Systemic effects of CFTR modulator therapy in cystic fibrosis: implications for organ function and quality of life
DOI:
https://doi.org/10.12775/QS.2026.58.72451Keywords
cystic fibrosis, CFTR, CFTR modulators, ivacaftor, elexacaftor, tezacaftor, pulmonary function, pancreatic insufficiency, fertility, triple therapyAbstract
Background: Cystic fibrosis (CF) is a chronic autosomal recessive disease caused by CFTR mutations, leading to impaired chloride and bicarbonate transport and the production of thick secretions. This results in progressive damage, mainly in the respiratory and gastrointestinal systems. CFTR modulators have recently transformed CF treatment by targeting the underlying defect.
Aim: To review the pathophysiology and clinical manifestations of CF and evaluate the effects of CFTR modulators on pulmonary and extrapulmonary systems.
Materials and Methods: A narrative literature review was conducted using PubMed and Google Scholar with keywords such as “cystic fibrosis”, “CFTR mutations”, “clinical manifestations”, and “CFTR modulators”.
Results: CFTR modulator therapies, have demonstrated significant clinical benefits. These include improvement in lung function, reduction in pulmonary exacerbations, and enhanced quality of life. Additionally, extrapulmonary effects were observed, such as partial restoration of pancreatic function, reduction of gastrointestinal symptoms and inflammation, improvement in nutritional status, and positive effects on reproductive health.
Conclusions: CFTR modulators represent a major advancement in CF therapy, improving both pulmonary and systemic outcomes. However, limitations such as variable response and limited access remain. Further studies are needed to assess long-term effects.
References
[1] Chen, Q., Shen, Y., & Zheng, J. (2021). A review of cystic fibrosis: Basic and clinical aspects. Animal models and experimental medicine, 4(3), 220–232. https://doi.org/10.1002/ame2.12180
[2] Anwar, S., Peng, J. L., Zahid, K. R., Zhou, Y. M., Ali, Q., & Qiu, C. R. (2024). Cystic
Fibrosis: Understanding Cystic Fibrosis Transmembrane Regulator Mutation Classification and Modulator Therapies. Advances in respiratory medicine, 92(4), 263–277. https://doi.org/10.3390/arm92040026
[3] Dickinson, K. M., & Collaco, J. M. (2021). Cystic Fibrosis. Pediatrics in review, 42(2), 55–
67. https://doi.org/10.1542/pir.2019-0212
[4] Chaudary, N., & Balasa, G. (2021). Airway Clearance Therapy in Cystic Fibrosis Patients Insights from a Clinician Providing Cystic Fibrosis Care. International journal of general medicine, 14, 2513–2521. https://doi.org/10.2147/IJGM.S274196
[5] Amoakon, J. P., Mylavarapu, G., Amin, R. S., & Naren, A. P. (2024). Pulmonary Vascular Dysfunctions in Cystic Fibrosis. Physiology (Bethesda, Md.), 39(4), 0. https://doi.org/10.1152/physiol.00024.2023
[6] Núñez-García, L. Á., Córdova-Fletes, C., Barboza-Cerda, M. C., & Garza-González, E.
(2026). Pseudomonas aeruginosa Biofilms in Cystic Fibrosis: Interactions, Methods, and Therapeutic Strategies. BioMed research international, 2026, 5328382. https://doi.org/10.1155/bmri/5328382
[7] Bode, S. F. N., Rapp, H., Lienert, N., Appel, H., & Fabricius, D. (2023). Effects of CFTRmodulator triple therapy on sinunasal symptoms in children and adults with cystic fibrosis. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 280(7), 3271–3277. https://doi.org/10.1007/s00405-023-07859-4
[8] Stone, R. G., Short, C., Davies, J. C., & McNally, P. (2024). Chronic rhinosinusitis in the era of CFTR modulator therapy. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 23(2), 208–213. https://doi.org/10.1016/j.jcf.2023.08.009
[9] Sellers, Z. M., Assis, D. N., Paranjape, S. M., Sathe, M., Bodewes, F., Bowen, M., Cipolli, M., Debray, D., Green, N., Hughan, K. S., Hunt, W. R., Leey, J., Ling, S. C., Morelli, G., Peckham, D., Pettit, R. S., Philbrick, A., Stoll, J., Vavrina, K., Allen, S., … Narkewicz, M. R. (2024). Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations. Hepatology (Baltimore, Md.), 79(5), 1220–1238. https://doi.org/10.1097/HEP.0000000000000646
[10] Ludovico, A., & Baroni, D. (2025). CFTR Modulators Counteract F508del CFTR Functional Defects in a Pancreatic Epithelial Model of Cystic Fibrosis. Life (Basel, Switzerland), 15(8), 1315. https://doi.org/10.3390/life15081315
[11] Ramsey, M. L., Li, S. S., Lara, L. F., Gokun, Y., Akshintala, V. S., Conwell, D. L., Heintz, J., Kirkby, S. E., McCoy, K. S., Papachristou, G. I., Patel, A., Singh, V. K., & Hart, P. A. (2023). Cystic fibrosis transmembrane conductance regulator modulators and the exocrine pancreas: A scoping review. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 22(2), 193–200. https://doi.org/10.1016/j.jcf.2022.08.008
[12] Sellers Z. M. (2020). Pancreatic complications in children with cystic fibrosis. Current opinion in pediatrics, 32(5), 661–667. https://doi.org/10.1097/MOP.0000000000000934
[13] Sankararaman, S., Hendrix, S. J., & Schindler, T. (2022). Update on the management of vitamins and minerals in cystic fibrosis. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 37(5), 1074–1087. https://doi.org/10.1002/ncp.10899
[14] Anton-Păduraru, D. T., Murgu, A. M., Bozomitu, L. I., Mîndru, D. E., Iliescu Halițchi, C. O., Trofin, F., Ciongradi, C. I., Sârbu, I., Eṣanu, I. M., & Azoicăi, A. N. (2024). Diagnosis and Management of Gastrointestinal Manifestations in Children with Cystic Fibrosis. Diagnostics (Basel, Switzerland), 14(2), 228. https://doi.org/10.3390/diagnostics14020228
[15] Taylor-Cousar J. L. (2020). CFTR Modulators: Impact on Fertility, Pregnancy, and Lactation in Women with Cystic Fibrosis. Journal of clinical medicine, 9(9), 2706. https://doi.org/10.3390/jcm9092706
[16] Roe, A. H., Merjaneh, L., Oxman, R., & Hughan, K. S. (2021). Gynecologic health care for females with cystic fibrosis. Journal of clinical & translational endocrinology, 26, 100277. https://doi.org/10.1016/j.jcte.2021.100277
[17] Naz Khan, F., Mason, K., Roe, A. H., & Tangpricha, V. (2021). CF and male health: Sexual and reproductive health, hypogonadism, and fertility. Journal of clinical & translational endocrinology, 27, 100288. https://doi.org/10.1016/j.jcte.2021.100288
[18] Kaltsas A. (2025). Cystic Fibrosis and Male Infertility: From Genetics to Future Perspectives in Assisted Reproductive Technologies. Genes, 16(9), 994. https://doi.org/10.3390/genes16090994
[19] Taylor-Cousar, J. L., Janney, R., Middleton, P. G., Jain, R., Nightingale, J., West, N. E., Shteinberg, M., Velez, D., & Kazmerski, T. M. (2024). A provider survey assessing fetal impact of CFTR modulator use in males with CF during assisted and unassisted reproduction and partner pregnancy. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 23(3), 412–416. https://doi.org/10.1016/j.jcf.2023.10.022
[20] Ferreira, F. C., Buarque, C. D., & Lopes-Pacheco, M. (2024). Organic Synthesis and Current Understanding of the Mechanisms of CFTR Modulator Drugs Ivacaftor, Tezacaftor, and Elexacaftor. Molecules (Basel, Switzerland), 29(4), 821. https://doi.org/10.3390/molecules29040821
[21] Regard, L., Martin, C., Da Silva, J., & Burgel, P. R. (2023). CFTR Modulators: Current Status and Evolving Knowledge. Seminars in respiratory and critical care medicine, 44(2), 186 195. https://doi.org/10.1055/s-0042-1758851
[22] Baroni D. (2025). Unraveling the Mechanism of Action, Binding Sites, and Therapeutic Advances of CFTR Modulators: A Narrative Review. Current issues in molecular biology, 47(2), 119. https://doi.org/10.3390/cimb47020119
[23] Meoli, A., Fainardi, V., Deolmi, M., Chiopris, G., Marinelli, F., Caminiti, C., Esposito, S.,
& Pisi, G. (2021). State of the Art on Approved Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulators and Triple-Combination Therapy. Pharmaceuticals (Basel, Switzerland), 14(9), 928. https://doi.org/10.3390/ph14090928
[24] Bacalhau, M., Camargo, M., Magalhães-Ghiotto, G. A. V., Drumond, S., Castelletti, C. H. M., & Lopes-Pacheco, M. (2023). Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis. Pharmaceuticals (Basel, Switzerland), 16(3), 410. https://doi.org/10.3390/ph16030410
[25] Harvey, C., Weldon, S., Elborn, S., Downey, D. G., & Taggart, C. (2022). The Effect of CFTR Modulators on Airway Infection in Cystic Fibrosis. International journal of molecular sciences, 23(7), 3513. https://doi.org/10.3390/ijms23073513
[26] Jimenez, D. G., García Romero, R., Martínez, A. R., & Vicente Santamaria, S. (2025). Treatment with CFTR Modulators for Cystic Fibrosis: What a Pediatric Gastroenterologist Needs to Know. Children (Basel, Switzerland), 12(9), 1104. https://doi.org/10.3390/children12091104
[27] Calthorpe, R. J., Goodchild, N., Gleetus, V., Premakumar, V., Hayee, B., Elliott, Z., Evans, B., Rowbotham, N. J., Carr, S. B., Barr, H., Horsley, A., Peckham, D., & Smyth, A. R. (2024). A grumbling concern: A survey of gastrointestinal symptoms in cystic fibrosis in the modulator era. NIHR open research, 3, 18. https://doi.org/10.3310/nihropenres.13384.2
[28] García Romero, R., López Cárdenes, C., Crehuá Gaudiza, E., Álvarez Beltrán, M., Murray Hurtado, M., Tutau Gómez, C., Loverdos Eseverri, I., Torcuato Rubio, E., García Volpe, C., Salcedo Lobato, E., Medina Martínez, M., Martin Fernández, C., Moreno Álvarez, A., Reyes Domínguez, A., González Jiménez, D., & Grupo de trabajo de Fibrosis quística y páncreas de la SEGHNP (2025). Improvement of intestinal inflammation after treatment with CFTR modulators in cystic fibrosis patients. Anales de pediatria, 102(5), 503836. https://doi.org/10.1016/j.anpede.2025.503836
[29] Eldredge, J. A., Oliver, M. R., & Ooi, C. Y. (2024). Cystic fibrosis liver disease in the new era of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. Paediatric respiratory reviews, 50, 54–61. https://doi.org/10.1016/j.prrv.2023.12.005
[30] Gramegna, A., Contarini, M., Aliberti, S., Casciaro, R., Blasi, F., & Castellani, C. (2020). From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis. International journal of molecular sciences, 21(16), 5882. https://doi.org/10.3390/ijms21165882
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Marta Zdunek, Maciej Stodulski, Anna Bulicz, Izabela Kasprzycka, Monika Kukla, Olga Kowalczyk, Joanna Dziarnowska, Sebastian Kozłowski, Justyna Fiks, Izabela Kmiecik
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 23
Number of citations: 0
