Cystic fibrosis is an autosomal recessive genetic disease that carries pathobiological properties and results from a genetic mutation on the cystic fibrosis transmembrane conductivity regulator (CFTR) gene [1]. In individuals with cystic fibrosis, the CFTR gene has been found to contain more than 1,000 mutations. The majority of these mutations affect the CFTR protein’s amino acids or slightly alter its DNA. The resulting aberrant channel never reaches the cell membrane to carry chloride ions because it disintegrates shortly after it is created. Disease-causing mutations in the CFTR gene change the way the chloride channel is made, how it functions, or how stable it is. Cells that line the airways of the pancreas, lungs, and other organs, therefore, create excessively thick and sticky mucus. The abnormal mucus obstructs the glands and airways, which results in the development of signs and symptoms unique to cystic fibrosis [2]–[5].

Despite the incidence being reported as 1/3000 in a small number of studies carried out in our nation, this rate is believed to be greater given the prevalence of consanguineous marriages. The most common clinical signs and symptoms are that pancreatic insufficiency and chronic obstructive pulmonary disease. The main reason for death is recurrent pulmonary infections [6].
Symptoms and Diagnosis of Cystic Fibrosis
Because cystic fibrosis affects several systems, it presents a wide range of clinical signs and symptoms. Parental consanguinity, a history of sibling deaths, meconium ileus, meconium perforation-peritonitis, obstructive jaundice, and a salty taste when kissed in the neonatal period; growth retardation in infancy, copious foul-smelling oily stools, recurrent respiratory tract infections, anemia, edema, rectal prolapse, recurrent wheezing attacks in childhood and ad In addition to these clinical signs, the measurement of a high sweat chloride concentration over the course of three distinct periods solidifies the diagnosis of CF [6].
Treatment of Cystic Fibrosis
Even though there is still no treatment for cystic fibrosis, research is continually being done. As stated in the text below, certain medications created to treat this disease are still in use today even though they don’t provide a full cure. However, there are a variety of treatments that can be used to ease the symptoms, stop complications, and make the illness easier to manage.
Prior to the creation of CFTR modulator therapy, there were only symptom-focused treatments for CF, but CFTR modulators focus on the root of the problem. Small molecule treatments known as CFTR modulators are currently marketed as four single or combination treatments: ivacaftor (IVA; Kalydeco®), lumacaftor/ivacaftor (LUM/IVA; Orkambi®), tezacaftor/ivacaftor (TEZ/IVA; Symdeko® or Symkevi®), and elexacaftor/tezacaftor (ELX/TEZ/IVA; Trikafta® or Kaftrio®). By concentrating on CFTR mutations that affect channel gating and conductance, IVA is a CFTR “potentiator” that extends the amount of time the CFTR protein channel is open. IVA is combined with one or more CFTR “correctors” in the remaining three CFTR modulator regimens. In order to enhance CFTR protein structure, processing, and trafficking to the cell surface, “correctors” typically target the most prevalent CFTR variant, the F508del mutation [7]–[10]. Medical studies with controlled, non – randomized designs have shown that CFTR modulator therapies are effective in treating those who have the condition. These investigations included LUM/IVA in F508del homozygous patients, TEZ/IVA in F508del homozygous patients or in individuals who are heterozygous for the G551D or R117H mutations, non-G551D gating mutations, or residual function mutations [11]–[16].

Conclusion
The genetic condition known as cystic fibrosis is not infectious. It develops as a result of a mutation in the region of the human genome that generates the CFTR protein. Despite the statistical rarity of the condition, those who have it experience a bad quality of life. Even though there is yet no conclusive cure, several treatments employed after a disease was identified aim to raise the quality of life for the ill person.
Due to the numerous systems that cystic fibrosis affects, a variety of symptoms are involved in both its diagnosis and treatment. Patients who have this condition must use respirators for the majority of their life. This is because, as was previously said, the masses that have developed in the respiratory tract make it challenging for the person to breathe.
References:
- M. R. Knowles and P. R. Durie, “What Is Cystic Fibrosis?,” https://doi.org/10.1056/NEJMe020070, vol. 347, no. 6, pp. 439–442, Aug. 2002, doi: 10.1056/NEJME020070.
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- L. L. Kulczycki, M. Kostuch, and J. A. Bellanti, “A clinical perspective of cystic fibrosis and new genetic findings: relationship of CFTR mutations to genotype-phenotype manifestations,” Am J Med Genet A, vol. 116A, no. 3, pp. 262–267, 2003, doi: 10.1002/AJMG.A.10886.
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- I. Ratbi et al., “Detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene rearrangements enriches the mutation spectrum in congenital bilateral absence of the vas deferens and impacts on genetic counselling,” Hum Reprod, vol. 22, no. 5, pp. 1285–1291, 2007, doi: 10.1093/HUMREP/DEM024.
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- “Kaftrio | European Medicines Agency.” https://www.ema.europa.eu/en/medicines/human/EPAR/kaftrio (accessed Dec. 12, 2022).
- “HIGHLIGHTS OF PRESCRIBING INFORMATION”, Accessed: Dec. 12, 2022. [Online]. Available: www.fda.gov/medwatch.
- “Symkevi | European Medicines Agency.” https://www.ema.europa.eu/en/medicines/human/EPAR/symkevi (accessed Dec. 12, 2022).
- T. Pribilski, “Product Monograph”.
- P. G. Middleton et al., “Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele,” New England Journal of Medicine, vol. 381, no. 19, pp. 1809–1819, Nov. 2019, doi: 10.1056/NEJMOA1908639/SUPPL_FILE/NEJMOA1908639_DATA-SHARING.PDF.
- H. G. M. Heijerman et al., “Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial,” The Lancet, vol. 394, no. 10212, pp. 1940–1948, Nov. 2019, doi: 10.1016/S0140-6736(19)32597-8.
- J. L. Taylor-Cousar et al., “Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del,” New England Journal of Medicine, vol. 377, no. 21, pp. 2013–2023, Nov. 2017, doi: 10.1056/NEJMOA1709846/SUPPL_FILE/NEJMOA1709846_DISCLOSURES.PDF.
- F. Ratjen et al., “Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial,” Lancet Respir Med, vol. 5, no. 7, pp. 557–567, Jul. 2017, doi: 10.1016/S2213-2600(17)30215-1.
- C. E. Wainwright et al., “ Lumacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR ,” New England Journal of Medicine, vol. 373, no. 3, pp. 220–231, Jul. 2015, doi: 10.1056/NEJMOA1409547/SUPPL_FILE/NEJMOA1409547_DISCLOSURES.PDF.
- S. M. Rowe et al., “Tezacaftor–Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis,” New England Journal of Medicine, vol. 377, no. 21, pp. 2024–2035, Nov. 2017, doi: 10.1056/NEJMOA1709847/SUPPL_FILE/NEJMOA1709847_DISCLOSURES.PDF.
Figure References:
- Wikipeadia (2022), Cystic Fibrosis, receipt date:10/12/2022 https://en.wikipedia.org/wiki/Cystic_fibrosis
- Thoracic Key (2016), Cystic Fibrosis 2, receipt date: 12/12/2022
Inspector: Ranya DEMİR