Changes in the paranasal sinuses and lungs in children with cystic fibrosis according to computed tomography during therapy with elexacaftor/tezacaftor/ivacaftor

Polypous rhinosinusitis (PRS) is one of the main manifestations of cystic fibrosis (CF). Elexacaftor/tezacaftor/ivacaftor (ETI) is a CFTR modulator that improves lung function and prevents the progression of PRS in CF by restoring transmembrane conductance.

The aim of the study was to evaluate the dynamics of the radiographic image of the paranasal sinuses (PNS) and chest organs (CHO) in children receiving the CFTR modulator ETI.

Methods. An examination of children with CF (n = 22) was conducted. X-ray examination was performed in the amount of computed tomography (CT) of the PNS and CHO before and after 12 months of therapy with ETI. The volume of PNS damage was assessed according to the Land - Mackay scale. The volume of lung damage was assessed according to the Brody scale. Lung function parameters (forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) and sweat conductivity) were also determined.

Results. A significant decrease in the Land - Mackay score from 15 to 5.5, marked improvements in the reduction of mucus plugs in the peripheral areas, a decrease in peribronchial infiltration, consolidation of lung tissue, and air traps were observed. An increase in FVC from 88.5% (84.0% - 102.3%) to 101% (92.5% - 102.3%), FEV₁ from 87.5% (77.8% - 106.0%) to 105% (96.0% - 110.5%), and a decrease in sweat test from 113.0 (101.0 - 120.0) mmol/L to 63.0 (50.0 - 77.0) mmol/L were observed.

Conclusion. ETI has been demonstrated to be highly effective in the treatment of PRS by improving lung function and reducing sweat test values.

1. Amelina E.L., Kashirskaya N.YU.,Kondratyeva E.I. et al. eds. [Cystic fibrosis patient registry in the Russian Federation. 2023]. Moscow: Medpraktika-M; 2025. Available at: https://mukoviscidoz.org/mukovistsidoz-v-rossii.html (in Russian).

2. Polyakov D.P., Daykhes N.A., Yunusov A.S. et al. [Chronic polypous rhinosinusitis and lung function in the profile of multi-organ pathology in children with cystic fibrosis in the Russian Federation]. Pul′monologiya. 2021; 31 (2): 207–215. DOI: 10.18093/0869-0189-2021-31-2-207-215 (in Russian).

3. Anaev E.Kh. [Modern approaches to the management of patients with bronchoectasia]. Pul′monologiya. 2020; 30 (1): 81–91. DOI: 10.18093/0869-0189-2020-30-1-81-91 (in Russian).

4. Wielpütz M.O., Mall M.A. Therapeutic improvement of CFTR function and reversibility of bronchiectasis in cystic fibrosis. Eur. Respir. J. 2024; 63 (3): 2400234. DOI: 10.1183/13993003.00234-2024.

5. Crowley C., Connor O.J.O., Ciet P. The evolving role of radiological imaging in cystic fibrosis. Curr. Opin. Pulm. Med. 2021; 27 (6): 575–585. DOI: 10.1097/MCP.0000000000000828.

6. Kondratiyeva E.I., Odinaeva N.D., Voronkova A.Yu.et al. [Efficacy of targeted therapy with lumacaftor/ivacaftor in children with cystic fibrosis (12-month follow-up)]. Arkhiv pediatrii i detskoy khirurgii. 2023; 1 (1): 50–58. DOI: 10.31146/2949-4664-apps-1-1-50-58 (in Russian).

7. Polyakov D.P., Ramazanova P.I., Pogodina A.A. et al. [Modifying effect of targeted therapy for cystic fibrosis on the course of chronic rhinosinusitis]. Vestnik otorinolaringologii. 2024; 89 (1): 88. DOI: 10.17116/otorino20248901175 (in Russian).

8. McNally P., Lester K., Stone G. et al. Improvement in lung clearance index and chest computed tomography scores with elexacaftor/tezacaftor/ivacaftor treatment in people with cystic fibrosis aged 12 years and older – the RECOVER Trial. Am. J. Respir. Crit. Care Med. 2023; 208 (9): 917–929. DOI: 10.1164/rccm.202308-1317OC.

9. Stahl M. Sensitive markers to detect progression of lung disease in children with cystic fibrosis. Eur. Respir. J. 2021; 58 (1): 2100236. DOI: 10.1183/13993003.00236-2021.

10. Bayfield K.J. Douglas T.A. Rosenow T. Time to get serious about the detection and monitoring of early lung disease in cystic fibrosis. Thorax. 2021; 76 (12): 1255–1265. DOI: 10.1136/thoraxjnl-2020-216085.

11. Zinreich S.J. Imaging for staging of rhinosinusitis. Ann. Otol. Rhinol. Laryngol. Suppl. 2004; 193: 19–23. DOI: 10.1177/00034894041130s506.

12. Brody A.S., Klein J.S., Molina P.L. et al. High-resolution computed tomography in young patients with cystic fibrosis: distribution of abnormalities and correlation with pulmonary function tests. J. Pediatr. 2004; 145 (1): 3–38. DOI: 10.1016/j.jpeds.2004.02.038.

13. Chuchalin A.G., Aysanov Z.R., Chikina S.Yu. et al. [Federal guidelines of Russian Respiratory Society on spirometry]. Pul′monologiya. 2014; (6): 11–24. DOI: 10.18093/0869-0189-2014-0-6-11-24 (in Russian).

14. Ministry of Health of the Russian Federation. [Clinical guidelines: Cystic fibrosis (mucoviscidosis)]. 2021. Available at: https://cr.minzdrav.gov.ru/view-cr/372_2 (in Russian).

15. Ministry of Health of the Russian Federation. [Clinical guidelines: Cystic fibrosis (mucoviscidosis)]. 2025. Available at: https://cr.minzdrav.gov.ru/preview-cr/372_3 (in Russian).

16. Union of Pediatricians of Russia. [Guidelines: Targeted therapy for Cystic fibrosis]. 2023. Available at: https://ostrovaru.com/2023/06/14/metodicheskie-rekomendaczii-po-targetnoj-terapii-kistoznogo-fibroza-2023-goda/ (in Russian).

17. Stapleton A.L., Kimple A. J., Goralski J. L. et al. Elexacaftor–tezacaftor–ivacaftor improves sinonasal outcomes in cystic fibrosis. J. Cyst. Fibrosis. 2022; 21 (5): 792–799. DOI: 10.1016/j.jcf.2022.03.002.

18. Di Gioia S., Lucca F., Venditto L. et al. Efficacy of elexacaftor–tezacaftor–ivacaftor on chronic rhinosinusitis in cystic fibrosis. Am. J. Otolaryngol. 2024; 45 (3): 104236. DOI: 10.1016/j.amjoto.2024.104236.

19. Castellanos C.X., Osterbauer B., Hasday S. et al. Improvement in sinonasal Quality‐of‐Life indicators for pediatric patients with cystic fibrosis treated with elexacaftor–tezacaftor‐ivacaftor. Int. Forum Allergy Rhinol. 2023; 13 (1): 72–75. DOI: 10.1002/alr.23036.

20. Bode S.F.N., Rapp H., Lienert N. et al. Effects of CFTR‐modulator triple therapy on sinu‐nasal symptoms in children and adults with cystic fibrosis. Eur. Arch. Otorhinolaryngol. 2023; 280 (7): 3271–3277. DOI: 10.1007/s00405-023-07859-4.

21. Polyakov D.P., Kondratyeva E.I., Voronkova A.Y., Ramazanova P.I. [Efficacy of triple targeted therapy against chronic rhinosinusitis in children with cystic fibrosis (case series)]. Meditsinskiy sovet. 2023; (19): 78–87. DOI: 10.21518/ms2023-399 (in Russian).

22. Sly P.D., Gangell C.L., Chen L. et al. Risk factors for bronchiectasis in children with cystic fibrosis. N. Engl. J. Med. 2013; 368 (21): 1963–1970. DOI: 10.1056/NEJMoa1301725.

23. Agarwal R. Bronchiectasis in acute pneumonia Pseudobronchiectasis. Chest. 2007; 132 (6): 2054–2055. DOI: 10.1378/chest.07-1529.

24. Aung A.K., Thompson P.J., Teh B.M., McGrath C. Pseudobronchiectasis after pertussis and mycoplasma infection. Am. J. Respir. Crit. Care Med. 2012; 186 (3): 292–294. DOI: 10.1164/ajrccm.186.3.292.

25. Wucherpfennig L., Triphan S.M.F., Wege S. et al. Magnetic resonance imaging detects improvements of pulmonary and paranasal sinus abnormalities in response to elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis. J. Cyst. Fibros. 2022; 21 (6): 1053–1060. DOI: 10.1016/j.jcf.2022.03.011.

26. Bec R., Reynaud-Gaubert M., Arnaud F. et al. Chest computed tomography improvement in patients with cystic fibrosis treated with elexacaftor–tezacaftor–ivacaftor: early report. Eur. J. Radiol. 2022; 154: 110421. DOI: 10.1016/j.ejrad.2022.110421.

27. Middleton P.G., Simmonds N.J. Cystic fibrosis modulator therapy canreverse cystic bronchiectasis. Respirol. Case Rep. 2023; 11 (7): e01172. DOI: 10.1002/rcr2.11724.

28. Gushue C., Eisner M., Bai S. et al. Impact of elexacaftor–tezacaftor–ivacaftor on lung disease in cystic fibrosis. Pediatr. Pulmonol. 2023; 58 (8): 2308–2316. DOI: 10.1002/ppul.26485.

29. Moloney F., Kavanagh R.G., Ronan N.J. et al. Ultra-low-dose thoracic CT with model-based iterative reconstruction (MBIR) in cystic fibrosis patients undergoing treatment with cystic fibrosis transmembrane conductance regulators (CFTR). Clin. Radiol. 2021; 76 (5): 393.e9–393.e17. DOI: 10.1016/j.crad.2020.12.003.