF (cystic fibrosis) patients; however, new treatments with CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators have led to weight gain, with some patients at risk of overweight and obesity. Objective: Our study aimed to analyze the evolution of BMI (body mass index) after one year of treatment with triple therapy and the factors associated with weight gain in CF patients undergoing treatment with triple therapy with CFTR protein modulators (ETI) (elexacaftor\/tezacaftor\/ivacaftor). Methods: We conducted a prospective, observational, longitudinal, multicenter study in patients diagnosed with cystic fibrosis, aged 18 years or older, with at least one F508del allele and who underwent ETI therapy for at least one year, from 2020 to 2023. One hundred and eight patients from two cystic fibrosis units in Spain, Princess University Hospital of Madrid (74 patients) and Central University Hospital of Asturias (HUCA) (34 patients), were included. Demographic data, anthropometric data, lung function, and exacerbations were collected, comparing the data in the previous year to the start of therapy with the results after one year of treatment. Multivariant models were developed to account for repeated weight and BMI measurements, using a mixed effects model approach and accounting for possible modifying factors Results: One hundred and eight patients were included in the study, 58 men (53.7%) and 50 women (46.3%) with a mean age of 29.5 \u00b1 9.4 years (18\u201359). Patient weight and BMI were recorded at baseline and at 3-month intervals during the study period. The weight increased from 59.6 kg to 62.6 kg and BMI increased from 21.9 kg\/m2 to 23.0 kg\/m2 after one year of treatment (p &lt; 0.0001 for both). The proportion of underweight individuals decreased after one year of ETI therapy, from 9.3% to 1.9%, while the proportion of overweight or obese individuals increased from 8.3% to 22.9 % at the same time (p &lt; 0.001). In relation to exacerbations, there is a significant increase in the number of patients who did not have any exacerbations after one year of treatment, which increased from 10.2% to 46.2% (p &lt; 0.001), while the number of patients who had &gt;4 exacerbations decreased significantly, from 40.7% to 1.9% (p &lt; 0.001). FEV1% (forced expiratory volume) increased from 63.9 \u00b1 20.9 to 76.8 \u00b1 21.4 (p &lt; 0.001) and the VR\/TLC (residual volume\/total lung capacity) value decreased from 45.1 \u00b1 10.9 to 34.9 \u00b1 6.2 (p &lt; 0.001). The proportion with FEV1% &gt; 80% increased from 23.1% before ETI therapy to 49.1% one year after ETI therapy. We performed multivariate mixed models to evaluate the evolution of BMI changes with time, accounting for repeated measures and for possible modifying factors. After the introduction of the triple therapy, patients included in the study had significant weight gain during the 12 months, and when including different covariates in the multivariate mixed model, we found that lower baseline BMI, lower baseline FEV1 and FVC (forced vital capacity), and higher VR\/TLC value and higher number of exacerbations were associated with higher BMI changes over the study period. Conclusions: CF patients treated with triple therapy experience significant weight gain, increasing the proportion of overweight patients. CF patients who experienced greater weight gain were those with worse BMI at the start of treatment, as well as patients with worse lung function and a greater number of exacerbations in the year before starting ETI therapy.<\/jats:p>","DOI":"10.3390\/nu16183103","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T10:56:57Z","timestamp":1726484217000},"page":"3103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Is Obesity a Problem in New Cystic Fibrosis Treatments?"],"prefix":"10.3390","volume":"16","author":[{"given":"Marta","family":"Sol\u00eds-Garc\u00eda","sequence":"first","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0463-5946","authenticated-orcid":false,"given":"Marta Mar\u00eda","family":"Garc\u00eda-Clemente","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA), Universidad de Oviedo, 33011 Oviedo, Spain"},{"name":"Servicio de Neumolog\u00eda, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Janeth","family":"Madrid-Carbajal","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario Central de Asturias (HUCA), 33011 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Pel\u00e1ez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud-HM Hospitales, Universidad Camilo Jos\u00e9 Cela, 28014 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Mar","family":"G\u00f3mez Punter","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Mar\u00eda","family":"Eiros Bachiller","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Mar\u00eda","family":"Gir\u00f3n Moreno","sequence":"additional","affiliation":[{"name":"Servicio de Neumolog\u00eda, Hospital Universitario La Princesa, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100690","DOI":"10.1016\/j.lanepe.2023.100690","article-title":"Registry of the Mukoviszidose e.V. and participating CF sites. Impact of elexacaftor\/tezacaftor\/ivacaftor on lung function, nutritional status, pulmonary exacerbation frequency and sweat chloride in people with cystic fibrosis: Real-world evidence from the German CF Registry","volume":"32","author":"Sutharsan","year":"2023","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.jcf.2022.01.009","article-title":"Worldwide rates of diagnosis and effective treatment for cystic fibrosis","volume":"21","author":"Guo","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1164\/rccm.201404-0670OC","article-title":"A functional anatomic defect of the cystic fibrosis airway","volume":"190","author":"Birket","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1002\/ppul.26982","article-title":"Predicting weight gain in patients with cystic fibrosis on triple combination modulator","volume":"59","author":"Stewart","year":"2024","journal-title":"Pediatr. Pulmonol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1513\/AnnalsATS.202404-439ED","article-title":"Cystic Fibrosis Transmembrane Conductance Regulator Modulators: Real-World Evidence Highlights Need for Worldwide Access","volume":"21","author":"Barry","year":"2024","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jcf.2021.11.012","article-title":"Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis","volume":"21","author":"Petersen","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liou, T.G., Kartsonaki, C., Keogh, R.H., and Adler, F.R. (2020). Evaluation of a five-year predicted survival model for cystic fibrosis in later time periods. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-63590-8"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bailey, J., Krick, S., and Fontaine, K.R. (2022). The Changing Landscape of Nutrition in Cystic Fibrosis: The Emergence of Overweight and Obesity. Nutrients, 14.","DOI":"10.3390\/nu14061216"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.jada.2008.02.020","article-title":"Clinical Practice Guidelines on Growth and Nutrition Subcommittee; Ad Hoc Working Group. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: Results of a systematic review","volume":"108","author":"Stallings","year":"2008","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_10","unstructured":"Cystic Fibrosis Foundation (2022). Patient Registry 2021 Annual Data Report, Cystic Fibrosis Foundation. Available online: http:\/\/www.cff.org\/Our-Research\/CF-Patient-Registry\/."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1056\/NEJMoa1709846","article-title":"Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del","volume":"377","author":"Munck","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.arbres.2023.05.017","article-title":"Experience with Elexacaftor\/Tezacaftor\/Ivacaftor in Patients with Cystic Fibrosis and Advanced Disease","volume":"59","author":"Sole","year":"2023","journal-title":"Arch. Bronconeumol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Carnovale, V., Iacotucci, P., Terlizzi, V., Colangelo, C., Ferrillo, L., Pepe, A., Francalanci, M., Taccetti, G., Buonaurio, S., and Celardo, A. (2022). Elexacaftor\/Tezacaftor\/Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation and Advanced Lung Disease: A 48-Week Observational Study. J. Clin. Med., 11.","DOI":"10.3390\/jcm11041021"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Salvatore, D., Padoan, R., Amato, A., Salvatore, M., Campagna, G., and On Behalf of The Italian Cf Registry Working Group (2024). Nutritional Trends in Cystic Fibrosis: Insights from the Italian Cystic Fibrosis Patient Registry. J. Clin. Med., 13.","DOI":"10.20944\/preprints202404.0869.v1"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/ppul.23033","article-title":"Overweight and obesity in patients with cystic fibrosis: A center-based analysis","volume":"50","author":"Hanna","year":"2015","journal-title":"Pediatr. Pulmonol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.jpeds.2018.05.018","article-title":"Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations","volume":"201","author":"Stallings","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jcf.2021.09.010","article-title":"CFTR modulators increase risk of acute pancreatitis in pancreatic insufficient patients with cystic fibrosis","volume":"21","author":"Gould","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12931-023-02451-0","article-title":"Heterogeneity of weight gain after initiation of Elexacaftor\/Tezacaftor\/Ivacaftor in people with cystic fibrosis","volume":"24","author":"Gramegna","year":"2023","journal-title":"Respir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1164\/rccm.202108-1986OC","article-title":"Clinical Effectiveness of Elexacaftor\/Tezacaftor\/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial","volume":"205","author":"Nichols","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jcf.2019.10.004","article-title":"Prevalence and factors associated with overweight and obesity in adults with cystic fibrosis: A single-center analysis","volume":"19","author":"Harindhanavudhi","year":"2020","journal-title":"J. Cyst. Fibros."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"872","DOI":"10.3945\/ajcn.112.051409","article-title":"Longitudinal trends in nutritional status and the relation between lung function and BMI in cystic fibrosis: A population-based cohort study","volume":"97","author":"Stephenson","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"578","DOI":"10.20960\/nh.620","article-title":"Excess weight in patients with cystic fibrosis: Is it always beneficial?","volume":"34","year":"2017","journal-title":"Nutr. Hosp."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.jcf.2021.12.014","article-title":"Nutritional status and lung function in children with pancreatic-sufficient cystic fibrosis","volume":"21","author":"Madde","year":"2022","journal-title":"J. Cyst. Fibros."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jcf.2013.02.008","article-title":"Update on cystic fibrosis-related diabetes","volume":"12","author":"Kelly","year":"2013","journal-title":"J. Cyst. Fibros."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/MCO.0b013e32832595b7","article-title":"Lipid metabolism in cystic fibrosis","volume":"12","author":"Worgall","year":"2009","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1002\/ppul.26806","article-title":"Nutritional status in the era of highly effective CFTR modulators","volume":"59","author":"Bass","year":"2024","journal-title":"Pediatr. Pulmonol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/18\/3103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:56:23Z","timestamp":1760111783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/18\/3103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,14]]},"references-count":27,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16183103"],"URL":"https:\/\/doi.org\/10.3390\/nu16183103","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,14]]}}}