Nutritional Status and Circulating Levels of Fat-Soluble Vitamins in Cystic Fibrosis Patients: A Cohort Study and Evaluation of the Effect of CFTR Modulators

TL;DR: The Working Group updated the nutritional guidelines including assessment and management at all ages and there are expanded chapters on pregnancy, CF-related liver disease, and CF-related diabetes, bone disease, nutritional and mineral supplements, and probiotics.

Abstract: During the past quarter century, the diagnosis and treatment of cystic fibrosis (CF) have been transformed by molecular sciences that initiated a new era with discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The knowledge gained from that breakthrough has had dramatic clinical impact. Although once a diagnostic dilemma with long delays, preventable deaths, and irreversible pathology, CF can now be routinely diagnosed shortly after birth through newborn screening programs. This strategy of pre-symptomatic identification has eliminated the common diagnostic "odyssey" that was a failure of the healthcare delivery system causing psychologically traumatic experiences for parents. Therapeutic advances of many kinds have culminated in CFTR modulator treatment that can reduce the effects of or even correct the molecular defect in the chloride channel -the basic cause of CF. This astonishing advance has transformed CF care as described fully herein. Despite this impressive progress, there are challenges and controversies in the delivery of care. Issues include how best to achieve high sensitivity newborn screening with acceptable specificity; what course of action is appropriate for children who are identified through the unavoidable incidental findings of screening tests (CFSPID/CRMS cases and heterozygote carriers); how best to ensure genetic counseling; when to initiate the very expensive but life-saving CFTR modulator drugs; how to identify new CFTR modulator drugs for patients with non-responsive CFTR variants; how to adjust other therapeutic modalities; and how to best partner with primary care clinicians. Progress always brings new challenges, and this has been evident worldwide for CF. Consequently, this article summarizes the major advances of recent years along with controversies and describes their implications with an international perspective.

TL;DR: O Ongoing monitoring of vitamin levels after ETI initiation is needed to screen for potential deficiencies and toxicities, particularly in light of case reports of hypervitaminosis A followingETI initiation.

TL;DR: A comprehensive overview of the literature on ELX/TEZ/IVA for CF can be found in this article , where the authors provide an overview of existing literature on triple combination therapy for CF.

TL;DR: Elexacaftor-tezacaft or-ivacaft or was efficacious in patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous CFTR modulator regimens were ineffective.

TL;DR: These data show that lumacaftor in combination with ivacaftors provided a benefit for patients with cystic fibrosis homozygous for the Phe508del CFTR mutation.

TL;DR: Elexacaftor plus tezacaftorplus ivacaftors provided clinically robust benefit compared with tezacftor plus ivACaftor alone, with a favourable safety profile, and shows the potential to lead to transformative improvements in the lives of people with cystic fibrosis who are homozygous for the F508del mutation.

TL;DR: A registry‐based study to determine prognostic indicators of 8‐year mortality and morbidity in young children with cystic fibrosis (CF) and clinical outcomes in 1998 is conducted.