Cystická fibróza (CF) je vrozené onemocnění vyvolané patogenními variantami genu CFTR. Projevuje se především chronickým sinopulmonálním onemocněním, postižením trávicího ústrojí s poruchou stavu výživy, vysokou koncentrací chloridů v potu a obstruktivní azoospermií. Kromě tradiční symptomatické léčby je v posledních letech dostupná modulátorová terapie, která cílí na chybějící nebo nefunkční CFTR protein. U nosičů alespoň jedné mutace F508del je indikována léčba kombinací elexakaftor, tezakaftor a ivakaftor, z ostatních mutací jsou pro monoterapii ivakaftorem vhodní nosiči tzv. gating mutací (např. G551D). Modulátorová léčba prokázala v klinických studiích zlepšení plicních funkcí, stavu výživy a kvality života a zásadně zlepšila prognózu nemocných CF. Hlavní nevýhodou modulátorové léčby je její vysoká cena.

Cystic fibrosis (CF) is a hereditary disease caused by pathogenic variants of the CFTR gene. It is mainly manifested by chronic sinopulmonary disease, digestive tract involvement with nutritional status disorders, high sweat chloride concentration and obstructive azoospermia. In addition to traditional symptomatic treatment, modulator therapy has become available in recent years, which targets the missing or dysfunctional CFTR protein. For carriers of at least one F508del mutation, treatment with a combination of elexacaftor, tezacaftor and ivacaftor is indicated; among other mutations, carriers of so-called gating mutations (e.g. G551D) are suitable for ivacaftor monotherapy. Modulator therapy has been shown in clinical trials to improve lung function, nutritional status, and quality of life, and leads to a significantly better prognosis for patients with CF. The main disadvantage of modulator therapy is its high cost.

• Keywords
• gen CFTR, modulátory CFTR proteinu,
• MeSH
• Cystic Fibrosis * therapy   MeSH
• Humans MeSH
• Cystic Fibrosis Transmembrane Conductance Regulator drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Anti-Bacterial Agents administration & dosage   MeSH
• Antibiotics, Antitubercular administration & dosage   adverse effects   therapeutic use   MeSH
• Humans MeSH
• Mycobacterium Infections * diagnosis   drug therapy   classification   MeSH
• Nontuberculous Mycobacteria * classification   pathogenicity   MeSH
• Mandatory Reporting MeSH
• Lung Diseases diagnosis   etiology   drug therapy   MeSH
• Tertiary Prevention MeSH
• Check Tag
• Humans MeSH

Pilíře léčby cystické fibrózy byly dlouhá léta tvořeny péčí o průchodnost dýchacích cest, agresivní antibiotickou léčbou plicní infekce a vysokokalorickou stravou spolu se suplementací pankreatickými enzymy. V posledních deseti letech je však dostupná modulátorová léčba cílená na jednotlivé patogenní varianty genu pro transmembránový regulátor vodivosti (cystic fibrosis transmembrane conductance regulator, CFTR). Jako vysoce účinnou modulátorovou léčbu pak označujeme terapii ivakaftorem u nosičů tzv. gating mutací (např G551D) a užití kombinace elexakaftor-tezakaftor-ivakaftor u nosičů alespoň jedné mutace F508deL

or many years, the mainstays of cystic fibrosis treatment have been airway patency care, aggressive antibiotic treatment of lung infection, and a high-calorie diet along with pancreatic enzyme supplementation. In the last ten years, however, modulatory treatment targeting individual pathogenic variants of the CFTR gene (cystic fibrosis transmembrane conductance regulator) has become available. As a highly effective modulator treatment, we refer to ivacaftor therapy in carriers of so-called gating mutations (e.g. G551D) and the use of the elexacaftor-tezacaftor-ivacaftor combination in carriers of at least one F508del mutation.

• Keywords
• vysoce účinná modulátorová léčba, ivakaftor, lumakaftor,
• MeSH
• Burkholderia cepacia MeSH
• Chlorides MeSH
• Cystic Fibrosis * drug therapy   genetics   pathology   MeSH
• Drug Therapy, Combination MeSH
• Humans MeSH
• Young Adult MeSH
• Mutation MeSH
• Nutritional Status MeSH
• Sweat chemistry   MeSH
• Cystic Fibrosis Transmembrane Conductance Regulator * genetics   drug effects   MeSH
• Check Tag
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• Publication type
• Meeting Abstract MeSH

• MeSH
• Cystic Fibrosis MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Case Reports MeSH
• Collected Work MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• pneumologie a ftizeologie
• gastroenterologie

Introduction: Seminal clinical trials with the triple combination of elexacaftor-tezacaftor-ivacaftor (ETI) demonstrated clinical efficacy in people with cystic fibrosis (pwCF) who carry at least one F508del mutation. However, due to exclusion criteria of these clinical trials, the effect of ETI was not studied in a substantial number of pwCF. Thus, we ran a single center trial to evaluate a clinical efficacy of ETI treatment in adult pwCF who were ineligible for enrollment in registration studies. Methods: PwCF on ETI with prior lumacaftor-ivacaftor therapy, severe airway obstruction, well-preserved lung function, or with airway infection with pathogens at risk of more rapid decline in lung function formed the study group, while all the others on ETI formed the control group. Lung function, nutritional status and sweat chloride concentration were assessed before and after initialization of ETI therapy over a 6-month period. Results: Approximately a half of the ETI-treated pwCF at the adult Prague CF center (49 of 96) were assigned to the study group. Their mean changes in body mass index ( + 1.04 kg/m2) and in sweat chloride concentration (-48.4 mmol/L) were similar to the control group ( + 1.02 kg/m2; -49.7 mmol/L), while the mean change in percent predicted forced expiratory volume in 1 s (ppFEV1; + 10.3 points) was significantly lower than in the control group ( + 15.8 points) (p = 0.0015). In the subgroup analysis, pwCF with severe airway obstruction (ppFEV1 <40) and pwCF with well-preserved lung function (ppFEV1 >90) showed a less potential for improvement in lung function during the ETI treatment than controls (median change in ppFEV1 + 4.9 points and + 9.5 points, respectively). Conclusion: PwCF not eligible for inclusion in clinical trials demonstrated improvement in lung function and nutritional status following the initiation of treatment with the ETI combination. Moderate increase in ppFEV1 was observed in those with severe airway obstruction or well-preserved lung function.

• Publication type
• Journal Article MeSH

• MeSH
• Respiratory System Abnormalities * classification   pathology   MeSH
• Cystic Fibrosis diagnosis   genetics   pathology   therapy   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Humans MeSH
• Lung Diseases therapy   MeSH
• Primary Graft Dysfunction MeSH
• Transplantation Conditioning MeSH
• Graft Rejection MeSH
• Lung Transplantation * nursing   adverse effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• Publication type
• Meeting Abstract MeSH