Диагностични методи при муковисцидоза в детската възраст

Резюме

Муковисцидозата (кистичната фиброза, cystic fibrosis, CF) е рядко автозомно-рецесивно мултисистемно заболяване, характеризиращо се с хронично прогресиращо протичане и значима заболеваемост още от ранна детска възраст. Ранната диагноза има ключово значение за прогнозата, тъй като позволява своевременно започване на комплексно лечение и подобрява дългосрочните клинични резултати. Диагностичният процес изисква съчетаване на клинична оценка с доказателства за CFTR дисфункция, установена чрез потен тест, генетични и функционални методи.

Настоящата обзорна статия представя съвременните диагностични подходи при муковисцидоза в детската възраст, с особен акцент върху функционалните изследвания на дишането, образните методи и перспективите за въвеждане на неонатален скрининг в България.

Ключови думи: муковисцидоза, CFTR, потен тест, неонатален скрининг, генетична диагностика, образна диагностика, функционални изследвания на дишането

Библиография

1. Atjen F, Bell SC, Rowe SM, et al. Cystic fibrosis. Nat Dis Primers. 2015;1:15010.

2. De Boeck K, Amaral MD. Progress in therapies for cystic fibrosis. Lancet Respir Med. 2016; published online Apr 1.

3. Marson FAL, Bertuzzo CS, Ribeiro JD. Personalized drug therapy in cystic fibrosis: from fiction to reality. Curr Drug Targets. 2015;16:1007–17.

4. Naehrig S, Chao CM, Naehrlich L. Cystic Fibrosis. Dtsch Arztebl Int. 2017;114(33–34):564–574. doi:10.3238/arztebl.2017.0564.

5. Quinton P. Cystic Fibrosis: Lessons from the Sweat Gland. Physiology. 2007;22:212–225.

6. Mickle JE, Cutting GR. Genotype-Phenotype relationships in cystic fibrosis. Med Clin North Am. 2000;84:597–607.

7. Willems P, Weeks S, Meskal A et al. Biological variation of chloride and sodium in sweat obtained by pilocarpine iontophoresis in adults. Lung. 2017;195:241–246.

8. Wallis C. Diagnosing cystic fibrosis: blood, sweat, and tears. Arch Dis Child. 1997;76:85–88.

9. Raina MA, Khan MS, Malik SA et al. Assessment of correlation between sweat chloride levels and clinical features of cystic fibrosis patients. J Clin Diagn Res. 2016;10:BC01–BC06.

10. Ooi CY, Durie PR. CFTR gene mutations in pancreatitis. J Cyst Fibros. 2012;11:355–362.

11. Castellani C, Cuppens H, Macek M Jr et al. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. J Cyst Fibros. 2008;7:179–196.

12. Bienvenu T, Lopez M, Girodon E. Molecular diagnosis and genetic counseling of cystic fibrosis and related disorders: new challenges. Genes. 2020;11:619.

13. Mishra A, Greaves R, Massie J. The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era. Clin Biochem Rev. 2005;26:135–153.

14. Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the Cystic Fibrosis Foundation. J Pediatr. 2017;181S:S4–S15.

15. Farrell PM, White TB, Howenstine M, et al. Diagnosis of cystic fibrosis in screened populations. J Pediatr. 2017;181S:S33–S44.

16. Munck A, Mayell SJ, Winters V, et al Cystic fibrosis screen positive, inconclusive diagnosis (CFSPID): a new designation and management recommendations for infants with an inconclusive diagnosis following newborn screening. J Cyst Fibros. 2015;14:706–713.

17. Castellani C, Southern KW, Brownlee K, et al. European best practice guidelines for cystic fibrosis neonatal screening. J Cyst Fibros. 2009;8:153–173.

18. Faria AG, Lima Marson FAL, deSouza Gomez CC, et al. Thirty years of sweat chloride testing at one referral center. Front Pediatr. 2017;5:222.

19. Guglani L, Stabel D, Weiner D. False-positive and false-negative sweat tests: systematic review of the evidence. Pediatr Allergy Immunol Pulmonol. 2015;28:198–211.

20. Ozgenc A, Yasar NE, Kucur M, et al The most common preanalytic problem of sweat testing: insufficient sweat volume. Int J Med Biochem. 2020;3:62–66.

21. Hauke A, Oertel S, Knoke L,et al. Screen-printed sensor for low-cost chloride analysis in sweat for rapid diagnosis and monitoring of cystic fibrosis. Biosensors. 2020;10:123.

22. Macedo A, Mathiaparanam S, Brick L, et al. The sweat metabolome of screen-positive cystic fibrosis infants: revealing mechanisms beyond impaired chloride transport. ACS Cent Sci. 2017;3:904–913.

23. Hill M, Twiss P, Verhoef TI, et al. Non-invasive prenatal diagnosis for cystic fibrosis: detection of paternal mutations, exploration of patient preferences and cost analysis. Prenat Diagn. 2015;35:950–958.

24. Mouawia H, Saker A, Jais JP, et al. Circulating trophoblastic cells provide genetic diagnosis in fetuses at risk for cystic fibrosis or spinal muscular atrophy. Reprod Biomed Online. 2012;25:508–520.

25. Chandler NJ, Ahlfors H, Drury S, et al. Noninvasive prenatal diagnosis for cystic fibrosis: implementation, uptake, outcome, and implications. Clin Chem. 2020;66:207–216.

26. Jeppesen LD, Hatt L, Singh R, et al. Cell-based non-invasive prenatal diagnosis in a pregnancy at risk of cystic fibrosis. Prenat Diagn. 2021;41:234–240.

27.  Байчева М. Чернодробно увреждане при муковисцидоза [дисертационен труд за придобиване на образователна и научна степен „доктор“]. София: Медицински университет – София; 2024.

28.  Колева Р, Бозаджиева Л, Митева Д, et al. Муковисцидозата на границата на две епохи: през погледа на амбулаторния специалист. Педиатрия. 2025;65(2):39-42.

Адрес за кореспонденция:

Проф. д-р Гергана Петрова Стоянова, дм

Клиника по педиатрия, УМБАЛ „Александровска“

ул. „Св. Георги Софийски“ №1, 1431 София

gstoyanova@medfac.mu-sofia.bg