The effect of age and genotype on lung function in children with cystic fibrosis

Identifying the initial manifestations of pulmonary functional disorders associated with cystic fibrosis (CF) is essential for timely correction of the therapy and improvement of the prognosis.

The aim of the study was to identify the age periods with the highest risk of a decrease in lung function in children with different CF genotypes.

Methods. Lung function (LF) was analyzed using spirometry results in CF patients aged 6 to 18 years from the Registry of patients with cystic fibrosis in the Russian Federation 2018.

Results. The forced expiratory volume in one second (FEV1) was statistically significantly lower in children aged 6 – 10 years with “severe” genotypes than in the children with “mild” genotypes. The lung function was reduced at 11 – 14 years of age in both “severe» and “mild” genotypes without any statistically significant difference. In general, the trend of a decrease in lung function in “severe” genotypes persists in the adolescent period from 15 to 18 years. The lung function is better in adolescents aged 15 – 18 with the “mild” variants of genotypes compared to the patients aged 11 – 14 years.

Conclusion. The “severe” variants of CFTR negatively affect LF of CF patients in all age groups. The LF values in patients with “mild” genotypes at the age of 15 – 18 years were higher than in children aged 11 – 14 years with the same genotypes. There is a need for improved programs of medical care for adolescents with CF.

1. Marson F.A.L., Bertuzzo C.S., Ribeiro J.D. Classification of CFTR mutation classes. Lancet Respir. Med. 2016; 4 (8): е37–38. DOI: 10.1016/S2213-2600(16)30188-6.

2. De Boeck K. Cystic fibrosis in the year 2020: disease with a new face. Act. Paediatr. 2020; 109: 893–899. DOI: 10.1111/apa.15155.

3. de Gracia J., Mata F., Álvarez A. et al. Genotype-phenotype correlation for pulmonary function in cystic fibrosis. Thorax. 2005; 60 (7): 558–563. DOI: 10.1136/thx.2004.031153.

4. McKone E.F., Goss C.H., Aitken M.L. CFTR genotype as a predictor of prognosis in cystic fibrosis. Chest. 2006; 130 (5): 1441–1447. DOI: 10.1378/chest.130.5.1441.

5. Shadrina V.V., Krasovskiy S.A., Kondratyeva E.I., Furman E.G. [Epidemiological and clinical features of “Middle-Urals” Variant L138ins in cystic fibrosis]. Meditsinskiy vestnik Severnogo Kavkaza. 2020; 15 (2): 283–288. DOI: 10.14300/mnnc.2020.15069 (in Russian).

6. Amelina E.L., Kashirskaya N.Yu., Kondratyeva E.I. et al., eds. [Russian Federation cystic fibrosis patients Registry. 2018 year]. Moscow: Medpraktika-M; 2020. Available at: https://mukoviscidoz.org/doc/registr/web_block_Registre_2018.pdf (in Russian).

7. Shadrina V.V., Kondratyeva E.I., Furman E.G. et al. [Basic clinical, laboratory and genetic characteristics of patients with cystic fibrosis living in the territory of the Perm Krai, other regions of the Volga federal district of the federal district and central region]. Permskiy meditsinskiy zhurnal. 2020; 37 (1): 48–62. DOI: 10.17816/pmj37148-62 (in Russian).

8. Kondratyeva E.I., Furman E.G., Shadrina V.V., eds. [Cystic fibrosis registry of Volga Federal district 2017]. Perm’: Izdatel’stvo PNIPU; 2020. Available at: https://rusneb.ru/catalog/000199_000009_07000426921/ (in Russian).

9. ECFS. ECFS Patient Registry. Updated: February13, 2019. Available at: https://www.ecfs.eu/projects/ecfs-patient-registry/project

10. Chuchalin A.G., Aisanov 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).

11. Miller M.R., Hankinson J., Brusasco V. et al. Standardisation of spirometry. Eur. Respir. J. 2005; 26 (2): 319–337. DOI: 10.1183/09031936.05.00034805.

12. [Healthcare issues and challenges in adolescents with cystic fibrosis]. (Translation from English). St. Petersburg: Progress kniga; 2014 (in Russian).

13. Furman E.G., Shadrina V.V., Vinokurova L.N. et al. [Communication skills of students of the pediatric faculty]. In.: [Deontological education and the formation of communication skills among students at a medical university: Materials of the educational-methodical conference]. Perm: PGMU im. akad. E.A.Vagnera Minzdrava RF; 2019: 160–165 (in Russian).

14. Welsh L., Robertson C.F, Ranganathan S.C. Increased rate of lung function decline in Australian adolescents with cystic fibrosis. Pediatr. Pulmonol. 2014; 49 (9): 873–877. DOI: 10.1002/ppul.22946.

15. Savushkina O.I., Chernyak A.V. et al. [A role of impulse oscillometry for diagnosis of mild bronchial obstruction]. Pul’monologiya. 2018; 28 (4): 391–398. DOI: 10.18093/0869-0189-2018-28-4-391-398 (in Russian).

16. Kerem E., Viviani L., Zolin A. et al. Factors associated with FEV1 decline in cystic fibrosis: analysis of the ECFS Patient Registry. Eur. Respir. J. 2014; 43 (1):125–133. DOI: 10.1183/09031936.00166412.

17. Geborek A., Hjelte L. Association between genotype and pulmonary phenotype in cystic fibrosis patients with severe mutations. J. Cyst. Fibros. 2011; 10 (3): 187–192. DOI: 10.1016/j.jcf.2011.01.005.

18. Leung G.J., Cho T.J., Kovesi T. et al. Variation in lung function and nutritional decline in cystic fibrosis by genotype: An analysis of the Canadian cystic fibrosis registry. J. Cyst. Fibros. 2020; 19 (2): 255–261. DOI: 10.1016/j.jcf.2019.06.007.

19. Liou T.G., Elkin E.P., Pasta D.J. et al. Year-to-year changes in lung function in individuals with cystic fibrosis. J. Cyst. Fibros. 2010; 9 (4): 250–256. DOI: 10.1016/j.jcf.2010.04.002.