Impact of Elexacaftor-Tezacaftor-Ivacaftor on Muscle Composition in Cystic Fibrosis: An AI-Assisted Chest CT-Based Body Composition Analysis.

ETI therapy was associated with a significant increase in skeletal muscle area (SMA) over time, while no such increase was observed in the no ETI group.

• The ETI group showed a significant increase in SMA over time (p < 0.001)
• Study included 102 adult people with cystic fibrosis (pwCF), 42 females (41%), mean age 33.9 ± 11.1 years
• AI-assisted body composition analysis was performed on chest CT images at the T12 level
• Minimum of six months between scans was required for inclusion

Inter- and intramuscular adipose tissue (IMAT), low-attenuation muscle area (LAMA), and IMAT/SMA ratio increased in both the ETI and no ETI groups.

• IMAT, LAMA, and IMAT/SMA ratio increased in both groups (all p < 0.05)
• These changes indicate progression of myosteatosis regardless of ETI treatment status
• IMAT/SMA ratio was calculated as a measure of relative fat infiltration within muscle
• LAMA reflects low-attenuation muscle area, associated with fat infiltration of muscle tissue

Skeletal muscle indices (SMI) showed alterations only in the ETI group, with divergent changes depending on the normalizing variable used.

• SMA/m2 increased significantly in the ETI group (p < 0.001)
• SMA/kg decreased significantly in the ETI group (p = 0.003)
• SMA/BMI decreased significantly in the ETI group (p = 0.006)
• No significant SMI alterations were observed in the no ETI group
• The decrease in weight- and BMI-adjusted SMI despite increased absolute SMA suggests disproportionate weight gain relative to muscle mass gain

Sex-specific analysis showed that SMA and myosteatosis increased regardless of sex in both treatment groups.

• SMA and myosteatosis increased regardless of sex (all p < 0.05)
• Weight-adjusted SMI decreased only in females receiving ETI therapy (p < 0.05)
• This sex-specific finding suggests that female pwCF on ETI may be at greater risk for sarcopenic obesity
• The study cohort included 42 females (41%) out of 102 total participants

Trends in the development of sarcopenic obesity were observed in adult pwCF, particularly in female pwCF undergoing ETI therapy.

• Sarcopenic obesity is characterized by simultaneous increase in fat mass and relatively insufficient muscle mass
• The pattern of increasing absolute SMA alongside decreasing weight-adjusted SMI and increasing IMAT supports a sarcopenic obesity phenotype
• This trend was most pronounced in female pwCF on ETI therapy
• Authors emphasized the importance of comprehensive body composition assessments and targeted interventions to optimize muscle mass and quality while managing adipose tissue accumulation

AI-assisted body composition analysis using chest CT at the T12 level was employed as a retrospective method to measure multiple muscle composition parameters in pwCF.

• Parameters measured included skeletal muscle area (SMA), inter- and intramuscular adipose tissue (IMAT), and low-attenuation muscle area (LAMA)
• The study was a retrospective observational design using routine chest CT scans
• CT-based body composition analysis at the T12 level was used as a proxy for whole-body muscle and fat assessment
• Height- and weight-related skeletal muscle indices (SMI) were calculated from raw measurements