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CME

, Volume 16, Issue 9, pp 9–21 | Cite as

Leben mit Mukoviszidose

Neue Herausforderungen für die Erwachsenenmedizin
  • Carsten SchwarzEmail author
  • Patience Eschenhagen
CME Fortbildung
  • 6 Downloads

Zusammenfassung

Die zystische Fibrose (CF), auch Mukoviszidose genannt, ist eine autosomal-rezessiv vererbte Stoffwechselkrankheit. Ein Defekt des Cystic-Fibrosis-Transmembrane-Conductance-Regulator(CFTR)-Gens verursacht einen verringerten Chlorid- und Bikarbonattransport an der Zellmembran, was Störungen an allen exokrinen Drüsen auslöst. Die Folge ist eine progressive Multiorganerkrankung. Mildere Verlaufsformen werden teilweise erst im Erwachsenenalter diagnostiziert. In den vergangenen Jahrzehnten ist die mittlere Lebenserwartung durch die Fortentwicklung der symptomatischen Therapie deutlich angestiegen. Durch innovative kausale Behandlungen wird sich dieser Trend höchstwahrscheinlich fortsetzen. Damit Betroffene maximal von diesen Therapiemöfglichkeiten profitieren können, ist eine frühe Diagnosestellung essenziell. Mit der deutschlandweiten Einführung des Neugeborenen-Screenings wurde ein wichtiger Schritt in diese Richtung unternommen. Patienten mit milderen Verlaufsformen werden jedoch teilweise vom Screening nicht erfasst oder wurden bereits vor der Screening-Einführung geboren. Daher sind klinische Verdachtsmomente und die Kenntnis atypischer Verlaufsformen der CF weiterhin entscheidend für die Diagnose.

Schlüsselwörter

CF-Neugeborenen-Screening CFTR-Modulatoren CFTR-Biomarker 

Literatur

  1. 1.
    L.Nährlich (Hrsg.), M.B., J. Wosniok, Deutsches Mukoviszidose-Register. Berichtsband 2017. Mukoviszidose e.V. & Mukoviszidose Institut gGmbH. 2018.Google Scholar
  2. 2.
    Foundation, C.F., https://www.cff.org/Trials/Pipeline. Cystic Fibrosis Foundation, Clinical Trials Pipeline.
  3. 3.
    G. Fanconi, E.U.C. Knauer, Das Coeliakiesyndrom bei angeborener zystischer Pankreasfibrose und Bronchiektasien.. Wien Med Wochenschr, 1936. 86: p. 753–756.Google Scholar
  4. 4.
    Rommens JM, I.M., Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, et al., Identification of the Cystic Fibrosis Gene: Chromosome Walking and Jumping. Science, 1989.Google Scholar
  5. 5.
    B Marshall, A.F., A Fink, D Loeffler, A Elbert, T O’Neil, T Rush, S Rizvi, 2017 Patient Registry Annual Data Report. CYSTIC FIBROSIS FOUNDATION, 2018. 2018.Google Scholar
  6. 6.
    CFTR2, Clinical + functional translation of CFTR. https://www.cftr2.org/mutations_history, 2018.
  7. 7.
    Fajac, I. and K. De Boeck, New horizons for cystic fibrosis treatment. Pharmacol Ther, 2017. 170: p. 205–211.CrossRefGoogle Scholar
  8. 8.
    Chang, E.H. and J. Zabner, Precision Genomic Medicine in Cystic Fibrosis. Clin Transl Sci, 2015. 8(5): p. 606–10.CrossRefGoogle Scholar
  9. 9.
    Bombieri, C., et al., Recommendations for the classification of diseases as CFTR-related disorders. Journal of Cystic Fibrosis, 2011. 10: p. S86–S102.CrossRefGoogle Scholar
  10. 10.
    Cutting, G.R., Cystic fibrosis genetics: from molecular understanding to clinical application. Nat Rev Genet, 2015. 16(1): p. 45–56.CrossRefGoogle Scholar
  11. 11.
    Terlizzi, V., et al., Clinical expression of cystic fibrosis in a large cohort of Italian siblings. BMC Pulm Med, 2018. 18(1): p. 196.CrossRefGoogle Scholar
  12. 12.
    C. Schwarz, U.D., J. Bend, B. Schulte-Hubbert, S. van KoningsbruggenRietschel, J.H. W. Bremer, S. Illing, A. Jung, J. Mainz, E. Rietschel, S. Schmidt, L. Sedlacek, C. Smaczny, B. Tümmler, O. M. Wielpützk, and I.B. M. Abele-Horn, F. Brunsmann, D. Dieninghoff, O. Eickmeier, H. Ellemunteri, R. Fischer, J. Grosse-Onnebrink, H. Hebestreit, M. Hogardt, C. Hügel, M. Hug, B. Kahl, A. Koitschev, M. Lübke, R. Mahlbergj, F. Mattner, A. Mehl, A. Möllerm, C. Muche-Borowskio, T. Nüßlein, M. Puderbach, S. Renner, F. Ringshausen, H. Sitterp, R. Vonberg, B. Wollschläger, H. Wilkens, J. Zerlik, S3-Leitlinie: Lungenerkrankung bei Mukoviszidose, Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa. 2017.Google Scholar
  13. 13.
    Doring, G., et al., Treatment of lung infection in patients with cystic fibrosis: current and future strategies. J Cyst Fibros, 2012. 11(6): p. 461–79.CrossRefGoogle Scholar
  14. 14.
    Schwarz, C., et al., Progress in Definition, Prevention and Treatment of Fungal Infections in Cystic Fibrosis. Mycopathologia, 2018. 183(1): p. 21–32.CrossRefGoogle Scholar
  15. 15.
    <026-022l_S3_Lungenerkrankung_bei_Mukoviszidose_Modul_1_2013-06-abgelaufen.pdf>.Google Scholar
  16. 16.
    Santos, V., et al., Cystic fibrosis - Comparison between patients in paediatric and adult age. Rev Port Pneumol (2006), 2017. 23(1): p. 17–21.Google Scholar
  17. 17.
    Wielputz, M.O. and M.A. Mall, MRI accelerating progress in functional assessment of cystic fibrosis lung disease. J Cyst Fibros, 2017. 16(2): p. 165–167.CrossRefGoogle Scholar
  18. 18.
    Renz, D.M., et al., Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters. Invest Radiol, 2015. 50(10): p. 733–42.CrossRefGoogle Scholar
  19. 19.
    Fernandez Fernandez, E., et al., CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease. Expert Rev Respir Med, 2018. 12(6): p. 483–492.CrossRefGoogle Scholar
  20. 20.
    Berkhout, M.C., et al., Sinonasal manifestations of cystic fibrosis: a correlation between genotype and phenotype? J Cyst Fibros, 2014. 13(4): p. 442–8.CrossRefGoogle Scholar
  21. 21.
    Hamilos, D.L., Chronic Rhinosinusitis in Patients with Cystic Fibrosis. J Allergy Clin Immunol Pract, 2016. 4(4): p. 605–12.CrossRefGoogle Scholar
  22. 22.
    Mainz, J.G., et al., Rhinosinusitis bei Mukoviszidose. 2015. 63(11): p. 809–820.Google Scholar
  23. 23.
    al., H.e., Impact of High- Versus Low-Risk Genotype on Sinonasal Radiographic Disease in Cystic Fibrosis. Laryngoscope, 2018.Google Scholar
  24. 24.
    Calton, J.B., et al., Paranasal sinus size is decreased in CFTR heterozygotes with chronic rhinosinusitis. Int Forum Allergy Rhinol, 2017. 7(3): p. 256–260.CrossRefGoogle Scholar
  25. 25.
    Chang, E.H., et al., Sinus hypoplasia precedes sinus infection in a porcine model of cystic fibrosis. Laryngoscope, 2012. 122(9): p. 1898–905.CrossRefGoogle Scholar
  26. 26.
    Grayson, J., et al., Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection. Int Forum Allergy Rhinol, 2017. 7(9): p. 904–909.CrossRefGoogle Scholar
  27. 27.
    Abuzeid, W.M., et al., Correlations between cystic fibrosis genotype and sinus disease severity in chronic rhinosinusitis. Laryngoscope, 2018. 128(8): p. 1752–1758.CrossRefGoogle Scholar
  28. 28.
    Aanæs, K., Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis. 2013. 12: p. S1–S20.Google Scholar
  29. 29.
    Safi, C., et al., Chronic Rhinosinusitis in Cystic Fibrosis: Diagnosis and Medical Management. Med Sci (Basel), 2019. 7(2).Google Scholar
  30. 30.
    Ooi, C.Y. and P.R. Durie, Cystic fibrosis from the gastroenterologist’s perspective. Nat Rev Gastroenterol Hepatol, 2016. 13(3): p. 175–85.CrossRefGoogle Scholar
  31. 31.
    Wilschanski, M. and I. Novak, The cystic fibrosis of exocrine pancreas. Cold Spring Harb Perspect Med, 2013. 3(5): p. a009746.CrossRefGoogle Scholar
  32. 32.
    Maleth, J., et al., Alcohol disrupts levels and function of the cystic fibrosis transmembrane conductance regulator to promote development of pancreatitis. Gastroenterology, 2015. 148(2): p. 427–39 e16.CrossRefGoogle Scholar
  33. 33.
    Yamada, A., et al., Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis. The Lancet Oncology, 2018. 19(6): p. 758–767.CrossRefGoogle Scholar
  34. 34.
    Freeman, A.J. and C.Y. Ooi, Pancreatitis and pancreatic cystosis in Cystic Fibrosis. J Cyst Fibros, 2017. 16 Suppl 2: p. S79–S86.CrossRefGoogle Scholar
  35. 35.
    Smyth, A.R., et al., European Cystic Fibrosis Society Standards of Care: Best Practice guidelines. J Cyst Fibros, 2014. 13 Suppl 1: p. S23–42.CrossRefGoogle Scholar
  36. 36.
    Howlett, C., et al., Partial restoration of pancreatic function in a child with cystic fibrosis. The Lancet Respiratory Medicine, 2016. 4(5): p. e21–e22.CrossRefGoogle Scholar
  37. 37.
    Davies, J.C., et al., Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. The Lancet Respiratory Medicine, 2016. 4(2): p. 107–115.CrossRefGoogle Scholar
  38. 38.
    Conway, S., et al., European Cystic Fibrosis Society Standards of Care: Framework for the Cystic Fibrosis Centre. J Cyst Fibros, 2014. 13 Suppl 1: p. S3–22.CrossRefGoogle Scholar
  39. 39.
    Borowitz, D., CFTR, bicarbonate, and the pathophysiology of cystic fibrosis. Pediatr Pulmonol, 2015. 50 Suppl 40: p. S24–S30.CrossRefGoogle Scholar
  40. 40.
    Keyzer, C., et al., Cystic fibrosis: unenhanced CT description of the appendix in asymptomatic adults. AJR Am J Roentgenol, 2014. 202(4): p. 759–64.CrossRefGoogle Scholar
  41. 41.
    Alfonso-Sánchez, M.A., et al., An evolutionary approach to the high frequency of the Delta F508 CFTR mutation in European populations. Medical Hypotheses, 2010. 74(6): p. 989–992.CrossRefGoogle Scholar
  42. 42.
    Kamal, N., P. Surana, and C. Koh, Liver disease in patients with cystic fibrosis. Curr Opin Gastroenterol, 2018. 34(3): p. 146–151.PubMedGoogle Scholar
  43. 43.
    Gominon, A.L., et al., Assessment of Liver Disease Progression in Cystic Fibrosis Using Transient Elastography. J Pediatr Gastroenterol Nutr, 2018. 66(3): p. 455–460.CrossRefGoogle Scholar
  44. 44.
    De Boeck, K., et al., Cystic fibrosis: terminology and diagnostic algorithms. Thorax, 2006. 61(7): p. 627–35.CrossRefGoogle Scholar
  45. 45.
    <026-023lS_2k_Diagnose_der_Mukoviszidose_2013-07-abgelaufen.pdf>.Google Scholar
  46. 46.
    Popli, K. and J. Stewart, Infertility and its management in men with cystic fibrosis: review of literature and clinical practices in the UK. Hum Fertil (Camb), 2007. 10(4): p. 217–21.CrossRefGoogle Scholar
  47. 47.
    Hodges, C.A., M.R. Palmert, and M.L. Drumm, Infertility in females with cystic fibrosis is multifactorial: evidence from mouse models. Endocrinology, 2008. 149(6): p. 2790–7.CrossRefGoogle Scholar
  48. 48.
    Rowe, S.M., J.P. Clancy, and M. Wilschanski, Nasal potential difference measurements to assess CFTR ion channel activity. Methods Mol Biol, 2011. 741: p. 69–86.CrossRefGoogle Scholar
  49. 49.
    Mall, M., et al., Assessment of CFTR function in rectal biopsies for the diagnosis of cystic fibrosis. J Cyst Fibros, 2004. 3 Suppl 2: p. 165–9.CrossRefGoogle Scholar
  50. 50.
    Lopes-Pacheco, M., CFTR Modulators: Shedding Light on Precision Medicine for Cystic Fibrosis. Front Pharmacol, 2016. 7: p. 275.CrossRefGoogle Scholar
  51. 51.
    Von der Hardt, S., Ullrich, Erwachsene mit Mukoviszidose. Es geht um mehr als die Lebensdauer. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2012. 55: 558–567.CrossRefGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Sektion Mukoviszidose, Christiane Herzog-Zentrum Erwachsenen-Mukoviszidose, Endoskopie und LungentransplantationCharité - Universitätsmedizin Berlin, Klinik für Pädiatrie m. S. Pneumologie und Immunologie, Campus Rudolf Virchow KlinikumBerlinDeutschland

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