Changes in volume-corrected whole-lung density in smokers and former smokers during the ITALUNG screening trial.

PURPOSE: To evaluate with a volume-corrected whole-lung approach changes in lung density over 2 years consistent with progression of pulmonary emphysema in smokers and former smokers enrolled in the ITALUNG trial of lung cancer screening using low-dose computed tomography (LDCT). MATERIALS AND METHODS: A total of 103 subjects (mean age 63±4 y with a pack-year history of at least 20) underwent 2 whole-lung LDCT examinations 2 years apart. Visual assessment was made independently by 2 experienced observers on the initial LDCT examination with a 0 to 4 grading system for each of 6 regions (right and left upper, mid, and lower lung). The whole-lung 15th percentile of attenuation coefficient and relative area (RA) at -910 HU, both corrected to the individual lung volume (Perc15v and RA910v), were measured on the 2 LDCT examinations. The intrasubject variability of Perc15v and RA910v was previously determined in 32 other subjects of the trial examined using the same scanner and technique twice over a 3-month interval for suspicious nodules. RESULTS: The 2 operators agreed on the presence of mild to severe emphysema (visual score ≥1 in at least 1 region) at initial LDCT examination in 24 (23%) of the 103 subjects. Fifteen subjects (15%) showed a Perc15v change between the 2 examinations exceeding the lower 95% limit of agreement, indicating progression of emphysema with a mean difference in lung density of -14.7%±2.6%. Ten of the 15 were identified as showing emphysema progression by RA910v as well. No association was observed between progression of emphysema and visual evidence of emphysema at initial LDCT examination, smoking status, or pack-years at baseline, or intervening changes in smoking habits. CONCLUSION: Once variations in inspiratory lung volumes are taken into account, changes in lung density over 2 years consistent with progression of pulmonary emphysema in elderly smokers and former smokers are uncommon.

Defining the intra-subject variability of whole-lung CT densitometry in two lung cancer screening trials.

RATIONALE AND OBJECTIVES: To define a statistically based variation of individual whole-lung densitometry above which a real increase of pulmonary extent can be suspected in lung cancer screening trials. MATERIALS AND METHODS: Baseline and 3-month follow-up low-dose computed tomography (LDCT) examinations of 131 smokers or former smokers recruited in the ITALUNG (32 subjects) and MILD (99 subjects) trials were compared using for each data set two different image processing tools for whole-lung densitometry. Both trials were approved by institutional review boards, and written informed consent was obtained from all participants. Assuming that no change of emphysema extent can occur in a 3-month interval, the Bland and Altman method was used to assess the agreement between baseline and follow-up LDCT examinations for lung volume, 15th percentile (Perc15) of lung density and Perc15 corrected for lung volume by application of a linear detrend on log-transformed data. RESULTS: Similar results were obtained in each data set using two different image processing tools. In the ITALUNG cohort the 95% limits of agreement (LoA) interval of volume corrected Perc15 was -9.7 to 10.7% using image processing method 1 and -10.3 to 11.5% using image processing method 2. In the MILD cohort, the 95% LoA interval of volume corrected Perc15 was -14.7 to 17.3% with both image processing methods. CONCLUSION: In the two considered lung cancer screening settings a range of 9.7-14.7% decrease of volume corrected Perc15 represents a statistically defined threshold to suspect a real increase of emphysema extent in serial LDCT examinations.