Cystic Fibrosis Diagnosis and Sweat Test
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Questions and Answers

What is the primary function of the CFTR protein?

  • To produce mucus in the respiratory tract
  • To facilitate the transport of Cl- and HCO3- ions across the epithelial cell membrane (correct)
  • To transport amino acids across the cell membrane
  • To regulate the expression of genes involved in cystic fibrosis

    • What is the normal range of Cl- concentration in sweat for a healthy individual?

  • Greater than 60 mM
  • Between 40-60 mM
  • Less than 60 mM (correct)
  • Less than 40 mM

    • Which of the following domains is NOT a component of the CFTR protein?

  • Intracellular nucleotide-binding domain
  • Transmembrane segment
  • Intracellular regulatory domain
  • Extracellular ligand-binding domain (correct)

    • What is the genetic location of the CFTR gene?

    <p>Locus 7q31.2</p> Signup and view all the answers

    What is the purpose of the sweat test in diagnosing cystic fibrosis?

    <p>To measure the concentration of Cl- and Na+ in sweat following stimulation with pilocarpine</p> Signup and view all the answers

    What is the primary function of Ivacaftor (VX-770) in the context of cystic fibrosis?

    <p>To increase Cl- transport as a CFTR potentiator</p> Signup and view all the answers

    In the Ussing chamber experiment, what is the purpose of amiloride?

    <p>To block Na currents</p> Signup and view all the answers

    According to the study by Van Goor et al., what can be inferred about the effectiveness of Ivacaftor?

    <p>It is more effective in bronchial epithelium from patients with G551D/F508del CFTR compared to homozygous F508del CFTR</p> Signup and view all the answers

    What is the purpose of forskolin in the Ussing chamber experiment?

    <p>To activate CFTR</p> Signup and view all the answers

    What is the genetic background of the bronchial epithelial cells used in the Ussing chamber experiment?

    <p>Both G551D/F508del CFTR and homozygous F508del CFTR</p> Signup and view all the answers

    What is the primary function of CFTR in the bronchial epithelium?

    <p>To mediate Cl- efflux and regulate the hydration of airway surface liquid</p> Signup and view all the answers

    What is the effect of PKA phosphorylation on the CFTR regulatory domain?

    <p>It induces a conformational change that opens the CFTR pore and allows Cl- flux</p> Signup and view all the answers

    In which year was Trikafta approved by the EMA?

    <p>2020</p> Signup and view all the answers

    What is the predicted increase in median survival for patients with CF treated with Trikafta between the ages of 12 and 17 years?

    <p>45.4 years</p> Signup and view all the answers

    What is the consequence of impaired CFTR function in the respiratory tract?

    <p>Dehydration and acidification of airway surface liquid, leading to impaired mucociliary clearance</p> Signup and view all the answers

    What is the role of adenylate cyclase in the cAMP signaling pathway?

    <p>It converts ATP to cAMP, leading to the activation of protein kinase A</p> Signup and view all the answers

    In which year was Trikafta approved by AIFA for prescription under the Italian public health service?

    <p>2022</p> Signup and view all the answers

    Who were the recipients of the 2024 Breakthrough Prize for the development of Trikafta?

    <p>Sabine Hadida, Paul Negulescu, and Fredrick Van Goor</p> Signup and view all the answers

    What is the defect in cystic fibrosis?

    <p>A mutation in the CFTR gene, leading to impaired Cl- efflux and Na+ reabsorption</p> Signup and view all the answers

    What is the name of Trikafta in the European market?

    <p>Kaftrio</p> Signup and view all the answers

    What is the effect of lumacaftor on F508del CFTR in vitro studies?

    <p>Increase in F508del CFTR maturation and chloride secretion</p> Signup and view all the answers

    What is the primary outcome of the lumacaftor-ivacaftor clinical trial in CF patients?

    <p>Improvement in lung function in CF patients</p> Signup and view all the answers

    What is the difference between lumacaftor and other CFTR correctors?

    <p>Lumacaftor is selective for correction of CFTR processing</p> Signup and view all the answers

    What type of assay was used to evaluate protein maturation in CF cell models?

    <p>Immunoblotting</p> Signup and view all the answers

    What is the advantage of combining lumacaftor with VX-770?

    <p>It is additive in increasing F508del CFTR maturation and chloride secretion</p> Signup and view all the answers

    Study Notes

    Cystic Fibrosis Diagnosis

    • A positive IRT test is followed by a sweat test and DNA test for clinical diagnosis.
    • Sweat test measures Cl- and Na+ concentrations in sweat after stimulation with pilocarpine.
    • In CF, sweat Cl- concentration is > 60 mM.

    CFTR Gene and Protein

    • The CFTR gene is located at 7q31.2 and codes for the CFTR protein.
    • CFTR is an anion channel for Cl- and HCO3- expressed on the apical surface of epithelial cells in exocrine organs.
    • The protein consists of 2 membrane spanning domains, 2 nucleotide-binding domains, and 1 regulatory domain.

    CFTR Function

    • CFTR is normally closed and opens following activation via the cAMP signaling pathway.
    • Activation involves ligand binding to a membrane receptor, adenylate cyclase activation, and protein kinase A phosphorylation of the CFTR regulatory domain.
    • This leads to a conformational change, pore opening, and chloride flux.

    Respiratory Tract

    • In bronchial epithelium, normal CFTR mediates Cl- efflux and limits Na+ reabsorption, maintaining airway surface liquid hydration.
    • In CF, mutant CFTR leads to impaired mucociliary clearance, dehydration, and acidification of airway surface liquid.

    CFTR Modulators

    • Ivacaftor (VX-770) is a CFTR potentiator that increases Cl- transport.
    • Lumacaftor (VX-809) is a CFTR corrector that increases F508del CFTR maturation and chloride secretion.
    • Combined treatment with lumacaftor and ivacaftor improves lung function in CF patients.

    Trikafta Treatment

    • Trikafta is a combination of tezacaftor, ivacaftor, and elexacaftor approved for CF patients with F508del CFTR.
    • Simulation models predict that Trikafta treatment increases median survival by 45.4 years compared to best standard care alone.
    • Trikafta has been approved by the EMA and AIFA for prescription under the Italian public health service.

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    Description

    This quiz covers the diagnosis of Cystic Fibrosis (CF) using the sweat test, which measures the concentration of chloride and sodium in sweat. Learn about the procedure and interpretation of results.

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