Elexacaftor/tezacaftor/ivacaftor influences body composition in adults with cystic fibrosis: a fully automated CT-based analysis

Sci Rep. 2024 Apr 24;14(1):9465. doi: 10.1038/s41598-024-59622-2.

Abstract

A poor nutritional status is associated with worse pulmonary function and survival in people with cystic fibrosis (pwCF). CF transmembrane conductance regulator modulators can improve pulmonary function and body weight, but more data is needed to evaluate its effects on body composition. In this retrospective study, a pre-trained deep-learning network was used to perform a fully automated body composition analysis on chest CTs from 66 adult pwCF before and after receiving elexacaftor/tezacaftor/ivacaftor (ETI) therapy. Muscle and adipose tissues were quantified and divided by bone volume to obtain body size-adjusted ratios. After receiving ETI therapy, marked increases were observed in all adipose tissue ratios among pwCF, including the total adipose tissue ratio (+ 46.21%, p < 0.001). In contrast, only small, but statistically significant increases of the muscle ratio were measured in the overall study population (+ 1.63%, p = 0.008). Study participants who were initially categorized as underweight experienced more pronounced effects on total adipose tissue ratio (p = 0.002), while gains in muscle ratio were equally distributed across BMI categories (p = 0.832). Our findings suggest that ETI therapy primarily affects adipose tissues, not muscle tissue, in adults with CF. These effects are primarily observed among pwCF who were initially underweight. Our findings may have implications for the future nutritional management of pwCF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / diagnostic imaging
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adult
  • Aminophenols* / therapeutic use
  • Benzodioxoles* / therapeutic use
  • Body Composition* / drug effects
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / physiopathology
  • Drug Combinations*
  • Female
  • Humans
  • Indoles* / therapeutic use
  • Male
  • Nutritional Status
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Pyrrolidines / therapeutic use
  • Quinolines*
  • Quinolones* / therapeutic use
  • Retrospective Studies
  • Tomography, X-Ray Computed
  • Young Adult

Substances

  • Aminophenols
  • Quinolones
  • Benzodioxoles
  • Drug Combinations
  • Indoles
  • Pyrazoles
  • Pyridines
  • Pyrrolidines
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • elexacaftor
  • ivacaftor
  • tezacaftor
  • elexacaftor, ivacaftor, tezacaftor drug combination
  • Quinolines