Rationale: Skeletal muscle fat infiltration progresses with aging and is worsened among individuals with a history of cigarette smoking. Many negative impacts of smoking on muscles are likely reversible with smoking cessation. Objectives: To determine if the progression of skeletal muscle fat infiltration with aging is altered by smoking cessation among lung cancer screening participants. Methods: This was a secondary analysis based on the National Lung Screening Trial. Skeletal muscle attenuation in Hounsfield unit (HU) was derived from the baseline and follow-up low-dose CT scans using a previously validated artificial intelligence algorithm. Lower attenuation indicates greater fatty infiltration. Linear mixed-effects models were constructed to evaluate the associations between smoking status and the muscle attenuation trajectory. Measurements and Main Results: Of 19,019 included participants (age: 61 years, 5 [SD]; 11,290 males), 8,971 (47.2%) were actively smoking cigarettes. Accounting for body mass index, pack-years, percent emphysema, and other confounding factors, actively smoking predicted a lower attenuation in both males (β_0=-0.88 HU, P<.001) and females (β_0=-0.69 HU, P<.001), and an accelerated muscle attenuation decline-rate in males (β_1=-0.08 HU/y, P<.05). Age-stratified analyses indicated that the accelerated muscle attenuation decline associated with smoking likely occurred at younger age, especially in females. Conclusions: Among lung cancer screening participants, active cigarette smoking was associated with greater skeletal muscle fat infiltration in both males and females, and accelerated muscle adipose accumulation rate in males. These findings support the important role of smoking cessation in preserving muscle health.

The authors have declared no competing interest.

This research is supported or partly supported by the following awards. National Science Foundation CAREER 1452485; National Cancer Institute (NCI) grants R01 EB017230 and R01 CA253923; NCI grant U01 CA196405; NCI grant U01 CA152662; grant UL1 RR024975-01 of the National Center for Research Resources and grant 2 UL1 TR000445-06 of the National Center for Advancing Translational Sciences; Martineau Innovation Fund grant through the Vanderbilt-Ingram Cancer Center Thoracic Working Group.

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This study is based on the publicly available data of the National Lung Screening Trial (NLST). The data were publicly available before the initiation of the present study. The data can be obtained at the The Cancer Data Access System of National Cancer Institute: https://cdas.cancer.gov/nlst/ NLST was approved by the institutional review board at each of the 33 participating medical institutions. Written informed consent was provided by each participant. The authors obtained permission to access and analyze the de-identified data collected by NLST researchers.

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Data analyzed during the study were provided by a third party. Requests for data should be directed to the provider indicated in the Acknowledgments.

https://cdas.cancer.gov/nlst/