Paediatric Thoracic Imaging in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Conductance Regulator Modulation

Abstract

Cystic fibrosis (CF) is one of the most common progressive life-shortening genetic conditions worldwide. Ground-breaking translational research has generated therapies that target the primary cystic fibrosis transmembrane conductance regulator (CFTR) defect, known as CFTR modulators. A crucial aspect of paediatric CF disease is the development and progression of irreversible respiratory disease in the absence of clinical symptoms. Accurate thoracic diagnostics have an important role to play in this regard. Chest radiographs are non-specific and insensitive in the context of subtle changes in early CF disease, with computed tomography (CT) providing increased sensitivity. Recent advancements in imaging hardware and software have allowed thoracic CTs to be acquired in paediatric patients at radiation doses approaching that of a chest radiograph. CFTR modulators slow the progression of CF, reduce the frequency of exacerbations and extend life expectancy. In conjunction with advances in CT imaging techniques, low-dose thorax CT will establish a central position in the routine care of children with CF. International guidelines regarding the choice of modality and timing of thoracic imaging in children with CF are lagging behind these rapid technological advances. The continued progress of personalised medicine in the form of CFTR modulators will promote the emergence of personalised radiological diagnostics.

Cystic fibrosis–related metabolic defects: crosstalk between ion channels and organs

“…However, recent medical breakthroughs, particularly the FDA approval of Trikafta in 2019 (VX18-445-104, ClinicalTrials.gov ID: NCT04058353), have increased life expectancy for patients with CF into the fifties and is continuing to rise, with some patients now living into their eighties ( 7 ). Trikafta is the first approved CF medication that affectively treats patients with the ΔF508 variant and has been approved for use in patients as young as two years of age ( 8 ). This combination of three drugs (elexacaftor, ivacaftor, and tezacaftor) targets the defective CFTR protein, modulating its ion channel activity and half-life at the cell surface, and is particularly effective at improving the function of the ΔF508 variant.…”