Quantitative analysis of computed tomography of the lungs in patients with lymphangioleiomyomatosis treated with sirolimus

Yuki Ko; Katsuaki Asakawa; Kazunori Tobino; Tsuyoshi Oguma; Toyohiro Hirai; Toshinori Takada; Kazuhisa Takahashi; Kuniaki Seyama; Multicenter Lymphangioleiomyomatosis Sirolimus Trial for Safety Study Group

doi:10.1016/j.heliyon.2020.e03345

Quantitative analysis of computed tomography of the lungs in patients with lymphangioleiomyomatosis treated with sirolimus

Heliyon. 2020 Feb 6;6(2):e03345. doi: 10.1016/j.heliyon.2020.e03345. eCollection 2020 Feb.

Authors

Yuki Ko^{1

2}, Katsuaki Asakawa³, Kazunori Tobino^{1

2}, Tsuyoshi Oguma⁴, Toyohiro Hirai⁴, Toshinori Takada⁵, Kazuhisa Takahashi², Kuniaki Seyama²; Multicenter Lymphangioleiomyomatosis Sirolimus Trial for Safety Study Group

Affiliations

¹ Division of Respiratory Medicine, Iizuka Hospital, Yoshio-Machi 3-83, Iizuka-Shi, Fukuoka 820-8505, Japan.
² Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Hongo 3-1-3, Bunkyo-Ku, Tokyo 113-8421, Japan.
³ Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Asahi-Dori 1-754, Chyuo-Ku, Niigata, 951-8520, Japan.
⁴ Division of Respiratory Medicine, Kyoto University Faculty of Medicine and Graduate School of Medicine, Kawara-Machi 54, Seigoin, Sakyo-Ku, Kyoto 606-8507, Japan.
⁵ Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Urasa 4132, Minami-Uonuma, Niigata, 949-7302, Japan.

Abstract

Objectives: We aimed to study sirolimus-related lung parenchymal changes by quantitative analysis of computed tomography (CT) of the lungs in patients with lymphangioleiomyomatosis (LAM).

Methods: We studied 20 participants from the Multicenter Lymphangioleiomyomatosis Sirolimus Trial for Safety study, who had undergone both thin-section CT scans and pulmonary function tests at baseline, 12, and 24 months. Quantitative CT parameters such as CT-derived total lung capacity, percentage of low attenuation area (LAA%), lung density histogram, fractal property of low attenuation area, and airway dimensions were analyzed, and correlations were conducted between the longitudinal change in each quantitative CT measurement and changes in pulmonary function were examined. Among 20 participants, pre-trial (n = 8) and post-trial (n = 16) CT data were also analyzed to deduce pathophysiologic implications of the serial changes in CT parameters during trial periods.

Results: FEV₁ significantly increased from baseline to 24 months (slope 3.71 ± 1.50 ml/month) whereas FVC didn't during sirolimus therapy. Strikingly, LAA%, and skewness and kurtosis of density histogram significantly increased from baseline to 24 months, while mean and mode CT values significantly decreased from baseline to 24 months. Statistically significant positive correlations were found between ΔFEV₁ and Δskewness (r = 0.465, p = 0.045). Taking the changes in lung density during pre-trial period into consideration, sirolimus decreases the area of -800 to -750 Housefield unit (HU) density and inhibits the decrease of -950 to -800 HU area during treatment, then producing the increased LAA% during the trial and post-trial periods. Given few sirolimus-related changes in airway dimensions, possible changes in lung mechanics may have contributed to increased FEV₁.

Conclusion: Our study suggests that the lung density histogram parameters, kurtosis, and skewness, may be useful as indicators of the efficacy of sirolimus.

Keywords: Airflow obstruction; Clinical research; Histogram; Kurtosis; Lung density; Physiology; Radiology; Respiratory system; Skewness; Women's health; mTOR inhibitors.